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Volume 2, Issue 4

October - December, 2014

Aims and Scope


El Mednifico Journal is an open access, quarterly, peer-reviewed journal from Pakistan that aims to
publish scientifically sound research across all fields of medicine. It is the first journal from Pakistan that
publishes researches as soon as they are ready, without waiting to be assigned to an issue. The journal
has certain unique characteristics:

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soon as they are ready, without waiting for an issue to come out. These articles are then
proofread, copyedited and arranged into four issues per volume and one volume per year
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Editorial Board
Senior Editor-in-Chief
Prof. Nazeer Khan

Executive Editors

Editor-in-Chief

Managing Editor

Syed Salman Ahmed,


Sajid Ali

Asfandyar Sheikh

Syed Arsalan Ali

Assistant Editor-in-Chief

Assistant Managing Editor

Haris Sheikh

Shanawer Khan

Senior Editors
Dr. Juan S Barajas-Gamboa
Prof. Asaad Javaid,
Dr. Ye Yang,
Dr. Abdul Hafeez Baloch,
Dr. Mansoor Husain,
Dr. Manit Arora
Dr. Muzaffar H Qazilbash,
Dr. Tasneem Z Naqvi,
Dr. Asim A Shah,

Prof. Shahid Wahab,


Dr. Samina Abidi,
Dr. Rashid Mazhar,
Dr. Mosaddiq Iqbal,
Prof. Javed Akram,
Prof. Abdul Bari Khan,
Prof. Ashraf Ganatra,
Dr. Raza Ur Rehman,
Dr. Waris Qidwai,

Dr. Muhammad Ishaq Ghori,


Dr. Akber Agha,
Dr. Adnan Mustafa Zubairi,
Dr. Saqib Ansari,
Dr. Mohsina Ibrahim,
Dr. Qamaruddin Nizami,
Dr. Samra Bashir,
Dr. Nabeel Manzar,
Muhammad Ashar Malik

Section Editors

Editors

Assistant Editors

Ali Sajjad,
Hafiz Muhammad Aslam,
Syed Askari Hasan,
Muhammad Uzair Rauf,
Syed Mumtaz Ali Naqvi

Statistics Editors

Shaikh Hamiz Ul Fawwad,


Gulrayz Ahmed,
Uzair Ahmed Siddiqui,
Dr. Hussain Muhammad
Abdullah,
Asfandyar Khan Niazi,
Muhammad Danish Saleem,
Iqra Ansari

Mehwish Hussain,
Syed Ali Adnan

Production Editors

Raza Mahmood Hussain,


Maheen Anwer,
Anum Saleem,
Hira Hussain Khan,
Imran Jawaid,
Hina Azhar Usmani,
Hira Burhan,
Kiran Yaqub,
Quratulain Ghori,
Bushra Iqbal,
Maria Rahim

Noorulain Chishti,
Muhammad Hamid
Chaudhary,
Adnan Salim,
Bushra Mufti,
Parisa Aijaz,
Marium Farooqi
ii

Table of Contents
FrontPage
Editorial Board
Call for Papers
Health Poster
Table of Contents

i
ii
iii
iv
v

Original Articles
Percutaneous drainage of abdominal fluids using available materials:
University of Benin teaching hospital experience

322

Blessing Ose-Emenim Igbinedion, Micheal Ibadin, Tobechukwu Tagbo Marchie,


Micheal Nkwor Okobia

The effects of n-3 fatty acids intake on PON1 activity and fatty acid status in
type 2 diabetic patients A pilot study

328

Zorica Rasic-Milutinovic, Tamara Popovic, Jasmina Debeljak-Martacic, Gordana Perunicic-Pekovic,


Suncica Borozan, Danijela Ristic-Medic, Milena Lackovic, Maria Glibetic

Married womens access to resources and decision making power in


Nekemte Town, West Ethiopia

334

Elias Teferi, Sileshi Garoma

Effectiveness of hand versus rotary instrumentation on retreatment of


curved canals

341

Ebru zsezer Demiryrek, Emre Bodrumlu

Assessment of childhood cancer at National Oncology Center in Sana'a city,


Yemen

345

Nabil Ahmed Al-Rabeei, Abdulhameed Ali Al-Thaifani, Ashwaq A Al-Ariki

A comparison of survival with chemoradiation therapy alone versus surgery


and post-esophagectomy chemoradiation in patients with esophageal
carcinoma

350

Manoochehr Aghajanzadeh, Abbas Rahimi, Dina Emami, Gilda Aghajanzadeh, Sina Khajeh Jahromi,
Hannan Ebrahimi

A retrospective comparison of docetaxel and paclitaxel as single-agent


second-line chemotherapy for advanced stage non-small cell lung cancer
Julide Celdir Emre, Aysegul Baysak, Gursel Cok, Ozer Ozdemir, Tuncay Goksel

353

Reproductive health complications among women: A study in a tertiary


hospital of Mumbai

357

Mousumi Gogoi, Sayeed Unisa

Types and frequency of pre-analytical errors at University of Gondar


hospital laboratory

363

Zelalem Addis, Tadelo Wondimagegn, Belaynesh Tachebele

Patterns of herbal use among patients attending family practice centers

366

S I Shalaby, Mosleh A Ismail, Nadia M Mansour, Heba M Abbas, Neelima Gupta

Reviews
The role of microRNAs in HIV infection

374

Marta Calado, Harapan Harapan

Patient specific instrumentation: A minimally invasive technique for knee


arthroplasty

379

Mahmoud A Hafez, Ashsish Jaiman, Hosamuddin Hamza

Development of nitroimidazopyrans and nitroimidaoxazoles for


tuberculosis chemotherapy

383

Mohammad Asif

Sleep and its disorders

389

Ahmed M Kabel, Ibrahim A Maghrabi

Case Reports
Ultrasound and MRI findings of syntelencephaly and correlation with
perinatal pathology

394

Nurtac Akgul, Cem Y Sanhal, Serap Toru, Inanc Mendilcioglu, Kamil Karaali

Right-sided diaphragmatic eventration with gastric volvulus and abnormal


rotation of liver

396

Rakesh Mehra, Uma Debi, Anupam Lal, Saroj Kant Sinha, Nadeem Parvez, Kaushal Kishor Prasad

Intestinal occlusion due to cryptogenic, multifocal, ulcerous, stenosing


enteritis treated by laparoscopy

399

Alejandro Weber Snchez, Pablo Weber, Rafael Carb, Jorge Fishleter

Embolization of uterine and ovarian artery anastomosis in the treatment of


menorrhagia secondary to adenomyosis and leiomyoma
Dustin Hofstede, Peter Munk, Roshni Patel, Nivmand Khorrami

vi

402

Ehlers Danlos syndrome in an edentulous patient with temporomandibular


joint dislocation

405

Renu Tanwar, Asha R Iyengar, K S Nagesh, Rishabh Kapila, Gurvinder Kaur

Intraosseous ganglion cyst of scaphoid: A case report

408

Nasir Muzaffar, Nissar Shah, Sulaiman Seth, Sheikh Ajaz

Half annular pancreas - a cadaveric case report

411

B Satheesha Nayak, Naveen Kumar, Srinivasa Rao Sirasanagandla, Ravindra S Swamy, S Sudarshan

Treatment option for deficient maxilla by bone expansion using D-shaped


bone expander for implant restorations

413

Satheesh B Haralur, Farhan K Shah, Nausheen Khan

Coexistence of a normal thyroid with a non-functional ectopic thyroid


tissue: a case report with review

416

Sunder Goyal, Snigdha Goyal, Shveta Narang, Isha Saini

Literature evaluation of a case with endometrial cancer and primary


cutaneous anaplastic large cell lymphoma

418

Feryal Karaca, Fatma Sert, Elif Cals, Emine Bagr, Erkut Erkut

Occult medullary carcinoma of thyroid - an unusual clinical and pathologic


presentation

421

Khalid S Aljabri, Samia A Bokhari, M Haq, A Durani, A Altayeb, S J Alzahrani, M Alshareef

Florid squamous and focal mucinous metaplasia in Warthins tumor


mimicking low grade mucoepidermoid carcinoma: A diagnostic dilemma on
fine needle aspiration cytology

424

Debjani Mallick, Sonia Gon, Riti Tushar Kanti Sinha, Gayatri Ghosh

Massive upper and lower gastrointestinal bleeding due to intra-abdominal


gossypiboma

426

Muharrem Karaoglan, Fuat Ipekci, Ismail Sert, Safak Ozturk, Azad Gazi Sahin

Treacher Collins syndrome - a report of two cases with review of literature

428

Priyadharshini Alva, Shishir Ram Shetty, Subhas Babu G, Anaya Madiyal

Essays
Child sexual abuse leads to psychological disorders: Literature review
Savera Aziz Ali, Sumera Aziz Ali

vii

430

Mucopolysaccharidosis type III, Sanfilippo syndrome: What does coarse


facies mean?

433

Avina Fierro, Hernandez Avia

Letters to Editor
A conservative approach to reattach fractured anterior tooth fragment

437

Amit Chaudhari, Priya Chaudhari

Appendices
Instructions to Authors
Sponsorship Proposal

ix
xiii

viii

322

http://www.mednifico.com/index.php/elmedj/article/view/233

Open Access

Original Article

Percutaneous drainage of abdominal fluids using available materials: University of Benin teaching
hospital experience
Blessing Ose-Emenim Igbinedion1,2, Micheal Ibadin1, Tobechukwu Tagbo Marchie1, Micheal Nkwor Okobia1

Abstract
Background: The role, function and practice of radiologists have expanded over the last three decades with attendant overlap and conflict
with other clinical disciplines. Interventional radiology has reduced the cost, hospital stay, complication rate, morbidity and mortality of
patients in most instances in comparison with traditional management. Unfortunately the necessary materials and trained manpower is
unavailable in most hospitals in our environment.
Methods: This study was a descriptive retrospective study of interventions performed at the nascent interventional section of the
Radiology department of University of Benin Teaching Hospital (UBTH), Benin, Nigeria. The data of all the percutaneous drainages of
abdominal fluid performed between January 2013 and February 2014 were retrieved. The materials used for the interventions were also
recorded.
Results: There were 13 females and 4 males who had percutaneous drainage (PD) of abdominal fluids performed during this period. The
mean age was 36.7 years. Three patients had ascitic fluid drainage, 4 had hepatic abscesses PD, 2 had subcutaneous abscesses PD, 2 had
hepatic cysts PD, 2 had endometriotic fluids PD, 1 had iliopsoas abscess PD and 3 had percutaneous nephrostomies. Materials utilized
ranged from intravenous cannulae, needle/stylet assemblage, Foleys catheter and pigtail catheters.
Conclusion: Radiological interventions can be successfully performed in Nigeria (and possibly Africa) using available materials despite
frustrating constraints in the acquisition of interventional materials and equipment which arise from poverty, inaccessible or expensive
materials, discouraging hospital management policies, and inter/intra-discipline conflicts. (El Med J 2:4; 2014)
Keywords: Interventional Radiology, Interventional Drainage, Percutaneous Drainage

Introduction
Interventional radiology (IR) is a therapeutic and diagnostic specialty
that comprises a wide range of minimally invasive image guided
therapeutic procedures as well as invasive diagnostic imaging [1].
Over the last three decades the role of radiologists has evolved and
is increasingly expanding. The evolution in interventional radiology
arose from cooperative innovations between manufacturers of IR
materials (such as Bill Cook) and interventionalists (such as Charles
Dotter). Interventions in radiology now occur with minimally invasive procedures that have resulted in reduction in patients morbidity, mortality, cost and hospital stay [2-4]. This new branch of medical
science requires multi-disciplinary knowledge and the comprehensive application of interventional techniques as well as corroboration
with clinicians [5]. Such interventions can be categorized into vascular and non-vascular. Drainage of abdominal fluid is non-vascular and
can serve both diagnostic and therapeutic functions. These fluids
that are so drained may result in abrupt resolution of the patients
clinical state especially if the fluid is symptomatic.

Unfortunately both the trained man-power for radiologic interventions and the manufacturers of such equipment are concentrated
within developed countries. In Africa, radiology trainees receive considerably less training in interventional radiology as compared to
their counterpart in other continents [6]. Consequently, performance
of radiological interventions is rare in several developing countries,
while in some (like Nigeria), it is sprouting fast in some geo-political
zones. In addition, despite the availability of some trained radiologists, procurement of necessary interventional materials is difficult.
In China, Li reported similar experiences of difficulty in purchasing
interventional radiology materials and poor economic capability of
patients [5]. Therefore, radiologists are constrained to the utilization
of available or alternative materials which may achieve similar results
but are less expensive.
Our aim in this study was to describe available materials used at our
health facility for drainage of abdominal fluids with the hope of inspiring others to source similar materials in the management of their
patients.

Abnormal abdominal fluids include abscesses, ascites, obstructive


uropathy (hydronephrosis and hydroureter), biliary tract obstruction
and cysts. Abscesses and cysts can be in any of the solid abdominal
organs or within the subcutaneous tissues. Traditionally, majority of
these fluids were drained by surgical operations until the advent of
minimally invasive techniques and the evolved role of radiologists.
Concomitantly interventional materials have evolved which has further improved the capabilities of such minimally invasive interventions. Hence, several devices are been developed and improved
upon to further increase the success rate of such minimally invasive
interventions and for better patient management.

This was a retrospective descriptive study of drained abdominal fluids performed at the Radiology Department of the University of Benin Teaching Hospital (UBTH) from January 2013 to February 2014
using medical devices that were available. Each procedure was performed after a written informed consent was signed by the patients
following detailed explanation of the procedure. The procedures
were performed under aseptic techniques and standard protocols.
No new technique was performed throughout this study. The Ethical
Committee of UBTH approved this study.

University of Benin, Nigeria


University of Benin Teaching Hospital, Nigeria

Correspondence: Blessing Ose-Emenim Igbinedion


Email: igbins2@yahoo.com

1
2

Materials and Methods

2014 Igbinedion et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Igbinedion BO, Ibadin M, Marchie TT, Okobia MN: Percutaneous drainage of abdominal fluids using available materials: University of Benin teaching hospital experience. El Mednifico Journal
2014, 2(4).

Igbinedion BO, Ibadin M, Marchie TT et al.

The materials used in this study were sourced locally, although manufactured in foreign countries. Some of the materials used are universally available. All the procedures were guided by the use of ultrasound units either using curvi-linear 3.5MHz or linear 7.5MHz
probes or both as required. One case of percutaneous nephrostomy
was performed by the additional use of intra-luminal injection of
contrast into the urinary tract under fluoroscopic guidance using the
Seldinger technique. The patients were followed for about three
months after the procedure for possible complications. Other necessary data were collected from the patients case notes and communications with the referring clinicians.

323

alcohol which was allowed to stay in the cavity for about 30 minutes
before it was aspirated in order to achieve sclerosis of the cavity.
Urinary diversion was done for patients with obstructive uropathy
(Table 2). We undertook this procedure with the urological team at
our center. The technique adopted is that of Seldinger which can be
found in standard textbook of interventional radiology. This procedure was done sonographically or combined with fluoroscopy. Antegrade pyelography was performed to ascertain the possible cause
and site of the obstruction under fluoroscopy if required. However,
no further intervention was performed. (Refer to Figures 1-7).

The statistical analysis was performed using SPSS version 17 (Illinois,


USA). Frequencies and measurement of central tendencies were calculated.

Results
The mean age of the patients was 36.7 18.5 years with a median
age of 33.0 years. The youngest patient was 2 years of age while the
oldest was 75 years. Females had a higher mean age of 41.5 years
while males had an average age of 21.0 years. Calculation of the
mean ages against the different fluid-type that was drained is presented in Table 1, which also shows that the highest mean age is in
the cystic fluid type, followed closely by hepatic abscess. There were
13 (76.5%) females in this study and 4 (23.5%) males. The sex distribution of the patients against various fluid-type drained is presented
in Table 1.
An intravenous cannula has a metallic needle over which a plastic
sheath is attached. The needle/sheath combination is introduced
into the cavity to be drained under ultrasound guidance. Proper localization of the needle tip is also confirmed when fluid is seen at
the hub of the intravenous cannula set. The needle is then withdrawn and the plastic sheath left in-situ. The tip of this plastic sheath
is non-cutting and as such can be advanced into the cavity or rotated
as desired during fluid drainage. Fluid aspirate were sent for microscopy, culture and sensitivity. Aspirate may also be sent for cytology
when required. We drained ascitic fluid, abscess and cyst using intravenous cannula, provided the IV needle set was long enough to access the fluid (Table 2).
Recurrent ascites, infected ascitic fluid and ascitic fluid from unknown origin were drained. The reason for draining the ascitic fluid
from unknown origin was to ascertain the cause of the fluid accumulation. Prophylactic antibiotics (ceftriazole and metronidazole) were
administered intravenously within one hour prior to the drainage of
suspected infected fluid while for the hepatic cyst drainage oral albendazole was administered to reduce complication from hydatid
anaphylaxis, should the hepatic cyst have arisen from hydatid cyst.
Direct needle/stylet was used in abscesses, cysts or loculated fluid
collections that were beyond the reaches of the intravenous cannula.
Typically 18G and 25cm long needle/stylet assemblage was utilized.
The stylet was removed on confirmation that the needle was within
the fluid cavity after which suction of the fluid was performed. With
the needle in-situ, albendazole suspension was instilled into the cavity and allowed to stay for 30 minutes before been aspirated. Similarly alcohol ablation was done (if required) with instillation of 95%

Figure 1: (a) ultrasound image of left iliopsoas abscess during drainage with the
needle/stylet arrowed. (b) After drainage, no residual abscess.

Figure 2: (a) Encysted intra-abdominal endometriotic cyst. (b) Reduced volume of cyst
during PD with needle/stylet within its lumen (arrowed).

Figure 3: Sonogram of PD in a 49 years male with subcutaneous abscess. (a) Intravenous


cannula needle tip within abscess cavity. (b) Post drainage of abscess.

Figure 4: Pyogenic hepatic abscess sonogram undergoing PD.

http://www.mednifico.com/index.php/elmedj/article/view/233

324

Percutaneous drainage of abdominal fluids using available materials

Table 1: The mean and sex distribution of the patients tabulated against the type of abdominal fluid that was drained
Type of fluid drained
Percutaneous
Cyst
Endometriosis
Ascites
Hepatic Iliopsoas Subcutaneous
Nephrostomy
abscess
abscess
abscess
24.0
52.5
24.5
21.3
51.0
32.0
49.0
Age in years (mean
19.2
0.7
0.7
15.3
19.3
SD)
1
0
0
1
1
0
1
Sex Male
count
25.0
0
0
25.0
25.0
0
25.0
%sex
33.3
0
0
33.3
25.0
0
50.0
%fluid
2
2
2
2
3
1
1
Female
count
15.4
15.4
15.4
15.4
23.1
7.7
7.7
%sex
66.7
100
100
66.7
75.0
100
50.0
%fluid
3 (17.6)
2 (11.8)
2 (11.8)
3 (17.6)
4 (23.5)
1 (5.9)
2 (11.8)
Total, n (%sex)

Total

36.7
18.5
4
100
23.5
13
100
76.5
17 (100)

Table 2: Distribution of fluid drained, instrumentation and some demographics information of the patients
Age
Sex Diagnosis
Procedure
Materials
Comment
(years)
F
Recurrent ascites
PD of ascitic fluid
18G IV cannula
Performed twice, 4 months apart. Exudative fluid.
33
M
Infected peritoneal fluid
PD + normal saline 18G IV cannula
Resolution of symptoms.
4
irrigation
F
Ascites from unknown cause
PD ascitic fluid for 22G IV cannula
Tiny pocket of ascitic fluid tapped under ultrasound
27
mcs
guidance.
F
Pyogenic hepatic abscess
PD + mcs
18G IV cannula
No residual fluid 2 weeks later. No recurrence.
45
M
Pyogenic hepatic abscess with PD + mcs
Needl/stylet and alcohol ablaNo recurrence 10 months later.
29
sickle cell anemia
tion
F
Pyogenic liver abscess
PD + mcs
Needle/stylet
No recurrence till date.
55
F
Pyogenic liver abscess
PD + mcs
18G IV cannula
Complete resolution
75
F
Hepatic cyst
PD + cytology and Needle/stylet, intra-cavitary alMultiple cysts (about 4), three drained the remainder
53
mcs
bendazole and alcohol ablation was to be drained at follow up. Patient lost to follow
up.
F
Hepatic
cyst
PD
+
cytology
and
Needle/stylet,
intra-cavitary
alRecurred fluid re-aspirated. Recurrence occurred 5 days
52
mcs
bendazole and alcohol ablation later. Open surgical drainage was successfully performed with omentum packed into cavity. No fluid reaccumulation 3 weeks later.
F
Encysted intra-abdominal enPDA and alcohol
IV cannula
Fluid re-accumulated 6 months later.
24
dometriosis
ablation
Foleys catheter.
Bleomycin ablation performed on the second drainage.
Patient still on follow up.
F
Abdominal endometriosis with PD with normal sa- IV cannula
Fluid re-accumulated 9 months later after stopping
25
recurrent ascites
line irrigation
Danazol therapy and was further drained.
F
Left iliopsoas abscess
PD + mcs
Needle/stylet
Loculated abscess recollected into main cavity about 2
32
PD and alcohol
Needle/stylet
weeks later which was drained. No recurrence 3 months
ablation
later.
F
Advanced
cervical
carcinoma
PC
nephrostomy
Bilateral
pigtail
catheter
inserPatient pulled out catheter a week later when agitated.
37
with bilateral hydronephrosis
tion using Seldinger technique
M
Bladder outlet obstruction
PC nephrostomy
Pigtail catheter insertion using
Palliative measure.
2
Seldinger technique
F
Ovarian caricinoma
PC nephrostomy
pigtail catheter insertion using
Palliative measure.
33
Seldinger technique
F
Subcutaneous abscess
PD
18G IV cannula
Resolution of symptoms
49
M
Post appendectomy subcutaPD
18G IV cannula
Resolution of symptoms. No recurrence till date.
49
neous abscess
Vol 2, No 4

Igbinedion BO, Ibadin M, Marchie TT et al.

325

led to abdominal distension, pain and breathing difficulties were


among the other reasons some of the procedures in this study were
performed.

Figure 5: Antegrade pyolographic image post-percutaneous nephrostomy in a


37 year old woman with bilateral obstructive uropathy secondary to cervical
carcinoma.

Figure 6: Ascitic fluid sonogram with echogenic debris in keeping with


infected ascites in a 4 year old boy showing the tip of an IV draining cannula
sheath in-situ.

Figure 7: Sonogram of a 52 year old woman with hepatic cyst been drained
using the sub-costal approach.

Discussion
Abdominal fluid collections have variable sources such as ascites, abscesses, biliary obstruction or ureteric obstruction. The goal of percutaneous interventional drainage in all such collections can be categorized into 3: obtaining fluid for diagnosis, draining fluid from an
abscess or symptomatic collection, or to treat recurrent collection by
instilling a sclerosing agent [7]. Consequently, infected fluid drainage
is not the only reason for percutaneous drainage (PD). Pain or pressure symptoms from large non-infected fluid collection or within the
urinary tract are also indications for drainage [8]. Consequently, pressure symptoms from endometriosis or other causes of ascites which

In the past, management of abscess was surgically performed [9]. PD


has replaced open surgical drainage in most situations, except when
the abscess is very large, multi-septated and in cases where PD failed,
sepsis is unabated, and when PD is impossible due to interposed
structures such as overlying bowels [3, 8, 9]. This is because the procedure markedly reduces morbidity and mortality when compared
with open surgical drainage by offering precise non-invasive localization of fluid collections, minimally invasive therapeutic techniques
and avoidance of general anesthesia in most cases [3]. Lesser cosmetic deformities from puncture site when compared to scars from
surgical drainage is another reason why percutaneous drainage is
advantageous, especially now that people pay special attention to
their personal appearance.
Drainage of abscess by radiologists can be performed either by direct needle aspiration or catheter insertion. Direct needle drainage is
done by image guided aspiration using an intravenous cannula or
needle/stylet assemblage. In our practice we used either intravenous
cannulae or needle/stylet assemblage depending on the site, size
and consistency of the fluid. Needle/stylet was used for deep-sited
abscesses because of its length while 18G intravenous cannula or
needle/stylet was used for viscid fluid. Consequently, ascitic fluid,
subcutaneous abscesses, hepatic abscess and endometriotic fluid
were drained by varying bore size of needles, while we used the needle/stylet assemblage to drain deep-seated hepatic abscess, iliopsoas abscess, hepatic cyst and endometriotic fluid. PD by catheter
insertion can be performed using either trocar or Seldinger method.
Catheter insertion usually require the use of fluoroscopy which is
used to monitor guide-wire manipulation in catheter placed with the
Seldinger technique. In another study, pulse lavage was advocated
in rare situations where percutaneously placed catheter drains were
not able to evacuate sticky, necrotic material from abscess cavity in
the liver instead of attempting open surgical drainage [10].
Radiological imaging is useful in making an impression of fluid accumulation and in its drainage. Ultrasound, computed tomography,
fluoroscopy, magnetic resonance imaging or a combination of any
of these imaging modalities are commonly utilized in accumulated
fluid management. Ultrasound is commonly used because of its nonionizing characteristic and like fluoroscopy can give real time imaging. However, bowel gas overlying or within the abscess limits evaluation by ultrasound. CT does not have this limitation, but because
of its radiation dose, it is not used as first-line interventional equipment for PD. However CT or CT fluoroscopy may be used in such
instances where ultrasound imaging is limited [8, 11]. Magnetic resonance imaging can image fluid collection including abscesses, but
it remains relatively unavailable in several Nigerian health institutions. In most Nigerian health institution, the radiologists and clinicians are frequently caught in the difficult web of imaging modality
choice on the background of impoverished patients and their inability to afford necessary health care. Fortunately, ultrasonography alleviates this problem by being used as a diagnostic tool and to guide
therapeutic interventions, particularly as it is cheap and readily available.
http://www.mednifico.com/index.php/elmedj/article/view/233

326

Intravenous cannulae are widely available in almost every hospital in


the management of patients. Knowledge of its applicability in PD is
low as most clinicians limit its use to setting of IV access for IV fluid
administration. We particularly found the 18G cannula suitable for
abscess drainage (which may be viscous) because of its relatively
wide bore (in comparison to 20 and 22G) and stiffer catheter sheath.
In addition, the catheter sheath of the intravenous cannula is noncutting and non-traumatic, allowing maneuvering when in-situ after
image guided introduction into the cavity where drainage is to be
performed. Consequently, it is recommended for single puncture
and immediate aspiration (for example by syringe suction) of ascitic
fluid and abscess. An intra-hepatic abscess located less than 5cm
from the anterior abdominal wall was successfully drained using this
method (Figure 8). The patient responded remarkably immediately
after the drainage and was discharged home two days later. Successful direct image guided needle aspiration of hepatic abscesses have
been reported in other studies with good outcome. It is considered
a simple and harmless technique for diagnosing and treating patient
with pyogenic liver abscess [12]. Furthermore, percutaneous needle
aspiration of multiple pyogenic abscesses under ultrasound guidance is a safe, effective, low cost procedure that is acceptable to patients and should always be undertaken before catheter drainage or
surgery [13].

Figure 8: Sonogram of PD in a 29 year old sickle cell anemic male.

High success rates have been described after repeated needle puncture drainage and after PD with temporary insertion of a drain, even
in multiple or multi-loculated abscesses [13-15]. A study reported a
frequency of 85%-90% successful treatment with percutaneous abscess drainage in children which was reported to be similar to that
in adults [8]. Zerem et al. opined that percutaneous catheter drainage (PCD) is more effective than percutaneous needle aspiration in
the management of liver abscess and that percutaneous needle aspiration should be used as a valid alternative for simple abscesses
50mm in diameter or smaller [9]. However other authors opinion
differed since multi-loculated abscesses have been drained using direct needle puncture [13]. Needle aspiration can also be done to
send aspirate for microscopy, culture and sensitivity. Similar to what
we practiced, direct needle aspiration has also been used in subcutanous abscesses [16].
In our practice, hepatic cyst were managed as if they were hydatid
cyst with a pre-interventional administration of oral albendazole
Vol 2, No 4

Percutaneous drainage of abdominal fluids using available materials

which is continued till 4 weeks after the drainage or discontinued on


receiving laboratory report that it is not an hydatid cyst. Some studies have successfully ablated hepatic cysts by use of alcohol similar
to what we did [17, 18]. However high recurrence rate has been reported when needle aspiration of hepatic cysts was performed [1920. In this study we had an hepatic cyst that recurred and was eventually managed surgically.
Indications for percutaneous nephrostomy (PCN) include urinary diversion, treatment of nephrolithiasis and complex urinary tract infections, ureteral intervention, nephroscopy and ureteroscopy [21]. At
present, the only indication for PCN in our center is for urinary diversion. The examination is performed either under ultrasound guidance or in combination with fluoroscopy. Ultrasound is used to gain
access into the dilated calyces after which the procedure is continued by the Seldinger technique. The use of ultrasound has been recognized to significantly reduced access time and radiation dose [21].
We undertook these procedures in conjunction with the urological
team with the patients interest as the main aim rather than engaging in tuft war. Such tuft wars have been reported between interventional radiologists and radiologists as well as with clinicians in various disciplines [22]. Fortunately, the materials for PCN were readily
available from local vendors.
Interventional radiology at our institution is budding with several
hiccups along its developmental path. Continuous training and infrastructural development is highly needed and the growth of this
branch of radiology is hampered by dwindling finances of the institution and relatively poorer patients when compared to similar situations in other continents. Sourcing of interventional materials is also
difficult as none of the manufacturer is located in Africa and vendors
consider investing in such business as not lucrative enough. But we
differ in opinion as successful interventions using such materials may
discourage surgical management of such cases and promote the
practice of radiological interventions. This impedance on interventional radiology evolution in Africa affects both the practice and
training of radiologists. Consequently, there is need for high income
countries, radiology vendors, radiologists and radiological organizations to help Africas postgraduate radiology training programs fulfil
their mission of training Africas next generation of radiologists [6].

Conclusion
Some non-vascular interventions were performed using available
tools at our institution. Radiologists should not be deterred by nonavailability of interventional materials locally but should seek innovative alternatives that will yield similar results.
Competing interests: The authors declare that no competing interests exist.
Received: 25 July 2014
Accepted: 29 December 2014
Published Online: 29 December 2014

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http://www.mednifico.com/index.php/elmedj/article/view/351

Open Access

Original Article

The effects of n-3 fatty acids intake on PON1 activity and fatty acid status in type 2 diabetic patients
A pilot study
Zorica Rasic-Milutinovic1, Tamara Popovic2, Jasmina Debeljak-Martacic2, Gordana Perunicic-Pekovic3, Suncica Borozan4, Danijela Ristic-Medic2,
Milena Lackovic1, Maria Glibetic2

Abstract
Background: Paraoxonase1 (PON1) enzymatic activity appears to play a role in maintaining the endothelial-atheroprotective effects of
high density lipoprotein (HDL)-cholesterol and has been linked to vascular disease and diabetes. The objective of this study was to
determine the effect of fish oil consumption on antioxidative capacity of HDL-cholesterol by measuring erythrocyte activity of antioxidant
enzymes [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and PON1], malonil dialdehide (MDA) parameter
of oxidative stress, metabolic parameters and phospholipids fatty acid status in type 2 diabetic patients.
Methods: Twenty patients (12 females, 8 males, mean age 536) received daily 4 g natural fish oil (1.2g n-3 fatty acids; 20:5n-3 [EPA] and
22:6 n-3 [DHA]) during 12 weeks.
Results: PON-1 activity increased by 105.2 % (p<0.05) and SOD increased by 23.5% (p<0.05). Improvement of PON-1 activity was associated
with serum n-3 fatty acid increment by 52% (p=0.01). Increased PON-1/HDL-C ratio (by 95%) was independently associated with changing
of MDA and 20:4n-6 (AA)/EPA ratio (p=0.01). HbA1c was improved significantly by 21% (p<0.01), and HDL-C by 19% (p=0.05).
Conclusion: Results of this study confirm that n-3 fatty acid status presented biomarker of intake and indicated that low dose of fish oil
(1.2 g EPA+DHA) added to a habitual diet improved antioxidant property of HDL-C, by increasing PON1 activity, as well as SOD and MDA
in type 2 diabetic patients. (El Med J 2:4; 2014)
Keywords: Type 2 Diabetes Mellitus, Oxidative Stress, HDL-C Dysfunction, Paraoxonase-1 Activity, n-3 PUFAs

Introduction
The primary protective effect of HDL was believed to be its pivotal
role in reverse-cholesterol transport; however, HDL also has antioxidative, anti-inammatory, and antithrombotic properties [1, 2]. HDLassociated PON1 is primarily responsible for the antioxidative properties of HDL in retarding the oxidation of LDL [3-5]. By modulating
the oxidation of LDL, PON1 abolishes the oxidized LDLstimulated
induction of monocyte-chemotactic protein-1 (MCP-1) production
by endothelial cells, thereby preventing monocyteendothelial cell
interaction in one of the earliest processes of atherosclerosis [6].
PON1 is low in patients with diabetes, leading to dysfunctional HDL
with impaired antioxidant capacity [7,8]. There is an inverse relationship between PON1 activity and circulating oxidized LDL levels in
type 2 diabetes (Type 2 DM) [9], indicating the major role of PON1
in retarding LDL oxidation. Mackness et al. have shown that adenovirus-mediated overexpression of human PON1 in a mouse model of
metabolic syndrome signicantly inhibited atherosclerosis development reducing oxidized LDL in both plasma and the artery wall [10].
According to a meta-analysis of published clinical trials, significant
dose-response effects of EPA and DHA on fasting blood glucose,
HbA1c, and triacylglycerole have been demonstrated in T2DM [11].
We established previously that supplementation with higher dose of
fish oil, 2.4 g/d EPA and DHA, could improve insulin resistance, HDLC and chronic inflammation in hemodialysis patients [12]. It is in accordance with evidence that fatty acids composition of membrane
phospholipids of insulin target tissues, such as liver, fat and skeletal
muscle, is critical factor influence insulin secretion and its biological
Department of Endocrinology, University Clinical Center Zemun/Belgrade,
University of Belgrade, Belgrade, Serbia
2Institute for Medical Research, Centre of Excellence in Nutrition and Metabolism,
University of Belgrade, Belgrade, Serbia
3Department of Nephrology, University Clinical Center Zemun/Belgrade, University
of Belgrade, Belgrade, Serbia
1

actions [13, 14]. However, there is limited data about the effect of
fish oil on oxidative status in Type 2 DM patients. Raised lipid peroxide level, malonil dialdehide (MDA) and lower anti oxidative enzyme
glutathione peroxidase (GSH-Px) activity were improved in Type 2
DM patients, after 2 months of combined therapy with antidiabetic
agents and n-3 fatty acids [15].
The presence of lower level of PON-1, and its association with some
long chain polyunsaturated fatty acids (PUFAs) in Type 2 DM patients
without coronary heart disease, encourages us to investigate the potential effects of n-3 PUFAs supplementation on improvement HDLcholesterol dysfunction, particularly PON-1 activity [16].

Subjects and Methods


Study population and design
We cross-sectionally evaluated 65 patients with type 2 diabetes
mellitus from outpatient clinic of University Clinical Center, Zemun
(Belgrade). For this intervention study we included cohort group of
twenty diabetic patients (12 females, 8 males, mean age 53 6 yrs,
BMI 27.97 1.61 kg/m2) with at least 2 years of diagnosed diabetes
since onset of the condition and 16 age- and gender-matched
healthy controls subjects. Exclusion criteria were heart failure (NYHA
III or IV), acute myocardial infarction, and acute infectious disorders,
within three months of the inclusion. Patients with renal failure [GFR
(glomerular filtration rate) lower than 60 mL/min] were excluded
from the study, as well as obese (BMI higher than 30kg/m2) patients.
Healthy controls were hospital staff and their relatives who were not

Department of Chemistry, Faculty of Veterinary Medicine, University of Belgrade,


Belgrade, Serbia
Correspondence: Tamara Popovic
Email: poptam@gmail.com

2014 Rasic-Milutinovic et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Rasic-Milutinovic Z, Popovic T, Debeljak-Martacic J, Perunicic-Pekovic G, Borozan S, Ristic-Medic D, Lackovic M, Glibetic M: The effects of n-3 fatty acids intake on PON1 activity and fatty acid
status in type 2 diabetic patients A pilot study. El Mednifico Journal 2014, 2(4).

Rasic-Milutinovic Z, Popovic T, Debeljak-Martacic J et al.

obese and who were taking only antihypertensive drugs (ACE inhibitors 6 patients, 38%). All study participants signed and provided an
informed consent document. The medical ethics committee of our
Clinical Center approved the study in accordance with the principles
of the Declaration of Helsinki.
All diabetic patients were treated with ACE inhibitors, beta blockers
10 patients, (50%), calcium channel blockers 12 patients (33%) and
aspirin 8 patients (40%). Serum glucose values were controlled with
oral antidiabetic drugs (sulfonylurea and metformin, glitazons are
withdrawn from our market) and diabetic diet. Patients with uncontrolled hyperglycemia (HbA1c higher than 9%) were excluded from
the study. None of the participants were using statins or other hypolipemic agents.
This study was a cross-sectional and follow-up dietary intervention
pilot study. Each patient received 4 capsules of natural fish oil (4
gr/day) orally administered in the fasting state during the follow-up
period of 12 weeks. An N-3 PUFAs dose was 1.2 gr (each gel capsules
was composed of 180 mg EPA plus 120 mg DHA, Natural Wealth
Company) per day. Patients were instructed to keep their usual diets
and level of physical activity relatively constant throughout the study
and to maintain stable body weights. Specific instructions were
given not to take any new supplements or increase the amount of
fish in the diet. The patients continued to consume (sunflower oilbased) n-6 PUFAs cooking oil, as part of their ordinary diabetic diet.
The diet control was done as usual for all study participants by interview during study period.
Anthropometric data, medical and drug history were obtained via
face-to-face interviews. The blood samples were taken to determine
serum phospholipids fatty acids composition before the beginning
and at the end of the twelve weeks n-3 PUFAs intervention period.
The fasting blood lipids, glucose, insulin, creatinine, high sensitivity
C-reactive protein (hsCRP) and HbA1c were assessed from the same
blood samples with a conventional autoanalyzer. Blood samples
were taken after 12h of overnight fasting. Fasting insulin and glucose
concentrations were used to calculate insulin resistance from the
HOMA-IR model (insulin (UI/mL) glucose (mmol/L)/22.5). HOMAbeta index, which represent the function of beta-cells, was also calculated from equation HOMA-beta = 20 x Insulin (UI/mL) / Glucose
(mmol/L) 3.5 [17].
Biochemical Analysis
Plasma glucose was assayed using the glucose oxidase method (Human Gesselheit, Wiesbaden, Germany). Plasma triglycerides (TG) and
total cholesterol were determined using enzymatic methods
(Boehringer Mannheim, Mannhein, Germany). HDL-C was measured
by precipitation with MgCl2 and dextran sulfate. Low-density lipoprotein cholesterol (LDL-C) was calculated using Friedewalds formula. Serum CRP levels were measured using a high sensitivity CRP
(hs-CRP) assay (Dade Behring Cardio-Phase hsCRP, Behring Nephelometer BNII, Dade Behring, Marburg, Germany). The assay was able
to detect a minimum hs-CRP concentration of 0.175 mgL-1.
Samples of blood were collected (in vacutainer tubes with anticoagulant) from patients early in the morning before a meal. Blood was

329

centrifuged and plasma was separated from erythrocytes. Erythrocytes were washed three times with saline and stored at -80oC. Serum PON-1 activity and plasma concentration were measured together with other enzymes of oxidative stress [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and, malonil dialdehide (MDA). The methods for measurement were previously described [16]. Serum phospholipids fatty acid analysis was
done by procedure previously described [16].
Statistical analysis
All statistical analyses were performed using SPSS for Windows v.20
(SPSS Inc., Chicago, IL). Data are expressed as mean standard deviation (SD). Nonparametric distributed variables are presented as
median (interquartile range). Means, or medians values were compared by Paired-Samples T Test or nonparametric Wilcoxon Two-Related Samples. Skewed variables were natural log-transformed for
further statistical analysis. Correlations were evaluated using Pearsons correlation coefficients. Multivariate stepwise regression analysis was carried out to determine the independent relationships between some variables and PON1 activity (or HDL-C corrected PON1
activity). Differences were considered statistically significant when
p<0.05.

Results
The demographic characteristics, biochemical parameters, inflammatory markers and oxidative stress enzymes of the study participants
are shown in Table 1. All participants completed the study and there
were no withdrawals. There was no statistical difference between diabetic patients and control subjects in age and BMI. Blood pressures,
HbA1c, plasma insulin, HOMA-IR and serum triglycerides levels were
significantly higher, whereas as expected HDL-C and PON 1 was
lower in diabetic patients. The level of MDA, advanced lipoxidation
end-product, was almost twice than in controls. Anti-oxidative enzyme SOD was, on the contrary, significantly lower in Type 2 DM patients. The other two anti-oxidative enzymes, GSH-Px and CAT, did
not differ as compared with control group.
After supplementation with n-3 PUFAs we noted significantly improvement of HbA1c, and not significant improve in glucose level,
HOMA-IR and HOMA-beta (Table 1). The level of HDL-C improved
with borderline significance, by 19% (p<0.05), whereas serum triglycerides, total cholesterol and LDL-cholesterol did not change significantly. There was no significant improvement of hsCRP level after
intervention, although there was a trend to decreased 17.5%
(p=0.20) compared to baseline levels (Table 1). MDA has shown significantly reduced production. The level of SOD improved significantly, increased by 23.5% (p=0.04). Nevertheless, the levels of GSHPx and CAT did not change significantly. We demonstrated
signicant improvement in PON1 activity (p=0.01), it was increased
by ~105%, as well as HDL-C corrected PON1 activity or PON/HDL-C
ratio, increased by ~95% (p=0.01).
Fatty Acid Composition of Plasma Phospholipids
The fatty acid (FA) profile of plasma phospholipids in patients with
T2DM was significantly different compared with control subjects (Table 2). The percentage of total saturated FA (SFA) was significantly
higher in Type 2 DM patients; however, total monounsaturated FAs
(MUFAs) was significantly lower than in control subjects (Table 2).
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Effects of n-3 fatty acids on PON1 activity in type 2 diabetics

Table 1: Demographic characteristics, biochemical parameters and oxidative stress enzymes in study participant at baseline and
after fish oil (FO) treatment
Control subjects
Type 2 DM patients
Type 2 DM patients
before treatment
after treatment
51.2212.06
53.155.85
Age
10/6
12/8
Gender (f/m)
2
26.174.28
27.971.61
26.403.70
BMI (kg/m )
125.6017.08
137.9515.93*
135.5016.45*
BP-systolic (mmHg)
77.458.59
82.2710.81*
80.40 + 11.40*
BP-diastolic (mmHg)
4.55 (4.00-4.87)
8.95 (7.80-9.90)**
7.95 (6.12-9.67)**
Fasting glucose (mmol/L)
8.25 (5.75-12.92)
8.84 (6.32-9.54)
10.09 (5.75-17.32)
Insulin (U/L)
**
1.65
(1.06-2.77)
3.47
(2.02-4.34)
3.09 (2.56-5.14)*
HOMA-IR
186 (95.71-236)
30.79 (25.71-32.48)**
56.76 (16.66-130.83)**
HOMA-beta
**
5.080.29
7.41.16
5.911.02 *
HbA1c (%)
5.420.49
5.071.07
4.990.87*
Total cholesterol (mmol/L)
1.420.15
1.040.19**
1.240.21*
HDL-C (mmol/L)
3.281.07
2.961.12
2.911.00
LDL-C (mmol/L)
**
1.030.13
2.090.88
1.830.86*
Triglycerides (mmol/L)
0.13 (0.10-0.15)
0.92 (0.49-6.20)**
0.76 (0.37-2.80)*
hsCRP (g/L)
*
1.140.15
2.150.25
1.460.19#
MDA (nmol/ml)
51.2213.06
22.079.78**
43.149.52*#
PON-1 (U/L)
*
36.228.44
21.489.58
41.0911.84#
PON1/HDL-C
*
61.702.30
39.560.96
48.203.52*
SOD (U/g Hb)
39.301.65
29.752.16
36.701.42
GSH-Px ((nmol/NADPH / min/mg Hb)
52.853.86
60.027.21
46.636.56
CAT (U/g Hbx104)
Results are expressed as means SD, or medians (inter quartile rang). Means, or medians values were compared by Paired-Samples T Test or nonparametric Wilcoxon Two-Related Samples.
*p<0.05; **p<0.01 according to level of control group; p<0.05, #p<0.01 according to level before supplementation

Table 2: Fatty acid profile of plasma phospholipids in control subject, Type 2 DM patients before and after fish oil (FO) treatment
Control group
Type 2 DM patients
Type 2 DM patients
before treatment
after treatment
*
26.092.10
27.782.30
28.971.78*
16:0
13.322.44
15.911.36*
16.342.22*
18:0
0.590.35
0.630.28
1.280.80*
16:1 n-7
*
21.472.41
10.741.53
9.891.83*
18:1 n-9
15.431.78
23.873.02**
22.784.53*
18:2 n-6 (LA)
**
2.741.23
0.790.22
2.920.94*
20:3 n-6
*
9.472.33
11.712.84
9.922.71
20:4 n-6 (AA)
0.790.54
0.660.40
1.050.69*
20:5 n-3 (EPA)
0.400.28
0.680.32*
0.550.37
22:4 n-6
0.750.68
0.880.26
1.050.30
22:5 n-3
2.881.18
2.590.53*
4.100.61* #
22:6 n-3 (DHA)
18.92 (5.31-34.81)
19.27 (12.03-34.14)
11.18 (6.28-14.21) *
AA/EPA
26.103.42
39.222.66*
36.192.97 *
n-6
3.922.07
3.650.81
5.560.91*#
n-3
*
8.734.17
11.343.08
6.691.43*#
n-6/n-3
30.024.64
46.053.15*
41.752.88 *
PUFA
**
22.062.58
12.881.68
11.921.85**
MUFA
*
39.812.42
43.692.80
45.322.66*
SFA
0.760.15
1.060.14**
0.920.11
PUFA/SFA
Results are expressed as means SD, or medians (inter-quartile range). Means, or medians values were compared by Paired-Samples T Test or nonparametric Wilcoxon Two-Related Samples.
*p<0.05; **p<0.01 according to level of control group; p<0.05, # p<0.01 according to level before supplementation

Vol 2, No 4

Rasic-Milutinovic Z, Popovic T, Debeljak-Martacic J et al.

Total PUFA, particularly n-6 PUFA, linoleic acid (LA, 18:2 n-6) and arachidonic acid (AA, 20:4 n-6), were significantly higher in Type 2 DM
patients, whereas n-3 PUFAs, particularly DHA, were significantly
lower. The ratio n-6/n-3 PUFA was significantly higher in diabetic patients, as well as the ratio of total PUFA/SFA. After the intervention
period of 12 weeks we noted significant increment of total n-3 PUFA,
by 52% (p=0.01), EPA by 19% (p=0.04) and DHA by 58% (p=0.01),
and significantly reduced n-6/n-3 ratio by ~59% (p=0.01) compared
to baseline levels (Table 2).
Univariate and Multivariate regression analysis with PON1
activity, PON1/HDL-C and respected clinical characteristics and
serum phospholipid PUFAs
First step was attempted to draw an association between changes of
PON1 activity and changes of metabolic variables, oxidative stress
parameters, as well as above mentioned changes of PUFAs. Variables
which significantly correlated with changes of PON1 or HDL-C corrected PON1 (Table 3 and Table 4), such as SOD, EPA, n-3 PUFA,
n-6/n-3 PUFA, HbA1c, MDA, AA/EPA were after that included
into multivariate stepwise regression analysis. Independent predictor for PON1 activity improvement was only n-3 PUFAs, accounting
for 21% variance (p=0.01) (Table 5). Furthermore, reduction of MDA
and improved AA/EPA ratio were significantly associated with improved HDL-C corrected PON1 activity, and explained 49% of the
variance (p<0.05) (Table 6). Hence, n-3 PUFAs supplementation, by
correction of AA/EPA ratio, participated in improvement of PON1 activity in Type 2 DM patients.
Table 3: Pearsons correlation coefficient (r) of differences in
serum paraoxoanase-1 activity (PON-1), and differences of
clinical variables, lipids, HOMA-IR, HbA1c, hs-CRP, and longchain FA in Type 2 DM patients
lnPON-1
r
.170
Ln HbA1c
.106
HDL-C
.210
Ln HOMA-IR
.147
Ln HOMA-beta
.294
MDA
.363*
SOD
.482*
EPA
.487*
n-3 PUFAs
.395*
n-6/n-3
*p<0.05; p values for correlation coefficients showing correlations between differences in serum
PON-1 (lnPON-1), and differences of SOD, EPA, n-3 PUFAs and n-6/n-3FA ratio.

Discussion
Although it has been suggested that n-3 fatty acids may have several
beneficial cardiovascular effects, such as antiarrhythmic properties,
antiatherogenic influences, plaque stabilization, vasodilation, and lipid level reduction, this remains unproven [18, 19]. Recently published meta-analyses on 14 randomized control studies showed insufficient evidence of secondary preventive effect of omega-3 PUFA
intake against overall cardiovascular events [20]. Furthermore, no
significant preventive effect of omega-3 PUFA was observed in subgroup analyses by the following: history of cardiovascular disease

331

(CVD), country location and, geographic area, duration and dosage


of EPA or DHA treatment, concomitant medication use, methodological quality of the trial, type of placebo material in the trial, or use of
fish oil supplementation only as treatment [20]. However, in animal
model of hyperinsulinemia, supplementation of dietary fish oil prevented the dysfunction of vascular endothelium in fructose-fed rats
by its ability to increase the expression of eNOS and decrease oxidative stress [21].
Table 4: Pearsons correlation coefficient (r) of differences in
serum paraoxoanase-1 activity (PON-1)/HDL-C ratio and
differences of clinical variables, lipids, HOMA-IR, HbA1c, hsCRP, and long-chain FA in Type 2 DM patients
lnPON-1
r
Ln HbA1c
.331*
MDA
.362*
SOD
.226
EPA
.218
AA/EPA
.420*
n-6/n-3
.278
*p<0.05; p values for correlation coefficients showing correlations between differences in serum
PON-1 (lnPON-1)/HDL-C ratio, and differences of HbA1c, MDA, and AA/EPA ratio.

Table 5: Stepwise multiple linear regression model showing


independent relationships of differences in PON-1 with
respected clinical characteristics and serum n-3 PUFAs
Beta*
p
.487
.01
n-3 PUFAs
After adjustment for age, SOD, 20:5 n-3, and n-6/n-3 PUFAs; Adj R2 = .21, *Regression coefficient

Table 6: Multiple regression analysis with PON-1/HDL-C


ratio with respected clinical characteristics and serum PUFAs
Beta*
p
.655
.01
MDA
.511
.05
AA/EPA n-3PUFAs
After adjustment for age, HbA1c, SOD, 20:5 n-3, and n-6/n-3 PUFAs
Adj R2= .49 *Regression coefficient

Our previously published data reported lower level of HDL-C, lower


PON1 activity, and higher level of n-6/n-3 PUFAs ratio in Type 2 DM
patients, and furthermore, inverse associations of LA and direct association of DHA with PON1 activity [16]. In this study we evaluated
the possible beneficial effect of n-3 PUFAs on HDL-C dysfunction in
Type 2 DM, preferably anti-oxidative activity. Our results clearly
demonstrate that dietary treatment with low dose of EPA and DHA,
for 12 weeks has the capacity to improve HDL-C and PON1 in Type
2 DM patients. At the same time we noted improvement of anti-oxidative enzymes, SOD, and positive trend of GSH-Px, as well as significant reduction of MDA. These results are in agreement with the data
of Kesavulu et al., who observed that n-3 fatty acids treatment could
modulate oxidative stress status in Type 2 DM, reduce MDA and significantly increase GSH-Px [15].
Recently, de Assis et al. have shown in animal model that supplementation with n-3 PUFAs decreased levels of lipoperoxidation and
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332

hepatic lipids and increased the SOD2 immunocontent in diabetic


rats [22]. In another study, 3g/d, n-3 PUFAs improved homocysteine
concentration, but did not change MDA level in diabetic patients
[23]. The opposite results were demonstrated by Pedersen et al. who
shown that LDL particles from Type 2 DM became signicantly less
resistant to oxidation after supplementation with n-3 PUFAs, 2.6g/d,
with borderline signicant LDL-MDA changes [24]. The latter supported the stata that in vivo LDL peroxidation could be increased
after fish oil supplementation.
However, the most important finding of our study was that supplementation with lower dose n-3 PUFAs could improve inadequate
anti-oxidative status of Type 2 DM. Furthermore, there was a beneficial decreasing trend of chronic inflammation together with antioxidative effect, presence of not significant changing of hsCRP .There is
large body of evidence that circulating HDL particles display multiple
anti-inflammatory actions which may significantly contribute to immunosuppresion of atherosclerosis [25, 26]. Animal studies have
shown that deficiency in PON1 predisposes to vascular inflammation
[27]. These results point out an important role of PON1 in anti-inflammatory activity of HDL.
We observed previously that supplementation with higher dose of
fish oil, 2.4g/d EPA and DHA, could improve insulin resistance,
dyslipidemia and TNF alpha, as parameter of chronic inflammation,
in hemodialysis patients [12]. Intervention studies among healthy individuals have shown no association between fish consumption or
omega-3 PUFAs intake, and glucose and insulin metabolism, or modestly increase the incidence of type 2 diabetes [28-30]. However, intervention studies among high-risk individuals have yielded inconsistent results. For example, in diabetic patients, both a decrease and
an increase in insulin sensitivity have been observed after fish oil
consumption. [11, 31-33].
It is assumed that HDL modulate glucose metabolism by multiple
mechanisms which include enhanced insulin secretion by beta-cells,
as a result of improved cellular cholesterol homeostasis [34, 35]. In
our study, an improvement of HDL-C was not associated with positive trend of beta-cell function (HOMA-beta) changes, and with reduction of insulin resistance (HOMA-IR). However, increased HDL-C
corrected PON1 activity, and that was associated with improved glucose homeostasis or reduced HbA1c, and ameliorates oxidative
stress.
After 4g/d natural fish oil supplementation we noted the changes of
EPA, DHA, total serum n-3 PUFAs, and also reduced n-6/n-3 PUFAs
ratio, as well as improved AA/EPA ratio in our diabetic patients. Results of this study confirm that n-3 fatty acid status in plasma phospholipids presented biomarker of dietary n-3 PUFAs intake.
It is important to emphasize that there are differences in biological
properties and mechanisms of action for AA and EPA. AA and EPA
are substrates for the enzymes involved in the production of eicosanoids. The conversion of AA through the cyclooxygenase or lipoxygenase pathways produces eicosanoids with high proinammatory
potency such as leukotriene B4 or thromboxane A2, whereas EPAderived compounds possess, in general, a lower potency in their actions. Because EPA and AA compete for some of the same enzymes
Vol 2, No 4

Effects of n-3 fatty acids on PON1 activity in type 2 diabetics

to produce these eicosanoids (cyclo-oxygenase-2 and lipoxygenase),


EPA is considered as anti-inammatory PUFA [36, 37].
Recently, a new family of anti-inammatory mediators has been discovered, called resolvins and protectins, synthesized from EPA and
DHA by activity of cyclo-oxygenase and lipoxygenase, that could also
play an important role in the resolution of the inammatory process
[38, 39]. Oh et al. found that DHA and EPA, the major ingredients in
fish oil, exert potent anti-inflammatory effects through functional
fatty acid receptor GPR120, mediating potent insulin sensitizing and
antidiabetic effects in vivo by repressing macrophage-induced tissue
inflammation [40]. As Type 2 DM is a condition with the presence of
chronic-inflammation and increased oxidative stress, supplementation with n-3 PUFAs is justified. However, we could not confirm significant improvement of inflammatory status measuring hsCRP, in
our Type 2 DM patients.

Conclusion
In conclusions, our results suggest that improvement of anti-oxidative function of HDL-C is independently associated with increase of
total serum n-3 PUFAs, or improvement of HDL-C corrected PON1
activity following supplementation with 4g/d fish oil (1.2gr EPA
+DHA). This can be explained by reduction of oxidative stress products and by improvement of AA/EPA ratio in plasma phospholipids.
The increment of SOD level suggest also that supplementation with
EPA and DHA could improve antioxidative status in type 2 diabetic
patients, emphasizing modulation of HDL dysfunction.
The limitation of study is small sample size, but the strength of this
study all together is association of PON1 activity improvement with
increment of n-3 PUFAs, in diabetic patients. It remains to be seen if
follow-up evaluation of the selected supplementation treatment in
larger group of diabetic patients will confirm the present results.
Acknowledgements: The study was supported by grants III 41030 and OI 175099
from Serbian Ministry of Education and Science.
Competing interests: The authors declare that no competing interests exist.
Received: 17 August 2014
Accepted: 27 December 2014
Published Online: 27 December 2014

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http://www.mednifico.com/index.php/elmedj/article/view/249

Open Access

Original Article

Married womens access to resources and decision making power in Nekemte Town, West Ethiopia
Elias Teferi1, Sileshi Garoma2

Abstract
Background: Gender equality and non-discrimination on the basis of sex are fundamental human rights. Studies in this respect are scarce
in Ethiopia in general and study area in particular. Hence, this study was aimed at assessing married womens access to resources and
decision making power and associated factors.
Methods: A cross-sectional community based household survey supplemented by qualitative study was conducted from April 1-30, 2012.
A sample of 845 married women was randomly selected from six sub cities of the town by using a multistage sampling technique. Three
focus group discussions were conducted to complement the quantitative data. Data was entered and analyzed using IBM SPSS statistical
software 20. Thematic analysis was used for qualitative data.
Results: Sixty three percent of the respondents reported that they had net access to resources. Access to resources was significantly
associated with the predictor variables such as age (AOR, 2.14; 95% CI: 1.33 to 4.12), access to media (AOR, 0.70; 95% CI: 0.007 to 0.714),
educational status, (AOR, 0.36; 95% CI: 0.19 to 0.67), income (AOR, 2.14; 95% CI: 1.24 to 3.72), and duration in marriage (AOR, 2.87; 95%
CI: 1.22 to 6.75). Also, 64.3% had net decision making power. Decision making power was significantly associated with access to media
(AOR, 0.32; 95% CI: 0.17 to 0.60), occupational status (AOR, 0.20; 95% CI: 0.10 to 0.42), duration of marriage (AOR, 0.39; 95% CI: 0.19 to
0.84) and number of children (AOR, 3.10; 95% CI: 1.65 to 5.80).
Conclusion: A significant proportion of the respondents had no access to resources and decision making power that needs an urgent
attention at all levels of societal hierarchy including policymakers, stakeholders and professionals to enhance womens access to resources
and decision making power. (El Med J 2:4; 2014)
Keywords: Access, Resources, Decision Making Power

Introduction
Gender equality and non-discrimination on the basis of sex are fundamental human rights. However, the national and customary laws
or societal structures result in differential treatment of women and
men including boys and girls [1, 2]. Large gender disparities in basic
human rights, in resources and economic opportunity, and in political voice are pervasive in many countries in spite of recent gains in
gender equity and equality [3-5]. Gender discrimination in access to
and control over resources and assets has a number of negative implications for both women and girls as well as for their households
and families. Moreover, when women own and control resources and
family assets, they will have increased decision-making power in the
household and are more likely to allocate resources to support the
welfare of all family members reducing poverty and hunger [6-8].
Indeed, we live in a male dominated world where gender power relations are clearly in favor of men. Of 1.3 billion people who live under absolute poverty around the globe, 70 percent are women. For
these women, poverty doesnt just mean scarcity and want. It means
denial of rights, opportunities curtailed and voices silenced. Currently, in an institutionalized patriarchal world women are systematically excluded from every sphere of public life, including areas of
leadership and decision making. At least 50% of the world populations are women. Women form the core of the family and household,
work longer hours than men in nearly every country, do more of the
total work than men and contribute more to the development of
their societies [9, 10].
Despite womens contribution to the development of society and
country at large, they do not enjoy the fruits of development equally
as their male counterparts due the multifaceted problem that they

face based on their gender [9]. Womens low status in Ethiopia, as


anywhere else, is expressed in different forms including their lack of
assets to ownership, leadership and decision making opportunities
and their multiple role that make them lag behind in every endeavor
[11]. Studies on womens empowerment are scarce particularly studies based on direct indicators of empowerment such as access to and
control over resources, decision making power on household matters, autonomy in seeking health care, attitude towards resisting wife
beating and attitude towards right to refuse sex with husband for
any reasons. As a result, there is lack of comprehensive knowledge
regarding different dimensions of womens empowerment and the
factors associated. This study, therefore, was conducted to examine
womens empowerment situation, access to and control over resources and decision making power in Ethiopia.

Methods and Materials


Study area and period
The study was conducted among married women in Nekemte town,
East Wollega Zone, Oromiya Regional state, West Ethiopia. Nekemte
town is located 331 kilometers away from Addis Ababa, Ethiopia. Administratively the town is divided into six sub cities. According to the
report of CSA of Ethiopia, at the end of 2011 the town has 18,336
households and the total population of 91,045 out of which 47,103
are females [12].
Study design and population
A community based cross-sectional household survey employing
quantitative and qualitative methods was conducted form April 130, 2012. All married women in Nekemte town during the study period who were residents of the study community for at least six

Department of Public Health, Ambo University, Ethiopia.


Adama Hospital Medical Colleges, Ethiopia.
Correspondence: Sileshi Garoma
Email: garomaabe@yahoo.com

1
2

2014 Teferi et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Teferi E, Garoma S: Married womens access to resources and decision making power in Nekemte Town, West Ethiopia. El Mednifico Journal 2014, 2(4).

Teferi E, Garoma S

months were the source population. Adequate sample size was computed using single population proportion sample size calculation
formula with the inputs of 95% confidence level, 5% desired precision, design effect of two and 10% non-response rate. Accordingly,
a sample size of 845 married women was calculated. Respondents
were selected using multistage sampling technique. The first stage
was the selection of three from six sub cities by simple random sampling method. Household census and numbering was done in the
selected sub-cities to fix a sampling frame. After identifying households with the target groups (married women), proportion to sample
size allocations were carried out based on the total number of the
selected households. Ultimately, systematic random sampling was
employed to identify respondents from the selected households as
a study unit. In a situation when the household has two or more
eligible subjects only one was selected by lottery method. Three focus group with a total of twenty four individuals participated in the
study.
Data collection
For quantitative part of the study, data was collected by 10 high
schools completed female interviewers using structured pre-tested
questionnaire adopted from Ethiopian demographic health survey of
2005. The questionnaire was translated to regional language by experts in both languages and back translated to English by another
person to ensure consistency and accuracy. Data collection process
was closely supervised by three Health Officers and principal investigators. In addition, focus group discussion (FGD) was conducted
with married women of the same socio-economic status in three randomly selected sub cities who were not involved in the survey. For
FGD, unstructured guide was used leaving participants stimulated to
open up and discuss freely.
The research team was recruited based on qualification, previous experience in data collection and fluency in both English and the regional language. Moreover, training was given for three consecutive
days in interview technique, and ethical issues, emphasizing the importance of safety of the participants and interviewers, minimization
of under reporting and maintaining confidentiality.
A pre-test of the instruments was carried out in a nearby town
(Gimbi) by considering 5% of the total sample size and appropriate
modifications was made after discussing with the supervisors and
data collectors as few minor differences were detected in the responses given such as skipping patterns and some other corrections
to have the final version before starting the actual data collection
process.
Measurements variables that have been theoretically, empirically
and conceptually linked to married womens access to resources and
decision making power such as age, religion, ethnicity educational
status, occupational status, number of children, duration in marriage
and income were taken as independent variables. These and other
related variables were categorized into groups where some of them
were further sub-divided for bi-variable and multivariable analysis.
The dependent variables were women access to resources and decision making power. In this study four access to resources indicators
(access to education, employment, bank account and media) were
selected and womens accesses to those resources were measured

335

for each of those the indicators provided in the questionnaire. Summary index was created where one point was given if the woman
had access to the indicators and zero if she had no access. For ease
of analysis, a woman is said to have access to resources if she had at
least access to two of the access to resources indicators [13-15]. For
decision making power, six indicators: decision making power on
husbands earnings, large household purchases, own health care,
number of children, contraceptive use and refusal of wife beating
were selected. Index was created to measure decision making power.
These indexes were made to sum the number of these six dimensions in which the woman participates, assigning a score of one if
she alone or jointly participated in the decision and zero if she did
not have major say. For ease of analysis, in this study a woman was
said to have decision making power if she had at least decision making power on four of the six dimensions as reported in other studies
[13-15].
Data analysis
Frequencies and variation were obtained for each variable and displayed on tables. Cross tabulation was done to determine the association between the explanatory and outcome variables. Binary logistic regression was done to describe the odds ratio and 95% confidence interval (95% CI) for determining the strength of association
between dependent and independent variables controlling for the
effect of possible confounders. The results were expressed as crude
and adjusted odds ratio relative to the reference category at statistical significance of 95% CI. A P-value of <0.05 was taken as a cut off
point for significance. The assumptions for binary logistic regression
analysis were checked to be satisfied.
Ethical considerations
The research was approved for scientific and ethical integrity by institutional review board in the College of Public Health and Medical
Sciences of Jimma University. Written consent from all respondents
and when necessary from their husbands was taken before data collection. Privacy was assured during the interview as some study
questions were related to sensitive issues and the interviewees were
informed that respondents had the right to be involved or not involved in the study.

Results
Socio-demographic characteristics
A total of 818 study subjects were interviewed making a response
rate of 96.8%. The socio-demographic characteristics of study subjects have been described in table 1. Two hundred eighty one respondents (34.3%) were in the age range of 25-34 years, with mean
age of 28.4 5.7 years. More than three in four (79.6%) were Oromo
by ethnicity. The majority (45.2%) was Protestant and 40.0% were
Orthodox Christian. Nearly one fourth (22.6%) had no formal education. Also, 232 (28.4%) were employed and 16.8% were merchants
and 54.4% were housewives. Regarding their income, 494 (60.4%)
earned less than 1000 ETB (Ethiopian Birr) per month.
Access to resources
Womens access to resources is limited. Even though, 63% had net
access to resources, 22.6% of women had no education; only 28.4%

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336

and 45.8% had access to employment and independent bank account, respectively. Majority of women had at least weekly exposure
to television [620 (75.8%)] and radio [519 (63.4%)]. But access to
newspapers or magazines was very minimal as only 260 (31.8%) had
the access. Similarly, the findings of the FGDs revealed that many
respondents did not have access to bank account and access to media.
Table 1: Socio-demographic and economic characteristics of
married women (n=818), Nekemte town, West Ethiopia, April
2012.
Variables
N
%
61
7.5
Age in years
15-24
281
34.3
25-34
271
33.1
35-44
205
25.1
44 and above
651
79.6
Ethnicity
Oromo
110
13.4
Amahara
46
5.6
Tigre
11
1.4
Others
372
45.5
Religion
Protestant
333
40.7
Orthodox
62
7.6
Catholic
51
6.2
Muslim
228
27.9
Educational Status Primary
152
18.6
Secondary
80
9.8
Certificate
173
21.1
Diploma and Above
185
22.6
Illiterate
232
28.4
Occupational Status Employed
138
16.9
Merchant
444
54.2
Housewife
4
0.5
Others
One participant said:
Ahhh! I am struggling with life only for my stomach. I only bother
for my daily bread.
Another 45 years old woman with six children reported that:
When I get the money from Equb I buy different foods stuffs like
teff (an important food grain) and other necessities to the family. I
rarely change my clothes leave alone access to bank account.
Similarly another 46 years women with four children responded saying:
Even if my husband reads newspaper most of the time I never look
at it but watch television at least once a week.
Factors associated with womens access to resources
In the final model, a number of socio-demographic factors were
identified as significant predictors of access to resources. Women
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Married womens access to resources and decision making power

who were in age group 45 and above had more access to resources
when compared to those in the age group of 15-24 years (AOR, 2.14;
95% CI: 1.33 to 4.12). Women who had no access to media/TV had
less access to resources (AOR, 0.12; CI: 0.04 to 0.38). Level of education and womens access to resources showed positive relationship
(AOR, 1.94; 95%CI: 0.64 to 5.92). Women with educational status of
diploma and above had two times more access to resources when
compared with women with primary education. Similarly, a significant association was observed between income and access to resources (AOR, 10.62; 95%CI: 4.44 to 25.41). Women who earn greater
than 2000 ETB per month had 10 times more access to resources
when compared with women having monthly income of less than
1000 ETB. The number of years in marriage also showed a significant
association with access to resources (AOR, 9.99, 95%CI: 3.71 to
26.95). Women who were in marriage for more than 10 years had 10
times more access to resources as compared with those who were
in marriage for 1-5 years. Number of children women showed a significant association in bi-variable analysis, but when controlled for
other predictors had no significant association (Table 2).
Womens decision making power
About 64.3% of the studied women had a net decision making
power over selected decision making power indicators. More than
three-fourth had decision making power on: the use of their husbands earnings, large house hold purchases, number of children
they want to have and contraceptive use. Six hundred forty-one
(78.4%) reported that they had participated in decision about their
own health care. Limited decision making power was observed on
decision on refusal of wife beating for any of the given reasons (Table 3). This finding was also supported by FGDs in which some participants indicated the husband is primarily responsible in making
decision on the selected decision making power indicators.
One participant said that:
The head of the family carries different responsibilities to perform
in the household as well as outside of it. One of the responsibilities
is to decide mainly on major household matters, so it is men who
should usually make them.
A 58 years old woman with five children and a 34 years woman with
two children said:
It is the husband who usually decides the number of children and
contraceptive use.
Factors associated with womens decision making power
Access to media was significantly associated with womens decision
making power (AOR, 0.32; 95% CI: 0.17 to 0.60). Decision making
power was increased with increase in frequency of access to media
as women with no exposure to media at all had less decision making
power when compared with women with daily exposure to media/TV. Similarly, occupational status has showed significant association with decision making power (AOR, 0.20; 95% CI: 0.10 to 0.42).
Housewives had less decision making power. Duration of marriage
showed significant association with womens decision making power
(AOR, 0.39; 95% CI: 0.19 to 0.84). Women who had been in marriage

Teferi E, Garoma S

337

Table 2: Crude and adjusted odds ratio from logistic regression on womens access to resources, Nekemte town, West Ethiopia,
April 2012.
Variables
Access to resources
COR (95 CI%)
AOR (95%CI)
Yes [N(%)] No [N(%)]
24(39.3)
37(60.7)
1.00
1.00
Age
15-24
183(65.1)
98(34.9)
2.88 (1.63-5.09)***
2.39 (1.18-6.82)*
25-34
179(66.1)
92(33.9)
3.00 (1.69-5.31)***
2.60(1.04-5.26)*
35-44
129(62.9)
76(37.1)
2.62 ( 1.46-4.71)***
2.14(1.33-4.12)***
>45
386(68.6)
177(31.4)
1.00
1.00
Frequency of watching TV
Daily
32(56.1)
25(43.9)
0.59 (0.34-0.92)
0.70 (0.007-0.81)*
Less than once a week
26(52.0)
24(48.0)
0.50 (0.28-0.89)*
1.11 (0.35-3.52)
At least once a week
71(48.0)
77(52.0)
0.42 (0.29-0.61)***
0.12 (0.04-0.38)***
Not at all
120(52.6)
108(47.4)
1.00
1.00
Educational status
Primary
69(45.4)
83(54.6)
0.75 (0.50-1.13)
0.36 (0.19-0.67)**
Secondary
42(52.5)
38(47.5)
1.99 (0.60-1.66)
0.67 (0.31-1.55)
Certificate
167(96.5)
6(3.5) 25.05 (10.66-58.60)***
1.94 (0.64-5.92)
Diploma and above
240(51.1)
230(48.9)
1.00
1.00
Income
< 1000
201(76.1)
63(23.9)
3.06 (2.19-4.28)***
2.14 (1.24-3.72)**
1000-2000
74(88.1)
10(11.9)
7.09 (3.58-14.06)*** 10.62 (4.44-25.41)***
> 2000
91(55.2)
74(44.8)
1.0
1.0
Number of years in
1-5
marriage
148(69.2)
66(30.8)
1.82
(1.19-2.78)*
2.87
(1.22-6.75)*
6-10
276(62.9)
163(37.1)
1.38(0.96-1.98)
9.99 (3.71-26.95)**
> 10
178(65.7)
93(34.3)
1.00
___
Number of children
1-2
196(60.5)
128(39.5)
0.80(0.52-1.12)
3-4
113(66.1)
58(33.9)
1.02(0.68-1.52)
5-6
28(53.8)
24(46.2)
0.61(0.33-1.11)
Above 7
*** = P < 0.001, ** = P < 0.01, * = P < 0.05, (level of significance)

for more than 10 years had less decision making power when compared to women who were in marriage for less than five years. A
significant association was also observed between number of children and decision power (AOR, 3.20; 95% CI: 1.20 to 8.52). Women
with seven and above children were three times more likely to have
decision making power as compared to those with one to two children. In the bi-variable analysis age showed significant association
with decision making power but when controlled for other variables
did not show association (Table 4).
Table 3: Distribution of respondents according to their response
towards wife beating, Nekemte town, West Ethiopia, April, 2012.
Husband justifiable to
Yes
No Don't know
hit his wife if (N=818)
[N (%)]
[N (%)]
[N (%)]
180 (22.0) 537(65.6)
101(12.4)
She goes out
186(22.7) 521(63.7)
111(13.6)
Neglects children
200(24.4) 497(60.8)
121(14.8)
Argues
178(21.8) 543(66.4)
97(11.8)
Refuses sex
180(22.0) 534(65.3)
104(12.7)
Burns food

Discussion
This study has highlighted married womens access to resources and
decision making power. The study has showed that women were seriously disadvantaged with regards to educational attainment. In this

study about one in four (22.6%) of the study subjects were found to
have no access to education. The finding was better than the findings of the study conducted in India in which 45% of married women
had no education. This difference in access to education might be
from differences in socio-demographic, cultural and norms they follow regarding gender equality and the position given for girls in the
house [16]. Regardless of different initiations made by governmental
and non-governmental organizations to increases educational coverage, this study revealed that one fourth of the study subjects did
not get access to education.
One of the areas of disparity between males and females is related
to the difference in employment status. Access to employment was
significantly low as only 28.4% of the respondents were employed.
This finding is similar to the study conducted in India in which 27.5%
studied married women had access to employment. Most probable
reason for the closeness of the result could be involvement of urban
women in both studies [16]. Having bank or savings accounts and
using them can be thought as a privilege of wealth, and an indicator
of womens ability to manage household monetary resources, which
could enhance interaction successfully with modern institutions. In
the current study less than half of studied married women (45.8%)
had bank or savings account that they used. Even if less than half of
the married women had access to bank account, this result is much
better than the findings of the study conducted in India, where only
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338

Married womens access to resources and decision making power

Table 4: Crude and adjusted odds ratio from logistic regression on womens decision making power, Nekemte town, west Ethiopia, April 2012.
Variables
Decision making power
COR (95% CI)
AOR(95% CI)
Yes [N(%)] No [N(%)]
39(63.9)
22(36.1)
1.00
--Age
15-24
195(69.4)
86(30.6)
1.28 (0.72-2.29)
25-34
173(63.8)
98(36.2)
0.99 (0.56-1.78)
35-44
119(58.0)
86(42.0)
0.78(0.43-1.41)
>45
429(76.2)
134(23.8)
1.00
1.00
Frequency of
Daily
watching TV
30(52.60
27(47.4)
0.35 (0.20-0.61)***
5.36(0.69-41.86)
< one a
week
30(60.0)
20(40.0)
0.47 (0.26-0.85)*
0.73(0.29-1.82)
At least once
37(25.0)
111(75.0)
0.10 (0.07-0.16)***
0.32 (0.17-0.60)***
Not at all
170(74.6)
58(25.4)
1.00
1.00
Educational staPrimary
tus
106(69.7)
46(30.3)
0.79(0.49-1.24)
0.71(0.43-1.18)
Secondary
68(85.0)
12(15.0)
1.93(0.98-3.83)
1.45(0.67-3.14)
Certificate
149(86.1)
24(13.9)
2.12
(1.25-3.58)**
0.64(0.29-1.40)
>Diploma
250(53.2)
220(46.8)
1.00
1.00
Income
< 1000
212(80.3)
52(19.7)
3.59 (2.52-5.11)***
0.94(0.58-1.52)
1000-2000
64(76.2)
20(23.8)
2.82 (1.65-4.80)***
0.99(0.50-1.93)
> 2000
204(87.9)
28(12.1)
1.0
1.00
Occupation
Employed
108(78.3)
30(21.7)
0.49 (0.28-0.87)*
0.52(0.24-1.14)
Merchant
211(47.5)
233(52.5)
0.12 (0.08-0.19)***
0.20***(0.10-0.42)
House wife
3(75.0)
1(25.0)
0.41(0.04-0.96)
0.50(0.04-6.68)
Others
133(80.6
32(19.4)
1.0
1.00
Number of years 1-5
in marriage
168(78.5)
46(21.5)
0.88(0.53-1.46)
0.61(0.31-1.18)
6-10
225(51.3)
214(48.7)
0.25 (0.17-0.39)***
0.39 (0.19-0.84)*
> 10
201(74.2)
70(25.8)
1.00
1.00
Number of chil1-2
dren
165(50.9)
159(49.1)
0.36 (0.26-0.51)***
3.10 (1.65-5.80)***
3-4
123(71.9)
48(28.1)
0.89(0.58-1.37)
2.18 (1.10-4.32)*
5-6
37(71.2)
15(28.8)
0.86(0.45-1.66)
3.20 (1.20-8.52)*
>7
*** = P < 0.001, ** = P < 0.01, * = P < 0.05, (level of significance)

15% of the married women had access to bank account [16]. This
better access to bank account may be because of the current government initiative in organizing women to form micro enterprise and
saving scheme as income generating activity in Ethiopia.
Media is an important source of information and exposure to new
ways of thinking and doing things. Listening radio, watching television, and reading newspapers or magazines are important leisure activities. Both of these characteristics of the media make access to it
an important indicator of womens empowerment by providing information and exposure to the world outside their home. Media exposure has potential for enabling empowerment; further, time spent
enjoying media reflects access to leisure time, typically available to
the more empowered who have greater control over their own time
use.
The current study showed that the majority of the studied women
had exposure to media as over three fourth (75.8%) of them had at
least exposure to television, about two third (63.4%) had access to
radio and about one third had access to newspapers or magazines
Vol 2, No 4

once weekly. In this study, womens access to television is very high


when compared with analysis of DHS of Malawi and Rwanda, in
which only 3.8 and 6.3% had access to television and respectively.
Regarding access to radio, 52% of Malawi and 39% Rwanda had access to radio at least per week which is almost similar when compared with the current study. It is possible to reason out that respondent in our study did have better access to television widely
used in all regions of Ethiopia. It could also be a time gap between
the two studies [2].
A number of socio-demographic factors were identified as significant
predictors of access to resources. As compared to those in age group
15-24, women who were in the age group of 45 and above had more
access to resources, corroborating with studies elsewhere [2, 17-20].
Duration of years in marital union has showed statistically significant
association with their access to resources which is in line with other
study reports [2, 19]. This is true because when age increases and
women have many children, respect given to them will also increase
which in turn increases access to resources. Moreover, the level of

Teferi E, Garoma S

education was associated with access to resources, which is consistent with study findings in other studies [2, 19, 20]. This is justified
as educated women have greater range of choices getting access to
and control over resources within the family as she can easily communicate with her husband without fear in comparison with those
with no education. This study also showed increasing trend of the
household socio-economic status from poorest to richest, is also associated with increased access to resources. This association goes
with the findings of other studies [2, 19].
More than three fourth of currently married women in this study had
decision making power on their husbands earnings, large household
purchases, own health care and on the number of children they
wanted to have. Accordingly, about one in four had no decision making power on husbands earnings, large household purchases, own
health care and number of children to have which clearly indicated
the existence of gender inequality which can in turn influences the
health and welfare of the women, family and the community. The
result of the study has shown that better decision making power was
seen in comparison with many studies carried out elsewhere [21- 24].
The reason for better decision making power can be justified as better Ethiopian government and non-governmental organizations initiatives to promote gender equality and as specified in millennium
development goals and time gap between the studies [2, 20, 25].
Regarding refusal of wife beating as indicator of decision making
power, more than 75% of the respondents in this study reported no
agreement for the five reasons mentioned (if the wife goes out without telling her husband, if she neglects the house or children, if argues with her husband, if refuses to have sex with her husband and
if she does not cook food properly). This finding was reported in the
study conducted on women empowerment and achievement of desired fertility in sub Saharan Africa indicating substantial variability
among the countries in the womens empowerment indicators [26].
The findings of the current study are much better when compared
to the Ethiopian demographic and health survey (EDHS) of 2005 [2].
The reasons given for better decision making power in the current
study could be involvement of the study subjects from both urban
and rural in previous study as access to resources and decision making power vary in urban and rural women.
Decision making power was significantly associated with the predictor variables such as access to media, occupational status, duration
in marriage and number of children. The findings of this study are
similar to findings of the study conducted in India in which women
who had completed at least middle level of education were involved
in decision making, had access to money. The results of the current
study are also consistent with the EDHS of 2005, which showed educational attainment of woman associated with decline in attitude
towards acceptance of wife beating [2].
As to the limitation of the study, the cross-sectional nature could
cause difficulty of determining the direction of the association between the study variables and the associations observed could only
be discussed in terms of plausibility. To the strengths, it is a community based study supplemented by qualitative method and the respondents were selected by random sampling technique with rela-

339

tively large sample size. Again, the study used standard and validated instrument from the EDHS [2]. In addition, the team used interviewers and supervisors who had past experiences of data collection from their respective community. Because of all these measures,
the study had an extremely high response rate.

Conclusion and Recommendations


Womens access to resources and decision making power were
greatly circumscribed. Many of the married women had no education, few were employed, and less than half had bank or savings account that they themselves used. Although a majority of women said
that husbands and wives should make decisions jointly, a significant
proportion felt that husbands should have major say in most decisions. Even though the findings from this study was somewhat better
in comparison with other studies, still more than one in three women
had no access to resources and no decision making power. Access
to resources and decision making power were negatively or positively associated with the predictor variables such as age, access to
media, educational status, income, and occupational status, duration
in marriage and the number of children.
Therefore, there is a need to make efforts to increase norms that
make women accessible to resources and enhance decision making
power in the study area. Besides, the promotion of primary education and socioeconomic development becomes vital, which needs
an urgent attention at all levels of community organizations including policymakers, stakeholders, professionals and other concerned
bodies. Interventions targeting behavioral and social factors promoting gender equality should be instituted through the involvement of
different stakeholders using a multi-sectorial approach and information dissemination tools. Moreover, extensive and longitudinal research is needed to validate the current findings.
Authors Contribution: The two authors were responsible for the design and
conduct of the study. The statistical analysis, the interpretation of findings and
drafting of the manuscript were done by the two authors. The authors read and
approved the final content of the manuscript.
Acknowledgements: We are very much grateful to Jimma University, Nekemte
town municipality, Nekemte town gender office for providing us important
information though out the study. Our thanks also go to the study participants for
their willingness to participate in the research.
Competing interests: The authors declare that no competing interests exist.
Received: 6 April 2014
Accepted: 7 September 2014
Published Online: 7 September 2014

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Open Access

Original Article

Effectiveness of hand versus rotary instrumentation on retreatment of curved canals


Ebru zsezer Demiryrek1, Emre Bodrumlu2

Abstract
Background: Various nickeltitanium (NiTi) rotary endodontic instruments have been developed to facilitate cleaning and shaping of
root canals. This study aimed to evaluate the efficiency, cleaning ability and safety of two different rotary NiTi instruments with a solvent
versus hand files in the removal of canal fillings.
Methods: Forty five simulated canals with 35 curves made of clear polyester resin were used in this study. All canals were prepared with
K-files and filled using cold lateral compaction of gutta-percha and AH Plus sealer. The teeth were randomly divided into three groups of
15 specimens each. Removal of gutta-percha was performed with the following techniques: Hedstrm files, ProTaper Universal rotary
retreatment system and Mtwo-R. All techniques were used with the solvent chloroform. The followings factors were evaluated: time taken
to reach working length, time for gutta-percha removal, total time, apically extruded material during filling removal and number of
fractured instruments. Pre- and post-reinstrumentation weights of all the blocks were recorded and efficacy capacity of each retreatment
technique was assessed.
Results: The canal wall clearance efficiency of ProTaper retreatment files were more successful than Mtwo-R and hand instruments. With
respect to the difference between pre- and post-reinstrumentation weights, Mtwo-R was the most effective instrumentation technique.
Regarding the mean time of retreatment and time required for reaching the working length, Mtwo-R instruments were significantly faster
than the others. In addition, the hand instrumentation was more successful comparing to others in terms of the amount of apically
extruded material.
Conclusion: Under experimental conditions, Mtwo-R/Mtwo and ProTaper retreatment instruments proved to be efficient and time-saving
devices for the removal of gutta-percha. (El Med J 2:4; 2014)
Keywords: Endodontics, Retreatment, Root Canal Instrumentation

Introduction
Technologic developments in endodontics allow clinicians to gain
insight into the retreatment of failing root canals. The major goal of
the retreatment is the complete removal of the root canal filling
material to reach to foramen apicale. The most common root canal
filling material requiring removal is gutta-percha. Gutta-percha
removal is usually accomplished by the use of hand instruments
alone, or in combination with rotary instruments with or without
solvents, and heat carrying instruments [1].
Various nickeltitanium (NiTi) rotary endodontic instruments have
been developed to facilitate cleaning and shaping of root canals. To
improve safety preparation and to prepare more appropriate
shapes, new instrument designs with noncutting tips, radial lands,
varying tapers and rake angles, and changing pitch lengths have
been developed. Rotary NiTi instruments have also been proposed
for the removal of filling materials from root canal walls, and several
studies have reported their efficacy, cleaning ability, safety and
working time [2-4].
In curved root canals, the removal of filling materials, and further
cleaning and shaping are more difficult than in straight canals and
more likely to cause instrument distortion or breakage. Studies on
the efficiency of removing canal filling in curved root canals are also
few [5-7].
Literature review reveals several studies on the effectiveness of
rotary and hand instruments, either simulated resin canals or
extracted teeth with curved canals [7-12]. The aim of the present
study was to investigate the efficacy of two rotary retreatment

systems and one hand instrumentation sequence to remove curved


simulated canal fillings.

Methodology
This study was performed at the Departments of Endodontics in
Ondokuz Mays University Dental Faculty, Samsun, Turkey. Forty five
simulated canals made of clear polyester resin (Viapal uP 004/64;
Vianova Resins, Hamburg, Germany) were used in this study. The
degree of canal curvature was 35. The diameter and the taper of all
simulated canals were equivalent to an ISO standard size 15 root
canal instrument. The 35 canals were 13 mm long, the straight part
was 5 mm and the curved part was 8 mm. The radius of the
curvature was 6.5 mm. The blocks were weighed with a digital
electronic balance (Shinko AF R-220, Shinko Denshi Co. Ltd., Tokyo,
Japan) for checking their standard weights in grams (W1).
Canal preparation
All the simulated canals were prepared by one experienced
operator. The working length was established 1 mm short of the
apex. The canals were prepared using K-files (Mani, Tochigi Ken,
Japan) with the step-back technique. Instrumentation was
standardized using a step-back technique with a size 30 K-file
reaching the full working length. The blocks were reweighed for
checking their standardization of preparation (W2). The canals were
debrided using 2.5% sodium hypochlorite, dried with paper points
and obturated using lateral compaction. A master gutta-percha cone
(Diadent, Burnaby, BC, Canada) size 30 was selected and tug-back
was checked. AH Plus sealer (Dentsply, DeTrey Gmbh, Konstanz,
Germany) was mixed according to the manufacturers instructions.
The master cone was coated with sealer and positioned into the

Department of Endodontics, Faculty of Dentistry, Ondokuz Mays University,


Samsun, Turkey
Correspondence: Ebru zsezer Demiryrek
Email: ebrudemiryurek@gmail.com

2014 Demiryrek et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Demiryrek E, Bodrumlu E: Effectiveness of hand versus rotary instrumentation on retreatment of curved canals. El Mednifico Journal 2014, 2(4).

342

canal. Then accessory cones were laterally compacted until they


could not be introduced more than 5 mm into the canal. After the
filling process, all the weights of each resin block were measured
(W3) and the blocks were stored in saline solution at 37C for 48
hours.
Retreatment techniques
All the simulated canals had 3 mm of obturation material removed
from the cervical part of the canal using Gates Glidden drills # 2 and
3 (Dentsply Maillefer, Ballaigues, Switzerland). After using the Gates
Glidden drills, a drop of chloroform solvent (Merck, Darmstadt, BRD,
Germany) was introduced into each canal to soften the gutta-percha.
Two or three additional drops of solvent were applied as required
to reach the working length. Sodium hypochlorite 2.5% irrigation
was used after each instrument. ProTaper and Mtwo-R/Mtwo rotary
retreatment instruments were driven with a torque-controlled
motor (X-Smart, Dentsply, Maillefer, Balaiggues, Switzerland)
according to the manufacturers instructions.
Teeth were divided into 3 groups, with each group consisting of 15
teeth.
Group 1 (n:15) with Hedstrm files: The canals were re-instrumented
in a crown-down technique with H-type file (VDW Antaeos, Munich,
Germany) sizes 45, 40, 35 and 30 in a circumferential quarter-turn
push-pull filing motion to remove gutta-percha and sealer from the
canal until the working length was achieved with a size 30 H-type
file.
Group 2 (n:15) with ProTaper Universal rotary retreatment system:
ProTaper Universal retreatment instruments were used in a hand
piece with adjustable torque (NiTi Anthogyr Control, Dentsply
Maillefer) according to the manufacturers instructions. The canal
filling material was removed by ProTaper Universal retreatment
instruments (Dentsply Maillefer, Ballaigues, Switzerland) following
the manufacturers instruction. In brief, D1 (9% taper, size 30), D2
(8% taper, size 25) and D3 (7% taper, size 20) were sequentially used
in a crown-down manner to reach pre-established working length;
they were manipulated in a brushing action. The rotational speed
was set at 500 rpm as recommended by the manufacturer. Root
canal refinement was accomplished with ProTaper Universal rotary
shaping [S1 (shaping file no.1; taper 211%; size 17) and S2 (shaping
file no.2; taper 411.5%; size 20)] and finishing [F1 (finishing file
no.1; taper 5.57%; size 20), F2 (finishing file no.2; taper 5.58%; size
25) and F3 (finishing file no.3; taper 59%; size 30)] instruments,
which were used in a gentle brushing action at a speed of 300 rpm
according to the manufacturers instruction.
Group 3 (n:15) with Mtwo-R/Mtwo rotary retreatment system: Mtwo
instruments were used with the air-driven torque-limited rotation
hand piece (Mtwo Direct VDW, Munchen, Germany) at 300 rpm.
Torque settings were selected with a turning ring chosen for each
file according to the manufacturers instructions. The root canal
filling material gradually was removed by Mtwo R2 (5% taper, size
25) and Mtwo R1 (5% taper, size 15) instruments, respectively, until
slight resistance was encountered. These two instruments were used
with circumferential filing movements and without downward
pressure. A C-pilot file (VDW) size 10 was used to negotiate the root
Vol 2, No 4

Effectiveness of hand versus rotary instrumentation

canal to full working length. After the working length was reached,
conventional Mtwo rotary instruments were used to remove the
filling material in a circumferential filing motion while pressing
against the root canal walls: Mtwo 4% taper, size 10; Mtwo 5% taper,
size 15; Mtwo 6% taper, size 20; Mtwo 6% taper, size 25 and Mtwo
5% taper, size 30.
The canal filling material was removed until the canal walls were
smooth and the initial working length was retained.
The evaluation of the coded specimen was performed by two
operators who could not identify the techniques and devices used
for retreatment. Extrusion of debris or canal filling material through
the apical foramen was controlled visually using a loupe with x5
magnification.
The specimens were scored for remaining canal filling material using
six categories according to the following scale of I to VI, used by
Hulsmann and Stotz [13]:
I. The canal filling material removed completely.
II. One to three small isles of the canal filling material (x<2 mm
long).
III. More than three small isles of the canal filling material (x<2 mm
long).
IV. One large piece of the canal filling material (x>2 mm long).
V. The canal filling material covering a length of more than 5 mm.
VI. Several isles of the canal filling material (x>2 mm extension).
The removal degree of the sealer was not assessed in this study.
Procedural incidents (perforations, blockages, loss of working
length, ledging, instrument fractures) were recorded.
After the removal of the filling material from the obturated
simulated canals by three techniques, the specimens were
reweighed (W4). The mean loss of weights between W3 and W4
were determined for efficiency capacity of each retreatment
technique and for each immersion period.
Statistical Analysis
Since there was a need of overall evaluation considering all variables
together rather than using univariate classical statistical testing
procedure for each variable separately, Data Envelopment Analysis
(DEA) was used in this study to calculate efficiencies of instruments.
Efficiency is defined, in a relative sense, as the distance between
observed input-output combinations and a best practice frontier.
DEA is one of several techniques that can be used to calculate a best
practice frontier [14]. Efficiency score equals one for efficient
instruments, and then decreases with inefficiency.
The efficiency of instruments was modelled in a multiple input,
multiple output framework. The amount of apically extruded
material, canal wall cleanliness, working safety and difference
between W3 and W4 after removal were outputs of the DEA model.
Two inputs were used for efficiency analysis: time taken to reach
working length and time period for gutta-percha removal. Efficiency
scores were calculated by using DEAP 2.1 computer program
developed by Coelli [15].

Demiryrek E, Bodrumlu E

Results
The measurements of W1 and W2 were exhibited that all the
simulated blocks were similar weights (p<0.05).
Based on the research results, Mtwo retreatment instruments had
the shortest time for reaching working length while that of hand
instrumentation was the longest. The same was the case in terms of
time period for gutta-percha removal (Table 1).
Table 1: Time taken to reach working length and time
period for gutta-percha removal
Time taken to reach
Period for guttaworking length
percha removal
Instruments
(T1)(sn)
(T2)(sn)
Mean
SD
Mean
SD
100.07
16.95
140.53
16.49
ProTaper
Mtwo-R/Mtwo
91.85
8.22
128.98
29.22
Hand
137.08
32.02
192.51
47.19
Research results also showed that hand instrumentation was more
successful than the others in terms of the amount of apically
extruded material. ProTaper retreatment instruments and MtwoR/Mtwo retreatment instruments followed it. In terms of the canal
wall cleanliness, ProTaper retreatment technique and hand
processing were more successful than MtwoR/Mtwo technique. The
same situation was the case when focusing on working safety. With
respect to the difference between W3 and W4, Mtwo-R/Mtwo was
the most effective instrument technique (Table 2). However, time
factor was ignored when interpreting the success of the
instruments. Efficiency analysis, therefore, was required considering
all variables together with time factor to reach more reliable results.
Table 2: The percentage of success of instruments in terms of the
amount of apically extruded material, canal wall cleanliness,
working safety and difference between W3 and W4 after removal.
The amount
Difference
of apically Canal wall Working
between
Instruments
extruded
cleanliness
safety
W3 and
material
W4
ProTaper
73.30
40.00
73.30
0.067
Mtwo-R
66.70
13.30
53.30
0.002
Hand
100.00
20.00
86.70
0.029
ProTaper retreatment system was the most efficient technique while
the hand instrumentation was the worst efficient technique in terms
of the results of efficiency of removal the filling materials (Table 3).

Discussion
The main goal of retreatment is to regain access to the constriction
by complete removal of the root canal filling material, thereby
facilitating sufficient cleaning and shaping of the root canal system
and final obturation [16, 17]. Different methodologies have been
reported during evaluation of remaining filling material including
longitudinal cleavage of teeth which may displace filling material

343

remnants, association of longitudinal and transverse cleavage,


cleavage and photographic recordings, visual examination through
cleavage and photography in association with radiographic
examination [5-12, 18]. The problems with sectioning teeth are that
it can disturb the remaining filling material. Therefore, the weight
measurement technique which was used in the studies of Zarrabi et
al. and Kele et al. was preferred for this study for assessing the
efficiency of each retreatment technique [19, 20].
Table 3: The efficiency scores for instruments
Instruments
Efficiency score
1.00
ProTaper
0.97
Mtwo-R/Mtwo
0.91
Hand
Gates-Glidden drills, recommended for gutta-percha removal at the
canal orifice level, were used in the coronal 3 mm of the canals [21].
This process facilitates access to the more apical portions of canals,
and provides a receptacle for the placement of solvent. Additionally,
in teeth with narrow curved roots, clinicians should avoid taking
these drills more than 2-3 mm apically, to avoid stripping perforation
of the canal wall.
Several techniques have been studied, seeking speed and
practicality in the maneuver of gutta-percha removal from the root
canal system and for many of them the use of a solvent seems to be
extremely valid in assisting in instrument removal of this material
[22, 23]. In the present study, chloroform solution during the
instrumentation was used because it is more efficient in dissolving
gutta-percha than other chemicals [24, 25]. Chloroform was quite an
effective solvent for gutta-percha. However, possible adverse health
effects from exposure to chloroform should not be overlooked [25].
It was not possible to remove all the traces of gutta-percha and
sealer from the canal walls with any of the techniques, which has
also been reported in other studies [26, 27]. Therefore, the use of
rotary NiTi instruments in root canal retreatment may decrease
patient and operator fatigue. In the present study, the retreatment
time ranged from 1.5 to 5 min. The rotary instruments were faster
than hand instruments in removing the obturation materials [13]. In
accordance with the present study, the use of rotary instruments has
been reported to decrease working time for canal filling materials
removal. However, the clearance efficiency of ProTaper retreatment
files were better than that of Mtwo-R/Mtwo files in the present
study. This difference in clearance efficiency between these two
rotary systems can be explained by ProTaper file that has a convex
triangular cross-sectional designed cutting blade for increased
flexibility and cutting efficiency.
Apically extruded debris might result in post instrumentation flare
up clinically or even failure of apical healing [13]. In the present
study, apically extruded debris was found regardless of the
technique used, and there were not statistically significant
differences between the groups. The amount of apically extruded
material in this study was below 0.1 mg.

http://www.mednifico.com/index.php/elmedj/article/view/248

344

Effectiveness of hand versus rotary instrumentation

Conclusion
Under the experimental conditions, Mtwo-R/Mtwo and ProTaper
NiTi retreatment instruments proved to be efficient and time-saving
devices for the removal of gutta-percha. Nevertheless, completely
cleaned canal walls could not be achieved with any of the
techniques under investigation.
Competing interests: The authors declare that no competing interests exist.
Received: 22 April 2014
Accepted: 11 December 2014
Published Online: 11 December 2014

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Open Access

Original Article

Assessment of childhood cancer at National Oncology Center in Sanaa city, Yemen


Nabil Ahmed Al-Rabeei1, Abdulhameed Ali Al-Thaifani1, Ashwaq A Al-Ariki2

Abstract
Background: No published studies assess childhood cancer and obstacles to receive cancer treatment in Yemen. The aim of this study
was to assess childhood cancer and obstacles to receive cancer treatment at National Oncology Center (NOC) in Sana`a city, Yemen.
Methods: A descriptive cross-sectional study of 119 children with cancer was conducted at the NOC in Sanaa city, Yemen from March to
May, 2012. Data was collected through face-to-face interview and retrospectively from patients' files. The data regarding sociodemographic characteristics, medical history of childhood cancer and obstacles to receive cancer treatment were collected by structured
questionnaire. The collected data was analyzed using the SPSS. A p-value <0.05 (2-sided) was considered statistically significant.
Results: One hundred and nineteen children with cancer and their parents were included in our study. The mean age and SD was 8.7
4.5 years. 63.9% of the participants were boys. Lymphomas were the most common cancer diagnosed, representing 35.3% of all childhood
cancers followed by leukemias (22.7%) and malignant bone tumors (12.6%). A high proportion of childhood cancer was diagnosed at
advanced stages and constituted for 58%. Tumor grading was mentioned in 25.2% of cases. Histology diagnosis was achieved in 89.1% of
cases. 80.7% did not receive cancer treatment on regular basis.
Conclusion: The study concluded that at the National Oncology Center, lymphomas were the most common childhood cancer diagnosed,
followed by leukemias and malignant bone tumors. The distribution of cancer was more in boys than girls. Poor service was the main
obstacle to received cancer treatment regularly. The study recommends that a national cancer registry should be introduced. (El Med J
2:4; 2014)
Keywords: Childhood Cancer, National Oncology Center, Yemen, Obstacles, Cancer Treatment

Introduction
Cancer is a group of diseases characterized by uncontrolled growth
and spread of abnormal cells [1]. According to World Health Organization (WHO), childhood cancer is becoming an increasingly important cause of morbidity and mortality worldwide [2]. Cancer is
next to injury, the second most common cause of childhood death
in developed countries [3, 4].
Cancer may affect people at all ages, even fetuses, but risk for the
more common varieties tends to increase with age. Incidence rates
are highest among infants, decline until age 9, and then rise again
with increasing age [5]. In all age groups, the incidence is significantly higher in boys than in girls; boys have an overall 20-25% excess risk for cancer due mainly to a greater risk of lymphomas, leukemias and central nervous system (CNS) tumors [3].
A study conducted by Bawazir, et al. to study prevalence of cancer
in Aden governorate and adjacent governorates through the information registered in the register for treatment aboard of the Aden
health offices (1989-1993) [6]. Out of 685 cases of cancer, 69 (10.1%)
were children aged 0-19 years. The distribution of childhood cancers
by sex were 43 (62.3%) in males and 26 (37.7%) in females.
The absence of a national cancer registry means there is a lack of
reliable data for evaluating the real situation of childhood cancer in
Yemen. There was no national survey in Yemen to estimate incidence
of childhood cancer. Despite the rising importance of this disease,
there is a lack of studies which characterize the incidence or distribution of different types of childhood cancer in Yemen.
To the best of our knowledge, this is the first study was done to assess childhood cancer and obstacles to receive cancer treatment in
Sana'a-Yemen. The aim of the study was to assess childhood cancer
1
2

Faculty of Medicine and Health Sciences, Sanaa University, Yemen


Faculty of Medicine and Health Sciences, Al-Hudaydah University, Yemen

and obstacles to receive cancer treatment at National Oncology Center in Sanaa city, Yemen

Methods
The study was conducted at the National Oncology Center (NOC) in
Sana'a city, Yemen. The NOC is the first and the only unique public
health center in Yemen Republic which provides chemotherapy, radiotherapy and laboratory investigations for patients with cancer. A
descriptive cross-sectional study was conducted in the above mentioned setting to assess childhood cancer and obstacles to receive
cancer treatment from March to May, 2012. A convenience sample
of 119 children with cancer was selected. Children were selected during their attendance at the NOC. The inclusion criteria were both sex
children attending the NOC for follow-up treatment and approved
to participate in the study.
The required sample size was calculated using EpiCalc program,
2000. When the size of the sample was calculated, researchers depended on the following criteria: proportion of childhood cancer in
Gulf center for cancer registration (GCCS) from 1998-2005 = 8.5%,
Precision = 5% [6]. A sample size (n) with 95% confidence level was
119 children. A structured questionnaire was compiled and adopted
questions from published studies and was administered in a face-toface interview with study participants. The questionnaire consisted
of demographic characteristics of children, medical history of childhood cancer and obstacles to receive cancer treatment.
Questions related to demographic data, habits and obstacles to receive cancer treatment were asked directly in a standard way to ensure data reliability. Medical history of childhood cancer was taken
by access to the patients medical record files to validate the provided data. When there were discrepancies between data sources,
Correspondence: Nabil Ahmed Al-Rabeei
Email: nabilalrabeei@hotmail.com

2014 Al-Rabeei et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Al-Rabeei NA, Al-Thaifani AA, Al-Ariki AA: Assessment of childhood cancer at National Oncology Center in Sana`a city, Yemen. El Mednifico Journal 2014, 2(4).

346

Assessment of childhood cancer at National Oncology Center

the data in the medical record files were used. In case, some data
was not available in the patients medical record files, data was extracted from the physician who was responsible for treatment of the
case. The primary site (topography) and histology (morphology) of
the neoplasms were classified according to the international classification of childhood cancer-3 (ICCC-3) based on international classification of diseases-oncology-3 (ICD-O-3) [7].
The collected data was analyzed using SPSS, version 16.0. Fisher's
exact test was performed for categorical variables to test for dependency (presence of relationship) between variables. Fisher's exact test
is more appropriate than the asymptotic chi-square when the table
contains cells with expected counts less than 5. Appropriate test of
significance was applied to determine the significance of association.
A p value <0.05 (2-sided) was considered statistically significant. Informed consent was obtained from parents of children. The survey
was approved by the nursing division and faculty of medicine and
health science, Sana'a University.

Results
The age of about 40.3% of the participating children fell between 59 years, followed by those with age between 10-14 years (26.9%),
while the least percent (13.4%) was among the age group 15-19
years. The mean age and SD was 8.7 4.5 years (8.7 4.6 years for
boys and 8.7 4.5 years for girls). Nearly two thirds (63.9%) of the
participants were boys, and more than the half (54.6%) of them were
urban residents. The majority of the children (70.6%) had a birth order <5. 95.8% of children were full-term and 84% without family history of cancer (Table 1).
Table 1: Demographic characteristics of children
Demographic characteristics
Current age
0-4 years
5-9 years
10-14 yeas
15-19 years
Sex
Boys
Girls
Place of residence
Urban
Rural
Birth order
<5
5
Gestational age
Full-term
Pre-term
Family history of cancer
Yes
No

n
23
48
32
16
76
43
65
54
84
35
114
5
100
19

%
19.3
40.3
26.9
13.4
63.9
36.1
54.6
45.4
70.6
29.4
95.8
4.2
84.0
16.0

Table 2 shows the distribution of childhood cancers according to


types. Lymphomas were the most common cancer diagnosed, representing 35.3% of all childhood cancers followed by leukemias
(22.7%), malignant bone tumors (12.6%), soft-tissue sarcomas
(8.4%), renal tumors (6.7%), CNS neoplasms (4.2%), germ cell tumor
(3.4%), other nervous system tumors (2.5%). Hepatic tumors, carcinomas and retinoblastoma, accounted for 1.7%, 1.7% and 0.8% re-

Vol 2, No 4

spectively. The proportion of different sites showed that, Non-Hodgkins lymphoma (NHL) was most frequently represented (23.5%) followed by lymphoid leukemia, which accounted for 21%, malignant
bone tumors, which occurred in 12.6%, Hodgkin's lymphoma (HL) in
11.8%, connective/soft-tissue in 8.4%, brain/nervous system in 6.7%,
kidney in 6.7% and other sites (myeloid Leukemia, eye, liver, spinal,
thyroid, ovarian and chest) in 9.2%.
Table 2: Distribution of types of childhood cancers
according to ICCC-3
Types of childhood cancers
n
27
Leukemias
42
Lymphomas
5
Central Nervous System
3
Sympathetic Nervous System Tumors
1
Retinoblastoma
8
Renal Tumors
2
Hepatic Tumors
15
Malignant Bone Tumors
10
Soft-Tissue sarcomas
4
Germ cell tumor
2
Carcinomas
119
Total

%
22.7
35.3
4.2
2.5
0.8
6.7
1.7
12.6
8.4
3.4
1.7
100

With regards to the stages of cancer at diagnosis, the results indicated that, the stages at diagnosis were available for 101 cancer
cases (84.9%) while 18 (15.1%) had an unknown diagnosis (Figure
1).

Distribution of Childhood Cancers


Unknown (15.1%)

In situ (0.8%)
Localized (26.1%)

Regional (32.8%)
Distant metastasis (25.2%)

Figure 1: Distribution of childhood cancers by stages at


diagnosis
Tumor grading was mentioned in 30 (25.2%) cases, while the majority of cases (74.8%) were labelled as cannot be assessed (Figure 2).
Histological diagnosis was achieved in 106 (89.1%) cases, compared
to 10 (8.4%) children who were diagnosed by cytology and only 3
(2.5%) were diagnosed by radiology (Figure 3).
With regards to distribution of childhood cancer by children characteristics, Fisher's exact test showed association of distribution of
childhood cancer by sex, age at diagnosis, governorates, place of residence and child birth order (P<0.05) while no relationship existed

Al-Rabeei NA, Al-Thaifani AA, Al-Ariki AA

347

with gestational age and family history of cancer (P>0.05). Furthermore, Fisher's exact test showed relationship in distribution of childhood cancer by maternal age father age (P<0.05) while no relationship according to mother smoking was seen during pregnancy
(P>0.05).

Figure 2: Distribution of childhood cancer by grades at diagnosis

Basis of diagnosis
Radiology
2.5%

Cytology
8.4%

Histology
89.1%

Figure 3: Distribution of childhood cancer by basis of diagnosis


The results of the study regarding obstacles to receive cancer treatment showed that 71 (74%) study participants stated that the poor
service/time taken to wait were the main obstacles to receive cancer
treatment regularly, 70 (72.9%) cases were hindered due to physical
condition of child and 66 (68.8%) lacked resources to travel. For 44
(45.8%) cases, the type of treatment was not available. 29 (30.2%)
lacked the funds to pursue some cancer drugs and in 24 (25%) cases,
health care workers were not present (Figure 4).

Figure 4: The obstacles to receive childhood cancer treatment

Discussion
The results of our study suggest that the most common forms of
childhood cancer were lymphomas, leukemias and malignant bone
tumors, which accounted for about 70.6% of all childhood cancers
diagnosed. Lymphomas in our study ranks first among cancer diagnoses for children ages 0 to 19, accounting for 35.3% of all childhood
cancer morbidity. The ratio of NHL:HL was 2:1 with male to female
ratio being 2:1. The proportion of lymphomas were higher than reported by Surveillance, Epidemiology and End Results (SEER) in
United States (US) and other Asian countries but lower than Europe
which is truly remarkable and novel, and needs to be further investigation [8, 9].

Non-Hodgkins lymphomas accounted for 23.5% of lymphomas and


Hodgkins lymphoma accounted for 11.8%. Lymphomas were more
common in boys than girls, and occurred at all ages, but the peak
was found to be between 5-9 years. Similar results were reported by
a study in Aden [6]. This study was consistent with study conducted
in Turkey, where the distribution of childhood cancer showed that
lymphomas were observed more frequently than leukemias and CNS
tumours [10].
Leukemia ranked second among cancer diagnoses for children ages
0 to 19 in our study, accounting for 22.7% of all childhood cancer
morbidity. Acute lymphocytic leukemia (ALL) represents about
92.5% of all childhood leukemias and acute myeloid leukemia accounted for 7.5% of leukemia cases. Leukemias were more common
in boys than girls and occur at age ranged from 0-14 years, but the
peak was occurs in aged 10-14 years. The proportion of leukemias in
our study were lower than reported by SEER, by Georgia and by Thailand and higher than reported by Hadramout governorate [11-14].
Similar result was found by USA [15]. The most common cancer type
diagnosed in United States between 19992005 was leukemias. In
Europe, leukemias constitute approximately one-third of cancers in
children aged 0-14 years) and 10% in aged 15-19 years [16]. This result is higher than reported in the present study.
Malignant bone tumors in our study made up the third category of
childhood cancers, accounting for 12.6% of all childhood cancers.
Malignant bone tumors were approximately same in boys and girls
and occurred at ages ranging from 5-19 years, but the peak was between 10-14 years. Osteosarcoma was the most common cancer in
this category, which in children often occurs in the bones around the
knee, and accounted for 60% while Ewings sarcoma was the second
bone tumor in this category, accounting for 40%. Bone tumors in our
study were higher than reported by MECC countries, European countries, SEER areas and in Asia [13, 17-19].
Soft tissue sarcomas were the fourth childhood cancer accounting
for 8.4% of all childhood cancers. Soft tissue sarcomas of children
and adolescents arise primarily from the connective tissues of the
body, such as fibrous tissue, adipose tissue, and muscle tissue. Rhabdomyosarcomas were the most common soft tissue tumor among
children younger than 20 years. Soft tissue sarcomas were more
common in boys than girls and occurred at all ages, but the peak
was between 0-9 years. The proportion of soft tissue sarcomas were
http://www.mednifico.com/index.php/elmedj/article/view/331

348

Assessment of childhood cancer at National Oncology Center

approximately similar to that reported by SEER [1]. The result of this


study was similar to the study from Turkey [20]. The incidence of soft
tissue sarcomas was higher as in other Asian populations [13].

of hepatic tumors in children are hepatoblastoma, most of which appear during the first 18 months of life and may be caused by an abnormal gene.

Renal tumors were the fifth childhood cancer accounting for 6.7% of
all childhood cancers. Renal tumors occurring in children comprise a
spectrum of morphologic subtypes, including some with benign histopathology. Wilms tumor accounted for 100% of malignancies of
the kidney among children. Wilms tumor was more common in boys
than girls and occurred among children younger than 15 years but
the peak was between 5-9 years. The relative frequencies of Wilms
tumor in the present study was higher than those reported from
Shanghai and western countries [21].

Carcinomas were the tenth childhood cancer, accounting for 1.7% in


our study. Carcinomas are rare in Yemeni children, as they are in
Thailand, and in general [13, 25]. Thyroid carcinoma accounted for
virtually all cases of cancer in this category. Carcinomas are very rare
among children. All of the carcinomas combined comprised 9.2% of
cancer in children younger than 20 [26]. Retinoblastoma had the
lowest frequency, accounting for 0.8 percent of all childhood cancers. Retinoblastoma is a rare tumor involving the retina of the eye,
or sometimes the pineal gland [1]. Retinoblastoma most often occurs
in younger children, usually before the age of 5 years [1]. The tumor
may be in one or both eyes [27]. Retinoblastoma is usually confined
to the eye and does not spread to nearby tissue or other parts of the
body. Retinoblastoma in our study was lower than reported by SEER,
Thailand and in neighboring countries [9, 28].

Central nervous system tumors in our study made the sixth category
of neoplasms in children, accounting for 4.2% of all childhood cancers. They were almost equal among males and females and occurred at ages ranging from 0-9 years. The most common types of
brain tumors were primitive neuroectodermal tumor (PNET). Other
common brain tumors in our study was medulloblastoma. The rate
in our study was lower than reported by SEER areas [22]. The proportion of CNS tumors in the present study was slightly lower than
in other Asian countries and markedly lower than in developed countries [9].
Germ cell tumors ranked seventh among cancer diagnoses for children aged 0 to 19 in our study, accounting for 3.4% of all childhood
cancer morbidity. Germ cell tumors were more common in girls than
boys and occurred among children younger than 15 years. Yolk sac
tumors and teratomas were the most common tumors in this category found in our study. Germ cell tumors are biologically diverse
and histologically heterogeneous, with a substantial proportion having benign rather than malignant behavior (particularly among
young children) [9, 23]. Germ cell tumors originate in primordial
germ cells, which may undergo germinomatous or embryonic differentiation. The results of the study were lower than reported by SEER
areas but similar compared to those reported by Georgia [12, 24].
In the present study, sympathetic nervous system tumors were the
eighth childhood cancer, accounting for 2.5% of all childhood cancers. Neuroblastoma accounted for virtually all cases of cancer in this
category. Neuroblastoma is a solid cancerous tumor that begins in
nerve tissue in the neck, chest, abdomen, or pelvis, but usually originates in the abdomen in the tissues of the adrenal gland. Two-thirds
of children with neuroblastoma are diagnosed when they are
younger than 5 years of age [1]. Although neuroblastoma may be
present at birth, it does not always proceed to become an invasive
malignancy, a circumstance unique to neuroblastoma. In contrast
with CNS malignancies, survival is highest among infants under 1
year of age, and declines with increasing age [1]. The proportion of
neuroblastoma in the present study was lower than reported in Thailand, Singapore, Japan, China and the Philippines [9, 13].
In the present study, hepatic tumors were the ninth childhood cancer, accounting for 1.7% of all childhood cancers and hepatoblastoma was the commonest tumor in this category. All tumors were
found in girls. A rare malignancy in childhood, liver tumors account
for just over 1 percent of childhood cancers [1]. More than two-thirds
Vol 2, No 4

Obstacles: The results of the study regarding obstacles to receive


cancer treatment showed that poor service/too long a wait, physical
condition of child, lack of resources to travel/too far to travel, type
of treatment not available, lack of funds to pursue some cancer drugs
were the main obstacles to receive cancer treatment regularly. However, there is extreme paucity of data addressing the pattern and
impact of abandonment on outcome of childhood cancer from India
and other Asian developing countries [29, 30]. Pisani and Hery reported that, misdiagnosis, refusal of treatment, abandonment of
therapy, toxic death, lack of resources and affordable drugs, and comorbidities all contribute to a poor outcome alongside other overwhelming challenges [31]. In India, quantifying the burden also faces
other barriers: parents may not recognize the signs of cancer, or not
have the resources to get the patient to a medical facility [32].
The limitation of the study was that many cancer patients in Yemen
still prefer to go abroad for treatment and are consequently not recorded. Therefore, it may be unreliable to attempt to calculate the
childhood cancer incidence in this study as it may be underestimated.

Conclusion
The three most common childhood cancer in our study were lymphomas, leukemias and malignant bone tumors, which represented
70.6% of all childhood cancer. The proportion of childhood cancers
was more among boys than girls, except for nervous system tumors.
A high proportion of childhood cancers (58%) was diagnosed at advanced (regional/metastasized) stages.

Recommendation
National cancer registry should be established to provide reliable
measure of cancer incidence rate in Yemen.
Competing interests: The authors declare that no competing interests exist.
Received: 3 May 2014
Accepted: 14 December 2014
Published Online: 16 December 2014

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http://www.mednifico.com/index.php/elmedj/article/view/332

Open Access

Original Article

A comparison of survival with chemoradiation therapy alone versus surgery and post-esophagectomy
chemoradiation in patients with esophageal carcinoma
Manoochehr Aghajanzadeh1, Abbas Rahimi2, Dina Emami1, Gilda Aghajanzadeh3, Sina Khajeh Jahromi4, Hannan Ebrahimi4

Abstract
Background: Esophageal cancer is usually incurable. Aggressive treatments involving multimodality therapies have been offered to
improve overall survival rates. It seems that various therapeutic approaches can have a different outcome and survival. The aim of our
study was to compare survival with chemoradiation therapy (CRT) alone versus surgery and post-esophagectomy chemoradiation therapy
(CRT-S) in patients with esophageal carcinoma.
Methods: This historical cohort study assigned 226 patients with stage I to III esophageal cancer who referred to Radio-oncology clinic
of Razi hospital from 2005-2011 for oncology treatment. Patients were categorized into two groups. One group treated by chemoradiation
therapy (CRT) alone and other group treated with surgery and post-esophagectomy chemoradiation. Overall survival of two groups was
compared. For statistical analysis SPSS was used and the comparison of groups was performed with Kaplan-Meier analysis and Log-rank
test.
Results: Of 266 patients with stage I to III esophageal cancer, 222 patients were in the CRT group and 44 patients were in the CRT-S
group. 22 patients had stage I, 82 had stage II and 118 had stage III. Median survival was 17 month for the CRT group and 18 month for
the CRT-S group. There was no significant difference in survival rate between chemoradiation therapy alone (CRT) and postesophagectomy chemoradiation therapy (CRT-S) (P>0.005).
Conclusion: Based on these data, we concluded that patients with tumors, especially of squamous cell carcinoma, that respond to initial
chemoradiotherapy did not derive any survival benefit from subsequent surgery and three-month mortality was significantly higher in
the surgery group. Surgery imposes a major emotional trauma and an excessive and unnecessary cost on the patient and the community
health system. We conclude that it is better to use CRT for patients with non-advanced esophageal cancer. (El Med J 2:4; 2014)
Keywords: Esophageal Cancer, Survival Rate, Chemoradiation

Introduction
Esophageal cancer is considered an invasive disease which usually
appears in an advanced stage and is a major cause of cancer deaths
overall. This cancer has more than 80% survival rate for early stage
disease with surgery. But this percentage decreases to 10% to 15%
for stage III with surgery alone [1-3]. Different survival rates have
been reported in the literature. Ellis reported 5-year survival as 24.7%
[4]. In patients with transhiatal esophagectomies performed for cancer, 65% of patients with stage I disease had 5-year survival, while
11% of those with stage III disease had 5-year survival [5]. In Orringers study, radiation as a single-modality therapy was used primarily
for palliation [5].
Different treatment protocols are used for esophageal cancer. Literature mentions that radiation therapy as sole treatment results in 6
to 17 percent survival [6, 7]. Chemotherapy is offered as treatment
for distant foci of tumor. However, the results from the use of chemotherapy as a single line of therapy are usually disappointing [8]. In
multiple randomized controlled studies, use of postoperative radiation therapy demonstrated either no increase or a decrease in survival; however, it may decrease the incidence of local tumor recurrence compared with resection alone [9-11]. Postoperative chemotherapy has also been compared with surgical management alone
and no difference in survival has been found between these two approaches in five-years [12, 13].
Law and colleagues suggested that preoperative chemotherapy was
safe and caused significant down-staging and an increased likelihood of curative resection. They also mentioned that survival was
Department of Thoracic Surgery, Guilan University of Medical Sciences, Rasht, Iran
Department of Radio-oncology, Guilan University of Medical Sciences, Rasht, Iran
3Respiratory diseases and TB Research Center, Razi Hospital, Guilan University of
Medical Sciences, Rasht, Iran
1
2

not better than that in the surgery-alone group [8]. However, Walsh
and Colleagues reported that patients assigned to multimodal therapy (consisting of chemotherapy, radiotherapy and surgery) had
more survival than patients assigned to surgery alone [14].
In most patients, despite continued refinement of operative techniques of esophagectomy, cumulative quality of life and functional
outcome of gastrointestinal tract after esophagectomy has remained
poor [15, 16]. Hence, the aim of our study was to evaluate a comparison of survival with chemoradiation therapy (CRT) alone versus surgery and post-esophagectomy chemoradiation therapy (CRT-S) in
patients with esophageal carcinoma.

Materials and Methods


This was a historical cohort study carried out on all patients with
esophageal cancer referring to the radiotherapy clinic of Razi Hospital, enrolled during 2004-2011 (304 patients). This paper is the result
of a thesis which was approved by the vice chancellery of research,
Guilan University of Medical Sciences, with ethics number 8745 and
registration number 601.
All the patients with esophageal cancer were entered in this study.
They were divided into two groups, chemoradiation (CRT) alone and
post-esophagectomy chemoradiation (CRT-S), in patients with
esophageal carcinoma based on the clinically operability of the patients and his/her decision. Patients receive two cycles of fluorouracil
and cisplatin concurrent with radiation therapy (40 Gy) given over a
3-weekperiod. Resection was performed 8 weeks after the initiation
of treatment.
Student Research Committee, Guilan University of Medical Sciences, Rasht, Iran
Correspondence: Sina Khajeh Jahromi
Email: sina.khajehjahromi@gmail.com

2014 Aghajanzadeh et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Aghajanzadeh M, Rahimi A, Emami D, Aghajanzadeh G, Khajeh Jahromi S, Ebrahimi H: A comparison of survival with chemoradiation therapy alone versus surgery and post-esophagectomy
chemoradiation in patients with esophageal carcinoma. El Mednifico Journal 2014, 2(4).

Aghajanzadeh M, Rahimi A, Emami D et al.

351

Of 304 patients with esophageal cancer, 38 patients were excluded


due to lack of access in the beginning. 222 cases out of 266 remaining patients were treated with CRT and 44 patients with CRT-S. None
of the patients had any esophageal metastasis in both treatment
groups, CRT and CRT-S.
Collection of information was through a questionnaire by filling out
the questionnaire with the records of patients in the radiotherapy
clinic that consisted of clinical history, physical exam and laboratory
and paraclinic evaluations with staging which was evaluated by CT
scans. Information collected was statistically analyzed via Log rank
test or Breslow or Tarone-wave. The Kaplan-Meier method was used
to estimate the survival rate and average survival and the Cox Regression was used to estimate the chances of survival to control confounding and basic factors.

Results

Discussion
Surgical therapy has remained the most common type of treatment
for potentially curable disease. Patients with resectable tumors are
still occasionally treated with non-operative protocols [17]. Some of
these patients are not candidates for or refuse surgical intervention.
For early stage disease, surgical resection can provide long-term survival rates as high as 80%. But for stage III of disease, 5-year survival
rates are only 10% to 15% with surgery alone [3, 4]. Radiation as a
single-modality therapy has been used primarily for palliation and
represents a form of local disease control, and chemotherapy offers
the treatment of distant foci of tumor [18]. In our patients, we did
not use chemotherapy or radiation alone for treatment of patients.
Postoperative use of radiation therapy or chemotherapy demonstrated no increase in survival compared with surgery alone [9-12].
Preoperative radiation therapy was used in five studies and only one
has demonstrated a survival benefit [19].

57% of cases were male and 43% were female. The mean age of all
cases was 6511 years. The age of 58% patients were over 65 years.
In 46% individuals, tumors affected the lower third esophagus. Pathology of 80% of patients was squamous cell carcinoma (SCC) and
in the next level, adenocarcinoma was seen in 15% of patients. Others were carcinoma-sarcoma and leiomyosarcoma. Most of the patients (62%) were in stage II of disease (CRT: 30% and CRT-S: 32%)
and about 38% were in stage III (CRT: 18% CRT-S: 14%).

In another study, 186 patients with squamous cell carcinoma were


treated in four arms: surgery alone, preoperative chemotherapy followed by surgery, preoperative radiotherapy followed by surgery, or
sequential chemotherapy and radiation therapy followed by surgery.
Although the addition of radiation therapy did not improve survival
compared with surgery alone, both preoperative radiotherapy and
combined preoperative chemo-radiotherapy produced significantly
better survival than did preoperative chemotherapy [20].

Average duration of survival in patients with esophageal cancer was


16.45 months. One-year overall survival was 49% and overall threeyear survival was 11.8%. There was no significant difference in survival time of these patients who were treated with chemoradiation
(CRT) alone and esophagectomy with CRT. Survival time of treated
men and women just with CRT was 16.58 and 16.57 months, respectively which did not have significant statistical difference. But in the
CRT-S group, the survival time of women was 24.46 months, and the
survival time of men was 13.77 months, which was significantly
greater in women than men (P<0.01).

Roth et al. published an early randomized trial comparing neoadjuvant cisplatin, vindesine, and bleomycin with surgical resection alone
[21]. No significant difference was demonstrated in overall median
survival (9 months). A survival advantage was seen in the subgroup
of patients who responded to chemotherapy. Schlag reported the
results of three cycles chemotherapy in patients with squamous cell
carcinoma [18]. There was no improvement in overall survival among
patients treated with chemotherapy, with a median survival of 10
months in both groups. Among patients who had a decrease in tumor size in response to chemotherapy, survival was prolonged (median 13 months) compared with patients who did not respond to
chemotherapy (median 5 months). Average duration of survival in
our patients with esophageal cancer was 16.45 months. One-year
overall survival was 49% and overall three-year survival was 11.8%.
Nygaard and colleagues studied a group of patients with squamous
cell carcinoma who received preoperative chemotherapy and radiation therapy compared with resection alone [19]. There was a trend
toward a higher rate of resectability among patients undergoing pretreatment (55% versus 37%) [19].

Survival time of patients below 65 years treated with CRT was 21.98
months and in patients over 65 years treated with CRT was 13.53
months, which was statistically significant (P<0.001). However survival time of the patients below 65 years treated with CRT-S was
17.49 months and in patients over 65 years was 16.57 months
(P<0.846) which was not statistically significant. There was no significant relation between the average survival of patients with treatment, anatomical location, pathological type and stage of disease.
Demographics of patients are further summarized in Table 1.
Table 1: Demographics of the patients
Method of
>65
<65
treatment
year
year
140
82
CRT
14m
22m
survival
14
30
CRT-S
19m
17m
survival

Males
126
16.5m
26
13.7m

No
Females
96
16.5m
18
24.4m

Histology
SCC
AC
180
32
17m
12m
35
6
16m
30m

Location of tumors
Lower 1/3
Middle 1/3
Upper1/3
99
83
34
15m
17m
21m
25
12
1
17m
20m
34m

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352

Prognosis and treatment of esophageal cancer is strongly dependent


on the stage of disease at diagnosis. However, multivariate analysis
to compare the effect of treatment on survival supported partially
the usefulness of multiple treatments [21]. But in similar studies like
ours i.e. the comparison of surgery and chemoradiation with CRT
alone, in literature we found only one study, Bedenne and his colleagues study from France that was a randomized study. In this
study, 259 patients with SCC esophageal were compared in two
treatment groups regarding the survival. Two-year survival in Group
A (surgery along with chemoradiation) was 34% and in Group B (just
CRT) was 40%. Average survival in Groups A and B were 17.7 and
19.3 months respectively. The rate of three-month mortality in
Groups A and B were 9.3% and 0.8% and respectively [22]. The results of this study proved that surgery does not have benefit for the
patients with locally advanced esophageal cancer who were responsive to CRT because it does not improve the survival rate and only
imposes a major emotional trauma to patients.
Therefore, it was recommended that CRT can be proposed as the
equivalent to the CRT along with surgery. But in our study, on a
larger group of patients with non-metastatic esophageal cancer with
local emissions (Stage IIB and III), 226 patients with esophageal cancer were assigned in two groups and their survival was compared;
there was no significant difference in the survival time of the patients
in two treatment groups regarding the type of the treatment. Therefore, the result of this study is similar to the result of Bedeenes study
[22]. We can emphasize that the adding of surgery into the CRT treatment in non-metastatic esophageal cancer has not any benefit.

Conclusion
In most patients, despite continued refinement of operative techniques of esophagectomy, cumulative quality of life and functional
outcome of gastrointestinal tract after esophagectomy has remained
poor. We recommend chemoradiation therapy (CRT) alone in stage
II and III esophageal cancer, because survivals of patients are equal
with esophagectomy and chemoradiation therapy (CRT-S) versus
chemoradiation therapy (CRT) alone and also CRT-S poses a major
emotional trauma and an excessive unnecessary cost on the patient
and the community health system.
Acknowledgments: This paper is the result of a thesis which was approved by the
Respiratory diseases and TB Research Center- Razi Hospital, Guilan University of
Medical Sciences, Rasht, Iran, with ethics number 5678 and record number 601. The
authors also wish to thank Ramin Sadeghi for editing the manuscript.
Competing interests: The authors declare that no competing interests exist.
Received: 1 May 2014
Accepted: 27 December 2014
Published Online: 27 December 2014

Chemoradiation therapy alone versus surgery and chemoradiation

5.
6.
7.
8.
9.
10.

11.

12.

13.

14.
15.

16.
17.
18.

19.

20.

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consecutive eight-year intervals with improved staging criteria. J Thorac


Cardiovasc Surg 1997, 113(5):836-846; discussion 846-838.
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353

Open Access

Original Article

A retrospective comparison of docetaxel and paclitaxel as single-agent second-line chemotherapy for


advanced stage non-small cell lung cancer
Julide Celdir Emre1, Aysegul Baysak2, Gursel Cok3, Ozer Ozdemir4, Tuncay Goksel3

Abstract
Background: A few chemotherapy agents are used for second line treatment of advanced stage lung cancer, and their benefits are limited.
The aim of our study was to compare response rates, survival and toxicity of single agent docetaxel versus paclitaxel in the second line
chemotherapy of advanced stage lung cancer.
Methods: Sixty two advanced stage lung cancer patients treated with a single agent taxane as second line chemotherapy between January
1997 and January 2006 were retrospectively analyzed. Chi-squared and Kaplan Meier methods were used for statistical analyses using SPSS
software program.
Results: Study population was composed of 51 males and 11 females with median age of 54.35 ( 8.18) years. 21 patients were treated
with single-agent paclitaxel whereas 41 patients were treated with single-agent docetaxel. Overall response rate was 14.3% in paclitaxel
group and 12.2% in docetaxel group (p>0.05). Median survival time was 32 weeks in paclitaxel group and 24 weeks in docetaxel group
(p>0.05). There was no difference regarding grade 3 or 4 toxicity between groups.
Conclusion: There was no statistically significant difference between docetaxel and paclitaxel groups in the second line chemotherapy of
advanced stage non-small lung cancer regarding response or toxicity. (El Med J 2:4; 2014)
Keywords: Lung Cancer, Second Line, Chemotherapy, Paclitaxel, Docetaxel

Introduction

Methods

Lung cancer is the leading cause of cancer deaths worldwide [1].


Non-small cell lung cancer (NSCLC) constitutes 80% of all lung cancer cases. Approximately 80% of non-small cell lung cancer patients
are diagnosed with locally advanced or metastatic disease [2]. Second line chemotherapy is regarded as a standard treatment for patients with good performance status that are nonresponsive to first
line chemotherapy or have progressive disease in the first six months
of treatment.

Sixty two advanced stage NSCLC patients treated with single agent
docetaxel or paclitaxel as second line chemotherapy between January 1997 and January 2006 were analyzed retrospectively. Treatment
response and toxicities of cases were evaluated according to the
World Health Organization (WHO) criteria. Complete regression of all
known lesions for at least 4 weeks was regarded as complete response, more than 50% decrement in the size of known measurable
lesions without appearance of new lesions was regarded as partial
response, more than 25% increment in the size of known lesions or
appearance of new lesions was regarded as progression and lack of
signs of progression or response was regarded as stable disease.

Combination chemotherapy regimens used in first line treatment


may be effective but disease progression is usually seen and shortens the survival times of patients [3, 4]. The purpose of second line
treatment is palliation of symptoms, improvement of life quality and
increment of survival time. Cytotoxic chemotherapeutics and epidermal growth factor receptor inhibitors and tyrosine kinase inhibitors
are used in second line treatment of NSCLC [5].
As no survival difference has been observed between single agent
and combination cytotoxic chemotherapeutics, single agent regimens are the preferred treatment options to avoid unnecessary toxicities. In the meta-analyses of Di Maio et al., combination cytotoxic
chemotherapy regimens had no survival benefit over single agent
regimens, but combination therapy group had statistically higher
grade 3 or 4 side effects [6]. Docetaxel, paclitaxel, pemetrexed, gemcitabine, topotecan and vinorelbine are the chemotherapeutics used
for second line treatment [7, 8]. In this study, we aimed to compare
response rates, survival times and side effects of docetaxel and
paclitaxel used as single agent second line chemotherapy of NSCLC
patients.

Department of Chest Diseases, Turgutlu State Hospital, Manisa, Turkey


Department of Chest Diseases, Izmir University School of Medicine, Izmir, Turkey
3Department of Chest Diseases, Ege University School of Medicine, Izmir, Turkey
1
2

The time between the end of first line chemotherapy and recurrence
were calculated and recorded. Progression free survival time was defined as the time between the end of second line chemotherapy and
progression. Overall survival time was defined as the time between
the end of second line chemotherapy and death. Performance status
was determined according to the Eastern Cooperation Oncology
Group (ECOG) scale. All patients were treated with 75 mg/m2 docetaxel or 175 mg/m2 paclitaxel with three week intervals.
Data were analyzed with SPSS for Windows version 16 using chisquared and Kaplan Meier survival analyses methods.

Results
Study population was composed of 51 males and 11 females with
median age of 54.35 8.18. 21 patients were treated with single
agent paclitaxel whereas 41 patients were treated with single agent
docetaxel as second line chemotherapy. There was no significant difference of demographic characteristics of patients between groups.
Performance status according to the ECOG scale showed 52 patients
Department of Chest Diseases, Egepol Hospital, Izmir, Turkey
Correspondence: Aysegul Baysak
Email: drbaysak@gmail.com

2014 Emre et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Emre J, Baysak A, Cok G, Ozdemir O, Goksel T: A retrospective comparison of docetaxel and paclitaxel as single-agent second-line chemotherapy for advanced stage non-small cell lung cancer.
El Mednifico Journal 2014, 2(4).

354

A retrospective comparison of docetaxel and paclitaxel

(83.8%) to have ECOG 0-1, 10 patients (16.2%) to have ECOG 2 performance status. All patients were treated with platinum based
chemotherapy doublets as first line chemotherapy, 4 cycles of chemotherapy were applied on average (2-6 cycles).
The reason of initiating second line chemotherapy was progression
during first line chemotherapy in 54.8% of patients, local recurrence
in 30.6% of patients, metastasis in 8.1% of patients, stable disease
during the course of first line chemotherapy in 4.8% of patients and
side effects due to first line chemotherapy in 1.6% of patients (Figure
1). Complete response was seen in 5 patients (12.2%) in docetaxel
group and 3 patients (14.3%) in paclitaxel group (p>0.05). Median
survival time was 32 7.2 weeks in paclitaxel group and 24 7.4
weeks in docetaxel group (p>0.05) (Figure 2).

Complete response was seen in 11.3% of patients, stable disease was


seen in 4.8% of patients. In the remaining 83.9% of patients, second
line chemotherapy was stopped because the absence of response in
59.7%, progression after initial response in 9.7%, side effect in 6.5%
of patients. 1.6% of patients stopped their second line treatment on
their own will (Figure 4).
There was no significant difference of response and side effects between single agent docetaxel and paclitaxel chemotherapy as second line treatment of advanced stage NSCLC.

Grade 3-4 toxicities


Anemia

Reasons for second line chemotherapy


Progression during
chemotherapy
Stable disease during
chemotherapy

30.6%

Side effects

Leukopenia
Granulocytopenia
Thrombocytopenia
Neurological side
Effects

54.8%
8.1%
1.6%

0
Metastasis

10

12

14

16

18

Figure 3: Comparison of grade 3-4 toxicities of groups

Local recurrence

4.8%

Second line chemotherapy endpoints

Figure 1: The reasons for second line chemotherapy

Complete response
1.6%

Survival times and response rates

6.5%
6.5%

35

9.7%
4.8%

30
25
20

Paclitaxel

15

59.7%

Docetaxel

10
5

No response
Cessation of treatment
due to patient's own will
Exitus
Side effects and stable
disease

Figure 4: Second line chemotherapy endpoints

0
Survival

Response rates

Figure 2: Comparison of survival times and response rates of


docetaxel and paclitaxel groups
There was no statistically significant difference regarding grade 3 or
4 toxicity between groups. Most common side effect was neutropenia, it was seen in 16 patients (25.8%) (10 in docetaxel and 6 in
paclitaxel group) in the grade of 3 or 4. Blood transfusion was
needed in 4 patients (6%), 2 patients in docetaxel group and 2 patients in paclitaxel group. Grade 3-4 neuropathy was seen in only
one patient in paclitaxel group (Figure 3).
Vol 2, No 4

Initial response then


progression
Stable disease

11.3%

Discussion
Second line chemotherapy is the treatment of choice in the patients
that have good performance status and are unresponsive to first line
chemotherapy or progressive in the first six months of treatment [1].
Second line chemotherapy of NSCLC had better effects in survival
and symptom palliation compared with best supportive care. In this
regard, cytotoxic chemotherapy or targeted treatments may be used
[5, 9]. Di Maio et al, observed no significant difference of overall survival between combination or single agent second line treatment,
whereas more side effects were present in the combination chemotherapy group [6]. So, single agent chemotherapy was recommended for second line treatment of NSCLC. In our study, we found

Emre J, Baysak A, Cok G et al.

no statistically significant difference between docetaxel and


paclitaxel as a single agent second line chemotherapeutic in the
treatment of advanced NSCLC, regarding response or toxicity.
Taxane group compounds (docetaxel and paclitaxel) constitute one
of the most important chemotherapeutics of recent years. Paclitaxel
is the prototypic member of taxane group chemotherapeutics extracted from Pacific yew, and docetaxel is the semi synthetic analog
of it. Both agents share similar mechanism of action with differences
in some aspects like in inhibition of depolymerization and affinity for
binding sites. There is lack of complete cross resistance between
them [10]. Both are used in the treatment of many malignancies, including NSCLC, breast cancer, ovarian cancer and head and neck tumors [11].
Docetaxel is a widely recognized chemotherapy agent for the second
line treatment of advanced NSCLC. Standard three weeks cycle of
docetaxel treatment was compared with weekly cycle dose scheme
and weekly applied dose scheme showed better compliance, better
response rates and less neutropenia, without a change in the overall
survival rates [12, 13]. We preferred three weeks cycles of single
agent docetaxel; major compliance problem was not observed.
After the promising results of phase II studies of docetaxel as a second line agent in previously treated patients, two phase III studies
were accomplished and docetaxel became the first chemotherapeutic agent with proven benefit in patients with recurrent or refractory
disease. In the first phase III study, although the response rates were
not high (5.5%), docetaxel (75 mg/m2, 3 weeks cycle) significantly
increased median and 1-year survival times when compared with
best supportive care (median survival time 7,5 months versus 4,6
months; p=0,010; 1-year survival rates 37% versus 12%) [7]. In the
second study, median and six months survival rates were similar for
docetaxel or vinorelbine or iphosphamide, but 1 year survival rates
were significantly higher with docetaxel (32% versus 19%, p= 0.025).
In another study of Gulhan et al with 33 patients, second line single
agent docetaxel chemotherapy was found to have response rates of
12.1% (4 patients) with median survival time 10.34 1.56 months
[14]. Our docetaxel group had similar response rates (12.2%) with
median survival time of 24 weeks.
Paclitaxel also showed a potential benefit in second line treatment.
After the phase II studies (Yasuda K et al. and Camps C et al.) and
randomized phase III study of second line single agent paclitaxel
chemotherapy, a study that evaluated all the patient groups showed
the beneficial effects of paclitaxel as a second line agent [16].
There is not any other trial comparing single agent docetaxel with
paclitaxel as second line chemotherapy in the literature, but Paz Ares
et al. compared docetaxel with paclitaxel poliglumex as a second line
therapy in 849 NSCLC patients [17]. Paclitaxel poliglumex, a macromolecule drug conjugate in which paclitaxel and poliglutamic acid
is bound together, lowers the systemic toxicity of peek concentrations of free paclitaxel. In this trial, median survival time was 6.9
months in both treatment arms (p=0.257), 1 year survival rate was
25% for paclitaxel poliglumex and 29% for docetaxel (p=0.134). Progression free survival were also similar between groups (2 months

355

for paclitaxel poliglumex vs. 2,6 months in docetaxel; p=0,075). Although survival parameters were similar, two drugs had different toxicity profiles. Alopecia and febril neutropenia was lower with
paclitaxel poliglumex, whereas grade 3 or 4 neuropathy was higher.
Also Kawahara et al, compared combination of either agents with
carboplatin in the first line treatment of advanced NSCLC patients,
and found similar response rates and survival [18]. Neurological side
effects of taxane group chemotherapeutics, especially for paclitaxel,
are frequently reported in the literature [19]. In our study there was
only one patient who had grade 3 or 4 neurological side effect due
to paclitaxel.

Conclusion
In our study, we compared two taxanes in second line treatment of
NSCLC. There was not any significant difference of survival, treatment response or side effects. But our study has some limitations,
such as the small sample size and retrospective study design. There
is need for larger, randomized prospective studies to make definitive
conclusions, but both agents seem to have similar effects.
Competing interests: The authors declare that no competing interests exist.
Received: 3 August 2014
Accepted: 27 December 2014
Published Online: 27 December 2014

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2. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of smallcell lung cancer in the United States over the last 30 years: analysis of the
surveillance, epidemiologic, and end results database. J Clin Oncol. 2006 Oct
1;24(28):4539-44
3. Gridelli C, Ardizzoni A, Ciardiello F, et al. Second-line treatment of advanced
non-small cell lung cancer. J Thorac Oncol 2008 Apr; 3(4):430-40
4. Siegel R, Ward EM, Brawley O, et al. Cancerstatistics, 2011. The impact of
eliminating socioeconomic and racial disparities on premature cancer deaths.
CA: Cancer J Clin. 2011 Jul-Aug; 61(4): 212-36
5. Thatcher N. First- and second-line treatment of advanced metastatic non
small-cell lung cancer: a global view. BMC Proc. 2008;2(Suppl 2):3-8.
6. DiMaio M, Chiodini P, Georgoulias V, et al. Meta-analysis of single-agent
chemotherapy compared with combination chemotherapy as second-line
treatment of advanced non-small cell lung cancer. J Clin Oncol 2009;
27(11):1836-43
7. Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of
docetaxel versus best supportive care in patients with non-small cell lung
cancer previously treated with platinum-based chemotherapy. J Clin Oncol
2000 May;18(10): 2095-103
8. Felip E, Gridelli C, Baas P, et al. Metastatic non-small cell lung cancer: consensus
on pathology and molecular tests, first-line, second-line, and third-line
therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010. Ann
Oncol 2011; 22(7): 1507-19
9. de Marinis F, Ricciardi S. Second-line treatment options in advanced non small
cell lung cancer. Eur J Cancer 2011; 47(Suppl 3):s.258-71
10. Von Hoff DD. The taxoids: same roots, different drugs. Semin Oncol 1997 Aug;
24(4 Suppl 13):S13-3-S13-10.
11. Guchelaar HJ, ten Napel CH, de Vries EG et al. Clinical, toxicological and
pharmaceutical aspects of the antineoplastic drug taxol: a review. Clin Oncol
(R Coll Radiol). 1994; 6(1):40-8
12. Bria E, Cuppone F, Ciccarese M et al. Weekly docetaxel as second line
chemotherapy for advanced non-small-cell lung cancer: meta-analysis of
randomized trials. Cancer Treat Rev. 2006 Dec; 32(8):583-7
13. Camps C, Massuti B, Jimenez A et al. Randomized phase III study of 3-weekly
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14. Gulhan M, Erturk A, Canbakan S et al. Second line chemotherapy with


docetaxel in advanced non small lung cancer: retrospective analysis of 33
cases. Solunum 2007; 9(2): 81-6
15. Yasuda K, Igishi T, Kawasaki Y et al. Phase II study of weekly paclitaxel in
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A retrospective comparison of docetaxel and paclitaxel

17. Paz-Ares L, Ross H, O'Brien M, et al. Phase III trial comparing paclitaxel
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http://www.mednifico.com/index.php/elmedj/article/view/191

Open Access

357

Original Article

Reproductive health complications among women: A study in a tertiary hospital of Mumbai


Mousumi Gogoi1, Sayeed Unisa1

Abstract
Background: In spite of the drastic reduction in maternal morbidity over the last few decades due to improvements in obstetric care,
maternal mortality remains to be a challenge in the developing world. Maternal mortality is the most extreme consequence of poor
maternal health and millions of women in developing countries experience life threatening and other serious health problems related to
childbirth. Concerning the issue of maternal morbidity and mortality, the study tries to find out the health complications during pregnancy,
delivery and post-delivery among women belonging to lower socio-economic strata in Mumbai city.
Methods: The study was based on primary data by interviewing 300 inpatients in a tertiary hospital of Mumbai during January to June
2013.
Results: Out of total, 97% women reported of any complications during pregnancy while 85% of women reported complications during
delivery. Of all respondents, excessive vomiting, weakness, anemia during pregnancy and prolonged labor, excessive bleeding during
delivery were highly reported. Complications were mostly reported by young, less educated and primiparous women. Most of the
pregnancies ended with live birth while a few reported of delivered stillbirth having any labor related complications. Higher proportion
of women received more than three antenatal care visits as the majority of women from lower strata had undergone check-up only when
they suffered from complications.
Conclusion: Usually women visit medical officer at the government hospital or local medical practitioner for check-ups. So, it is necessary
to improve services available and availed during complications related to childbirth. (El Med J 2:4; 2014)
Keywords: Reproductive Health, Pregnancy, Delivery, Maternal Morbidity

Introduction
The concept of reproductive health has long been discussed and the
need to focus on reproductive morbidity as a measure of reproductive health has evolved. Compounded with socio-cultural factors, the
result is poor treatment seeking and hence poor quality of life. Maternal and reproductive health is a social phenomenon as much as a
medical event, where access to and use of maternal and reproductive health care services are influenced by contextual factors. Millennium Development Goal-5 (MDG) is focused on reducing maternal
mortality and achieving universal access to reproductive health care.
Under MDG 5, India has committed to reducing maternal mortality
to 108 deaths per 100,000 live births by 2015. The latest estimates of
maternal mortality rate (MMR) in India, from 2007-2009, show a national average of 212 deaths/100,000 live births, a decline of 89
deaths per 100,000 live births since 20012003 [1].
Globally, about 8 million women suffer pregnancy-related complications and more than half a million die from those complications.
More than 80 percent of maternal deaths are preventable. In developing countries, one woman in 16 may die due to pregnancy-related
complications [2]. Around 15 percent of all pregnant women develop a potentially life-threatening complication that calls for skilled
care, and some will require a major obstetrical intervention to survive
[3].
Maternal mortality is the most extreme consequence of poor maternal health. Millions of women in developing countries experience life
threatening and other serious health problems related to pregnancy
or childbirth. It has also ascertained that pregnancy-related problems
have far-reaching consequences on the overall reproductive health
of women, in addition to their contribution to maternal mortality [4].

Women in developing countries face a high risk of severe complications during pregnancy and delivery. These can lead to adverse consequences for their own health and that of their offspring [5].
One study reveals that, in each year, over 50 million women experience pregnancy related complications. Fifteen million of these lead
to long-term illness or disability often because they have no access
to medical care, because pregnancy has exacerbated already existing
malnourishment or illness, or because the medical care that they do
manage to access is substandard [6]. The impact of reproductive
health morbidity on womens health is particularly serious in developing countries like India where weak or non-existent systems of
health care make the diagnosis and treatment of these conditions
difficult [7]. On the other hand, health policy in India has floundered
in its management of both the demand and supply sides [8]. Under
these circumstances there is a need in the scientific community to
give more stress on maternal health, in essence their reproductive
health problems.
Need for the study
Over the period in India, institutional delivery is increasing, and the
government is also encouraging for institutional delivery. However,
it has been found from different studies that women specially belonging to low socio-economic strata who face problems during
pregnancy will opt for institutional delivery. Lack of knowledge
about obstetric complications often delays service seeking, resulting
in tragic consequences, where women die at home or on their way
to the health facility. Identification of problems, timely care-seeking
and appropriate management of obstetric complications is, therefore, essential to reducing maternal mortality and morbidity. For
women with pregnancy complications or those who are at risk for
problems during labor, delivery at hospitals is a good choice for

International Institute for Population Science (IIPS), Mumbai, India


Correspondence: Mousumi Gogoi
Email: gogoi.mousumi2008@gmail.com

2014 Gogoi et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Gogoi M, Unisa S: Reproductive health complications among women: A study in a tertiary hospital of Mumbai. El Mednifico Journal 2014, 2(4).

358

them. Hence, it is important to examine delivery related complications and treatment seeking behavior among women who come for
delivery at hospitals.
Objective
The broad objective of the study was to find out the self-reported
reproductive health complications during pregnancy, delivery and
after delivery among women belonging to lower socio-economic
strata in Mumbai city.

Materials and Methods


Study Area
Mumbai city was selected for the study purpose due to convenience
of availability of hospital records on antenatal check-ups and other
health records. Being a metropolitan city, the situation in Mumbai is
very typical. In this context the study tries to bring out the womens
reproductive health complications from a hospital based study. A
tertiary hospital was purposively selected to know about reproductive health related complications among women that come from
lower socio-economic strata of Mumbai.
Method
The present study seeks to collect self-reported reproductive health
complications (during pregnancy, delivery and after delivery)
through primary survey from inpatient interviews in a tertiary hospital of Mumbai. Quantitative data was collected from a total of 300
inpatients, who were selected based on their consent for participating in the interview. The study was conducted from January to May
2013, and the study respondents were those came for delivery at the
selected hospital. In this study the main focus was given on those
women belonging to lower socio-economic strata. Among all the respondents, most were from nearby slum areas of the hospital, and
they came for the particular hospital due to easy accessibility during
an emergency.
The data was collected from women (inpatients) using structured
schedule with open-ended questions. The questionnaire was developed in multiple stages. Women were asked about their personal
view on coming to that particular hospital and service received. The
questions were asked about their self-reported reproductive health
complications during pregnancy, delivery and after delivery and the
socio-economic and demographic characteristics of the respondents
were also asked.
Bivariate analysis and cross tabulation were done to analyze the
health complication during pregnancy, delivery and after delivery
among women with lower socio-economic status. For analysis the
data of any complication during pregnancy, delivery and after delivery were taken as dependent variable, whereas other womens characteristics were taken as independent variable. All dependent variables were categorized as 1: having any complication and 0: otherwise. Some of the reported complications were grouped together in
the analysis according to the similarity of complications.
Ethical approval
The ethical consent was taken from all the respondents for the participation in the interview. The protocol was approved by the Ethics
Committee.
Vol 2, No 4

Reproductive health complications among women

Results
Profile of the respondents
Table 1 represents the demographic profile of the studied women in
the selected hospital. The mean age of the respondents was 25
4.06 years. The highest numbers of respondent (inpatients) were in
the age group of 20-24 years (45.7%) whereas only 3.3 per cent of
respondents belonged to less than 20 years of age. The mean age at
marriage of the respondent was 19 2.71 years. More than half of
the total respondents were married before completing 20 years of
age (56.6%). The mean age at first birth was around 21 2.95 years.
About 32% of the births for the interviewed women were of the first
order, 49% of second order and 19% were of third or higher order.
Table 1: Demographic characteristics of the surveyed inpatients in a tertiary hospital of Mumbai
Background Characteristics
%
N
3.3
10
Age of Women
Less than 20 years
(mean 25.25 4.06) 20-24 years
45.7 137
33.3 100
25-29 years
17.7
53
More than 30 years
56.6 170
Age at marriage
Less than 20 years
(mean 19.50 2.71) 20-25 years
39.7 119
3.7
11
More than 25 years
44.0 132
Marriage Duration
Less than 5 years
(Mean 5.73 4.03)
45.0 135
5-10 years
11.0
33
More than 10 years
23.9
49
Age at First Birth
Less than 20 years
(Mean 21.48 2.95) 21-24 years
65.9 135
10.2
29
More than 25 years
32.0
96
Birth order
One
48.7 146
Two
19.3
58
Three and more
52.0 156
Sex of the Child
Male
48.0 144
Female
Distribution and Prevalence of pregnancy complications in the
study area
Table 2 represents the pregnancy complications reported by the interviewed women in Mumbai. The prevalence of pregnancy complications was 97%, whereas among the specific pregnancy complications, excessive vomiting was found highest, followed by paleness/giddiness/weakness (61%) and other complications (56%) during pregnancy. Other pregnancy complication included jaundice,
itching, acidity, breathing problem, body pain and typhoid, etc. Prevalence of the complication like anemia was about 43 percent while,
excessive fatigue and hypertension/high blood pressure during
pregnancy was found in 41% and 27% of women respectively. About
19% of women reported the problem of swelling of hands, feet and
face and 13% of women reported of having vaginal discharge. Convulsions (not from fever) and malaria during pregnancy were 14%
and 6% respectively while, a negligible percent reported of having
visual disturbance (2.4%) during pregnancy.

Gogoi M, Unisa S

359

Table 2: Percentage of women reporting pregnancy complication (group-wise) by background characteristics in Mumbai
Background Variables
Pregnancy Complications (Group-wise)
Swelling of hands and face, Excessive Severe Other reported
hypertension and fever
vomiting anemia complications
Age of Women
Less than 20 years
30.0
80.0
30.0
30.0
20-24 years
47.4
66.7
38.6
24.8
41.0
70.1
46.9
26.0
25-29 years
More than 30 years
66.0
50.9
47.2
24.5
Age at first birth
Less than 19 years
51.0
59.6
39.6
38.8
46.7
62.7
48.5
22.2
20-25 years
More than 25 years
52.4
57.1
33.3
19.0
Birth Outcome
Live birth
48.3
65.6
42.2
25.3
33.3
66.7
66.7
33.3
Still birth/Neonatal death
Parity of women
One
47.9
75.8
38.5
25.0
43.2
62.1
43.8
25.3
Two
60.3
57.1
46.4
25.9
More than two
Type of Delivery
Normal
51.9
64.2
43.2
25.8
53.8
57.2
30.8
15.4
Caesarean
35.7
64.3
28.6
21.4
Forceps
Number of ANC visit
1-3 times
48.7
51.4
35.1
25.0
47.3
70.3
46.8
24.2
More than 3 times
Table 2 shows the group-wise distribution of complications during
pregnancy in the study area. First group includes complications such
as swelling of hands, feet, face, hypertension and high fever. Second
and third group consist of excessive vomiting and severe anemia
during pregnancy while the fourth group includes all other complications reported by women during the interview. Women aged
above 30 years reported of having first group of complications almost twice as frequently as women aged below 20 years. In case of
reporting complications like, excessive vomiting, the highest percentage was found among younger aged women (80%), and it decreased by 51% among women more than 30 years. Older women
were more severely anemic (47%) while it decreased among lower
aged women in the study area. All whose who were aged more than
25 years at first birth, reported more complications of swelling of
hands, feet, and face, hypertension and high fever during pregnancy
as compared to women whose age at first birth was 20-25 years.
However, excessive vomiting and severe anemia was highly reported
by women whose age at first birth was in the age group of 20-25
years.

N
10
132
97
53
47
134
21
289
4
91
145
56
251
13
28
75
217

Experience of stillbirth and neonatal death was mostly reported by


women suffering from complications as excessive vomiting and severe anemia at the time of pregnancy (66.7% for both categories).
Analysis showed that women with more than two parity, had more
pregnancy complications of swelling of hands, feet, face, hypertension, high fever (60.3%) and severe anemia (46.6%), whereas excessive vomiting was highly reported by women with their first parity
(75.8%). If we see by type of delivery, caesarean delivery was found
higher among women who reported of having first group of complications during pregnancy (53.8%). All the reported complications
were concentrated among women who received more than three
antenatal check-ups during pregnancy in the study area.
Distribution and Prevalence of delivery complications in the
study area
This section includes the health complications reported by the interviewed women during delivery. Each interviewed woman who had
a birth during the survey was asked if she had experienced delivery
complication such as premature labor, prolonged labor (above 10
hours), obstructed labor, excessive bleeding, breech presentation,
convulsion, high blood pressure during delivery. Figure 2 shows the
specific complications among women during delivery where prolonged labor was the most commonly reported by women. Nearly
half (48.8%) of the women had prolonged labor during delivery. The
second highest complication reported by women was excessive
bleeding. Thirty six percent of interviewed women had the complication of excessive bleeding during delivery followed by obstructed
labor (33.1%) and breech presentation (11.8%). Of all the interviewed women, about 85% reported any complication during delivery in the studied area (Figure 2).

Figure 1: Percentage of women reporting types of complications


during pregnancy in Mumbai
http://www.mednifico.com/index.php/elmedj/article/view/191

360

Figure 2: Percentage of women reporting type of delivery


complication in Mumbai
Prevalence of delivery complications group-wise by socio-demographic characteristics of the respondents is shown in table 3. The
reported delivery complications have been grouped into two sections based on the similarity of the complications. First group (i.e.
group A) includes labor related complications like premature labor,
prolonged labor and obstructed labor during delivery. The second
section i.e. group B includes excessive bleeding, breech presentation,
convulsion/high B.P and other reported complications during delivery. Section three (group C) comprises the complications reported
by the both groups (A & B).
Labor and group B type of complications are mostly reported by
women aged more than 30 years. Complications of both groups
(A+B) is found higher among younger aged women, and they decrease with age. Most of the cases of reported delivering stillbirth

Reproductive health complications among women

and neonatal mortality was among women having both labor related
and other complications during delivery i.e. 50% and 25% respectively. The frequency of any labor complication (premature, prolonged and obstructed labor) was higher among women who were
in their second parity followed by women with more than two children. Women who received less antenatal check-ups (only once) during pregnancy reported more complications of both types as compared to women who received at least three and more antenatal
check-ups during pregnancy. There was no positive association between womens educational status in reporting of any delivery complications because it is more biological in nature rather than social
and economic.
Distribution and Prevalence of post-delivery complications in
the study area
This particular section of the study deals with the prevalence and
distribution pattern of post-delivery complications among women in
the studied area. Figure 3 presents the type of post-delivery complications reported by the interviewed women. The women were asked
about the type of complication, if any, just after delivery. Majority of
the respondents replied with fever and abdominal pain (98.3%).
Weakness and anemia were other leading conditions among women
after delivery. More than half of the women had complication of abscess in breast and poor breastfeeding practices whereas burning
menstruation was another highly reported post-delivery complication. During the survey time, no cases had been found having complication or any symptom of psychosis.

Table 3: Percent distribution of women reporting delivery complication (group-wise) by background characteristics in Mumbai
Background Variables
Delivery Complications (Group-wise)
Labor complication
Excessive bleeding, breech
Both
(A)
presentation, convulsion/high BP (B)
(A)+(B)
Age of Women
42.5
12.6
44.9
Less than 25 years
25-29 years
53.0
13.3
33.7
54.5
13.6
31.9
More than 30 years
Birth Outcome
Live birth
48.0
12.8
39.2
50.0
25.0
25.0
Still birth/ Neonatal death
Parity of women
One
37.9
12.6
49.4
56.3
11.8
31.9
Two
More than two
45.8
16.7
37.5
Type of Delivery
49.2
11.5
39.3
Normal
Caesarean
20.0
50.0
30.0
42.9
7.1
50.0
Forceps
Number of ANC visit
Only one time
43.8
6.2
50.0
52.6
7.0
40.4
1-3 times
More than 3 times
47.2
15.6
37.2
Education
38.5
15.4
46.1
Less than 5 years
5-10 years
50.3
11.6
38.1
42.3
11.5
46.2
More than 10 years
Total
48.0
13.0
39.0

Vol 2, No 4

Gogoi M, Unisa S

Figure 3: Percentage of women reported of having any


post-delivery complications in Mumbai
Severity of health complications in the study area
The severity of complications during antenatal, natal and post-natal
complications is shown in Table 4. A total of 97% of all respondents
reported at least one morbid symptom during pregnancy, and 48%
reported symptoms of a potentially serious nature such as
preeclampsia (hypertension) and fever. Severe vomiting (65.4%) was
the most common complication among the interviewed women.
Forty-three percent of the women reported of having severe anemia
during pregnancy for the most recent birth. During the delivery itself,
more than half of the respondents experienced the conditions that
were potentially life-threatening, the most common of which were
prolonged labor and hemorrhage. About 99% of women had any
type of post-delivery complication out of the total interviewed. The
most common post-natal disorder exhibited symptoms of possible
infection just after delivery. Ninety eight percent of the respondents
had such infection (high fever, lower abdominal or pelvic pain) while
9% reported acute and immediately dangerous symptoms such as
hemorrhage and loss of consciousness/convulsions. Ninety six percent women also reported of having complications like weakness
and burning menstruation just after delivery.

Discussion
This paper studies the prevalence of reproductive health complications during pregnancy, delivery and after delivery among women
from the lower socio-economic strata in Mumbai. Majority of the
studied women had any type of complications during pregnancy,
delivery and just after delivery and among them pregnancy and
post-delivery complications were found higher as compare to reported delivery complications. Excessive vomiting is considered as
one of the most common pregnancy complications and mostly
found among younger aged women.
Any type of pregnancy and delivery complications were seen among
younger women whereas a post-delivery complication was found
higher among older aged women in the study area. Majority of the
women who had any specific pregnancy and delivery complications
did so in their first parity. One of the studies found that the vaginal
discharge is more common in lower socio-economic class [4]. But in
this study, reporting of complications like vaginal discharge was not
higher among women as compared to other complications.

361

In the present study, educational status of women was one of the


most important determinants of reproductive health complications.
It may be due to the fact that higher educated women are more
aware of the probable health complications during the reproductive
period. Attainment of education clears various misconceptions
about many illnesses and encourages preventive practices. These
facts have observed in various studies conducted in India [9]. One of
the most important finding coming from the study was that, reporting of any pregnancy, and delivery complications was higher among
women who had received more than three antenatal care while any
type of post-delivery complication was slightly lower among women
receiving three antenatal check-ups during pregnancy. This could be
because women with higher complications visit more health care facilities in the study area.
Table 4: Percentage of women with regards to severity of reproductive health
complications in Mumbai
%
N
48.0 144
Antenatal Potentially life threatening conditions (e.g. swelling
of hands and face, hypertension, fever)
65.4 191
Severe vomiting
42.7 125
Anemia
Potentially life threatening conditions (e.g. labor
57.3 172
Natal
>10 hours, excessive bleeding, convulsion/high BP)
9.0
27
Postnatal Potentially life threatening conditions (e.g.
excessive bleeding, edema/convulsion)
Symptoms of infection (e.g. high fever, lower ab98.3 292
dominal or pelvic pain)
Associated conditions (e.g. weakness, burning men- 96.3 289
struation)
Earlier studies reveal that, in developing countries where the prevalence of several treatable diseases is very high, maternal health services provide a unique opportunity to detect and treat these diseases. Although certain obstetric emergencies cannot be predicted
through antenatal screening, women at least can be educated to recognize symptoms leading to potentially serious conditions and take
immediate action [4]. Even though metro cities are demographically
developed, the prevalence of self-reported reproductive health complications is quite high among women who were interviewed in the
selected hospital. Several studies conducted in India have documented high prevalence of self-reported reproductive health complications such as lower abdominal pain, irregular vaginal bleeding
and weakness among women in reproductive age [10-12].

Conclusion
The prevalence of reproductive health complications (during pregnancy, delivery and after delivery) is very high among women who
belong to lower socio-economic strata in Mumbai city. As a metropolitan city of India, a gap is seen in health care knowledge and
among poor and non-poor strata. There is a need to minimize the
gaps in women's reproductive health and prioritize restructuring of
various health program in a better way to meet the women's needs.

http://www.mednifico.com/index.php/elmedj/article/view/191

362

Acknowledgments: The authors would like to thank HOD (Gynecology


Department) of Shatabdi Hospital for allowing us to collect data. The authors would
also like to thank staff and respondents for their co-operation and help during data
collection.
Competing interests: The authors declare that no competing interests exist.
Received: 13 May 2014
Accepted: 29 December 2014
Published Online: 29 December 2014

References
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India. Health Transition Review 1995, 5(2):127-142.
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Alihonou E, Patel V: Effects of severe obstetric complications on womens
health and infant mortality in Benin. Tropical Medicine and International
Health 2010, 15(6): 733-742 doi: 10.1111/j.1365-3156.2010.02534.x

Vol 2, No 4

Reproductive health complications among women

6. Datta KK, Sharma RS, Razack PMA, Ghosh TK, Arora RR: Morbidity pattern
amongst rural pregnant women in Alwar, Rajasthan A cohort study. Health
and Population Perspectives and Issues 1980, 3: 282-292.
7. Pachauri S: Womens Reproductive Health in India: Research Needs and
Priorities (Chapter 1) in Listening to Women Talk about Their Health Issues and
Evidence from India. Edited by Gittelsohn et al, Har-Anand Publications, 1995.
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http://www.populationcouncil.net/uploads/pdfs/implementing.pdf.
8. Rishyasringa B: Social Policy and Reproductive Health (Chapter 10) in Womens
Reproductive Health in India. Edited by Ramasubban and Jejeebhoy, Rawat
Publication 2000.
9. Parashar A, Gupta BP, Bhardwaj AK, Sarin R: Prevalence of RTIs among women
of reproductive age group in Shimla City. Indian Journal of Community
Medicine 2006, 31:15-17.
10. Bang RA, Bang AT, Baitule M, Choudhary Y, Sarmukaddam S, Tale O: High
prevalence of gynaecological diseases in rural Indian women. Lancet 1989, 1
(8,629): 85-88.
11. Bhatia JC, Cleland J: Self-reported symptoms of gynecological morbidity and
their treatment in South India. Studies in Family Planning 1995, 26 (4): 203216.
12. Singh V, Gupta MM, Satyanarayana L, Parashari A, Sehgal A, Chattopadhya D,
Sodhani P: Association between reproductive tract infections and cervical tract
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Diseases 1995, 22 (1): 25-33.

http://www.mednifico.com/index.php/elmedj/article/view/160

363

Open Access

Original Article

Types and frequency of pre-analytical errors at University of Gondar hospital laboratory


Zelalem Addis1, Tadelo Wondimagegn2, Belaynesh Tachebele2

Abstract
Background: As many as 93% of errors encountered in the diagnostic process are largely due to lack of standardized procedures in the
pre-analytical phase of quality assurance. Hence, the aim of this study was to assess the types and frequency of pre-analytical errors in
University of Gondar hospital.
Methods: This was a cross sectional study that involved prospective evaluation of request papers and samples sent to the hospital
laboratory for hematological and clinical chemistry analysis. Data was collected by laboratory professionals and summarized into different
categories of pre-analytical quality indicators.
Results: A total of 1533 (750 for hematology and 783 for clinical chemistry) samples with their respective request papers were evaluated
in this study. In general, none of the request papers contained all the information that they were supposed to contain. One or more of
patient identification parameters were missing in 8.7% of the request papers. Name of the requesting physician and address of the sender
were missing from 44.5% and 6.5% of the request papers. Clinical information of the patients was missing in about 98% of the requests.
Examination of the samples showed that 1.02%, 2.8% and 0.98% of the samples were hemolyzed, insufficient for analysis and clotted
respectively.
Conclusion: This study showed the existence of different pre-analytical errors in the laboratory studied. The laboratory can evaluate itself
based on some of the pre-analytical quality indicators and should strive for improving its quality for maximum patient benefit. (El Med J
2:4; 2014)
Keywords: Pre-Analytical Errors, Laboratory, Diagnostics

Introduction
Laboratory data are an integral, often pivotal part of the complex
decision making process, influencing up to 70% of medical diagnoses. However, up to 0.5% of all laboratory test-results have been estimated to be erroneous and one fourth of these errors have consequences for the patient, which include a delayed test result or new
sample collection, but may also have a life threatening impact and
tragic consequences, such as the administration of unnecessary
chemotherapy or the onset of coma. The dependence of patient
management on laboratory data highlights the need for ensuring
the quality of these services [1-4].
Laboratory quality has been historically determined by the accuracy
of the analytical phase. Following the development of high-quality
analytical techniques, analytical error is no longer the main reason
for error in the laboratory testing process. Majority, up to 68.2%, of
laboratory errors occur in the pre-analytical phase, which refers to
procedures performed neither in the clinical laboratory nor under
the control of laboratory personnel, e.g. completion of a laboratory
request form, specimen identification, phlebotomy, sample handling
and transportation to the laboratory [1, 5, 6].
Pre-analytical phase is much more vulnerable to uncertainties and
accidents, which can substantially influence patient care. It has been
noticed that as many as 93% of errors encountered within the entire
diagnostic process are largely due to lack of standardized procedures
for sample collection, including patient preparation, specimen acquisition, handling and storage. Those errors relating to extra-analytical
phases are harder to control [7-9].
Thus, in order to improve patient safety, reduction of the frequency

1
2

College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia


University of Gondar Hospital Laboratory, Gondar, Ethiopia

of pre-analytical errors should be an important issue for all health


care providers. So the aim of this study was to assess types and frequency of pre-analytical errors in University of Gondar hospital Laboratory.

Methods
Study Area
The study was conducted in Gondar University Hospital (GUH) laboratory service department, North West Ethiopia. GUH is a tertiary level
teaching hospital that serves more than 4 million people from the
surrounding zones and nearby regions. GUH provides surgical, medical, pediatrics, gynecology and obstetrics, ophthalmology services
to the community in addition to training student, conducting research and outreach services (community service). The hospital has
a regional level laboratory with 7 sections and a separate reception
room.
According to the report a year before the study the annual volumes
of samples received in each laboratory was 9,960 for urinalysis,
14,800 for clinical chemistry, 8,000 for serology, 11,520 for hematology, 9,600 for microbiology, 9,000 for parasitology and 10,200 for
anti-retroviral therapy laboratory. The overall work flow of the laboratory is partially computerized, i.e., physicians order tests on preprinted paper ordering slips and as orders arrive in the laboratory,
they are registered in the computer system. Computer printed results are taken by porters to the office of each physicians. During the
study period the laboratory was recognized as a three star level laboratory in the WHO-AFRO accreditation system, which is step wise
recognition of evolving fulfillment of ISO15189 standard [16].

Correspondence: Zelalem Addis


Email: addiszelalem151@gmail.com

2014 Addis et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Addis Z, Wondimagegn T, Tachebele B: Types and frequency of pre-analytical errors at University of Gondar hospital laboratory. El Mednifico Journal 2014, 2(4).

364

Study design and study period


A prospective cross sectional study was conducted from April 30,
2013 up to May 30, 2013 in the clinical chemistry and hematology
laboratories of GUH Laboratory.
Data collection and analysis
Data was collected by two methods; one was by careful inspection
of the samples sent to the laboratory based on the pre-analytical
quality indicators and the second was by checking the test requisition papers for their completeness. All types of pre-analytical errors
were documented by laboratory technologists working in the respective laboratories using a data collection sheet prepared for this
purpose and later verified by the investigators. The recorded preanalytical variables were categorized into error types related to appropriate utilization of the test requisition paper and quality of the
sample collected for analysis.
Data was analyzed using SPSS-version 16 computer software and
summarized using percentages and frequencies and presented using
tables.

Results
In this study a total of 1533 (783 clinical chemistry and 750 hematology) samples and their request papers were prospectively examined.
The results of requisition papers examined are indicated in Table 1.
Table 1: Frequency of missed parameters on the laboratory test
request format
Parameters
Clinical
Hematology
Total
chemistry
N (%)
N (%)
N (%)
3 (0.38)
15 (2)
18 (1.2)
Hospital number
0 (0)
0 (0)
0 (0)
Patients name
25 (3.2)
83 (11.1)
108 (7)
Patients age
29 (3.7)
105 (14)
134 (8.7)
Patients sex
783 (100)
750 (100) 1533 (100)
Patients address
409 (52.2)
273 (36.4) 682 (44.5)
Physicians name
35 (4.5)
70 (9.3)
105 (6.8)
Sender address
398 (50.8)
143 (19.1) 541 (35.3)
Date of specimen
collection
783 (100)
750 (100) 1533 (100)
Time of specimen
collection
766 (97.8)
733 (97.7) 1499 (97.8)
Clinical information
Patient information: Even though all request papers were filled with
patients name, none of them had information about the address of
patients. Hospital number, patients age and sex were missing in
1.2%, 7% and 8.7% of the request papers respectively. Clinical information was mentioned only in 2.2% of the request papers.
Requesting physician information: The name and address (ward or
OPD) of the requesting physicians was not filled in 44.5% and 6.8%
of the request papers assessed.

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Pre-analytical errors at University of Gondar hospital laboratory

Specimen related information: The date of specimen collection was


filled in 35.3% of the request papers but none of the request papers
contained the time of specimen collection.
The other observation made was assessment of specimen quality
with respect to collection using appropriate container, hemolysis,
clotting (only for hematology) and volume. Accordingly, all the samples were collected using appropriate containers. Insufficient volume
was the most frequently encountered error related to the sample,
accounting for 2.8%. The frequency of clotting and hemolysis was
0.98% and 1.04%, respectively. In general the frequency of errors related to sample quality was 4.82% (Table 2).
Table 2: Frequency of errors related to specimens collected for
analysis
Parameter
Clinical
Hematology
Total
chemistry
N (%)
N (%)
N (%)
0 (0)
0 (0)
0 (0)
Use of inappropriate
container
7 (0.9)
9 (1.2) 16 (1.04)
Hemolysis
12 (1.5)
31 (4.1)
43 (2.8)
Insufficient volume of
sample
N/A
15 (2) 15 (0.98)
Clotting
19 (2.4)
55 (7.3) 74 (4.82)
Total

Discussion
Physicians generally depend on the results of laboratory testing to
provide definitive answers to their clinical impression. Unfortunately,
there are errors that affect laboratory test results and these errors are
of utmost importance, as laboratory data influences 70% of medical
diagnosis and can significantly impact on the cost and outcome of
patient treatment [13, 14].
In this study, the frequency of pre-analytical errors in GUH laboratory
was assessed based on quality indicators related to specimen quality
and appropriate utilization of test requisition papers. Accordingly
134 (8.7%) of the test request papers sent to the laboratory lacked
one or more of the patient identification parameters including hospital number (1.2%), age (7%) and sex (8.7%). The results of this
study were higher than an Indian study that reported an overall patient identification problem in 2.8% of the requested tests [9]. In another study from India, sex and age of patients were missed in 1.41%
and 1.32% of the requests respectively which is still lower than the
current report [5]. Lower values were also reported from Nigeria [14].
These higher values in our study may be related to workload and
difference of the requesting physicians in valuing these parameters.
The possible reasons for this high value may be different but by identifying these reasons ensuring accuracy and authenticity of the details of patient identification is mandatory as it makes laboratory results less error prone [5].
Another important information missed from the request papers in
this study was the name of the requesting physicians, where 44.5%
of the request papers lacked this information. In addition the senders

Addis Z, Wondimagegn T, Tachebele B

365

of 6.8% of the requested tests were unknown. Lack of such information is important barrier of communication between the laboratory personnel and the clinician. This indicates that communication
of critical and lifesaving reports is very difficult which may end up
with unacceptable loss of many lives.

Acknowledgments: We acknowledge University of Gondar for funding this


research. We are also grateful to the laboratory workers who were involved during
the data collection process.
Competing interests: The authors declare that no competing interests exist.
Received: 3 April 2014
Accepted: 7 January 2015
Published Online: 7 January 2015

A study from Cape Town revealed that 7.5% and 36.3% of the physicians requesting thyroid function test didnt state the date and time
of sample collection respectively [6]. But our report showed higher
values where 35.3% and 100% of the requesting physicians didnt
state the date and time of specimen collection, respectively. When
compared to the Nigerian study, date of specimen collection was
better stated in our study (the Nigerian study reported 36.5%) even
though the time of specimen collection was better in the Nigerian
study, at least 10.3% of the request papers were filled [14]. These
parameters may be missed by the requesting physicians for inpatients and by the laboratory personnel for outpatients. Both hematological and clinical chemistry tests are affected by date and time
of specimen collection [8, 17]. Indicating the date and time of specimen collection has an important meaning in the interpretation of
results and if this is done inappropriately it will lead to diagnostic
errors. Hence, every effort should be made such errors as far as they
are preventable [18].

References

When quality related to samples collected was considered, 2.8% of


the samples were insufficient for analysis and 0.98% were hemolyzed
and clotted. Both higher and lower values were reported from Indian
clinical chemistry laboratory and relatively similar results were found
from a university hospital elsewhere in the world [11, 13]. On the
other higher frequency of hemolysis (19.5%) and clotting (14.2%)
were observed on samples collected for coagulation analysis in Italy
[15]. Lower values in our study may be due to the short study period
and sample size. But this does not mean that the results of this study
are lower since we are dealing with the life of human beings. Hemolysis may significantly affect the reliability of laboratory tests for a variety of biological reasons; hence, attention should be given to avoid
in vitro hemolysis beginning from the patients bedside to analysis
and storage [19].

Conclusion
This study showed that pre-analytical errors related to appropriate
utilization of test request papers and quality of samples collected are
common in the assessed sections. Improper patient identification,
absence of physicians name, missing date and time of specimen collection, lack of sender address and complete absence of clinical date
were observed in the request papers examined. Hemolysis, insufficient sample volume and clotting were also common in the hospital
laboratory. With this limited report, the whole story of pre-analytical
errors cant be addressed; hence, further in depth study, to identify
details of pre-analytical errors starting from the patient bedside up
to analysis, should be conducted. Introduction of computerized order entry systems may minimize inappropriate utilization of test requisition papers. Hence, the management should work on computerized data management system.

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3. Sharma, P. Preanalytical Variables and Laboratory Performance. Indian Journal
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6. Zemlin A.E., Nutt, L., Burgess, L.J, Eiman, F., Erasmus, R.T. Potential for medical
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9. Ashakiran, S., Sumati M.E., Murthy, N.K. A study of pre-analytical variables in
clinical biochemistry laboratory. Clinical Biochemistry 2011, 44: 944945
10. Goswamia, B., Singha, B., Chawla, R., Mallika, V. Evaluation of errors in a clinical
laboratory: a one-year experience. Clin Chem Lab Med 2010, 48:6366
11. Chawla, R., Goswami, B., Tayal, D., Mallika, V. Identification of the Types of Preanalytical Errors in the Clinical Chemistry Laboratory: 1-Year Study at G.B. Pant
Hospital. Labmedicine 2010, 41:89-92
12. Wiwanitkit,V. Types and frequency of preanalytical mistakes in the first Thai
ISO9002:1994 certified clinical laboratory, a 6 month monitoring. BMC
Clinical Pathology 2001, 1:5
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14. Adegoke, O. A., Idowu, A. A., Jeje, O. A. Incomplete laboratory request forms
as a contributory factor to pre-analytical errors in a Nigerian teaching hospital.
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pre-analytical problems for inpatients samples in coagulation laboratory.
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Fine G, Zeh C, Njukeng PA, Mboup S, Sesse DE, Messele T, Birx DL, Nkengasong
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Plebani M. Haemolysis: an overview of the leading cause of unsuitable
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http://www.mednifico.com/index.php/elmedj/article/view/160

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http://www.mednifico.com/index.php/elmedj/article/view/348

Open Access

Original Article

Patterns of herbal use among patients attending family practice centers


S I Shalaby1, Mosleh A Ismail2, Nadia M Mansour2, Heba M Abbas2, Neelima Gupta3

Abstract
Background: Complementary and Alternative Medicine (CAM) is common in both developing and developed countries. This crosssectional descriptive study was conducted to identify the prevalence of herbal use among patients, factors associated with herb use, the
most common herbs used, medical conditions for herb use and factors that might affect herbal use among patients.
Methods: The study was carried out on 300 patients attending two primary health care centers at Fanara village, Ismailia, Egypt. Study
population was allocated randomly using a systematic random sample. A structured questionnaire consisting of three sections was
designed to fulfill the study objectives: personal and socio-demographic characteristics, background knowledge of herbal use and
exploring the belief towards herbal therapy.
Results: The prevalence of herbal medicine (HM) use was 76.7%. The most frequent herb used by participants was peppermint (32.6%),
the most common indications of herbs were respiratory problems (47.3%) and the most common method of use was boiling. About 71%
were of the opinion that herbs were beneficial for health and knowledge of herb usefulness was significantly related with all
sociodemographic characteristics except for family size, income and smoking status. A statistically significant relationship existed between
previous herbal use and old age particularly at the age of 50 (p<0.001), and ex-smokers were significantly related to herbal remedies
(p=0.02). Employment status was significantly related to previous herbal use (88.1%) (p=0.004).
Conclusion: Beliefs of safety of HM were significantly associated with education (high; p=0.03), job (employee; p=0.01), smoking (current
smokers; p=0.01) and health insurance coverage (uncovered; p=0.02). (El Med J 2:4; 2014)
Keywords: Herbal Medicine, Alternative Medicine, Complementary Medicine, Primary Health Care

Introduction
Complementary and alternative Medicine (CAM) is common in both
developing and developed countries [1]. It is booming globally especially in developed countries. However, over 80% of the population in developing countries depend on traditional healing modalities including herbal remedies for health maintenance and therapeutic management of diseases [2]. The use of CAM increased from
33.8% in 1990 to 42.7% in 1997 in the United States [3]. It was evident that between 1997 and 2002, these trends remained stable and
CAM use was reported by 72 million U.S adults. Other countries are
not an exception where two-thirds of the German population and
one-fifth of the British population are trying at least one form of CAM
every year [4, 5]. Also, the frequency of CAM use has been estimated
to be 33% in Finland (WHO, 2002), and 49% in Australia [6]. Among
Saudi residents of the Riyadh region, 68% of the respondents had
used alternative medicine [7]. In a study conducted in Palestine regarding the use of CAM, 72.8% of respondents used at least one type
of CAM [8].
Herbs are plants or plant parts used for their scent, flavor or therapeutic properties. The scope of herbal medicine is sometimes extended to include fungal and bee products, as well as minerals, shells
and certain animal parts [9]. Herbal medicine products are dietary
supplements that people take to improve their health. Many herbs
have been used for a long time for claimed health benefits. They can
be sold as tablets, capsules, powders, teas, extracts and fresh or dried
plants. However, some can cause health problems, some are not effective and some may interact with other drugs [10]. The World
Health Organization (WHO) estimates that 80 percent of the world's
population presently uses herbal medicine for some aspect of primary health care [11]. In fact, according to WHO, approximately 25%
Department of Complementary Medicine, Medical Division, National Research
Center, Cairo, Egypt
2Family Medicine Department, Faculty of Medicine, Suez Canal University,
Ismaileya, Egypt
1

of modern drugs used in the United States have been derived from
plants [11].
In Egypt, a family-based study was carried out in Bir El Abd area,
North Sinai Governorate to study complementary and alternative
practices in Bedouin Community. It revealed that 38% of the studied
population had used CAM at some time in the past in their life.
Herbal/nutritional therapies were the most frequently used (37 %) as
CAM therapy, followed by cupping (36%) [12]. In the Middle Eastern
region, there are more than 2600 known plant species; about 200
250 of them are still in use for the treatment and prevention of various diseases. The number of herbal-derived substances that are in
use as traditional compounds is about 286. The most recent survey
conducted on the potential uses of plant species of the coastal Mediterranean region in Egypt recorded 230 species belonging to eight
families. About 200 of these species have medicinal value, of which
142 are common species, 30 are occasional, while seven are rare.
Greater emphasis is required on the role of treating physicians to
screen and counsel their patients about their use of CAM therapy in
their daily practice [13].
This study was conducted to identify the patterns of herbal use and
factors that might affect such use among primary health care patients at Fanara village, aiming to improve knowledge, attitude and
practices of patients towards herbal use.

Materials and Methods


The cross sectional descriptive study was carried out on patients
(n=300) attending two primary health care centers at Fanara village,
belonging to Ministry of Health and Population (MOHP) and Family
Practice Center affiliated to the Faculty of Medicine, Suez Canal University (FOM/SCU). Study population was allocated randomly using
Department of Animal Science, MJP Rohilkhand University, Bareilly. India
Correspondence: Neelima Gupta
Email: guptagrawal@rediffmail.com

2014 Shalaby et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Shalaby SI, Ismail MA, Mansour NM, Abbas HM, Gupta N: Patterns of herbal use among patients attending family practice centers. El Mednifico Journal 2014, 2(4).

Shalaby SI, Ismail MA, Mansour NM et al.

367

a systematic random sample. A structured questionnaire consisting


of three sections was designed to fulfill the study objectives: personal and socio-demographic characteristics of the participants (age,
gender, and education, income of the family, smoking habits and
coverage with health insurance of the respondent), enquiry about
background knowledge, use of herbs of the respondent and exploring the belief of the respondent towards herbal therapy. Testing feasibility and reliability of the questionnaire was done by conducting
pilot study on 100 volunteers.

alone, with no statistically significant relation between using herbs


alone and other socio-demographic characteristics of participants
(Table 6). Moreover, there was significant relation between beliefs of
efficacy of herbal remedies and female gender (p=0.005), age group
(older p<0.001), education (non-educated p=0.004), job (retired
p<0.001) and health insurance coverage (uncovered p=0.001) (Table
7). The knowledge of herb usefulness was significantly related with
all socio-demographic characteristics of participants except for family size, income and smoking status (Table 8).

Informed consent was obtained from the participants to share the


information in the study and answer the questionnaire, after sharing
with them the objectives of the study. Also, confidentiality of data
was assured. The participants were invited to structured interview
with the researcher. In case of children <10 years, the mother or father was invited to attend the interview. The obtained data were
coded, entered and processed on a personal computer using Statistical Package of Social Science (SPSS). The appropriate statistical
tests was used to identify significant difference. Chi square test was
used for categorical data. Statistical significance was considered at
p-value <0.05.

Belief of safety of herbal therapy was significantly associated with


education (high: p=0.03), job (employee: p=0.01), smoking (current
smokers: p=0.01) and health insurance coverage (uncovered p=0.02)
(Table 9).

Results
The study included all age groups above one year age, with a female
predominance (62.3%). Intermediate level was the main educational
level (36%). The main job categories of participants were housewives
(35.3%). More than half had less than 5 family members. 55.3% had
sufficient income. Majority of participants (81.3%) were non-smokers
and about 60% were not covered by health insurance (Tables 1, 2).
In the present study, the prevalence of herbal use was 76.7%. The
most frequent herbs used were peppermint (32.6%), fenugreek
(31.7%), ginger (21.3%) and Hibiscus (20.4%) followed by Caraway
(14.8%). The commonest indications of herbs were respiratory problems (47.3%), followed by gastrointestinal problems (37%), colitis
(21%) and hypertension (18.7%). The most common method of use
was boiling. Other methods included eating raw, infusion, vapor
bath and concoction (Table 3).
Regarding beliefs of participants towards herbal therapy, the current
study revealed that about 71% of participants believed that herbs
were beneficial for health and herb shops were the major source of
their information (80.4%). Moreover, about 59% believed in safety of
herbs and 80% believed in the use of herbs and medication combinations. However, only 19% thought that herbs were better than
medications while 57% discussed their use with doctors (Table 4).
The results of our study showed that a statistically significant relationship existed between previous herbal use. Old age, particularly
at the age of 50 (p<0.001), and ex-smokers (p=0.02) were significantly related to use of herbal remedies. The majority of participants
who used herbs were not covered by public health insurance
(p=0.02). Employment status was significantly related to previous
herbal use as 88.1% of working participants had previously used
herbs (p=0.004) (Table 5).
It was also found that using herbs alone was significantly related to
old age and smoking status. Ex-smokers (69.9%) had used herbs

This study concluded that herbal therapy use was highly prevalent
among primary care patients. However, there was a demand for better and consistent information on HM regarding effectiveness and
safety. The main challenges in the context of primary healthcare are
to promote and upgrade the knowledge and skills of the providers
about HM to ensure patient safety and to support patients in their
self-management.
Table 1: Socio-demographic characteristics of study
participants (n=300)
Characteristic
N
Sex
Male
113
Female
187
87
Age (years)
1-18
19-24
37
132
25-49
44
50+
Education
Below age
14
26
Illiterate
29
Read/write
Basic
98
108
Intermediate
25
University
Job
Below age
6
91
Student
Retired
13
Housewife
106
20
Employee
Manual worker
64
157
Family size
<5
112
5-6
7+
31
166
Income
Sufficient
134
Insufficient
Smoking
Never
244
23
Ex-smoker
33
Current smoker

%
37.7
62.3
29.0
12.3
44.0
14.7
4.7
8.7
9.7
32.7
36.0
8.3
2.0
30.3
4.3
35.3
6.7
21.3
52.3
37.3
10.3
55.3
44.7
81.3
7.7
11.0

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368

Table 2: Health insurance membership and use of herbs


among study participants (n=300)
Characteristic
N
181
Health Insurance No
119
Yes
Previous use of
No
70
herbs
230
Yes

Patterns of herbal use among patients

%
60.3
39.7
23.3
76.7

Table 3: Types of herbs, indications and methods used by study


participants (n=300)
Herb
N
%
2
4.3
Hibiscus
Indication Respiratory
(47; 20.4%)
problems
1
2.1
Hypotension
44
93.6
Hypertension
4
8.5
Method
Boiling
43
91.5
Concoction
18
81.8
Licorice
Indication Hypotension
(22; 9.6%)
1
4.5
Colitis
3
13.6
Diabetes
2
9.1
Method
Boiling
20
90.9
Concoction
11
100.0
Dome
Indication Hypertension
(11; 4.8%)
1
9.1
Method
Boiling
10
90.9
Concoction
12
46.2
Habbet elbaraka Indication Respiratory
(26; 11.3%)
problems
9
34.6
Gastrointestinal
problems
4
15.4
Colitis
1
3.8
Diabetes
26
100.0
Method
Boiling
4
46.2
Thyme
Indication Respiratory
(9; 3.9%)
problems
4
34.6
Gastrointestinal
problems
1
15.4
Colitis
9
3.8
Method
Boiling

Discussion
The results of the current study revealed the prevalence rate of previous herbal use among study population to be 76.7%, the results
being consistent with a study conducted among United Arab Emirates citizens (76%) [14]. This may be due to similarity in cultures. In
a Turkish study the prevalence was 55.4%, while it was 33.9% and
18.9% in studies conducted in Malaysia and USA, respectively [1517]. These levels of herbal use are different from the current study
and this may be due to different socio-economic levels and cultural
factors.
With regards to the socio-demographic and economic factors related
Vol 2, No 4

to previous herbal use, statistically significant relationship existed


between previous herbal use and old age particularly at the age of
50+ (95.5%) (p<0.001). Similar results have been obtained showing
a statistically significant relationship between 45-64 years and previous herbal use with p<0.001 [17]. Also, this study showed statistically
significant relationship between the female gender and previous
herbal use while the present research revealed that females uses
more herbal remedies than males but with no statistical significance.
Table 4: Knowledge, beliefs and sources of information about
herbs among study participants (n=300)
Participants
N %
Know that herbs are good for health
214 71.3
Discussed the use of herbs with doctor
171 57.0
176 58.7
Believe use of herbs is safe
Believe use of herbs is effective
220 73.3
Believe combined use of herbs with drugs is better 239 79.7
57 19.0
Believe use of herbs is better than medications
Sources of information Friend
32 13.9
Relative
42 18.3
22 9.6
Pharmacy
Herbs shop
185 80.4
4 1.7
Others
The observation that all ex-smokers significantly used herbal remedies (p=0.02) is in agreement with Kennedys study which revealed
that previous smoking is significantly related to use of herbal remedies (p<0.001) [17]. Also, the current study revealed that there was
a statistically significant relationship between previous herbal use
and health insurance coverage; the majority of participants who
used herbs were not covered by public health insurance (p=0.02).
This may be explained by the increased cost of conventional medicine that cannot be obtained completely without public health insurance; thus patients depend on herbal remedies instead due to
their lower costs. In comparison to the above study, the results revealed that those with public insurance have the lowest use rates
whereas those with private insurance only reported the highest use
rates (effect of insurance coverage, p<0.001).
On the other hand, the current research indicated that the employment status is significantly related to previous herbal use as 88.1%
of working participants had previously used herbs compared to
72.2% among non-working ones (p=0.004). Also, the results of study
conducted in India to assess the prevalence of herbal medicine home
use and concomitant use with pharmaceutical medicines in Jamaica
[18] reported that the employment status is significantly related to
previous herbal use (p<0.001).
The current research reports that the five most frequent herbs used
by participants were: peppermint (32.6%), fenugreek (31.7%), ginger
(21.3%) Hibiscus (20.4%), Caraway (14.8%). On the other hand, results of an American study revealed that the five most commonly
used herbs were aloe (41.2%), garlic (28.8%), ginseng (24.5%),
Echinacea (21.8%) and St. John's Wort (20.9%) [19]. Another American study revealed that the most common herbal remedies are Gin-

Shalaby SI, Ismail MA, Mansour NM et al.

369

Table 5: Relation between participants use of herbs and their socio-demographic characteristics and health insurance
Characteristic
Previous use of herbs
2 test
No
Yes
N
%
N
%
33
29.2
80
70.8
3.49
Sex
Male
37
19.8 150
80.2
Female
33
37.9
54
62.1
33.14
Age (years)
1-18
16
43.2
21
56.8
19-24
19
14.4 113
85.6
2549
2
4.5
42
95.5
50+
13
18.8
56
81.2
1.20
Education
None
51
24.8 155
75.2
Basic/intermediate
6
24.0
19
76.0
High
60
27.8 156
72.2
8.52
Job status
Not working
10
11.9
74
88.1
Working
3
50.0
3
50.0
22.73
Job
Below age
35
38.5
56
61.5
Student
1
7.7
12
92.3
Retired
21
19.8
85
80.2
Housewife
2
10.0
18
90.0
Employee
8
12.5
56
87.5
Manual worker
35
22.3 122
77.7
0.66
Family size
<5
26
23.2
86
76.8
5-6
9
29.0
22
71.0
7+
36
21.7 130
78.3
0.56
Income
Sufficient
34
25.4 100
74.6
Insufficient
61
25.0 183
75.0
7.67
Smoking
Never
0
0.0
23
100.0
Ex-smoker
9
27.3
24
72.7
Current smoker
34
18.8 147
81.2
5.28
Health Insurance
No
36
30.3
83
69.7
Yes

p-value

0.06
<0.001*

0.60

0.004*
<0.001*

0.72

0.45
0.02*

0.02*

(*) Statistically significant at p<0.05

seng, Ginkgo biloba, Garlic supplements, Glucosamine with or without chondroitin and St. John's wort [17]. Turkish study results revealed that the most common herbs used by participants were:
23.9% used lime, 15.1% sage tea, 13.3% thyme, 4.4% nettle, and 4.4%
mint and this difference may be explained by the difference in the
medical conditions the herbs were needed for and also the climatic
conditions between the two countries [15].
The results of the current investigation showed that the most common medical conditions for which herbal remedies were used included respiratory problems (47.3%), followed by gastrointestinal
problems (37%) and colitis (21%). These results resemble the other
two American studies which showed that the most common indications of herbal use were headache or chest cold, followed by stomach or intestinal conditions and musculoskeletal conditions [3, 17].
The results of the current research showed that most participants
used one or two herbs (40% and 30.4% respectively) followed by the
use of three herbs and more than three herbs. This result is similar
Vol 2, No 4

to the results from a previous study that showed that majority of


users (33.5%) used one herb but different in that 17.2% used two
herbs, 21% used four or more herbs and 9.8% used three [17].
The results of the current study found that the most common
method for herbal preparation and use was boiling, followed by infusion and eating raw herbs, compared to the results of a precious
study, where the most common method of preparation was by infusion or boiling in water [18].
The current research assessed the knowledge of patients about
herbal therapy and results revealed that about 71% of participants
knew that herbs were good for health. When compared with a study
conducted in Iran between October 2003 and October 2004 for assessment of knowledge, attitude and practice of herbal medicine in
Tehran, results were quite similar as it showed that the knowledge
rate was 75.6% [20]. This similarity could be explained by the similar
culture of both countries.

370

Patterns of herbal use among patients

Table 6: Relation between participants use of herbs alone and their socio-demographic characteristics and health insurance
Characteristic
Use herbs alone
2 test
p-value
No
Yes
N
%
N
%
3.24
0.07
37
46.3
43
53.8
Sex
Male
Female
88
58.7
62
41.3
20.92
<0.001*
Age (years)
1-18
30
55.6
24
44.4
15
71.4
6
28.6
19-24
2549
70
61.9
43
38.1
50+
10
23.8
32
76.2
2.81
0.25
25
44.6
31
55.4
Education
None
Basic/intermediate
89
57.4
66
42.6
11
57.9
8
42.1
High
0.00
0.95
85
54.5
71
45.5
Job status
Not working
Working
40
54.1
34
45.9
7.54
0.18
1
33.3
2
66.7
Job
Below age
33
58.9
23
41.1
Student
Retired
3
25.0
9
75.0
48
56.5
37
43.5
Housewife
7
38.9
11
61.1
Employee
Manual worker
33
58.9
23
41.1
3.95
0.14
60
49.2
62
50.8
Family size
<5
54
62.8
32
37.2
5-6
7+
11
50.0
11
50.0
2.28
0.13
65
50.0
65
50.0
Income
Sufficient
60
60.0
40
40.0
Insufficient
6.22
0.04*
Smoking
Never
103
56.3
80
43.7
7
30.4
16
69.6
Ex-smoker
Current smoker
15
62.5
9
37.5
0.73
0.39
Health Insurance
No
83
56.5
64
43.5
42
50.6
41
49.4
Yes
(*) Statistically significant at p<0.05

The current study assessed the rate of disclosure of herbal remedies


use by participants with their physicians and found that 57% of them
discussed their use with doctors and this is the same rate as that
found in the American study which assessed factors associated with
herbal use among urban multiethnic primary care patients and revealed that the rate of disclosure of herbal use was 57%; 40% of all
of the survey respondents believed that taking prescription medications and herbal medicines together was more effective than taking
either alone while the rate found in the current research was 80%
[21].
The current research studied the beliefs of safety and efficacy of
herbal therapy among participants and results revealed that 73%
thought about their effectiveness, in comparison with a study conducted in India during June-August 2005 to assess perceived efficacy
of herbal remedies by users accessing primary healthcare, 86.8% of
participants believed in efficacy of herbal remedies [22]. About beliefs of safety of study population, results of the current study
showed that 59% believed in the safety of herbs, while in another
Vol 2, No 4

study, 29.4% of participants thought that it was purely natural and


harmless [15].
The current research studied factors related to the use of herbal remedies alone and the results showed that using herbs alone was significantly related to two factors only: age group, as most of the older
persons (76.2%) had used herbs alone (p<0.001) and smoking status,
as ex-smokers (69.9%) used herbs alone (p=0.04). Comparing these
results to another study, the prevalence of herb use alone was lowest
in people aged 65 years and older and highest in 3554 old which is
inconsistent with our study results [18]. Also, the study found that
prevalence of herb use alone was lowest among the retired and
highest amongst those employed whilst concomitant herbdrug use
was highest in the retired and lowest in students and there was a
statistically significant association of herb use with educational level,
gender, possession of health insurance and religion, whereas none
of these factor was of statistical significance in our current study results.

Shalaby SI, Ismail MA, Mansour NM et al.

371

Table 7: Relation between participant knowledge about herbs usefulness and their socio-demographic characteristics and health
insurance
Characteristic
Know herbs are useful
2 test
p-value
No
Yes
N
%
N
%
7.81
0.005*
Sex
Male
43
38.1
70
61.9
43
23.0
144
77.0
Female
35.27
<0.001*
45
51.7
42
48.3
Age (years)
1-18
19-24
10
27.0
27
73.0
27
20.5
105
79.5
2549
4
9.1
40
90.9
50+
11.07
0.004*
Education
None
12
17.4
57
82.6
71
34.5
135
65.5
Basic/intermediate
3
12.0
22
88.0
High
5.28
0.02*
Job status
Not working
70
32.4
146
67.6
16
19.0
68
81.0
Working
31.29
<0.001*
1
16.7
5
83.3
Job
Below age
Student
45
49.5
46
50.5
1
7.7
12
92.3
Retired
23
21.7
83
78.3
Housewife
Employee
1
5.0
19
95.0
15
23.4
49
76.6
Manual worker
5.44
0.07
Family size
<5
36
22.9
121
77.1
5-6
40
35.7
72
64.3
10
32.3
21
67.7
7+
0.85
0.36
Income
Sufficient
44
26.5
122
73.5
Insufficient
42
31.3
92
68.7
3.94
0.14
76
31.1
168
68.9
Smoking
Never
Ex-smoker
4
17.4
19
82.6
Current smoker
6
18.2
27
81.8
11.31
0.001*
39
21.5
142
78.5
Health Insurance
No
Yes
47
39.5
72
60.5
(*) Statistically significant at p<0.05

The investigated factors by the present study can be related to beliefs of efficacy of herbal remedies and the results indicate that participants belief in herbs effectiveness were significantly associated
with sex (female p=0.001), age group (older p<0.001), education
(non-educated p=0.03), job (retired p<0.001) and health insurance
coverage (uncovered p=0.01). However, these factors were of no statistical significance except for age which is a significant predictor variable (p=0.036) while gender, family income, ethnicity and number
of years of formal education were not significant predictors of the
patient's perception of efficacy of herbal remedies [22].
When describing the relation between patients disclosure of using
herbal remedies to their physicians and the different demographic
and socioeconomic factors results, the current study found that age
was a significant variable that makes a difference in discussing herbal
use with physicians (p<0.001) as older the age, greater are the
chances of discussing herbal use with doctors. This result was in
agreement with a study conducted to assess patient disclosure

about herb and supplement use among adults in the US which also
found that old age is significantly related to discussing herbs use
with the doctor [23].
Also, our study found that there was a statistically significant relationship between education level and job category with discussing
herbal use with doctors (p=0.002) as the higher the education level
is, the lower is the rate of discussing herbal use with doctors. Retired
persons were more likely to discuss herb use with doctors followed
by working persons, either employees or manual workers, and the
least level was among non-workers either house wives or younger
(p<0.001). These results were inconsistent with the results of a previous study, which found that there was no statistically significant
relationship between neither the educational level of participants,
nor their job category [23].
The current research studied the socio-demographic factors that are
significantly related to knowledge of herb usefulness and found stahttp://www.mednifico.com/index.php/elmedj/article/view/348

372

Patterns of herbal use among patients

Table 8: Relation between participants discussing the use of herbs with doctors and their socio-demographic characteristics and
health insurance
Characteristic
Discussed herbs use with doctors
2 test
p-value
No
Yes
N
%
N
%
3.34
0.07
Sex
Male
41
36.3
72
63.7
88
47.1
99
52.9
Female
33.45
<0.001*
46
52.9
41
47.1
Age (years)
1-18
19-24
25
67.6
12
32.4
54
40.9
78
59.1
2549
4
9.1
40
90.9
50+
12.97
0.002*
Education
None
17
24.6
52
75.4
98
47.6 108
52.4
Basic/intermediate
14
56.0
11
44.0
High
4.45
0.035*
Job status
Not working
101
46.8 115
53.2
28
33.3
56
66.7
Working
22.33
<0.001*
5
83.3
1
16.7
Job
Below age
Student
50
54.9
41
45.1
0
0.0
13
100.0
Retired
46
43.4
60
56.6
Housewife
Employee
7
35.0
13
65.0
21
32.8
43
67.2
Manual worker
5.99
0.053
Family size
<5
58
36.9
99
63.1
5-6
58
51.8
54
48.2
13
41.9
18
58.1
7+
1.59
0.21
Income
Sufficient
66
39.8 100
60.2
Insufficient
63
47.0
71
53.0
2.14
0.14
113
46.3 131
53.7
Smoking
Never
Ex-smoker
2
8.7
21
91.3
Current smoker
14
42.4
19
57.6
0.46
0.50
75
41.4 106
58.6
Health Insurance
No
Yes
54
45.4
65
54.6
(*) Statistically significant at p<0.05

tistically significant relations with all socio-demographic characteristics of participants except for family size, income and smoking status
as knowledge was significantly higher among females (p=0.005), old
age group 50+ (p<0.001), highly educated (p=0.004), working
(p=0.02), employee (p<0.001) and those not covered with health insurance (p=0.001). Also there was a statistically significant relationship among those who knew that herbs were good for health, and
using herbs alone (p=0.04), but there are limited researches studying
herbal usefulness knowledge related factors which handicapped the
researcher from discussing these results. Therefore, further researches should be encouraged on factors associated with
knowledge of herbal usefulness.

Conclusion
Beliefs of safety of herbal medicine were significantly associated with
education (high; p=0.03), job (employee; p=0.01), smoking (current
smokers; p=0.01) and health insurance coverage (uncovered;
p=0.02). Further researches are needed to discuss the factors related
Vol 2, No 4

to beliefs of safety of herbal therapy as studies are limited in this


area.
Competing interests: The authors declare that no competing interests exist.
Received: 30 July 2014
Accepted: 8 January 2015
Published Online: 8 January 2015

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Shalaby SI, Ismail MA, Mansour NM et al.

373

Table 9: Relation between participants belief of herbs safety and their socio-demographic characteristics and health insurance
Characteristic
Discussed herbs use with doctors
2 test
p-value
No
Yes
N
%
N
%
3.11
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45
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65
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374

http://www.mednifico.com/index.php/elmedj/article/view/256

Open Access

Review

The role of microRNAs in HIV infection


Marta Calado1, Harapan Harapan2,3,4

Abstract
MicroRNAs (miRNAs) are a class of approximately 22-nt long non-coding RNAs found in eukaryotes. miRNAs are involved in the specific
regulation of both protein-coding and putatively non-coding genes by post-transcriptional silencing. Evidences support the idea that
mammals continue to employ non-coding RNA to silence viruses. Although HIV-1 infection modulation by miRNAs is unclear, there are
several hypotheses that may possibly explain the confounded nature of miRNAs effects in virus-infected host systems. Studies of the
interactions of HIV-1 and miRNAs might generate new insights into the mechanism of HIV-1 infection, for instance, whether HIV-1 infection
affects the miRNA pathways and whether miRNA pathways target the HIV-1 genome to modulate infection. Research into how HIV-1 infection
affects the host miRNA pathway also could improve our understanding of the mechanisms underlying HIV-1 mediated pathologies and T
lymphocytes depletion. In this paper, we discuss several possible mechanisms of interaction between miRNAs and HIV-1 including silencing
of cellular mRNAs sequences that relevant to HIV-1 replication. (El Med J 2:4; 2014)
Keywords: MicroRNA, miRNA, Non-coding RNA, Virus Silencing, HIV

Introduction
The human genome encodes only approximately 20,000 protein
coding genes, representing <2% of the total genome sequence [1,
2]. However, with advance technology, it has been determined that
at least 90% of the genome is actively transcribed [3]. The human
transcriptome is more complex than a collection of protein-coding
genes and their splice variants, showing extensive antisense, overlapping and non-coding RNA (ncRNA) expression [4, 5]. NcRNAs are
grouped into two major classes based on transcript size: small
ncRNAs and long ncRNAs [6]. Long ncRNAs are mRNA-like transcripts
ranging in length from 200 nucleotides (nt) to ~100 kilobases (kb)
lacking significant open reading frames. However, small ncRNAs class
ranges from 18 to 200 nt in length [6]. Small ncRNAs include the
well-documented microRNAs (miRNAs). miRNAs are a class of approximately 22-nt long non-coding RNAs found in eukaryotes
(RNAi12), that are involved in the specific regulation of both proteincoding and putatively non-coding genes, by post-transcriptional silencing or infrequently by activation.
Several studies support the idea that mammals continue to employ
ncRNAs to silence viruses. Piwi-interaction RNAs (piRNAs), short interfering RNAs (siRNAs), and Dicer-processed miRNAs have been
shown to suppress mammalian endogenous retroviruses [7-9]. Bioinformatics analyses also have extended this notion of antiviral defense to diverse human miRNAs that can target many types of viruses
[10]. Specifically, miRNA-regulation of HIV-1 infection has been experimentally verified and independently reported by several groups
of investigators [11-15]. Previously, we have discussed the role of micRNAs on tuberculosis infection and also other non-communicable
disease [10, 16, 17]. In this paper, we present current and emerging
knowledge on the roles of miRNAs on HIV infection that may facilitate the design of miRNAs as effective antiretroviral agents.

HIV infection: Overview


HIV is the causative agent of acquired immunodeficiency syndrome
(AIDS), a disease leading to systemic failure of the immune system.
Centro de Patognese Molecular, Unidade de Retrovrus e Infeces Associadas,
Faculdade de Farmcia, Universidade de Lisboa, Portugal
2Medical Research Unit, School of Medicine, Syiah Kuala University, Banda Aceh,
Indonesia
3Tropical Diseases Centre, School of Medicine, Syiah Kuala University, Banda Aceh,
Indonesia
1

HIV-1 primarily infects CD4+ T cells and infection can be divided into
two phase: an acute phase (early phase), and a chronic infection
phase, which can last for 10-20 years before the onset of AIDS [1821]. HIV-1 is a relatively small RNA virus, composed of two identical
single stranded 9,7kb RNA molecules. The genome consists of several secondary structures (LTR, TAR, RRE, PE, SLIP, CRS, and INS) and
nine genes (gag, pol, env, tat, rev, nef, vif, vpr, and vpu) encoding 19
proteins.
The replication cycle begins by sequential interactions between viral
envelope glycoprotein and cellular receptors that ultimately lead to
viral envelope and cell membrane fusion. The cellular receptors involved in these initial events are the CD4 molecule and a member of
seven-transmembrane, G-protein-coupled, receptors (GPCRs) family,
referred as co-receptor. After cell entry and uncoating, the viral genetic material is reverse transcribed (RT) into cDNA by RT enzyme
and integrated as double-strand DNA into the host genome before
directing viral gene expression. HIV-1 relies on the cellular transcription and translation machineries for the synthesis of viral genomic
proteins [22]. In most cases, HIV-1 successfully hijacks cellular pathways and bypasses restriction factors for optimal replication leading
to continuous rounds of infection, replication and cell death. The
continuous viral replication causes CD4+ T cells decrease and progression to AIDS.
HAART treatment revealed the existence of a pool of resting memory
CD4+ T cells harboring integrated, but silent, HIV-1 provirus [23, 24].
This latent reservoir is the major obstacle for virus eradication by
HAART. Therefore, it is necessary to understand how HIV latency is
established and maintained [25]. A challenge in AIDS treatment is
the need to activate latent viral reservoirs.

MicroRNA: Biogenesis and Mechanisms of Action


Recent findings suggest a restriction role played by non-coding
RNAs. This concept seems to make sense because more than 70% of
human DNA is transcribed into non-coding RNAs (ncRNAS), while
Postgraduate Study, Infectious Diseases, Faculty of Medicine, Dentistry and Health
Sciences, The University of Western Australia, WA, Australia
Correspondence: Harapan Harapan
Email: personal@harapanharapan.com

2014 Calado et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Calado M, Harapan H: The role of microRNAs in HIV infection. El Mednifico Journal 2014, 2(4).

Calado M, Harapan H

375

less than 2% of the human genome encode for proteins [26]. There
are several forms of ncRNAs, such as siRNAs, miRNAs and piRNAs [2732].

40S/60S ribosomes are prohibited from joining during the elongation process or facilitating proteolysis of nascent polypeptides [10,
35, 37, 39].

Bioinformatics studies predicts that up to 1000 miRNAs exist [33].


miRNAs are named as miR- plus numbers (e.g., miR-18), although
there are a few exceptions. miRNAs of similar sequence are usually
distinguished by an additional letter following the miRNA number
(e.g., miR-125b). A miRNA of identical mature sequence may appear
at several genomic loci with different precursor sequences. In such a
case, the different miRNA genes are distinguished by the addition of
another number at the end of the sequence (e.g., miR-125b-1) [34].

The indirect on translational repression occurs via mRNA deadenylation and degradation [37, 39]. Deadenylation of mRNAs is mediated
by glycinetryptophan protein of 182 kDa (GW182) proteins, the
components of miRISC, poly(A)-binding protein (PABP), and Argonaute (AGO) protein [35, 36]. Argonaute (AGO) proteins are core
components of the miRISC which are directly associated with miRNAs [36]. Then this molecule will interacts with the CCR4/CAF1 deadenylase complex to facilitate deadenylation of the poly(A) tail [36,
35]. Following deadenylation, the 50-terminal cap is removed by the
decapping enzyme, decapping DCP1-DCP2 complex [35]. Endonucleolytic cleavage and mRNA degradation miRNA-mediated are
helped by AGO2 [36].

Biogenesis
miRNAs are processed from RNA polymerase II (RNAPII)-specific transcripts of independent genes or from introns of protein-coding
genes. This initial miRNA precursors, known as pri-miRNAs, are processed into ~70 nt hairpin structures known as pre-miRNAs, in the
nucleus by a nuclear enzyme complex known as the microprocessor
that contains an endoribonuclease, Drosha, and a double-stranded
RNA binding protein, DiGeorge syndrome critical region 8 (DGCR8)
[10]. This process is called as DroshaDGCR8 step. Drosha is an RNase
III enzyme which contains two RNase domains which cleave the 50
and 30 ends, releasing the pre-miRNA [35]. Some pre-miRNAs are
produced from very short introns (mirtrons) that bypass the Drosha
DGCR8 step [36].
The pre-miRNA is exported from the nucleus to the cytoplasm by
Exportin-5 (XPO5) [36]. In the cytoplasm, the pre-miRNA is further
cleaved by another RNase III enzyme, Dicer, which removes the loop
to yield the ~22 nucleotide miRNA duplex [37]. After being unwound
by a helicase, one strand of miRNA is destined to be the mature
miRNA called as guide strand and the complementary strand, called
as passenger strand or miRNA*, is rapidly degraded [37]. The thermodynamic stability of the miRNA duplex termini and the identity of
the nucleotides in the 30 overhang determine which strands act as
the guide strand [38]. Then the guide strand is incorporated into a
miRNA-induced silencing complex (miRISC) [15, 36].

Mechanism of Action
Guided by the sequence complementarity between the small RNA
and the target mRNA, miRNARISC-mediated gene inhibition is commonly divided into three processes: (a) sites specific cleavage, (b)
translational inhibition and (c) enhanced mRNA degradation (10).
Once incorporated into a cytoplasmic RISC, the miRNA will specify
cleavage if the mRNA has sufficient complementarity to the miRNA,
or it will repress productive translation if the mRNA does not have
sufficient complementarity to be cleaved but does have a suitable
constellation of miRNA complementary sites [15].
The miRISCmRNA interaction can lead to several modes of direct
and indirect on translational repression [37]. Direct on translational
repression involves: (a) Initiation block: The miRISC inhibits translation initiation by interfering with eIF4F-cap recognition and 40S
small ribosomal subunit recruitment or by antagonizing 60S subunit
joining and preventing 80S ribosomal complex formation; (b) Postinitiation block: premature ribosomal drop-off, the 40S/60S ribosomes are dissociated from mRNA, stalled or slowed elongation, the

Relationship between HIV and the miRNAs


Studies of the interactions of HIV-1 and miRNAs might generate new
insights into the mechanism of HIV-1 infection. For instance, it would
be useful to know if HIV-1 infection affects the miRNA pathways and
if miRNA pathways target the HIV-1 genome to modulate infection
[40]. Research into how HIV-1 infection affects the host miRNA pathway could improve our understanding of the mechanisms underlying HIV-1 mediated pathologies and T lymphocytes depletion. Previous study suggested that miRNAs may regulate up to 92% of the
genes in human [41].
HIV-1 infection modulation by miRNAs is unclear. However, there are
four hypotheses that may possibly explain the confounded nature of
miRNA effects in virus-infected host systems: (a) HIV-1 infection
changes host miRNA function to initiate successful viral invasion and
latency; (b) The host miRNA systems may consequentially target the
HIV-1 genomic elements or its genes to innate immune response; (c)
HIV-1 miRNAs are produced from both sense and antisense transcripts to target either its own viral transcript or host genes for immune compromise; and (d) The interplay of miRNA and target mRNA
between host and HIV-1 can be organized into regulatory modules
(cis- and trans-regulation) of essential biochemical pathways as critical determinants of host cell fate and survival.
Based on these scenarios, miRNAs can modulate HIV replication in
two different ways: directly targeting HIV RNA and targeting the
mRNAs that encode host cell factors relevant to HIV replication.

miRNAs directly targeting HIV RNA


There are many studies that demonstrate the directly targeting of
HIV RNA. Hariharan et al was the first to attempt searching for miRNAs that directly target sites in the HIV genome [15]. They used target prediction software and identified five miRNA target sites in the
HIV genome: miR-29a, miR-29b, miR-149, miR-324-5p, and miR-378.
Another study by Ahluwalia et al confirmed that miR-29a inhibited
nef expression, leading to repressed HIV replication in Jurkat cells
[12]. Further experiments validated an inhibitory effect of miR-29a
on HIV replication and also predicted target sites for 11 miRNAs in
the HIV-1 3 UTR [14]. More recently, Sun et al confirmed the inhibition of HIV-1 infection by miR-29a and also by miR-29b [42].

http://www.mednifico.com/index.php/elmedj/article/view/256

376

Changes in miRNA expression profiles, i.e. downregulation of a large


pool of miRNAs, have been observed in human HeLa cells transfected with the infectious molecular clone pNL4-3 [43]. Huang et al
discovered a group of five cellular miRNAs that inhibit HIV-1 expression in primary resting CD4+ T cells via interactions with the 3 UTR
of HIV-1 RNA [11]. Cellular miRNAs bind to the 3 UTR of HIV-1 miRNAs and can inhibit the translation of almost all HIV-1-encoded proteins, including tat and rev, key regulators of viral gene transcription
and viral RNA translocation. miR-28, -125b, -150, -223, and -382, were
identified via deletion analysis of the 1,2 kb region, and mutation of
these sites significantly neutralized the inhibition [11]. These cellular
miRNAs have also been shown to inhibit viral strains directly isolated
from resting CD4+ T cells of HIV-1 infected individuals [11]. Thus, the
miR-28, -125b, -150, -223, and -382 cellular miRNAs may likely participate in maintaining or establishing the latency of all strains of HIV1 in resting CD4+ T cells, as observed in patients with suppressive
highly active antiretroviral therapy (HAART). Wang et al reported that
four of the miRNAs characterized by Huang et al were also responsible for differences between monocytes and macrophages in their
permissivity to HIV infection [13]. Recent work by Houzet et al confirmed the inhibitory effect of miR-29 and identified four new miRNAs that target HIV-1: miR-133b, miR-138, miR-149, miR-326 [44]. All
these studies suggest that, in different cells and contexts, different
miRNAs may selectively regulate HIV-1 infection through direct targeting of viral sequences.

Silencing of cellular mRNAs sequences that encode host


cell factors relevant to HIV replication
Genome-wide screenings have recently identified several hundred
host proteins that regulate optimal HIV-1 replication in human cells
[43, 45-48]. It was discovered that miR-198 targets the cyclin T1
mRNA, which encodes a HIV-1 Tat cofactor, to confer differences in
permissiveness between monocytes and macrophages to HIV infection [49]. In other study, Chiang and colleagues also found that, in
different cellular contexts, other miRNAs regulate cyclin T1, such as
miR-27b, miR-29b, miR-223, miR-150, that can explain the expression
differences of HIV in resting versus activated T cells [50]. Triboulet
and colleagues found that HIV-1 infection was also associated with
either up- or downregulation of specific miRNA clusters [51]. For instance, the miR-17/92 cluster, which encodes for seven miRNAs,
among which miR-17-5p and miR-20a that target the histone acetyltransferase and p300/CBP-associated factor (PCAF), another cellular
cofactor of the viral Tat protein, was substantially decreased. The authors proposed that this gene regulatory axis may help understand
how latent virus reservoir could be activated.
Recently, it was reported a set of six miRNAs that repress the expression of a tat cofactor, which was noted also to be enriched in monocytes: miR-15a, miR-15b, miR-16, miR-20a, miR-93, miR-106b [52]. In
the same years, Zhang et al found that miR-217 was induced by tat
and that miR-217 increased HIV-1 expression by targeting SIRT-a
(sirtuin-1), a host protein that deacetylates and inactivates tat function [53]. These findings, all together, illustrate the complex miRNAmediated positive and negative regulatory events that influence viral
replication.

Vol 2, No 4

The role of microRNAs in HIV infection

Cellular miRNAs can affect viral replication and, conversely, it is possible that infection by mammalian viruses changes cellular miRNA
profiles. The first report of this effect was shown by Yeung et al [43].
A replication-competent HIV-1 molecular genome was transfected
into HeLa cells, demonstrating repression of the majority of the cellular miRNAs. Hayes and colleagues, infected CEM T cells with HIV-1
and observed changes in 145 miRNAs with the repression of 22 cellular miRNAs appearing to correlate with the RNAi-suppressing activity of tat [54].
In a separate in vivo HIV-1 infection of primary peripheral blood mononuclear cells (PBMCs), Sun et al reported reduced expression of a
set of six miRNAs (miR-21, miR-155, miR-29a, miR-29b, miR-29c, miR142-3p), and the increased expression of miR-223 [42]. Houzet et al
made the first investigation of this issue [55]. They studied PBMCs
from 36 HIV-1-seropositive individuals and compared them with corresponding samples from 12 uninfected controls. From the seropositive individuals, it was found 59 miRNAs that were down-regulated
in PBMCs, and they noted that the pattern of miRNA changes was
different depending on whether the infected individuals had high
CD4+ T cells and low viral load, high CD4+ T cells and high viral load,
low CD4+ T cells and low viral load, or low CD4+ T cells and high viral
load.
Hence, Bignami et al examined changes in 377 miRNAs in CD4+ T
cells from HIV-1-seropositive patients and matched it with controls
[56]. They profiled miRNAs in elite HIV-1 controllers, multiply HIV-1
exposed but uninfected individuals, and treatment-nave HIV-1 infected patients. They found that the miRNA profiles from the elite
HIV-1 controllers and treatment-naive HIV-1 infected individuals
were virtually indistinguishable but that they differed from the
miRNA profiles in multiply HIV-1 exposed uninfected persons. The
result suggests that miRNA profiling could distinguish between HIV1 infected and HIV-1 exposed but uninfected individuals. A separate
in vivo study was performed by Witwer et al, who compared miRNA
profiles in PBMCs from healthy individuals, elite HIV-1 controllers,
and viremic HIV-s patients [57]. They observed the downregulation
of miR-150 and miR-29 family members in viremic patients, similar
to the published results of Houzet et al, and also the downregulation
of miR-150 and miR-125b, in agreement with the earlier findings of
Huang et al [11, 55].
While there are several effective drugs for HIV/AIDS treatment, ongoing attempts to develop a useful HIV-1 vaccine and a protective
antiviral microbicide face significant challenges. The regulation of
HIV-1 infection by host miRNAs that directly target the viral genome
is possible; however it remains uncertain how effective these cellular
miRNAs are in influencing HIV-1 infection. It is complicated to control
HIV-1 infection through miRNA targeting of cellular factors because
they affect the expression of genes that could inhibit but also facilitate HIV infection. It is necessary to further investigate the relationship between HIV-1 and RNA silencing pathways. Such studies can
provide new insights into the persistence of the virus in infected patients and allow the development of new anti-HIV-1 therapies.

Calado M, Harapan H

Competing interests: The authors declare that no competing interests exist.


Received: 16 August 2014
Accepted: 15 November 2014
Published Online: 15 November 2014

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Open Access

Review

Patient specific instrumentation: A minimally invasive technique for knee arthroplasty


Mahmoud A Hafez1, Ashsish Jaiman2, Hosamuddin Hamza1

Abstract
Patient specific instrumentation (PSI) is considered a minimally invasive technique regardless of whether the skin incision is small or
traditionally long. PSI provides two pieces of instruments to replace the complex conventional instruments that may reach up to 100 pieces.
PSI eliminates the need for using the invasive intramedullary rods that perforate the medullary canal leading to higher risk of bleeding, fat
embolism, infection and fractures. PSI also reduces operative time and speeds the recovery of patients. In this review, the authors collect the
data given on total knee arthroplasty (TKA) using PSI. The criteria for TKA as well as the development of different surgical techniques and
how PSI would benefit the surgeons and patients to conduct a successful surgery have been discussed. (El Med J 2:4; 2014)
Keywords: Patient Specific Instrumentation, Total Knee Arthroplasty, Minimally Invasive

Introduction
Total knee arthroplasty (TKA) is an effective method in the treatment
of severe osteoarthritis of the knee joint. TKA aims to restore neutral
limb alignment and establish adequate soft tissue balance. Malalignment may lead to pain, stiffness, instability, wear, osteolysis and increased risk of loosening. The aim of the surgery is to make proximal
tibial and distal femoral bone cuts at 90 degrees to their respective
mechanical axis [1].
TKA is considered one of the most successful orthopedic procedures,
and since its introduction in 1960, much effort has been paid for improving the designing of the implants, standardization of surgical
techniques, fixation methods, and infection prevention measures [2,
3]. Survival rate after TKA for old age group (>60 years old) has been
determined to be as high as 85-95% in 10-20 years, as opposed to
young, active and obese patients as well as cases difficult for revision
[4-14].
Computer-assisted orthopedic surgery (CAOS) is an enabling technology that has the ability to improve accuracy and reproducibility
of TKA surgical techniques. CAOS aims to provide the best option for
TKA based on perfect preoperative picture which accurately shows
the position of the center of the joint in order to provide even alignment and perfect level of bone cuts. It also aims at avoiding intramedullary perforation and solving the problem of in-between sizes.
CAOS thus decreases the number of instruments and, in turn, the
cost effectiveness and operative time [15]. Moreover, with computer
assistance, even unexperienced surgeons are able to get better
alignment immediately and constantly [16]. Improved alignment has
led to better survival rates and clinical results. Merloz et al found that
nearly 40-50% of revision knees could be prevented if perfect alignment and perfect ligament balancing is ensured [17].

Criteria for TKA


In TKA, the location and angle of insertion of femoral intramedullary
rod are very important and account for coronal and sagittal orientation of femoral component [18-20]. Minor changes in location of entry point of intramedullary rod increase the chances of malalignment
and put the knee in the category of outlier. The intramedullary rod

can lead to malalignment if its insertion angle and its position in canal are not accurate [21-23]. Opening the medullary canal also predisposes the surgical subject to more bleeding, more chances of infection and embolism and chance of fracture [24-26]. The rotational
orientation of femoral component can be determined by the palpable axes within the knee joint (mainly epicondylar and posterior condylar axes). The transepicondylar axis is less predictable and significantly more externally rotated than the anteroposterior axis [23, 27,
28]. The femoral component sizing is not fully proven [29]. The stylus
of the anterior referencing systems has the limitations that it may
lead to posterior placement of stylus or possible undersizing [27]. A
study by Parratte et al concluded that postoperative mechanical axis
does not affect the 15-year survivorship of implants [30].
Another problem that may risk notching or decrease the space between the posterior coronal cut on the distal femur and the transverse cut on proximal tibia (flexion gap) is the in-between sizes.
Navigated TKA can oversize femur. In the conventional instrumentation system, the femoral sagittal cut angulation is determined by the
position of intramedullary rod being in certain degrees of flexion to
mechanical axis. In navigated TKA, this cut is at 90 degrees to the
mechanical axis (placing the femoral component in extension) in
comparison to conventional technique. The femur gets oversized because of this relative extension and to prevent notching (particularly
in curved femurs). The inner surface of the anterior part of femoral
implant should lie flushed with the anterior cortex, replicating the
patients anatomy [27, 31].
Surgical factors are very important for the long-term durability of implants [32-35]. The tendency to leave the knee in slight flexion or to
put femoral component in internal rotation has been noticed. Minor
errors in bone cuts cannot be visualized in conventional technique
[36]. The fiddle factor, the assembly, disassembly and sterilization of
several tools might affect the accuracy of bone cuts and put the patient under the risk of contamination [37].

Patient specific instrumentation


Patient specific instrumentation (PSI) is a new concept that develops
different aspects of computer assisted technologies to perform vir-

The Orthopedic Unit, October 6 University, Giza, Egypt


SafdarJang Hospital, Ministry of Health & F.W., Govt. of India, New Delhi, India
Correspondence: Hosamuddin Hamza
Email: hosamuddinhamza@gmail.com

1
2

2014 Hafez et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Hafez MA, Jaiman A, Hamza H: Patient specific instrumentation: A minimally invasive technique for knee arthroplasty. El Mednifico Journal 2014, 2(4).

380

Patient specific instrumentation

tual surgery and produce patient specific instruments based on preoperative imaging. It does not have the drawbacks of navigation and
robotics, such as high cost and complexity.
Cost, operative time, alignment and number of outliers are all questionable; they might vary according to each orthopedic teamwork
results. Cost is a perceived barrier to using the custom-fit positioning
technique, and Mont et al have found that surgeons who use this
technique have reduced procedure time [38]. A prospective, randomized trial by Hamilton et al has shown that PSI did not shorten
surgical time or improve alignment, compared with the conventional
technique, but reduced the required number of trays [39].
In addition to the time of the theatre (that has economic implications
too), the navigation systems are costly, need training and have a
learning curve. Experienced surgeons complain of not getting the
feel of the knee [40]. In terms of the cost factor, a few surgeons
have suggested to utilize navigation-system-equipped orthopedic
hospitals as referral hospitals, where complicated cases can be referred [41, 42]. PSI exploits the accuracy of computer and matches
the patients anatomy. It decreases the surgical time and soft tissue
dissection (which makes simultaneous bilateral TKA safer) and is
proven affordable too [43].
In an experimental study by Hafez et al, a number of 45 TKA (29
plastic and 16 cadaveric knees) were performed using PSI without

conventional instrumentations, intramedullary perforation, tracking


nor registration [44]. The study revealed mean errors for alignment
and bone resection within 1.7 and 0.8 mm (maximum, 2.3 and 1.2
mm, respectively) [1].
PSI requires a CT scan or MRI of the patients knee (in addition to the
routine X-rays). Ensini et al treated 25 patients with a CT-based PSI
system and other 25 patients with an MRI/X-ray-based system, and
both PSI systems showed good alignment in the coronal plane in all
stages. However, for a few measurements, a better performance was
observed in the MRI/X-ray-based system than in the CT-based system
[45]. However, MRI has been shown to provide a suboptimal accuracy and inferior quality 3D image of the knee. White et al have found
that the 3D bone models generated from MRI were dimensionally
less accurate and visibly inferior in comparison to CT-based 3D models [46]. The external surfaces of MRI models were rough because of
soft tissue structures which could not be removed by the threshold.
The technique of segmentation (removal of soft tissues) of an MRI
data is difficult, time consuming, subjective and imperfect. In fact,
many research works have focused on improving segmentation of
MRI-based data [47].
The preoperative planning for a technique of PSI for TKA includes
sizing, alignment and bone cutting based on imaging and then designing and producing femoral and tibial templates that act as cutting blocks (Figure 1).

Figure 1: Patient specific instrumentation technique.

Majority of the conventional jigs (navigation system is also based on


these jigs) is based on the Caucasian anatomy. Fitting a different-size
implant to an individual requires either cutting the implant, bone or
soft tissue, which increases the role of surgeon in pain management
and infection control [48]. The main idea of PSI is that knee-joint arthroplasty procedures can be individualized, with benefits including
precise realignment of the normal mechanical axis of the operated
Vol 2, No 4

lower limb, minimized resection of the patients bony tissue, reduced


surgical time, simplified instrumentation, reduced perioperative and
postoperative blood loss, no need of femoral medullary cavity reaming and reduced rate of thromboembolic complications.
The custom-fit TKA is designed to recreate the natural prearthritic
alignment of the patients knee with the goal of increasing function.

Hafez MA, Jaiman A, Hamza H

Individuals who undergo custom-fit placement show better stability


and postoperative mechanical axis alignment and also possess acceptable clinical outcome at three months. The consistent sizing of
the implants, secure fit of the femoral and tibial guides, short operative duration, low transfusion rate and lack of fat emboli support
continued use of the custom-fit technique [49-51].
Walker et al found that while newer technologies can offer further
improvement in total knee systems, implementation will be strongly
affected by the need to satisfy the competing requirements [52].
However, Boonen et al compared patient specific to intramedullaryaligned TKA and found that the fraction of outliers for patient specific TKA was relatively higher, although it has proven better accuracy, lower blood loss rate and shorter operating time [53].
Roh et al assessed the precision and reliability of patient specific TKA
in comparison with the conventional technique. They concluded that
the accuracy was comparable between 2 patients groups (outliers
in hip-knee-ankle angle was 12% in the PSI group and 10% in the
conventional instrument group) whereas sagittal alignment and
femoral component rotation did not differ in terms of outliers. Moreover, they reported that the PSI procedures have been aborted frequently, incurring expenses that did not benefit patients [54].
Another comparison between the conventional and patient specific
TKA procedures shows that PSI technology is superior to conventional instrumentation in achieving a neutral mechanical axis following TKA, but it needs further follow-up to ascertain the long-term
impact of these findings [55]. PSI allows the optimum balance of
technology and conventional surgery by reducing the complexity of
conventional alignment and sizing tools. Thus, the advantages of accuracy and precision claimed by computer navigation techniques are
achieved without the disadvantages of additional intraoperative inventory, new skills, or surgical time [56].
Although this technique could be used for routine primary knee, another study has shown the clinical application for a few absolute indications of PSI (e.g., old malunited distal femur supracondylar osteotomies, ASA grade 3-4 patients where time of surgery is important
and hemophilic arthropathy where intramedullary jigs have to be
avoided and surgery time has to be decreased) [44].
PSI system enables less number of instrumentations and less stress
during surgery. It can benefit the hospital by improving operating
room time efficiencies by shorter setup time and eliminating the
cleaning, sterilization and inventory costs [57]. It will definitely improve ergonomics at work place and might prevent burn-out of the
orthopedic surgeons (as it relieves the clinician from multiple intraoperative decisions), particularly when a recent economic model
has predicted a supply side crisis [58-60].
PSI has an additional benefit on surgical teaching. Trainees can learn
preoperative planning on software and order the manufacturer to
make a virtual bone model. Simulation can play an important role
for the training surgeons [61]. The surgeons can use PSI as pin locators and can check the intraoperative accuracy of these locators before making the bone cuts.

381

Competing interests: The authors declare that no competing interests exist.


Received: 6 September 2014
Accepted: 17 November 2014
Published Online: 17 November 2014

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383

Open Access

Review

Development of nitroimidazopyrans and nitroimidaoxazoles for tuberculosis chemotherapy


Mohammad Asif1

Abstract
The conventional approach to antitubercular drug development requires introduction of novel molecules for the treatment of resistant
mycobacterium strains. The nitroimidazopyrans, nitroimidaoxazoles and other analogs are being studied as antitubercular agents and their
characteristics form the basis of this review. These new tuberculosis treatments shorten the duration of treatment and/or reduce the number
of doses, improve the coverage of MDR-TB/XDR-TB and are more effective in treatment of latent TB infection. (El Med J 2:4; 2014)
Keywords: Antitubercular Agents, Nitroimidazopyrans, Nitroimidaoxazoles

Introduction
The increasing spread of multidrug resistance tuberculosis (MDR-TB)
and the obstinate nature of persistent infections possess challenges
to treatment with currently used anti-TB drugs. This situation is exacerbated by the increasing emergence of multidrug resistance tuberculosis (XDR-TB) [1, 2]. Although TB can be cured, current treatment is complex and long lasting. Direct observed treatment, shortcourse (DOTS) therapy improves fulfillment for the complicated and
long-lasting regimen. MDR and XDR-TB is even more complex and
expensive to treat [3, 4].
Recent increase in awareness for neglected diseases has led to new
research and development of new anti-TB drug molecules. Modern
molecular and genetic tools have resulted in impressive improvements in the understanding of the basic physiology of Mycobacterium tuberculosis (Mtb). An adequate number of promising compounds for effective treatment have been developed [5-7]. Furthermore, some compounds are either derivatives of existing drugs or
target the same cellular processes as currently used drugs [8-11]. The
advanced knowledge about Mtb metabolism and physiology needs
to be translated into validated targets that can be used for screening
of new anti-TB lead compounds [12-14].
Tuberculosis (TB) is a chronic infectious disease caused by mycobacteria, including primarily Mycobacterium tuberculosis, but M. bovis
and M. africanum, M. canetti, and M. microti can also cause tuberculosis, although the latter species do not usually infect healthy adults.
Tuberculosis, an airborne communicable disease, is caused by transmission of aerosolized droplets of M. tuberculosis. Mycobacterium is
a genus of bacteria, which grows slowly under aerobic conditions
and is distinguished by acid-fast staining. They are gram positive,
non-motile, rod-shaped, obligate aerobic bacteria belonging to the
family Mycobacteriaceae. Several species, including M. tuberculosis,
M. bovis, M. africanum, M. microti, M. canetti, M. kansasii, M. avium,
and M. leprae, are intracellular pathogens of higher vertebrates [15,
16].
The cell wall of Mycobacterium species, in its full structural and functional integrity, is essential for their growth and survival in the infected host. Mtb possesses a cell wall dominated by covalently linked
mycolic acids, arabinogalactan and peptidoglycan (AGP), the mycolic
acids of which are complemented by glycolipids such as ,-trehalose monomycolate (TMM). This mycolic acid based permeability

barrier shields the organism from environmental stress and contributes to resistance against many antibiotics [17].
Unique problems associated with mycobacteria include:

intracellular bacteria;
complex outer membrane;
very slow growing;
ability to remain quiescent for decades;
toxicity of effective drugs;
poor patient compliance;
resistance is wide spread

Mtb also has the ability to colonize macrophages in the lung. Mtb
cell (the tubercle bacillus) is engulfed by a macrophage, which encloses the bacteria into the phagosome compartment. Typically, the
phagosome fuses with the lysosome which contains degradative enzymes, low pH, reactive oxygen species, etc., to destroy foreign particles. As the bacterium multiplies, it kills the macrophage, releasing
more bacteria to be taken up by more macrophages [17].

Tuberculosis-HIV combination
Current estimates reveal that one-third of the 42 million people living with HIV/AIDS worldwide are co-infected with tuberculosis (TB).
As per WHO reports, approximately 90% of the patients having both
TB and HIV died within a few months after clinical symptoms. Therefore, WHO has warned the world for even greater TB-HIV crisis and
has called for wide availability of free anti-TB drugs to those living
with HIV. As per WHO, HIV is spreading rapidly in India with the largest number of TB cases in the World [11, 18, 19].

Drug resistant tuberculosis


Drug resistance displayed by Mtb is an important obstacle for the
treatment and control of TB. This resistance has traditionally been
attributed to the unusual multi-layer cell envelope and active multidrug efflux pumps. Recent insights into mechanisms that neutralize
the toxicity of antibiotics in the cytoplasm have revealed other systems that function in synergy with the permeability barrier and efflux
systems to provide natural resistance. Drugs inhibiting these intrinsic
systems would enable many antibiotics, which are already available
but have not been used for TB, to gain new activities against Mtb
[17].

Department of Pharmacy, GRD (PG) IMT, Dehradun, (Uttarakhand), India


Correspondence: Mohammad Asif
Email: aasif321@gmail.com

2014 Asif et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Asif M: Development of nitroimidazopyrans and nitroimidaoxazoles for tuberculosis chemotherapy. El Mednifico Journal 2014, 2(4).

384

Nitroimidazopyrans and nitroimidaoxazoles for TB

Multi-drug resistant tuberculosis


Multi-drug-resistance (MDR) TB refers to simultaneous resistance to
at least two or more of the five first-line anti-TB drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin). Multi-drugresistance arises from sharing of genes between different species or
genera, generally mediated by small pieces of extra-chromosomal
DNA, known as transposons or plasmids. Treatment for MDR-TB is
long lasting, less effective, costly, and poorly tolerated [20, 21].

Extensively-drug resistant tuberculosis


Extensively-drug resistant (XDR) TB, by definition, is the resistance to
at least isoniazid and rifampicin, in addition to any quinolone and at
least one injectable second-line agent (any fluoroquinolone, capreomycin, amikacin, kanamycin). The principles of treatment for MDRTB and XDR-TB are the same. The main difference is that XDR-TB is
associated with a much higher mortality rate than MDR-TB, because
of the reduced number of effective treatment options. Hence, there
is an urgent need for novel drugs that are active against Mtb in order
to shorten the duration of tuberculosis therapy [17].

Need of new anti-tubercular drugs


The five first-line drugs for the treatment of TB are highly effective
and the rate of severe adverse reactions are low and second line
drugs may be less effective than the first-line drugs or may have
more toxic side-effects. However, unpleasant side effects, relatively
long duration of treatment and non-compliance to treatment regimen are drawbacks. Such non-adherence with the course of treatment leads to treatment failure and the development of drug resistance. Second line drugs used for MDR-TB are more expensive, less
effective and more toxic than the five drug standard regimen [11,
18]. The goal now is to develop bactericidal drugs in a cost-effective
manner, which efficaciously treat infectious MDR/XDR strains and latent infections with shortened treatment periods as well as reduced
frequency of dosage.
Some molecules that are being/should be pursued for development
of novel anti-TB agents are highlighted in the subsequent paragraphs [20, 22-25].

Nitroimidazopyran and nitroimidaoxazole analogs


Nitroimidazopyran and nitroimidaoxazole
A series of bicyclic nitroimidazopyrans (NAP) have recently been reported to possess anti-TB activity (Figure 1). One of the compounds,
PA-824 has emerged as a lead molecule as it is effective against both
replicating and latent Mtb cells with a minimum inhibitory concentration (MIC) ranging from 0.015 to 0.25 g/mL. Poly and MDR
strains are susceptible to PA-824, indicating that there is no crossresistance with current drugs [26]. Another orally active analog PA
1343 has been developed and is in preclinical studies with MIC of
0.015 g/mL. The compound OPC-67683, a nitro-dihydroimidazooxazole derivative is found to possess highly potent activity against TB,
including MDR-TB at a concentration (MIC) range of 0.006-0.024
g/mL [17]. In this series, the lead compounds are CGI 17341 and
PA824/PA1343. The target enzyme for the compounds is involved in
cell wall synthesis [28].

Vol 2, No 4

Figure 1: Structures of nitroimidazopyran and nitroimidaoxazole.

Further research must involve trying and identifying more efficacious


molecules. However, two major areas of concern also need to be addressed- possible mutagenicity resulting from the presence of a nitro
group, and the opportunity for the ready development of drug resistance. The latter is prompted by the fact that the nitroimidazoles
induce a high rate of mutation. Furthermore, the obligate activating
(reducing) enzyme, using a flavin co-factor, is not essential for the
survival of mycobacteria, leading to suspicions that this might cause
the ready emergence of MDR bacteria [28]. Since the drugs will inevitably be used in combination therapy, these issues, whilst still
needing consideration, should not be viewed in too pessimistic a
light.
Nitroimidazole PA-824
Nitroimidazole PA-824 and its analogs are new nitroimidazole derivative for the treatment of TB. After activation by a mechanism dependent on Mtb F420 factor, PA-824 acts mainly by inhibiting the
synthesis of cell wall components through molecular targets that are
yet to be identified. In vitro, PA-824 showed high activity against
drug-sensitive and drug-resistant Mtb strains, indicating that there is
no cross-resistance with current TB drugs. Moreover, PA-824 exhibited bactericidal activity against both replicating and static bacteria
in vitro [28]. Bactericidal activity of PA-824 against non-replicating
bacteria was comparable to that of RIF [29]. The PA-824 at doses
ranging from 25 to 100 mg/ml showed reduction in the bacterial
burden in spleen and lungs of mice. Although PA-824 was found to
be significantly more efficient than INH or moxifloxacin in clearing
the infection during the continuation phase, it was not better than
that of RIF and INH combination [30].
In long-term treatment experiments performed to determine its sterilizing capacity, administration of PA-824 as monotherapy in mice led
to a decrease in bacterial counts in the lungs comparable to that
obtained with RIF or INH monotherapy. After 12 weeks of treatment
with PA-824, RIF or INH, a complete eradication of the bacterial load
was not achieved in any of the treated mice [29]. When a 6-month
treatment regimen containing PA-824 in combination with RIF, INH
and PZA was tested in mice, any of the PA-824 containing regimens
resulted superior to the standard first line regimen in terms of more
rapid reductions of the bacterial burden during treatment and lower
rates of relapse after treatment [31]. Further investigations are required to assess the potentiality of PA-824 to improve the treatment
of both drug-susceptible and MDR-TB. PA-824 entered in clinical trials.

Asif M

Compound, PA 824, displayed MIC values ranging from 0.015 to 0.25


mcg/ml against cultured replicating Mtb. This was not the most active member of the series. It showed impressive efficacy when administered orally to both Mtb-infected mice (25 mg/kg) and guinea
pigs (40 mg/kg), and was comparable to INH at 25 mg/kg. It displayed low levels of toxicity with an acute toxic threshold value of
1000 mg/kg single dose, and a chronic threshold value of >500
mg/kg daily for 28 days. A related compound, PA 1343 is claimed to
be even more active than PA 824, although the MIC value quoted,
0.015g/ml, against Mtb in vitro, falls within the range of those for
PA 824. Furthermore, when PA1343 was administered by oral gavage
to mice infected with Mtb, treatment at 25 mg/kg was effective and
comparable to PA 824 and INH. Oral bioavailability of PA 1343 in
mice was 74% with a half-life of 4.2 hours. In contrast, PA 824 has
poor oral bioavailability, 2% which is attributed to its low aqueous
solubility of 0.02 mg/ml. This can be markedly improved using a lipid
coated cyclodextrin formulation, but for TB treatment this is probably not a feasible option due to cost consequences. Despite the
promising data on PA 824 and PA 1343 and generic claims that mutagenicity is not a problem, the presence of the nitro moiety in these
compounds raises concerns about the possibility of genotoxicity and
this issue remains to be addressed [32, 33].
While pursuing PA-824's remaining development activities, it is essential to maximize the potential of this class of compounds by identifying superior compounds and improving on PA-824's properties
as a drug. The enzyme dihydro lipoamide acyltransferase (dlaT) acts
as a potential target for the chemotherapy of Mtb. The Mtb dlaT is a
component of two important multi-subunit complexes: pyruvate dehydrogenase, the enzyme that catalysis the synthesis of Acetyl Coenzyme A, and peroxynitrite reductase, a defense against oxidative
or nitrosative stress [34]. The DlaT has been shown to be required
for full virulence in vivo in mice, while in in vitro experiments, mouse
macrophages can readily kill intracellular Mtb mutants lacking dlaT
[35].

385

In vitro at 0.04 to 0.3 g/ml the compound inhibited both drug-susceptible and MDR strains of Mtb and showed no cross-resistance
with INH, RIF, SM or EBM. Against Mtb in vitro, its activity was comparable to that of INH and RIF and superior to SM, ciprofloxacin, norfloxacin and the oxazolidinone, DuP 721. In Mtb-infected mice, oral
treatment with CGI 17341 on days 11 and 12 post infection resulted
in an ED50 of 7.7 mg/kg and a significant dose-dependent increase
in survival time. Unfortunately despite the initial promise of CGI
17341, its development was terminated most likely as a result of perceived lack of commercial potential and mutagenicity [27]. In a revival of interest into the 5-nitroimidazoles, a series of nitro imidazopyrans has been identified for the treatment of TB. These compounds were not mutagenic and showed potent bactericidal activity
against replicating and static Mtb, including MDR strains.
Nitroimidazole OPC-67683
It belongs to a subclass of mycolic acid inhibitors, thus it interferes
with the biosynthesis of the mycobacteria cell wall. MICs of this compound were determined using standard and clinically isolated Mtb
strains, including MDR strains. In vitro, OPC-67683 showed high activity against drug-sensitive as well DR strains with MICs ranging 624 ng/mL. No cross-resistance with any of the current first-line drugs
was observed. Moreover, OPC-67683 showed strong intracellular activity against H37Rv strain of Mtb residing within human macrophages and type II pneumocytes. Studies in animal models showed
that OPC-67683 is effective against MtbH37v and MDR-TB strains in
vivo starting from a concentration of 0.03125 mg/body. Furthermore,
OPC showed in vivo efficacy against Mtb H37Rv strain even in mice,
starting form a concentration of 0.00781 mg/body. When tested in
mouse models for chronic TB, OPC-67683 showed a 6-7 fold higher
activity compared to first line drugs isoniazid and rifampicin. No antagonist activity could be observed when OPC-67683 was used in
combination with currently used anti-TB drugs in vivo. Pharmacokinetics studies in mice, rats and dogs revealed that this compound is
relatively well absorbed after oral dosing at 3 mg/kg. The bioavailability in each species was 35-60% with a concentration 3-7 times
higher in the lung than in the plasma. The compound was well distributed in most tissues.

The identified compounds are active against specific distinct molecular targets, including inhibitors of DNA gyrase, peptide deformylase
(PDF) inhibitors and analogs of quinolone electron transport inhibitors. Bacterial peptide deformylase belongs to a subfamily of metalloproteases catalyzing the removal of N-terminal formyl group from
newly synthesized proteins. PDF is essential for bacterial growth but
is not required by mammalian cells, so represents a promising target
for the development of a new generation of broad-spectrum antibacterial agents. PDF inhibitors include VIC-104959 (LBM415) and
BB-83698 [36]. PDF inhibitor BB-3497 was recently found to have potent in vitro activity against Mtb [37]. This finding suggests that PDF
inhibitors can find application in TB treatment. Recently, anti-TB
drugs targeting ATP synthesis have been shown to be particularly
effective, even against non-replicating bacteria. The identification of
compounds able to inhibit the electron transport process could lead
to the development of more effective drugs active against both replicating and non-replicating bacilli.

Tryptanthrin (Figure 2) is a potent structurally novel indoloquinazolinone alkaloid, active against MDR strains of Mtb, having MIC value
of 0.51.0 g/mL [38].

Nitroimidazole CGI 17341


The Ciba-Geigy 5-nitroimidazole derivative, CGI 17341, has shown
considerable potential for the treatment of TB in preclinical studies.

Oxazolidinones (Figure 3) are totally synthetic, orally active anti-bacterial agents. Some of the morpholine and thiomorpholine analogs
of oxazolidinones like linezolid and U-100480 have shown potent in

Other recently discovered anti-tubercular agents


Some of recently discovered anti-Tb agents are discussed below.
Tryptanthrin

Figure 2: Structure of tryptanthrin.

Oxazolidinones

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386

Nitroimidazopyrans and nitroimidaoxazoles for TB

vitro activity against Mtb, whereas the other oxazolidinone derivatives displays lethal toxicity in the rat models [26].

Purine Analogs

9-Benzylpurines (Figure 7), with a variety of substituents at 2, 6


and/or 8 positions, have been shown to possess high inhibitory activities against Mtb. Anti-TB activities of 6-arylpurines and 9-sulphonylated or sulphenylated-6-mercaptopurines are also known [40, 41].

Figure 3: Structures of oxazolidinones.

Clofazimine analogs

The tetramethylpiperidine substituted phenazines B4169 and B4128


(TMP phenazines) have been found to possess significantly more activity against Mtb, including MDR clinical strains than clofazimines
(Figure 4). Recently, new conjugates of phenazine with phthalimido
and naphthalimido moieties (Figure 5) have been designed and synthesized as anti-tubercular compounds. Some of the compounds in
this new class of phenazine have shown promising results in the inhibition of Mtb as well as their clinical isolates. The study by Kamal
et al revealed that there is a potential to design such type of phenazine hybrids for the development of new anti-tubercular agents [17].

Figure 4: Structures of clofazimine analogs.

Figure 7: Structure of 2-chloro-4-(2furanyl)-9-benzopurine.

Diarylquinolines

Diarylquinolines are a new class of anti-TB agents, and are more potent than existing agents with a longer duration of action. Single
dose may inhibit bacteria growth for a week. Diarylquinolines are
structurally different from both fluoroquinolones and other quinoline classes. DARQ R207910 (Figure 8) is a member of a new chemical
class of anti-TB agents and has a MIC value equal to or lower than
reference compounds. It has a unique specificity towards mycobacteria including atypical species important in humans such as Mycobacterium avium complex (MAC), M. kansai, and the fast growers M.
fortium and M. abscessus. This anti-TB specific spectrum differs from
that of isoniazid, which has very poor activity against MAC. This class
works by a novel mechanism of action but resistance develops in
monotherapy. It is being added to the combination of isoniazid, rifampin and pyrazinamide. No cross-resistance with other anti-TB
agents occurs. In studies based on sequencing the genomes of susceptible and resistance strains, to find the cellular target, the only
difference found is in the atpE gene which codes for the proton
pump associated with ATP synthase [42, 43].

Figure 5: Structures of phenazine with phthalimido and naphthalimido moieties.

Nitrofuranyl Amides

A series of nitrofuran derivatives (Figure 6) have been tested against


Mtb H37Rv [39]. One compound in this series has shown excellent
minimum inhibitor concentration (MIC) value 0.025 g/mL, which is
comparable to that of the frontline anti-tubercular agents like isoniazid and ethambutol. The nitro group is necessary for biological activity.

Figure 6: Structure of a nitrofuran derivative.

Vol 2, No 4

Figure 8: Structure of diarylquinolines


(R207910).

1,2,4-Benzothiadiazines

Sulfonamides are well known for their antibacterial property. 1,2,4benzothiadiazine dioxides have a close relation to sulfonamides.
Studies in this direction have afforded some molecules based on
1,2,4-benzothiadiazine system that exhibits interesting antitubercular activity [44, 45]. New anti-TB agents from 1,2,4-benzothiadiazine
system were explored by incorporating other heterocyclic rings like
pyridine and pyrazine moieties (Figure 9). Several other molecules
like pyrroles, quinoxaline-1,4-dioxides and alkylsulfinyl amides (Figure 10), have also been prepared and tested for their anti-TB activity
[46, 47].

Asif M

387

the development of new drugs and accelerate their delivery to patients. A major limitation currently is the difficulty of diagnosing patients with TB [52, 53]. This problem is even more acute in the case
of XDR-TB because the disease is so rapidly fatal that most patients
will die before the results of their diagnosis are available. Rapid, reliable and field adapted diagnostic tools for TB and DR-TB are an integral part of treatment strategies and urgently need to be developed. The combination of MDR and XDR-TB and HIV infection leads
patients to develop a highly aggressive form of TB that causes death
in a very short time [17, 54, 55]. The emergence and rapid spread of
MDR and XDR-TB in high HIV prevalence settings represent a major
threat to global health [56-58].
Figure 9: Structure of 1,2,4-benzothiadiazine by incorporating pyridine and pyrazine.

Competing interests: The authors declare that no competing interests exist.


Received: 22 April 2014
Accepted: 19 November 2014
Published Online: 19 November 2014

References

Figure 10: Structure of some new compounds with pyrrole, quinoxaline-1,4-dioxide and
alkyl sulfinyl amide moieties.

Thiolactomycin

Naturally occurring (5R)-thiolactomycin (Figure 11) exhibits potent


in vivo activity against many pathogenic bacteria, including gramnegative and gram-positive bacteria and Mtb. Thiolactomycin is a
thiolactone antibiotic obtained from fermentation broth of Nocardia
species, a strain of actinomycetes. It shows complete inhibition of
growth of the virulent strain M. tuberculosis at 25 g/mL [48]. New
conjugates of phenazine with phthalimido and naphthalimido moieties have been designed as antitubercular compounds. Some of the
compounds in this new class of phenazine hybrids have shown
promising results in the inhibition of Mtb as well as their clinical isolates (sensitive and resistant). There is a potential to design such type
of phenazine hybrids for the development of new antitubercular
agents [49]. It was reported that 2 and/ or 4-substituted thioquinazoline derivatives were identified as a possible pharmacophore for antitubercular activity [50].

Figure 11: Structure of thiolactomycin.

Discussion and Conclusion


It is crucial that adequate research be performed into new compounds that act through novel mechanisms which are able to target
new molecular targets, in order to avoid cross-resistance with drugs
currently in use. Recently, some compounds have been shown to be
active against MDR and XDR-TB strains in human patients [18, 20,
51]. There is an urgent need for new TB drugs, in order to speed up

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Open Access

Review

Sleep and its disorders


Ahmed M Kabel1,2, Ibrahim A Maghrabi1

Abstract
Sleep is a natural state characterized by reduced or absent consciousness, relatively suspended sensory activity and inactivity of voluntary
muscles. Sleep is divided into rapid eye movement and non-rapid eye movement sleep. Human sleep needs vary by age and among
individuals and sleep is considered to be adequate when there is no daytime sleepiness or dysfunction. Disruption of sleep can be caused by
a variety of causes. Sleep disorders may be serious enough to interfere with normal physical, mental and emotional functioning. Management
of sleep disorders includes behavioral and psychotherapeutic treatment, rehabilitation and management, medications and other somatic
treatment. (El Med J 2:4; 2014)
Keywords: Sleep Disorders, Rapid Eye Movement

Introduction
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity and inactivity of nearly all voluntary muscles. It is distinguished from wakefulness by a decreased ability to react to stimuli and is more easily
reversible than being in coma. Sleep is a heightened anabolic state
accentuating the growth and rejuvenation of the immune, nervous,
skeletal and muscular systems [1].
The purposes and mechanisms of sleep are only partially clear and
the subject of many studies. Sleep is sometimes thought to help to
conserve energy, though this theory is not fully adequate as sleep
only decreases metabolism by about 510% [2].

Physiology of sleep
Sleep is divided into two broad types: rapid eye movement (REM)
and non-rapid eye movement (NREM or non-REM) sleep. NREM is
further subdivided into three stages as follows [3]:

NREM stage 1: This is a stage between sleep and wakefulness.


The muscles are active and the eyes roll slowly, opening and
closing moderately;
NREM stage 2: In this stage, it gradually becomes harder to
awaken the sleeper;
NREM stage 3: The sleeper is less responsive to the environment.
Many environmental stimuli no longer produce any reactions.

REM sleep
The sleeper enters REM where most muscles are paralyzed. REM
sleep is turned on by acetylcholine secretion and is inhibited by neurons that secrete serotonin. This level is also referred to as paradoxical sleep because the sleeper, although exhibiting EEG waves similar
to awaking state, is harder to arouse than at any other sleep stage.
Vital signs indicate arousal and oxygen consumption by the brain is
higher than when the sleeper is awake [2, 4].

Functions of REM sleep

Most dreams occur during REM sleep. Deprivation of REM may lead
to psychological disturbances and dramatic shift in subsequent sleep
patterns when the subject is allowed to sleep without interruption.
The longer the deprivation, the larger and longer the REM rebound,
suggesting that REM sleep is physiologically necessary. However, the
purpose of REM sleep or dreaming remains largely unexplained [4].
There is activation of sensory systems during REM sleep. The visual
system is intensely activated and all dreams have visual experiences.
Neuroimaging studies have indicated activation of the limbic system,
suggesting a biologic basis of activation of memories and emotions
in REM sleep. Studies in animals indicated that those neurons that
had been active during the day fired at a significantly higher rate in
REM sleep than inactive neurons, suggesting that a general function
of REM sleep is processing of the information acquired during the
day [6].
Neural mechanisms involved in the sleep-wake cycle
The bodys sleep-wake cycle is usually under the control of circadian
rhythm which is regulated by the suprachiasmatic nucleus of the hypothalamus. Incoming light transduced by retinal ganglion cells is
believed to be the primary factor synchronizing circadian rhythm.
Serotonin acts as a modulatory neurotransmitter which inhibits the
effects of light on the system and is associated with different aspects
of the sleep-wake cycle. There is minimal serotonergic input during
REM sleep and maximal input directly following REM. Thus, these
neurons may normally inhibit phasic REM events and their silence
during REM sleep indicates a termination of this inhibition [7]. On
the other hand, many sleep-promoting factors have been identified,
including muramyl peptides, lipopolysaccharides, prostaglandins, interleukin-1, interferon-alpha 2, tumor necrosis factor, sleep-inducing
peptide and vasoactive intestinal peptide. Besides enhancing sleep,
they exert effects on the body temperature and on the immune response [8].

Sleep proceeds in cycles of REM and NREM, usually four or five of


them per night. There is a greater amount of deep sleep earlier in
the night, while the proportion of REM sleep increases in the two
cycles just before natural awakening [5].

In the past few years, it has been established that the cholinergic
activating system is important in waking and REM sleep. REM-on
neurons (selective activity during REM sleep) in the brainstem use
acetylcholine as a neurotransmitter. Most of the physiologic events
of REM sleep have effector neurons located in the brainstem reticular

Department of Clinical Pharmacy, College of Pharmacy, Taif University, Saudi


Arabia
2Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt

Correspondence: Ahmed M Kabel


Email: drakabel@gmail.com

2014 Kabel et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Kabel AM, Maghrabi IA: Sleep and its disorders. El Mednifico Journal 2014, 2(4).

390

formation. These neurons are important for the rapid eye movements and the muscle atonia of REM sleep [9].
Many peptides such as substance P are co-localized with acetylcholine in brainstem neurons. They may modify responsiveness to acetylcholine and may have independent actions. In addition, histamine-containing neurons are located in the posterior hypothalamus
and are REM-off. The histamine system has been considered as one
of the wakefulness promoting systems, in agreement with drowsiness as a common side effect of antihistames [10].
Orexin is a hypocretin that has been associated with feeding behaviors and also has been found to have a role is the sleep behavior.
Many areas of the brain associated with the sleep-wake cycle, specifically the lateral and dorsal hypothalamus, have orexin neurons and
receptors. Orexin has been found to activate norepinephrine neurons in the locus ceruleus which are believed to play a role in promoting wakefulness [11].
Sleep timing
Sleep timing is controlled by the circadian clock, sleep-wake homeostasis and, within certain limits, willed behavior. The circadian clock
works with adenosine, a neurotransmitter that inhibits many processes associated with wakefulness. Adenosine is created over the
course of the day and high levels of adenosine lead to sleepiness.
The timing is affected by one's chronotype. It is the circadian rhythm
that determines the ideal timing of a correctly structured and restorative sleep episode [12].
Homeostatic sleep propensity (the need for sleep as a function of
the amount of time elapsed since the last adequate sleep episode)
must be balanced against the circadian element for satisfactory
sleep. Along with corresponding messages from the circadian clock,
this tells the body it needs to sleep. Sleep duration is affected by the
gene DEC2. Some people who have a mutation of this gene sleep
two hours less than normal [13].
Optimal amount of sleep
Human sleep needs vary by age and among individuals, and sleep is
considered to be adequate when there is no daytime sleepiness or
dysfunction. One of the most significant determinants of a persons
normal sleep pattern is age. REM sleep occupies about 20-25% of the
sleep time in normal young adults. The daily total sleep requirement
declines steadily throughout childhood and adolescence and then
often declines further with old age [14].

Sleep disorders
A sleep disorder is a medical disorder of the sleep patterns of a person. Some sleep disorders are serious enough to interfere with normal physical, mental and emotional functioning. Disruptions in sleep
can be caused by a variety of causes. When a person suffers from
difficulty falling asleep and staying asleep with no obvious cause, it
is referred to as insomnia [15]. Dyssomnia refers to a group of sleep
disorders with the symptoms of trouble falling asleep or maintaining
sleep, which may cause an elevated sense of sleepiness during the
day.
Insomnia is characterized by many symptoms including trouble with
Vol 2, No 4

Sleep and its disorders

retaining sleep, fatigue, decreased attention and dysphoria. Individuals with insomnia often worry about the negative health consequences, which can lead to development of anxiety and depression
[16]. In addition, sleep disorders may also cause the patient to sleep
excessively, a condition known as hypersomnia. Management of
sleep disturbances that are secondary to mental, medical, or substance abuse disorders should focus on treatment of the underlying
conditions [17].
Insomnia
Insomnia refers to difficulty in sleeping. Many different physiological
and psychological factors can interfere with sleep. Evaluation of the
patient with insomnia should be directed to identify the contributing
factors and treat those for which therapy is available. Patients with
primary insomnia have been shown to have less diurnal sleepiness,
higher heart rate, higher body temperature and greater metabolic
activity than age and gender matched controls. The most severe
cases of primary insomnia have an insidious onset during childhood
and follow a chronic course.
Insomnia can be classified as transient, acute or chronic [16, 18]:

Transient insomnia lasts for less than a week. It can be caused by


another disorder, by changes in the sleep environment, by the
timing of sleep, severe depression or by stress. Its consequences
sleepiness and impaired psychomotor performance are similar to those of sleep deprivation [5].
Acute insomnia is the inability to consistently sleep well for a
period of less than a month. This occurs despite adequate opportunity and circumstances for sleep and often results in problems with daytime function. Acute insomnia is also known as
short term insomnia or stress related insomnia [19].
Chronic insomnia lasts for longer than a month. It can be caused
by another disorder or it can be a primary disorder. People with
high levels of stress hormones or shifts in the levels of cytokines
are more likely to have chronic insomnia. Its effects vary according to its causes including muscular fatigue, hallucinations
and/or mental fatigue. Chronic insomnia can cause double vision
[18].

Hypersomnia
Hypersomnia is trouble staying awake and excessive daytime sleepiness. Patients usually complain of fatigue, headache, decreased energy and difficulty in concentration [20]. The most common causes
of hypersomnia are insufficient sleep, medications, sleep apnea and
narcolepsy:
Insufficient sleep: Many people do not schedule sufficient time for
sleep at night and sleepiness is to be expected due to sleep deprivation. This is managed by education the patient about healthy sleep
habits [21].
Sleep apnea: It is a condition in which patients periodically stop
breathing while asleep. There are two types of sleep apnea- central
and obstructive. The most common cause of sleep apnea is due to
temporary obstruction of the upper airway. The extreme changes in
the concentrations of oxygen and carbon dioxide in the blood that
develop after 1 minute or more without air rouse the sleeper, and a

Kabel AM, Maghrabi IA

few noisy choking gasps refill the lungs [22]. Obstructive sleep apnea
is the most common medical cause of excessive daytime sleepiness.
Usually, the patients are not aware of the episodes because they are
brief and arousal is only partial. So, the history must be obtained
indirectly from a spouse or roommate.
Manifestations include loud snoring, pauses in breathing, gasping for
breath during sleep, dull headache and automatic behaviors. Polysomnography is used to confirm the diagnosis and to quantify the
severity [23]. The most effective treatment of obstructive sleep apnea is nasal continuous positive airway pressure which raises the
pressure in the oropharynx and thus in the upper airway, reversing
the pressure gradient across the wall of the airway and keeping it
open [24].
Narcolepsy: Narcolepsy is a syndrome consisting of excessive daytime sleepiness and disordered regulation of REM sleep resulting in
intrusion of components of REM sleep into NREM sleep and the waking state. It has 2 types which include narcolepsy-cataplexy subtype
and narcolepsy without cataplexy [25, 26].
Idiopathic hypersomnia
They are poorly defined conditions characterized by excessive daytime sleepiness and not diagnosed as narcolepsy (No REM abnormalities during polysomnography) [27].
Parasomnias
It means abnormal behavior during sleep. The most undesirable
movements or behaviors that occur during sleep are associated with
NREM sleep, probably because the atonia of REM sleep prevents
most movements of any kind [28].
NREM sleep parasomnias

These are relatively common in children but they rarely lead to medical attention unless they are frequent and intense. In most cases,
they resolve by late adolescence. They may represent a disorder of
arousal from slow wave sleep resulting in episodes of only partial
awakening [29]. They include night terrors, sleepwalking and restless
leg syndrome:
Night terrors: These are sudden, partial arousal from sleep associated
with screaming and motor activity. These episodes occur during the
first third of the major sleep episode and begin with a terrifying
scream followed by intense anxiety and signs of autonomic hyperactivity. Persons with night terrors may not fully awaken after an episode and usually have no detailed recall of the event the following
morning. There is believed to be a genetic component to this phenomenon [30].
Sleepwalking (Somnambulism): It is considered as a disorder of impaired arousal. Sleepwalking is defined as repeated episodes of arising from sleep and walking about. It usually occurs during the first
third of the sleep episode. Upon awakening, the person has amnesia
for the episode. Episodes typically last less than 10 minutes [31].
Restless legs syndrome (RLS): It is a sensorimotor disorder that may
severely affect sleep. It is characterized by a strong urge to move the
legs accompanied by a strange feeling in the leg. The attacks are
precipitated by rest with inactivity and they become worse in the

391

evening or night than in the morning. The periodic leg movements


may occur during sleep and/or while lying or sitting up awake. RLS
involves a disorder of the transition states between wake and sleep.
Although RLS produces chronic loss of sleep, there is no profound
frank sleepiness in the daytime. RLS patients report fatigue and trouble concentrating during the day but do not fall asleep and appear
to be overstimulated in the daytime [32].
Early-onset RLS (starting before age 45) appears to result mostly
from iron metabolism abnormality producing brain iron insufficiency. The impaired iron status produces a hyperdopaminergic state
with an exaggerated circadian pattern of dopamine release. The iron
deficiency probably also disrupts other neurotransmitter systems,
such as hypocretin (orexin) and histamine [33]. Late-onset RLS (starting after age 45) has more diverse causes, but patients appear to
have dopamine abnormalities similar to those in early-onset RLS
cases.
RLS etiology appears to have both a genetic and a strong environmental component, with the genetic component more important for
early- than for late-onset RLS. Dopaminergic agonists and levodopa
provide effective treatment for RLS because the pathophysiology
may involve brain dopamine abnormalities. Also there is evidence
for involvement of hypocretin-1 (orexin-A) and histamine [32, 34].
REM sleep parasomnias

REM sleep behavior disorder (RBD): In this condition, the atonia that
normally accompanies REM sleep breaks down and patients act out
parts of dreams. This is a motor and behavioral disorder typically affecting middle-aged or older males. The vigorous and violent behaviors of RBD commonly result in injury. It includes intermittent loss of
the usual skeletal muscle atonia of REM sleep, with increased muscle
tone and/or excessive muscle twitching.
RBD can be an acute or chronic disorder. Acute RBD, found in drug
withdrawal or intoxication states, is generally a reversible condition.
Chronic RBD requires pharmacotherapy and is commonly associated
with many other conditions, especially synucleinopathies (Parkinson
disease, dementia with Lewy bodies and multiple system atrophy)
[29].
A close association of RBD with narcolepsy-cataplexy has been described, and there are patients with overlapping parasomnias,
demonstrating motor-behavioral dyscontrol extending across NREM
and REM sleep. The probable cause of RBD is pontine tegmental lesions, involving serotonergic and cholinergic neurotransmission. It is
thought that RBD results from lesions related to any underlying neurological disorder [35].
Nightmare disorder (dream anxiety): This condition consists of repeated awakenings with detailed recall of extended and very frightening dreams. The awakenings are more frequent in the second half
of the sleep period. On awakening, the person rapidly becomes alert
and oriented [36].

Diagnosis of sleep disorders


The following tests are used to diagnose insomnia [23]:
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392

Sleep diary: Tracking sleep patterns may help a doctor reach a


diagnosis;
Epworth Sleepiness Scale: a validated questionnaire that is used
to assess daytime sleepiness;
Polysomnogram: a test measuring brain and muscle activity including breathing during sleep.
Multiple sleep latency test: a test for daytime sleepiness, usually
administered the day after overnight polysomnography.
Actigraphy: a test used to assess sleep-wake patterns, usually for
a week or more. Actigraphs are wrist-worn devices, about the
size of a wristwatch, that measure movement.
Mental health examination: Because insomnia may be a symptom of depression, anxiety or another mental health disorder,
examination of the mental status, mental health history and
basic mental evaluations may be important parts of the assessment for a person complaining of insomnia.

Treatment of sleep disorders


Treatments for sleep disorders generally can be grouped into four
categories including behavioral and psychotherapeutic treatment,
rehabilitation and management, medication and other somatic treatment [17].
None of these general approaches is sufficient alone for all patients
with sleep disorders. The choice of a specific treatment depends on
the patient's diagnosis, medical and psychiatric history as well as the
experience of the treating clinician. Often, behavioral/psychotherapeutic and pharmacological approaches can effectively be combined
to maximize therapeutic benefits. Management of sleep disturbances that are secondary to mental, medical, or substance abuse disorders should focus on treatment of the underlying conditions [23].
Medications and somatic treatments may provide the most rapid
symptomatic relief from some sleep disturbances. Certain disorders
like narcolepsy, are best treated with drugs such as Modafinil. Others,
such as chronic and primary insomnia, may be more responsive to
behavioral interventions. Special equipment may be required for
treatment of several disorders such as obstructive apnea, the circadian rhythm disorders and bruxism. In these cases, when severe, an
acceptance of living with the disorder, however well managed, is often necessary [23, 25].
A number of studies suggests that hypnosis may be helpful in alleviating some types and manifestations of sleep disorders in some patients. Acute and chronic insomnia often respond to relaxation and
hypnotherapy, along with sleep hygiene instructions. Hypnotherapy
also helps with nightmares and sleep terrors. There are several reports of successful use of hypnotherapy for parasomnias specifically
for head and body rocking, bedwetting and sleepwalking. Hypnotherapy can be carried out with benzodiazepines such as temazepam
which is a commonly prescribed drug for insomnia and other sleep
disorders [37, 38].
Competing interests: The authors declare that no competing interests exist.
Received: 26 May 2014
Accepted: 24 November 2014
Published Online: 24 November 2014

Vol 2, No 4

Sleep and its disorders

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Kabel AM, Maghrabi IA

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http://www.mednifico.com/index.php/elmedj/article/view/232

Open Access

Case Report

Ultrasound and MRI findings of syntelencephaly and correlation with perinatal pathology
Nurtac Akgul1, Cem Y Sanhal2, Serap Toru3, Inanc Mendilcioglu2, Kamil Karaali1

Abstract
Background: Holoprosencephaly (HPE) is a complex brain malformation characterized by impaired midline cleavage of the embryonic
forebrain. Syntelencephaly (SE) is an uncommon and distinct subset of holoprosencephaly. In cases with syntelencephaly, hemispheric
fusion does not occur at rostral forebrain but rather across posterior frontal region. Here we report ultrasound and magnetic resonance
findings of a fetal case with syntelencephaly, which is an extremely rare prenatal diagnosis, and its correlation with fetal autopsy.
Case Presentation: A 20-year-old woman gravida 2, para 1 at 26th week of gestation was referred to our perinatology unit for second
opinion ultrasound (US). The couple was third degree consanguine and their first child suffered from hearing loss with no detectable
etiology. On axial and sagittal planes of grayscale US, bilateral ventriculomegaly, absence of cavum septum pellucidum and
interventricular septum with the presence of interhemispheric fissure and suspected agenesis of corpus callosum were detected.
Additionally, coronal examination revealed suspected cerebral hemispheric fusion and absence of interhemispheric fissure near the fetal
vertex. Fetal cranial magnetic resonance imaging (MRI) revealed dilatation at all anatomic regions of lateral ventricles and no
interventricular septum. Interhemispheric fissure was present at anterior frontal and occipital regions. However, the middle part of the
interhemispheric fissure was absent and the fusion of both hemispheres was evident between posterior frontal and parietal regions.
Additionally, the midbody of corpus callosum was absent. These findings were considered as the characteristics of SE. Amniocentesis
revealed normal karyotype and the couple chose pregnancy termination after our disclosure about the possible poor postnatal prognosis
of the entity.
Conclusion: The diagnosis of fetal HPE and its subtypes is important to determine prognosis and proper parental counselling. As in our
case, multidisciplinary approach should be performed for the accuracy of the diagnose and fetal brain MRI may play an important role in
more subtle cases. (El Med J 2:4; 2014)
Keywords: Syntelencephaly, Prenatal, Diagnosis, Ultrasound, MRI, Autopsy

Introduction
Holoprosencephaly (HPE) is a developmental field defect of impaired
midline cleavage of the embryonic forebrain [1]. Alobar, semilobar
and lobar HPE are the major subtypes of this anomaly. Syntelencephaly (SE), is an uncommon and distinct subset of HPE. In cases with
SE, hemispheric fusion does not occur at rostral forebrain but rather
across posterior frontal region [2]. Because of this feature, some authors name SE as middle interhemispheric variant [3]. Here we report
a fetal case with SE which is an extremely rare prenatal diagnosis.

present at anterior frontal and occipital regions (Figures 1a, 1b).


However, the middle part of the interhemispheric fissure was absent
and the fusion of both hemispheres was evident between posterior
frontal and parietal regions. Additionally, the midbody of corpus callosum was absent. These findings were considered as the characteristics of SE. Amniocentesis revealed normal karyotype and the couple
chose pregnancy termination after our disclosure about the possible
poor postnatal prognosis of the entity.

Case Report

A 20-year-old woman gravida 2, para 1 at 26th week of gestation, was


referred to our perinatology unit for second opinion ultrasound (US).
The couple was third degree consanguine and their first child suffered from hearing loss with no detectable etiology. The couples
personal and family history were otherwise unremarkable. In the current pregnancy, she did not report any drug use, had no history of
fever and radiation exposure.
On axial and sagittal planes of gray scale US, bilateral ventriculomegaly, absence of cavum septum pellucidum (CSP) and interventricular
septum with the presence of interhemispheric fissure and suspected
agenesis of corpus callosum (ACC) were detected. Additionally, coronal examination revealed suspected cerebral hemispheric fusion
and absence of interhemispheric fissure near the fetal vertex (Figure
1).
Fetal cranial magnetic resonance imaging (MRI) (1.5 Tesla) revealed
dilatation at all anatomic regions of lateral ventricles (15 mm at
atrium) and no interventricular septum. Interhemispheric fissure was
Department of Radiology, Akdeniz University, School of Medicine, Turkey.
Department of Perinatology, Akdeniz University, School of Medicine, Turkey.
3Department of Pathology, Akdeniz University, School of Medicine, Turkey.
1
2

Figures 1 (a), 1(b): Coronal T2A sequence of MRI revealing the presence of
interhemispheric fissure at the anterior frontal 1(a) and occipital regions 1(b).
Note the bilateral dilatation of posterior horns of lateral ventricles 1(b)

Unfortunately, long interval between initiation of medication (misoprostol) and birth caused maceration and inadequate autopsy of the
fetal brain. Nevertheless, HPE, agenesis of corpus callosum, dysgenetic optic chiasm and separate optic nerves were detected (Figure 2).
Correspondence: Serap Toru
Email: serap_toru@yahoo.com

2014 Akgul et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Akgul N, Sanhal CY, Toru S, Mendilcioglu I, Karaali K: Ultrasound and MRI findings of syntelencephaly and correlation with perinatal pathology. El Mednifico Journal 2014, 2(4).

Akgul N, Sanhal CY, Toru S et al.

395

In the differential diagnosis of SE, semilobar and lobar HPE are


ranked. Noncleaved anterior brain with the presence of posterior falx
and interhemispheric fissure are the components of semilobar form
[8]. However, in lobar type the cortical nonseperation is less diffuse
with a variable degree at the basal frontal layers and cingulate gyrus
[9]. An apparent mass within the third ventricle that is formed by
the fusion of fornices is another important finding in lobar HPE [10].

Figure 2: Cranial autopsy denoting separate and parallel optic nerves (black
arrows)

Discussion
Bilateral dilatation of lateral ventricles detected during the routine
prenatal care was the initial referral cause of this case to our perinatology unit. The CSP, i.e. a fluid filled cavity between the leaves of
the septum pellucidum, was an important landmark in fetal neurosonogram and the second major finding in our case was the absence
of CSP. It is known that CSP non-visualization is not only associated
with malformations of prosencephalic development which include
agenesis/dysgenesis of corpus callosum, septo-optic dysplasia (SOD)
and isolated absence of CSP, but also spectrum of HPE. Moreover
schizencephaly, severe chronic hydrocephalus and acquired fetal
brain injury are other associated abnormalities of the disability in CSP
imaging [4].
Beneath the direct ultrasound diagnosis of ACC on the midsagittal
view of the fetal head, indirect signs like colpocephaly, spear-shaped
ventricles, non-visualization of CSP and/or atrial width >9.9 mm were
mentioned to be the clues for diagnosis in fetus [5]. Prenatal diagnosis of SOD is difficult and the described imaging features of SOD
are; hypoplasia or agenesis of the septum pellucidum, boxlike and
downpointing frontal horns of ventricles and optic tract hypoplasia
[6]. Isolated absence of CSP with normally developed adjacent structures is another alteration.
The term HPE spectrum depicts cerebral and facial malformations
that is the result of absent or incomplete division of the forebrain
(prosencephalon) due to a primary defect in induction and patterning, during the third week of gestation [7]. It is relatively straightforward to diagnose alobar HPE because of the severe findings like single ventricle, absent midline structures (CSP, falx cerebri, third ventricle, corpus callosum) and fused thalami. On the other hand, with
the US findings of our case (bilateral ventriculomegaly, absence of
CSP and interventricular septum, suspected ACC and hemispheric fusion), our initial diagnosis was the less severe types of HPE spectrum.
Our radiology departments MRI report revealed additional and more
clear findings on US like presence of interhemispheric fissure at anterior frontal and occipital regions, absence of interhemispheric fissure and falx at posterior frontal and parietal regions, fusion of both
cerebral hemispheres between posterior frontal and parietal regions
and absence of the body of corpus callosum. We considered these
features as the characteristics of SE.

In summary, as reported by Malinger et al., the presence or absence


of fused anterior horns is the most useful US parameter in the differential diagnosis of fetuses with absent CSP. Fused anterior horns
points HPE, whereas separated anterior horns indicates one of the
possible diagnosis of isolated agenesis of CSP, SOD, SE or a disruptive
process in hydrocephalus [11]. In our case, karyotype analysis and
general morphologic examination disclosed no aberrations. Although a cluster of syndromes and genetic alterations have been reported to be associated with HPE, data regarding cases with SE is
limited to a mutation in ZIC2 gene that is related to neural tube closure and differentiation of the embryonic roof plat [12].

Conclusion
The diagnosis of fetal HPE and its subtypes is important to determine
prognosis and proper parental counselling. As in our case, multidisciplinary approach should be performed for the accuracy of the diagnosis and fetal brain MRI may play an important role in more subtle cases.
Competing interests: The authors declare that no competing interests exist.
Received: 27 May 2014
Accepted: 31 August 2014
Published Online: 31 August 2014

References
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http://www.mednifico.com/index.php/elmedj/article/view/213

Open Access

Case Report

Right-sided diaphragmatic eventration with gastric volvulus and abnormal rotation of liver
Rakesh Mehra1, Uma Debi2, Anupam Lal1, Saroj Kant Sinha2, Nadeem Parvez2, Kaushal Kishor Prasad2

Abstract
Background: Diaphragmatic eventration is permanent elevation of an immobile hemidiaphragm. It is commonly described on the left
side and very rarely on the right side. It usually is associated with acute gastric volvulus with strangulation. Sometimes it is complicated
with malrotation of abdominal contents. Mesenteroaxial volvulus is usually primary, without an underlying diaphragmatic defect.
Case Presentation: A 50-year-old male presented with occasional shortness of breath and intermittent abdominal pain for past four
months. Chest examination revealed decreased movements on right side. Chest X-ray showed elevated right hemidiaphragm and minimal
left sided mediastinal shift. Fluoroscopy revealed decreased movement of the right hemidiaphragm. Contrast enhanced CT scan of the
chest and abdomen revealed that right hemidiaphragm was raised and reaching up to the level of horizontal fissure. Mild basal atelectasis
was present in underlying lung parenchyma. There was herniation of liver with mild rotation, right kidney, hepatic flexure of colon, few
jejunal loops, abdominal fat and few mesenteric vessels into the right thoracic cavity. Upper gastrointestinal contrast study revealed
displacement of antrum above the gastroesophageal junction. A diagnosis of eventration of right diaphragm with abnormal rotation of
liver and mesenteroaxial gastric volvulus was made.
Conclusion: The prompt diagnosis of right diaphragmatic eventration with mesenteroaxial gastric volvulus and abnormal rotation of liver
is critical to avoid catastrophic complications of ischemia, perforation and strangulation as early management in such cases without gastric
necrosis is associated with less postoperative morbidity and mortality. (El Med J 2:4; 2014)
Keywords: Diaphragmatic Eventration, Mesenteroaxial Volvulus

Introduction
Eventration of diaphragm is abnormal elevation of part or whole of
hemidiaphragm and most often is characterized by a developmental
anomaly of the diaphragm musculature [1]. The abnormally wide
subdiaphragmatic space provides the potential for abnormal rotation of abdominal viscera allowing them to herniate in the chest. It
is more commonly described in the left side with a marked mediastinal displacement towards right, and is very rare on right side [2].
To the best of our knowledge this is the first case report describing
right sided diaphragmatic eventration with abnormal rotation of
liver and mesenteroaxial gastric volvulus.

Case Report

Figure 1: Axial CECT image demonstrating elevated right hemidiaphragm


with herniation of right kidney, hepatic flexure and jejunal loops.

A 50-year-old male presented with occasional shortness of breath


and intermittent abdominal pain for past four months. There was no
history of trauma. General physical examination was normal. Chest
examination revealed decreased movements on right side. Laboratory investigations were within normal limits. Chest X-ray showed
elevated right hemidiaphragm and minimal left sided mediastinal
shift. Fluoroscopy was performed which revealed decreased movement of the right hemidiaphragm as compared to left hemidiaphragm; however, there was absence of paradoxical movements of
the right diaphragm. Ultrasonography also confirmed the fluoroscopic findings (Figures 1 and 2).
Contrast enhanced CT scan of the chest and abdomen revealed that
right hemidiaphragm was raised and reaching up to the level of horizontal fissure. Mild basal atelectasis was present in underlying lung
parenchyma. Rest of the right lung was normal. The heart was displaced to the left side. No obvious defect was seen in continuity of
the diaphragm; however, it appeared thinned out.

Department of Radiodiagnosis, Postgraduate Institute of Medical Education and


Research, Chandigarh, India.
2Department of Superspeciality of Gastroenterology, Postgraduate Institute of
Medical Education and Research, Chandigarh, India.
1

Figure 2: Coronal MPR: Thinned out diaphragm with abnormal rotation and
herniation of liver.

Correspondence: Uma Debi


Email: debi_uma@yahoo.co.in

2014 Mehra et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Mehra R, Debi U, Lal A, Sinha SK, Parvez N, Prasad KK: Right-sided diaphragmatic eventration with gastric volvulus and abnormal rotation of liver. El Mednifico Journal 2014, 2(4).

Mehra R, Debi U, Lal A et al.

There was herniation of liver with mild rotation, right kidney, hepatic
flexure of colon, few jejunal loops, abdominal fat and few mesenteric
vessels into the right thoracic cavity. The stomach was seen beneath
the right dome with suggestion of mesenteroaxial volvulus. The
great vessels of mediastinum and major abdominal vessels were normal in contrast opacification. There was no evidence of significant
mediastinal, mesenteric and retroperitoneal lymphadenopathy. Upper gastrointestinal contrast study was subsequently performed to
characterize the type of volvulus. It revealed displacement of antrum
above the gastroesophageal junction. However, there was no hold
up of contrast and the contrast flowed freely from the stomach into
the duodenum (Figure 3).

Figure 3: Barium spot radiograph showing antrum characteristically lying


above gastroesophageal junction suggestive of mesenteroaxial volvulus.

With these radiological findings, a diagnosis of eventration of right


diaphragm with abnormal rotation of liver and mesenteroaxial gastric volvulus was made.

Discussion
Diaphragmatic eventration refers to permanent elevation of an immobile hemidiaphragm in which peripheral muscular attachment is
normal with no interruption in peritoneal or pleural layers. True
eventration of diaphragm is always a congenital condition due to a
defect of development of one portion or the entire central part of
the diaphragm and is characterized by muscular aplasia and subsequent abnormal elevation of an intact hemidiaphragm. Pathologically, a total eventration of hemidiaphragm consists of a thin membranous sheath attached peripherally to normal muscle at points of
origin from the rib cage, sternum, ribs and dorsolumbar spine [3].
Diaphragmatic eventrations are rare with incidence <0.05%, more
common among males and are more likely to affect the left hemidiaphragm [4]. On the other hand in acquired eventration there is a
loss of contractility of the muscle that leads to progressive muscular
atrophy and distension of the dome. It can be secondary to trauma,
infection such as polio, herpes zoster, diphtheria or influenza, neoplastic disorders or autoimmune pathologies directly involving the
diaphragm or the phrenic nerve [3]. It usually occurs in adults; however, it tends to remain undetected as it is mostly asymptomatic.

397

The patient may present with chest complaints, e.g. respiratory distress and dyspnea on exertion or abdominal complaints, e.g. epigastric pain, belching and dysphagia. The abnormally wide subdiaphragmatic space resulting from diaphragmatic eventration creates
the potential space for additional malformations like malrotation of
the intestines, transposition of abdominal organs, megacolon, hypospadias, pulmonary hypoplasia, defects of the ribs, cardiac anomalies, renal ectopia, cerebral agenesis, hydrocephalus and exomphalos. It may be further complicated by acute gastric volvulus, chronic
gastric volvulus or chronic recurrent volvulus of the splenic flexure
of the colon [5].
Gastric volvulus is an abnormal rotation of all or part of stomach that
may lead to closed loop obstruction and possible strangulation. The
stomach is held in its normal position by its natural four ligaments.
The gastrophrenic ligament and the retroperitoneal attachment of
the second part of the duodenum provide the superior and inferior
fixation. The gastrohepatic ligament tethers the lesser curve, the gastrocolic ligament connects the stomach to the transverse colon, and
the gastrosplenic ligament tethers the greater curve. The absence or
stretching of these ligaments can cause a volvulus [6].
Gastric volvulus is usually divided into two main subtypes: organoaxial and mesenteroaxial. Rarely a combined type may be present.
Organoaxial volvulus is far more common than mesenteroaxial volvulus and accounts for approximately two-thirds of cases of gastric
volvulus. It occurs when the stomach rotates along its long axis and
becomes obstructed, with the greater curvature being displaced superiorly and the lesser curvature located more caudally in the abdomen.
Secondary gastric volvulus is usually of organoaxial type and is seen
in association with post-traumatic or paraesophageal hernia, diaphragmatic hernia or eventration [7]. Primary gastric volvulus is usually of mesenteroaxial type where the diaphragm is usually intact
and the pathology lies in the abnormal fixation of stomach owing to
lax attachments. The stomach rotates around a line passing parallel
to the gastrohepatic omentum. The rotation is usually partial (less
than 180). It is seen in association with wandering spleen or congenital asplenia and rarely with diaphragmatic eventration [7]. Organoaxial volvulus generally presents with acute symptoms of obstruction or strangulation. In contrast nonspecific abdominal pain
and respiratory symptoms, as seen in our patient may be the presenting features of partial gastric volvulus with diaphragmatic eventration. As the symptoms are nonspecific, diagnosis is often delayed
in the elderly or after complications have occurred.
Gastroesophageal reflux and gastric ulcerations are the most common complications of chronic gastric volvulus. Gastroesophageal reflux may contribute to intermittent abdominal pain. Our patient had
right sided diaphragmatic eventration with secondary mesenteroaxial volvulus, which is a rarity. It was a chronic volvulus as there was
no sign of obstruction on imaging. It might have occurred due to
increased right subdiaphragmatic space leading to rotation of liver
and further stretching of the gastrohepatic ligament and predisposing to volvulus.

http://www.mednifico.com/index.php/elmedj/article/view/213

398

Eventration of diaphragm invariably occurs on the left side with mediastinal displacement towards the right side. In uncomplicated
cases it is usually asymptomatic and is incidentally detected on chest
radiograph. Contralateral mediastinal displacement with unilateral
elevation of the diaphragm goes more in favor of eventration in contrast to unilateral diaphragmatic palsy [8].
Eventration allows abdominal contents to enter into the thorax, although the continuity of the diaphragm is intact, in contrast to diaphragmatic hernia. Ultrasonography reveals about the integrity of
the diaphragm with the content of eventration and other diaphragmatic pathologies. Fluoroscopy is considered the most reliable way
to document diaphragmatic paralysis. The diaphragmatic muscle is
thin and weak with movement reduced, paradoxical or absent on
fluoroscopy [9]. Other imaging modalities such as CT and MRI may
be performed as adjuvant technique in cases where the diagnosis
still remains in doubt.
Eventration complicated by intestinal malrotation can be further
evaluated on barium studies as in our case where right sided eventration was complicated by rotation of liver and gastric volvulus. An
upper gastrointestinal (GI) series may be performed to evaluate the
rotation of the stomach, as well as to detect passage of ingested oral
contrast material into the duodenum. Organoaxial volvulus is diagnosed on barium studies by demonstration of the greater curvature
superior to the lesser curvature and mesenteroaxial by demonstrating displacement of antrum above the gastroesophageal junction
[10]. Multidetector row CT often is performed in the setting of epigastric pain and vomiting and can help confirm the rotation of the
herniated stomach and the transition point. Asymptomatic patients
are managed conservatively but patients with symptoms require surgery.

Vol 2, No 4

Diaphragmatic eventration with gastric volvulus

In conclusion, this case is presented to alert the physicians about the


rare association of right diaphragmatic eventration with mesenteroaxial gastric volvulus and abnormal rotation of liver, the prompt diagnosis of which is critical to avoid catastrophic complications of ischemia, perforation and strangulation as early management in such
cases without gastric necrosis is associated with less postoperative
morbidity and mortality.
Competing interests: The authors declare that no competing interests exist.
Received: 14 July 2014
Accepted: 4 November 2014
Published Online: 4 November 2014

References
1. Wayne ER, Campbell JB, Burrington JD, Davis WS. Eventration of the
diaphragm. J Pediatr Surg. 1974; 9:64351.
2. Seaton A. Abnormalities and Diseases of the Diaphragm. In: Seaton A, Seaton
D, Leitch AG (eds) Crofton and Douglas's Respiratory Diseases, 5th edn.
Blackwell Science, Oxford. 2000:123449.
3. Frechette E, Cloutier R, Deslauriers J. Congenital eventration and acquired
elevation of the diaphragm. In: Pearson FG, Cooper JD, Deslauriers J, et al (eds)
Thoracic Surgery, 2nd edn. Philadelphia, Churchill Livingstone. 2002:1537-49.
4. Chin EF, Lynn RB. Surgery of eventration of the diaphragm. J Thorac Surg 1956;
32:6-14.
5. Lorimier AA. Eventration of the diaphragm. In: Ashcraft KW, Holder TM (eds),
Pediatric Surgery. Philadelphia, W.B.Saunders. 1993:204-17.
6. Ascherman SW, Bednarz WW, Olix NL. Gastric volvulus. Arch Surg 1958; 76:6219.
7. Jayanthi V, Vidyanathan V, Mathai V, Muthusami JC, Jesudason SB. Traumatic
eventration of diaphragm complicated by mesenteroaxial volvulus of the
stomach. Trop Gastroenterol 1994; 15:169-72.
8. Sutton D. Textbook of Radiology and Imaging. 7th edn. London Churchill
Livingstone. 2003:51-2.
9. Eren S, Ceviz N, Alper F. Congenital diaphragmatic eventration as a cause of
anterior mediastinal mass in the children: imaging modalities and literature
review. Eur J Radiol 2004; 51:85-90.
10. Peterson CM, Anderson JS, Hara AK, Carenza JW, Menias CM. Volvulus of the
gastrointestinal tract: Appearances at multimodality imaging. Radiographics
2009; 29:1281-93.

http://www.mednifico.com/index.php/elmedj/article/view/251

399

Open Access

Case Report

Intestinal occlusion due to cryptogenic, multifocal, ulcerous, stenosing enteritis treated by laparoscopy
Alejandro Weber Snchez1, Pablo Weber2, Rafael Carb3, Jorge Fishleter2

Abstract
Background: Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is characterized by stenotic zones and multiple mucosal
ulcerations in the small bowel. The diagnosis is clinical and histopathological based on the history of periodic attacks of intestinal
obstruction, vomiting and abdominal pain. According to our knowledge, this is the only report of treatment of CMUSE via laparoscopy.
Case Presentation: A 47-year-old man arrived to the emergency room with intense colicky pain initiated 24 hours before arrival,
accompanied by nausea, gastrobiliary vomiting, constipation and inability to pass flatus. Physical examination revealed abdominal
distension, generalized abdominal tenderness to palpation, peristalsis with metallic tone, no signs of peritoneal irritation, and extremities
with mild edema. Laboratory exams showed hyperglycemia, hyponatremia and hypoalbuminemia. Plain abdominal X rays reveled dilated
loops of small bowel and fluid levels mainly on the left hemiabdomen, suggesting mechanical ileus. No evidence of free air in the
abdomen was found. Intravenous fluids and electrolyte replacement was initiated and a nasogastric tube was inserted for decompression.
Medical management failed to improve the symptoms after 24 hours, so an exploratory laparotomy was performed. The affected segment
was resected laparoscopically. Pathology reported multiple sites of ulceration concerning the mucosae and submucosae, myenteric
plexus hypertrophy and pseudo pyloric gland metaplasia. Multiple eosinophils and neutrophils were detected. Patient was discharged
from the hospital on the fifth postoperative day and started with prednisolone 30mg/day for 3 months. Three years after he has not had
any other episode of intestinal obstruction.
Conclusion: Diagnosis of CMUSE must be considered in cases of repeated attacks of small bowel obstruction and when stenotic areas
and superficial ulcers are found. Laparoscopic surgery should be considered in patients with repeated attacks of intestinal obstruction
and in whom CMUSE is suspected because it permits a diagnosis and resection of the affected segments with the advantages on the
minimal invasive surgery. (El Med J 2:4; 2014)
Keywords: CMUSE, Intestinal Occlusion, Laparoscopy, Stenosis

Introduction
Small bowel obstruction may be caused by a variety of pathologies,
the most frequent being adhesions, hernias or tumors. A very rare
and poorly recognized cause of intestinal occlusion known as cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is characterized by multifocal stenosis and ulcerations, and is different from
Crohns disease. The purpose of this paper is to present the case of
a patient with CMUSE treated with minimally-invasive surgery.

Case Report

out pathology, abdominal distension, generalized abdominal tenderness to palpation, peristalsis with metallic tone, no signs of peritoneal irritation, and extremities with mild edema.
Laboratory exams showed: glucose 142 mg/dl, hyponatremia 4.4
g/dl, hypoalbuminemia 2.5 g/dl. The rest of the studies were within
normal range. Plain abdominal X-rays reveled dilated loops of small
bowel and fluid levels mainly on the left hemiabdomen suggesting
mechanical ileus. No evidence of free air in the abdomen was found.

A 47-year-old man arrived to the emergency room with a complaint


of intense colicky pain initiated 24 hours before arrival, accompanied
by nausea, gastrobiliary vomiting, constipation and inability to pass
flatus. He also reported a 10 kilogram weight loss in the past twelve
months. He had history of similar episodes treated with conservative
management (intravenous fluids and nasogastric tube). Two years
before, he had an attack of abdominal pain attributed to gallbladder
disease. For this reason a laparoscopic cholecystectomy was performed without symptomatic improvement. He also reported that in
his previous abdominal pain attacks, plain X-rays and CT scan did not
show any specific abnormalities. He denied allergies or smoking. He
had a car crash 8 years before, no other surgical procedures or disease was reported. Family history was irrelevant for the pathology.

Intravenous fluids and electrolyte replacement was initiated and a


nasogastric tube was inserted for decompression. Medical management did not improve the symptoms after 24 hours, so an exploratory laparotomy was performed. One 10mm trocar was inserted
through the umbilicus and two additional 5mm trocars were placed,
one in the left iliac fossa and another at the left flank. Approximately
at 100cm from the ileocecal valve, we found a bowel wall thickening
with mesentery fat adhered to it and a 10cm long stenotic segment
with dilatation of the proximal intestinal loops. There were no intestinal adhesions or abnormal masses. The affected segment was resected laparoscopically (Figure1) with a linear stapler, and an endto-end anastomosis was performed. The surgical piece was extracted
trough the umbilical incision.

Physical examination revealed body mass index of 20 kg/m2, pulse


95 bpm, respiratory rate 18 per minute, blood pressure 125/85
mmHg, temperature 37C and oxygen saturation 92%. Further examination revealed dry oral mucosal membrane, cardiopulmonary with-

Pathology reported multiple sites of ulceration concerning the mucosae and submucosae, myenteric plexus hypertrophy and pseudo
pyloric gland metaplasia. Multiple eosinophils and neutrophils were
detected. No granulomas or data that suggested Crohns disease
was found, chronic ulcerative nongranulomatous jejunitis was excluded (Figures 2, 3). Recovery was satisfactory. He was discharged

Departamento de Ciruga General, Hospital ngeles, Lomas, Mexico.


Facultad de Ciencias de la Salud de la Universidad Anhuac Mxico Norte, Mexico.
3Cirujano General, Hospital ngeles, Lomas, Mexico.

Correspondence: Alejandro Weber Snchez.


Email: awebersanchez@gmail.com

1
2

2014 Snchez et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Snchez AW, Weber P, Carb R, Fishleter J: Intestinal occlusion due to cryptogenic, multifocal, ulcerous, stenosing enteritis treated by laparoscopy. El Mednifico Journal 2014, 2(4).

400

from the hospital on the fifth postoperative day and started with
prednisolone 30mg/day for 3 months. Three years after, he has not
had any other episode of intestinal obstruction.

Intestinal occlusion due to CMUSE treated by laparoscopy

mainly in Asia and Europe. It is known that it is not associated with


the use of non-steroid anti-inflammatory (NSAIDs), or systemic inflammatory reactions [1-5].
Perlemuter in France has the largest series reported with 17 cases.
He suggested that CMUSE may be related to a particular form of polyarteritis nodosa or non-classified vasculitis [6]. Chang classified it in
CMUSE-I (idiopathic CMUSE) and CMUSE-V (vasculitis-related
CMUSE), but not all authors agree, with many stating that any type
of vasculitis should be described as it and not as CMUSE [7]. Others
have suggested it may be related to the over-stimulated production
of fibrous tissue and disturbance of collagen degradation.

Figure 1: Surgical Piece: Resected part of the small intestine.

Figure 2: Hypertrophic muscularis mucosae (hematoxylin and eosin, 4X).

Figure 3: Pyloric metaplasia of ileum. In the inferior central part of the picture,
we can visualize a group of small cells with clear cytoplasm. This is the best
indicator of a chronic process with exacerbation and remission in the small
intestine (hematoxylin and eosin, 10X).

Discussion
Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) was first
described in 1964 by Debray. It is a rare idiopathic disease of the
small bowel whose origin and pathophysiology has not been clearly
established. Only 50 cases have been described all over the world,
Vol 2, No 4

Matsumoto reported 12 cases in Japan. In his paper, he described


ulcers in the small intestine with tendency to stenose, with chronic
intestinal bleeding and anemia being the predominant manifestations [8]. There is also some evidence that suggests an autoimmune
component. Several cases were reported with low levels of CH50 and
C2 suggesting a possible relationship between these pathologies [4].
Patients with this disease may present with some form of enteropathy, causing loss of proteins, as in the case of the patient we report
[1, 9].
The clinicopathological features of CMUSE include unexplained repeated episodes of small bowel obstruction caused by multiple segmental strictures with mucosal ulceration mainly in the jejunum and
ileum. Symptoms may be chronic diarrhea, vomiting, abdominal
pain, loss of weight, and occasionally melena [7]. The histopathologic characteristics are stenotic areas of 1cm to 2cm in length, occasionally an inflammatory infiltrate with neutrophils, monocytes
and eosinophils can be observed. Intestinal vessels are normal or
thinned with inflammatory infiltrate, thrombosis and endophlebitis.
There are no specific laboratory tests for the diagnosis of CMUSE.
Blood tests are usually normal without association to inflammatory
processes. Image studies usually only show signs of intestinal obstruction and are not specific for diagnosis. Due to the location of
the lesions, endoscopy and colonoscopy are not useful. Enteroscopy
with double balloon has been described useful because it allows direct visualization of the ulcers. The use of endoscopic capsule is not
recommended because it can get stuck in the sites of obstruction
[10].
CMUSE is a diagnosis of exclusion. It must be distinguished from
other pathologies that cause ulcers in the small intestine such as infections by Campylobacter, Shigella, Yersinia or Salmonella and other
diseases that can cause small bowel ulcers and stenosis, such as
chronic use of NSAIDs or Crohns disease. In CMUSE there are no
granulomatous changes in the bowel, fistulas or clinical and laboratory features of systemic inflammation as in Crohns disease. Surgical
trauma, chronic non-granulomatous ulcerative jejunoileitis, and
some forms of intestinal ischemic vasculopathy are other differential
diagnosis which must be distinguished [2-4].
In the case we report, the patient already presented several episodes
of intestinal obstruction without definitive diagnosis. There was no
clinical evidence of inflammatory bowel disease, vascular disease,
trauma, tumor, or chronic use of NSAIDs. Even thought he had history of surgical procedures, no evidence of abdominal adhesions or

Snchez AW, Weber P, Carb R, et al.

extraluminal pathology was found. The intestinal occlusion was secondary to the intraluminal stenosis.
Steroids may be useful. The duration of the treatment is of one or
two years, but it can last longer due to recurrences or poor response
to the therapy [10]. When the response is poor, it may be due to an
abnormal type of CMUSE [4]. Azatioprine, methotrexate and mesalazin are other drugs with variable response, but none has shown
significant effectiveness.
The treatment of choice in patients with mechanical intestinal obstruction that does not respond to the medical treatment is surgery.
As far as we know, this is the only case reported treated with minimally invasive procedure, which has advantages compared to conventional surgery because it allows entire exploration of small and
large intestine. Intestinal resection may be fully performed laparoscopically. Post-operative adhesions are less and the patient recovers
rapidly with less complications.

Conclusion
Pathophysiology of CMUSE is still unknown. The diagnosis must be
considered in cases of repeated attacks of small bowel obstruction
and when stenotic areas and superficial ulcers are found. Laparoscopic surgery should be considered in patients with repeated attacks of intestinal obstruction and in whom CMUSE is suspected because it permits a diagnosis and resection of the affected segments
with the advantages on the minimal invasive surgery.

401

References
1. Jeffries GH, Steinberg H, Sleisenger MH. Chronic ulcerative
(nongranulomatous) jejunitis. Am J Med. 1968;44:4759.
2. Freeman HJ. Multifocal Stenosing Ulceration of the Small Intestine. World J
Gastroenterol. 2009;39:4883-85.
3. Seamus H, Bourke B, Broderick A, Phelan E, McDermott M. Cryptogenic,
multifocal, ulcerous, and stenosing enteritis as a manifestation of enterocolic
venopathy. J Pediatr Gastroenterol Nutr. 2008;47:10709.
4. Van Buren G, Teichgraeber DC, Ghorbani RP, Souchon EA. Sequential stenotic
strictures of the small bowel leading to obstruction. World J Gastroenterol.
2007;40:5391-93.
5. Nazal L, Bustos C, Corts P, Torres J, Jerez R, Rolln A. Enteritis ulcerativa
estenosante multifocal criptognica (CMUSE) diagnosticada por enteroscopa
doble baln: Una forma de vasculitis intestinal?. Gastroenterol. Latinoam.
2010;21:23-26.
6. Perlemuter G, Guillevin L, Legman P, Weiss L, Couturier D, Chaussade S.
Cryptogenetic multifocal ulcerous stenosing enteritis: an atypical type of
vasculitis or a disease mimicking vasculitis. Gut. 2001;48:333338.
7. Chang DK, Kim JJ, Hwang Choi, Eun CS, Han DS, Byeon JS, Kim JO. Double
balloon endoscopy in small intestinal Crohns disease and other inflmatory
diseases such as cryptogenic multifocal ulcerous stenosing enteritis (CMUSE).
Gastrointest Endosc. 2007;66:S96-98.
8. Matsumoto T, Lida M, Matsui T, Yao T. Chronic nonspecific multiple ulcers of
the small intestine: a proposal of the entity from Japanese gastroenterologists
to Western enteroscopists. Gastrointest Endosc. 2007;66:S99-S107.
9. Kohoutov D, Bures J, Tycov V, Brtov J, Tachec I, Rejchrt S, Vacek Z, Repk
R, Kopcov M. Severe cryptogenic multifocal ulcerous stenosing enteritis. A
report of three cases and review of the literature. Acta Medica (Hradec
Kralove). 2010;53:25-9.
10. Kwon SO, Kim YS, Kim SY, Hong SW, Lee HK, Moon JS. A case of Cryptogenic
Multifocal Ulcerous Stenosing Enteritis: Differential Diagnosis from Crohns
disease. J. Gastrointestin Liver Dis. 2012,21:309-12.

Competing interests: The authors declare that no competing interests exist.


Received: 18 August 2014
Accepted: 10 November 2014
Published Online: 10 November 2014

http://www.mednifico.com/index.php/elmedj/article/view/251

402

http://www.mednifico.com/index.php/elmedj/article/view/267

Open Access

Case Report

Embolization of uterine and ovarian artery anastomosis in the treatment of menorrhagia secondary to
adenomyosis and leiomyoma
Dustin Hofstede1, Peter Munk2, Roshni Patel2, Nivmand Khorrami2

Abstract
Background: Adenomyosis is a benign uterine condition that causes menorrhagia and dysmenorrhea. Although hysterectomy is considered
a definitive treatment, it is not an ideal option for women who wish to preserve their fertility. Minimally invasive procedures such as uterine
artery embolization (UAE) have the potential to eliminate surgery for women who have failed conservative and medical treatment for
adenomyosis and leiomyoma.
Case Presentation: This case report discusses a 54-year-old female who presented with menometrorrhagia refractory to medical treatment.
Pelvic T2 MRI revealed findings consistent with adenomyosis and leiomyoma. Elective UAE was performed and follow up was scheduled at
3, 6 and 12 months.
Conclusion: This case provides a review of UAE, the efficacy of UAE for the treatment of leiomyoma and adenomyosis, the primary causes
of treatment failure, and what has been done to address these shortcomings. UAE has significant promise for the treatment of these
disorders. However, establishing UAE as a first line treatment requires further research. (El Med J 2:4; 2014)
Keywords: Adenomyosis, Leiomyoma, Radiology, Interventional, Uterine Artery Embolization, Uterine-ovarian Artery Anastomosis

Introduction
Adenomyosis is a benign focal or diffuse deposition of endometrial
glandular and stromal tissue within the myometrium [1, 2]. The prevalence of the disorder ranges from 10% to 18%. Thirty-five percent
of patients may be asymptomatic, while those who are symptomatic,
menorrhagia occurs in 50%, dysmenorrhea in 30%, and bulk related
symptoms such as back and pelvic pain and frequent urination in
20% [1, 2].
The diagnosis of adenomyosis is made by transvagninal ultrasound
showing focal or diffuse areas of myometrial hypoechogenicity [2].
Alternatively, T2 pelvic MRI revealing an increased junctional zone
thickness of at least 10mm and focal or diffuse hyperintense signals
within the low signal myometrium is diagnostic [2].
Treatment of adenomyosis consists of conservative, medical, surgical, and interventional means. Conservative treatment involves
NSAIDs and acetaminophen. These are effective for pain in most
cases, but have no effect on bleeding [3]. Medical treatment involves
hormone cycling using oral contraceptives, intrauterine devices, continuous GnRH agonists, and androgenic steroids [3]. Definitive treatment is achieved with hysterectomy; however, this is not a suitable
option for women wishing to preserve fertility [1, 2]. Myomectomy
is another surgical procedure that also cannot guarantee preservation of fertility [1, 2]. Women who have failed conservative and medical treatment and are wishing to preserve fertility, have a quick recovery, and avoid invasive inpatient procedures can opt for UAE [1,
2]. Patients choosing UAE should be made aware of its risks which
include post embolization syndrome, aberrant embolization, particle
migration, endometritis, septicemia, and, rarely, infertility.
UAE involves the use of polyvinyl alcohol (PVA) particles ranging in
size from 100 to 900 micrometers suspended in saline and contrast
solution to occlude the helicine branches of the uterine artery (UA).
This markedly limits blood supply to fibroid and adenomyotic tissue.

American University of the Caribbean School of Medicine, United States.


University of British Columbia Hospital/Vancouver General Hospital, Vancouver
B.C, Canada.

1
2

Percutaneous access of the right femoral artery is obtained to advance a guide wire proximally under fluoroscopic guidance to the
bifurcation of the aorta. Once positioned there, the guide wire is
turned and advanced distally to the contralateral UA. Finally, catheter placement over the wire can then be easily achieved, and under
fluoroscopy, proper placement of the catheter prior to particle injection can be determined. Satisfactory embolization of the targeted
vessels is achieved once contrast stasis and/or retrograde flow in the
UA is seen. Again under fluoroscopy, occlusion of the vessels is confirmed with disappearance of anterograde flow into the helicine
branches. Reversal of the catheter system allows for ipsilateral embolization.

Case Report
Clinical History
The patient was a 54-year-old Caucasian female who presented with
irregular, heavy, painful menstrual cycles. The initial work up consisted of CBC, pelvic exam and ultrasound. Based on the results of
initial studies, an MRI pelvis was ordered as part of additional
workup. Based on the patients presentation, a differential diagnosis
of endometrial hyperplasia, endometrial or cervical polyps, endometrial carcinoma, adenomyosis, and sub-mucosal leiomyoma was
made. The patient was initially treated conservatively and medically
with no avail, thus, deeming the patient eligible for UAE.
Imaging
Sagittal T2 pelvic MRI (Figure 1) revealed an anteverted uterus with
a thickened endometrium and uterine wall, a junctional zone thickness of approximately 12mm, and foci of hyper-intense signals
within the myometrium consistent with deposition of endometrial
glandular and stromal tissue. Focal hypo-intense signal was appreciated adjacent to the endometrium, consistent with a submucosal fibroid. Pre-embolization fluoroscopy revealed the helicine branches
and confirmed catheter placement before particle injection (Figure
2). Satisfactory embolization was confirmed by displaying stasis
Correspondence: Dustin Hofstede.
Email: dustin.hofstede@gmail.com

2014 Hofstede et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Hofstede D, Munk P, Patel R, Khorrami N: Embolization of uterine and ovarian artery anastomosis in the treatment of menorrhagia secondary to adenomyosis and leiomyoma. El Mednifico Journal
2014, 2(4).

Hofstede D, Munk P, Patel R et al.

and/or retrograde flow of contrast in the UA and disappearance of


the helicine branches (Figure 3). Angiography of the right UA revealed a very small vessel and an absence of helicine branches post
catheterization (Figure 4). This was an indication that an anastomosis
between the uterine and ovarian arteries possibly existed on the
right. Aortography, using pigtail catheter at the level of the renal arteries, allowed identification of the ovarian arteries (OA) (Figure 5).
Selective right OA angiography, using a microcatheter, revealed right
helicine branches consistent with anastomosis between the right OA
and UA (Figure 6). Embolization of the distal OA was then performed
(Figure 7). Follow up was scheduled at 3, 6 and 12 months.

403

endometrial hyperplasia and adenocarcinoma in women with this


condition [2].
UAE in the treatment of patients with fibroids has been generally
accepted by Interventional radiologists and gynecologists considering that 80 to 93% of patients report short-term symptomatic relief
at 3 and 6 month follow up, and 68% remain asymptomatic longterm [1, 2, 5]. Occluding blood supply to fibroids and myometrial
glandular tissue reduces the size and amount of tissue without causing complete uterine necrosis as a result of collateral circulation that

Figure 3: Post embolization sequence showing contrast


flow stasis indicating satisfactory embolization.
Figure 1: T2 pelvic MRI showing submucosal fibroid (white
arrow) and areas of andenomyotic tissue at the thickened
junctional zone (red arrow).

Figure 4: Catheterization of the right


internal iliac showing the right uterine
artery (arrow).

Figure 5: Aortograpy at the level of the


renal artery take off displaying the
ovarian arteries.

Figure 2: Pre-embolization fluoroscopy sequence of the left


UA following selective catheterization showing numerous
helicine branches.

Discussion
Adenomyosis is a benign focal or diffuse deposition of endometrial
glandular and stromal tissue within the myometrium [1, 2]. Thirtyfive percent of patients may be asymptomatic while 50% present
with menorrhagia, 30% with dysmenorrhea, and 20% with bulk related symptoms such as back and pelvic pain and frequent urination
[1, 2]. Dysmenorrhea and menorrhagia may be a result of uterine
instability and poor contractibility of a fibrotic uterus secondary to
endometrial tissue deposition [1, 2]. Approximately 80% of women
diagnosed with adenomyosis have other uterine pathologies [2].
Leiomyoma occur in 53% while endometriosis and endometrial
polyps each account for 2-20% [2]. There is also an increased risk of

Figure 6: Selective microcatheterization of the right ovarian


artery showing prominent blood supply to the uterus
indicated by the appearance of the helicine branches.

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404

Embolization of uterine and ovarian artery anastomosis

Failure of UAE is also attributed to adenomyosis co-existing with fibroids. UAE seems to infarct the fibroids but leaves much of the adenomyotic myometrium intact. Its success seems to be related to
particle size [1, 2]. There is a significantly higher success rate in
groups that received 250-355 and 500-710 micron PVA particles than
in those who received only 355-500 or 250-355 micron particles [2].
At 2 year follow up, 56% of the patients remain asymptomatic with
decreased thickness of junctional zone on MRI while 82% of patients
reported significant symptomatic improvement [1, 2, 5]. The limitation of the latter figure is that it is subjective without standardized
assessment [5].

Conclusion
Figure 7: Post embolization sequence of the
right ovarian artery showing contrast flow
stasis indicating satisfactory embolization.

quickly develops. Historically, adenomyosis has been difficult to treat


definitively without turning to hysterectomy [2]. While UAE provided
symptomatic relief in 63% of patients with pure adenomyosis at 3
year follow up in one study, many interventional radiologists are reluctant to offer UAE due to the variability of long term efficacy reported in the literature [2]. It seems that long-term efficacy is higher
and more consistent in patients with adenomyosis concomitant with
fibroids when common causes of failure are addressed during the
procedure [2].
It is reported that 4-19% of UAE fail, partly attributed to uterine and
ovarian artery anastomosis (UOAA) [4]. The prevalence of UOAA is
reported to be 21%. Therefore, many interventional radiologists opt
for aortography following bilateral embolization in an attempt to
identify an anastomosis [5]. Bilateral UAE plus UOAA embolization
has an approximately 9% failure rate compared to 19% with bilateral
UAE alone (4). UOAA embolization is not without risks. There is a 6%
risk of ovarian failure and/or premature menopause induction in all
women, and 16% risk in women older than 45 [4].

Vol 2, No 4

The results in the literature show significant promise for the use of
UAE in treatment of adenomyosis, but the data gathered so far has
been insufficient to advocate UAE as a first line treatment [5]. In future, randomized controlled studies need to be conducted to establish the efficacy and safety of UAE as a first line treatment [5]. Additionally, optimizing the technique of UAE in the treatment of adenomyosis and an evaluation of how long-term outcomes can be improved should be done [2].
Competing interests: The authors declare that no competing interests exist.
Received: 29 August 2014
Accepted: 10 November 2014
Published Online: 10 November 2014

References
1. Kim MD, Kim S, Kim NK, Lee MH, Ahn EH, Kim HJ, Cho JH, Cha SH (2007). Long
term results for Uterine Artery Embolization for Symptomatic Adenomyosis.
American Journal of Roentgenology 188: 176-181 (PMID: 17179361).
2. Englander MJ (2008). Uterine Artery Embolization for the treatment of
Adenomyosis. Seminars in Interventional Radiology 25: 387-393 (PMID:
21326580).
3. Goodwin SC, Spies JB (2009). Uterine Fibroid Embolization. N Engl J Med
361:690-697 (PMID: 19675331).
4. Razavi MK, Wolanske KA, Hwang GL, Sze DY, Kee ST, Dake MD (2002)
Angiographic Classification of Ovarian ArterytoUterine Artery Anastomoses:
Initial Observations in Uterine Fibroid Embolization. Radiology 224: 707-712
(PMID: 12202703).
5. Popovic M, Puchner S, Berzaczy D, Lammer J, Bucek RA (2011). Uterine Artery
Embolization for the Treatment of Adenomyosis: A Review. J Vasc Interv Radiol
22: 901-909 (PMID: 21570318).

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405

Open Access

Case Report

Ehlers Danlos syndrome in an edentulous patient with temporomandibular joint dislocation


Renu Tanwar1, Asha R Iyengar2, K S Nagesh2, Rishabh Kapila3, Gurvinder Kaur4

Abstract
Background: Ehlers Danlos syndrome (EDS) is heterogeneous genetic syndrome involving connective tissue. It is characterized by clinical
signs of skin hyper-extensibility, delayed wound healing with atrophic scarring, joint hypermobility, easy bruising and generalized
connective tissue fragility. Oral cavity is not immune to these systemic effects.
Case Presentation: A 40 year old Indian male patient reported to the Department of Oral Medicine and Radiology with chief complaint of
clicking in front of ear and difficulty in closing the mouth properly as his jaw seems to get stuck sometimes. The problem started about
two years back when patient underwent full mouth extraction due to mobility in all teeth. On general examination certain anomalous
features were observed which included hyper-extensibility of fingers of the hands and cigarette paper scars on legs and foot. The patient
was completely edentulous and could touch tip of tongue to the tip of nose. Panoramic and temporomandibular joint (TMJ) limitation
views were taken and MRI of TMJ was advised. Based on history and clinical features; we came to diagnosis of TMJ dislocation and Ehlers
Danlos syndrome. Patient was advised to avoid wide opening of the mouth. Since the medical condition of the patient was capricious for
implants prosthesis, the patient was advised to use relined complete denture.
Conclusion: Ehlers Danlos syndrome is a rare genetic disorder of connective tissue. Oral manifestation and dental consideration for such
cases should be well evaluated and managed appropriately. (El Med J 2:4; 2014)
Keywords: Ehlers Danlos Syndrome, Indian Rubber Man Syndrome, Temporomandibular Joint Dislocation, Gorlins Sign

Background
Ehlers Danlos syndrome (EDS) is a heterogeneous genetic syndrome
involving connective tissue. It is characterized by clinical signs of skin
hyper-extensibility, delayed wound healing with atrophic scarring,
joint hypermobility, easy bruising and generalized connective tissue
fragility. Defects in either collagen processing enzymes or collagen
structures are ubiquitous in all subtypes of EDS leading to collagen
fragility throughout the body. Oral cavity is not immune to the systemic effects of such defects. The oral and maxillofacial manifestations of EDS are discussed herewith in context to temporomandibular joint (TMJ) dysfunctions and edentulous state. The main aim of
this case report is to create awareness among dental professionals
about the complications of EDS and to propose guidelines for dental
management of such patients in various specialties of dentistry.

(Gorlins sign) (Figure 2). Panoramic and TMJ limitation views were
taken and MRI of TMJ was advised to assess the status of TMJ (Figures 3 and 4). TMJ limitation views revealed condylar process of left
and right side. TMJ were placed anterior to articular eminence in
open mouth position suggestive of increase in range of motion in
both right and left side of TMJ. Sagittal spin echo T2 weighted MRI
of TMJ revealed head of condyle placed anterior to the articular eminence in open mouth views and crumpled shape of articular disc in
left TMJ (Figures 5-8).

Case Report
A 40 year old Indian male patient reported to the Department of Oral
Medicine and Radiology with chief complaint of clicking in front of
ear and difficulty in closing the mouth properly as his jaw seems to
get stuck sometimes. The problem started about two years back
when patient underwent full mouth extraction due to mobility in all
teeth. The patient told that the extraction wounds healed late and
he had problems maintaining sutures in the mouth as they eventually led to ulcerations.

Figure 1: (a) Cigarette paper, hemosideric and atrophic scars on legs and feet
of patient; hallux valgus of both toes; (b) Depressed scar over the forehead
on left side.

On general examination, certain anomalous features were observed


which included hyper-extensibility of fingers and hands, and cigarette paper scars on legs and feet (Figure 1). The patient did not give
a history of any cardiovascular or hematological problem. On intraoral examination, mouth opening was 50 mm, patient was completely edentulous and could touch tip of tongue to the tip of nose
Department of Oral Medicine And Radiology, SGT Dental College and Hospital,
Budhera, Gurgaon, Haryana, India
2Department Of Oral Medicine and Radiology, D A P M R V Dental College,
Bangalore, India
3Department Of Oral Medicine and Radiology, Gian Sagar Dental College, Sunam,
Punjab, India
1

Figure 2: Gorlins sign positive and


absence of lingual frenulum.

Department of Pedodontics and Preventive Dentistry, SGT Dental College and


Hospital, Budhera, Gurgaon, Haryana, India
Correspondence: Renu Tanwar
Email: renu_bds7@yahoo.co.in

2014 Tanwar et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Tanwar R, Iyengar AR, Nagesh KS, Kapila R, Kaur G: Ehlers Danlos syndrome in an edentulous patient with temporomandibular joint dislocation. El Mednifico Journal 2014, 2(4).

406

Ehlers Danlos syndrome in an edentulous patient

Figure 3: Panoramic radiograph showing flattening of left condylar process


and edentulous maxillary and mandibular ridges.

Figure 8: MRI findings for closed mouth view for left TMJ.

Figure 4: TMJ limitation view showing condylar process of left and right side
TMJ placed anterior to articular eminence in open mouth position.

Based on history and clinical features; we came to diagnosis of TMJ


dislocation and Ehlers Danlos syndrome. Patient was advised to
avoid wide opening of the mouth. He was also well informed about
medical basis of his dental problem and referred for rheumatology
and general medicine consultation. Since the medical condition of
the patient was capricious for implants prosthesis, the patient was
advised to use relined complete denture.

Discussion
Ehlers Danlos syndrome is a rare genetic disorder of connective tissue, largely characterized by joint hypermobility, skin hyper-extensibility, easy bruising, delayed wound healing with atrophic scarring
and connective tissue fragility [1, 2]. The prevalence of EDS is between 1 in 5000 and 1 in 10,000 and is observed throughout the
world affecting both genders without racial predisposition [2, 3].

Figure 5: MRI findings for open mouth view for right TMJ.

The various types of EDS were classified initially into ten types based
on nomenclature proposed in year 1986 in Berlin. This nomenclature
was modified in year 1997 in Villefranche, France to clarify diagnostic
parameters and new nosology of 6 types was devised [4, 5].
Ehlers Danlos syndrome is caused by a genetic defect causing an
error in processing or synthesis of fibrillar collagen i.e. Types I, II, III,
V and XI [6, 7]. Three fundamental mechanisms are proposed for etiopathogenesis of EDS which are as follows:
a) Deficiency of collagen processing enzymes such as lysyl hydroxylase, procollagen-N-peptidases;
b) Dominant negative effects of mutant collagen -chains;
c) Haploinsufficiency.

Figure 6: MRI findings for open mouth view for left TMJ.

Figure 7: MRI findings for closed mouth view for right TMJ.

Vol 2, No 4

Hence, the inherited disorders of collagen biosynthesis such as Ehlers Danlos syndrome (EDS) present with specific manifestations depending upon the distribution and functions of fibrillar collagen i.e.
Types I, II, III, V and XI. In the orofacial structures, the major fibrillar
collagen types found are Types I, III, V [8]. As the metabolism of fibrillar collagen is altered in EDS, the structural abnormalities of connective tissue produces clinical symptoms in different orofacial structures which are discussed in Table 1.
In TMJ ,the fibrocartilage structure, the supporting ligaments, the interarticular disc and retrodiscal tissue are composed mainly of collagen (types I, III, V) and alteration in structure of collagen fibrils leads
to joint laxity with subluxation eventually causing TMJ hypermobility
and recurrent joint dislocation. Characteristically, classical, hypermobility and achondroplasia type EDS patients exhibit this presentation

Tanwar R, Iyengar AR, Nagesh KS et al.

more frequently [5, 9]. The majority of subjects report with symptoms such as increase in mobility of TMJ during mouth opening, myofascial pain, internal joint derangement, permanent locking, clicking and crepitations [10, 11]. In one study, many of subjects with EDS
reported with decrease in joint hypermobility with increase in age
[12, 13]. According to De Coster, in cases with recurrent joint dislocation or patient joint hypermobility in TMJ and increased tissue fragility, the practitioner should be suspicious of a connective tissue
involvement [7].
Table 1: Dental manifestations in Ehlers Danlos
syndrome based on deficiency in fibrillar collagen I, III, V
Orofacial structures Types of
Effects of collagen
collagen
deficiency
I,
III,
V
Delayed
healing
of
Bone
extraction sockets, Bone
resorption.
TMJ hypermobility with
Temporomandibular I, III, V
recurrent dislocation,
joint
increased risk of
hemarthrosis locking or
trismus in later stages.
I, III
Abnormal pulp morphology,
Tooth/Pulp/Dentin
pulp calcification, root deformity, congenital absence
of teeth, supernumerary
teeth, enamel hypoplasia.
I, III, V
Increased risk of bleeding,
Oral mucosa
tearing of sutures, increased
fragility of oral mucosa and
delayed healing of wounds.
I, III, V
Mobility of teeth due to
Periodontal
rapid loss of attachment in
ligament
young age.
Gorlins sign, Metenier sign,
Miscellaneous
High arched palate, absence
of lingual frenulum.
In our present case, the chief complaint was hypermobility of temporomandibular joint disorder as patient complaint of inability to
close his mouth often because of jaw being stuck. When assessed
with other manifestations such as Gorlins sign, absence of lingual
frenulum and papyraceous scars on foot, the diagnosis was suggestive for Ehlers Danlos syndrome.
Management of temporomandibular disorders in EDS patient is a
matter of concern especially for dental health care professionals [1417]. The fragility of retrodiscal collagen fibers in EDS patients is extremely high and therefore the major role of treatment of TMJ disorders in EDS patients should be aimed at reduction of stress on retrodiscal fibers. First, the range of mandibular opening must be restricted and activities which involve the wide opening of mouth
must be strictly avoided. Yawning must be controlled by gentle pressure on the chin to avoid excessive opening. Dental appointment
should not be lengthy and physiotherapeutic intervention such as

407

mandibular exercise should also be moderate. Finally, oral surgical


procedures to repair retrodiscal tissues are strictly contraindicated
because of poor healing of tissues and unusual scar formation .In our
case, the management of TMJ disorder was challenging as the patient was edentulous and was giving a long standing history of locking of jaws. With prosthodontics consultation, it was decided to give
the patient relined dentures to reduce trauma to the oral mucosa.
Patient was educated for his condition and was motivated for physiotherapeutic intervention.

Conclusion
Ehlers Danlos syndrome is a rare genetic disorder of connective tissue. Oral manifestation and dental consideration for such cases
should be well evaluated and managed appropriately.
Competing interests: The authors declare that no competing interests exist.
Received: 19 July 2014
Accepted: 27 November 2014
Published Online: 27 November 2014

References
1. Mao JR, Bristow J. The Ehlers Danlos syndrome: on beyond collagens. Journal
of Clinical Investigation 2001; 107:1063-9.
2. De Paepe A, Malfait F. Bleeding and bruising in patients with Ehlers Danlos
syndrome and other collagen vascular disorders. British Journal Of
Heamtology 2004; 127:491-500.
3. Gorlin RJ,Cohen MM, Levin LS.Ehlers Danlos syndrome.in:syndromes of head
and neck.3rd ed. New york:oxford university press;1990.p 429-41.
4. Scully C, Langdon J, Evans J. Marathon of eponyms: 5 Ehlers-Danlos syndrome.
Oral Diseases 2009;15(7):517- 8.
5. Paparia LA, Jackson K. Ehlers Danlos Syndrome - A Historical Review. British
Journal Of Heamtology 2008;141:32-35.
6. Castori M. Ehlers-Danlos Syndrome,Hypermobility Type:An Underdiagnosed
Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and
Systemic Manifestations. ISRN Dermatology 2012;1-22.
7. Abel MD, Carrasco LR. Ehlers-Danlos syndrome: classifications, oral
manifestations, and dental considerations. Oral Surgery Oral Medicine Oral
Pathology Oral Radiology Endodontics 2006;102(5):582-90.
8. De Coster PJ, Martens LC, Paep AD. Oral health in prevalent types of ehlers
Danlos syndrome. Journal of Oral Pathology and Medicine 2005;34:298-307.
9. Letourneoa Y, Perusse R, Buitheui H. Oral manifestation of Ehlers Danlos
syndrome. Journal of Canadian Dental Association 2001;67:330-4.
10. Fernandes NF, Schwartz RA.A "hyperextensive" review of Ehlers-Danlos
syndrome. Cutis 2008;82(4):242-8.
11. Thexton A. A case of Ehlers Danlos Syndrome presenting with recurrent
dislocation of temporomandibular joint. British Journal of Oral Surgery
1965;27:190-3.
12. Miller V J, Zelter R,Yoeli Z, Bonder L. Ehlers Danlos syndrome, fibromyalgia,and
Temporomandibular disorder: report of an unusual combination. Cranio
1997;15:267-9.
13. Goodman RM, Allison ML. ChronicTemporomandibular joint subluxation in
ehlers Danlos syndrome: report of a case .Journal of Oral Surgery 1969;27:65961.
14. Hagberg C, Korpe L,Berglund B. Temporomandibular joint problems and self
registration of mandibular opening capacity among adults with Ehlers Danlos
syndrome. A questionnaire study. Orthodontic Craniofacial Research
2004;7:40-6.
15. Myers D E. Ehlers Danlos Syndrome as a cause of Temporomandibular joint
disorders. Anesthesthesis progress 1985;23-4.
16. Akinbami B O. Evaluation of the mechanism and principles of management of
Temporomandibular joint dislocation.Systematic review of literature and a
proposed new classification of Temporomandibular joint dislocation. Head
and neck medicine 2011;7:10.
17. Ancillao A, Galli M, Cellitti C, Castori M, Albertinni, Camereto F.
Temporomandibular Joint mobility in adult females with Ehlers Danlos
syndrome. Journal of Craniomaxillary Diseases 2012;1:88-94.

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408

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Open Access

Case Report

Intraosseous ganglion cyst of scaphoid: A case report


Nasir Muzaffar1, Nissar Shah1, Sulaiman Seth1, Sheikh Ajaz1

Abstract
Background: Intraosseous ganglion cysts are rare causes of hand and wrist pain. Differential diagnosis of painful cystic radiolucent carpal
lesions includes osteoid osteoma and osteoblastoma. Isolated cases of ganglion cysts occurring in the lunate, scaphoid, pisiform, hamate,
triquetrum, capitate, metacarpal, and phalanx have been reported.
Case Presentation: A case of intra-articular intraosseous ganglion cyst of the scaphoid is presented. A 32-year-old right-handed man
presented with a 2 year history of progressive left-wrist pain. No history of trauma was reported. Conservative treatment with antiinflammatory medications before referral was unsuccessful. This case was treated with curettage and bone grafting having excellent results
with visual and analog pain scores reduced from 68 to 11 and range of motion was 90 extension to 80flexion and full grip strength.
Conclusion: Cases of intraosseous ganglions are reported in literature mostly in lower limbs and lunate among carpals, with scaphoid being
a rare site of the involvement. In this report, we described a symptomatic case which was successfully treated by intralesional curettage,
and autogenous bone grafting. (El Med J 2:4; 2014)
Keywords: Intraosseous Ganglion, Scaphoid, Curettage, Bone Grafting

Introduction
Intraosseous ganglion is a cystic lesion that contains gelatinous material, most often occurs in middle-aged patients, and is regarded as
similar to soft-tissue ganglion. The etiology is unknown, but association with degenerative joint disease has been considered. An intraosseous ganglion has been defined as a benign cystic and often
multiloculated lesion made up of fibrous tissue, with extensive mucoid changes, located in the subchondral bone adjacent to a joint
[1]. Intraosseous ganglions, although share same pathology as the
soft tissue ganglions, are rare entities and further rare in carpals.

in glass holding position for 5 weeks. After that, gradual mobilization


started and full range of motion achieved at 7 weeks.

Case Report
A 32-year-old male, mechanic by occupation, presented with a 2
years history of left wrist pain. The patient complained of a dull aching pain that worsened by usual activity of the left upper extremity
and relieved by rest. The various conservative management options
such as splinting and NSAIDS did not fully relieve his symptoms.
There was no history of any definite trauma.
On examination marked tenderness was present in region of the volar scaphoid proximal pole as well as overlying the dorsal radial styloid and snuff box. There was no swelling or palpable mass around
the wrist. The grip strength was symmetrically normal. The range of
motion of the wrist was normal and comparable to the contralateral
wrist. The conventional radiographs revealed a well-defined radiolucent lesion radiographs within the scaphoid without collapse of the
bone (Figure 1). CT confirmed a cystic lesion with normal appearance
of other parts of the scaphoid (Figure 2).
His hematological investigations including hemogram, ESR, RA factor, uric acid, serum calcium, phosphate, alkaline phosphatase, were
within normal limits. The patient was operated using a volar approach under fluoroscopic guidance and the scaphoid was exposed
(Figure 3). The cyst was evacuated en bloc (Figure 4). Then, the cavity
was packed using cancellous bone from the distal of the radius. The
joint capsule and wound was closed and the wrist was immobilized

Figure 1: Radiograph of lytic lesion in scaphoid.

Figure 2: CT of scaphoid showing lesion in scaphoid.

Hospital for Bone and Joint Surgery, Barzalla, Srinagar, Kashmir, India
Correspondence: Nasir Muzaffar
Email: drnasir@in.com

2014 Muzaffar et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Muzaffar N, Shah N, Seth S, Ajaz S: Intraosseous ganglion cyst of scaphoid: A case report. El Mednifico Journal 2014, 2(4).

Muzaffar N, Shah N, Seth S et al.

409

it the intraosseous ganglion cyst [7]. Various synonymous terms include synovial bone cyst, ganglionic cystic defect of bone and subchondral bone cyst.

Figure 3: Intraoperative photograph of cyst curetted from scaphoid.

Figure 4: Cyst excised en bloc.

Patient returned to full employment at 8 weeks. The patient was totally free from earlier symptoms, with full grip strength, 3 months
after operation. Over 6 month period, trabeculations were being
noted within the grafted scaphoid (Figure 5). The pathology report
described a cystic lesion with a delicate wall of fibro-connective tissue cells without true epithelial lining. Gross and microscopic findings were characteristics of an intraosseous ganglion cyst.

The differential diagnosis of a lytic painful lesion consists of chondroblastoma, enchondroma, fibrous dysplasia, osteoblastoma, osteoid osteoma, giant cell tumor, chondromyxoid fibroma, unicameral
bone cyst, osteoarthritis, rheumatoid arthritis and intraosseous ganglion cyst. Intraosseous ganglion has been reported most commonly
in the epiphyses of long tubular bone [8]. Most frequently, they develop in the subchondral bone of the lower limb, primarily the hip,
knee, and ankle, with the femoral head and the medial malleolus
being the two most common locations.
Schajowicz et al. reported 88 cases, 16 involving the carpal bones,
including scaphoid, lunate, triquetrum, and capitate [9]. Lesions in
scaphoid are reported very rarely. The radiographs show a well-defined osteolytic lesion. The pathologic finding is similar to its soft
tissue ganglion in all respects, with a smooth translucent wall composed of compressed collagen fibrins devoid of synovial lining. This
type of cyst contains a highly viscous clear mucin consisiting of high
concentration of hyaluronic acid in combination with glutamine, albumin and glucosamine.
Intraosseous ganglion cysts may be most easily confused pathologically with the juxta-articular cysts of osteoarthritis [10]. The earlier
age of occurrence and the absence of other stigmas of osteo-arthritis
are helpful in differentiating them. Curettage of the cyst and packing
with cancellous bone graft were performed in most reported cases
[4]. Various theories have been published about the origin of the
Interosseus ganglion, but the main etiology is still not clear.
There are two types of intraosseous ganglia: one originating by penetration of an extra-osseous ganglion into the underlying bone, the
other one is an idiopathic type [11]. The mechanism for the penetrating type is the erosion of an extraosseous ganglion through the
bone [12]. The primary or idiopathic type has no apparent extraosseous communication. The idiopathic type of ganglion cyst appears to
originate from modified mesenchymal or synovial cells at the capsule-synovial interface due to repeated minor injury, which explains
high prevalence of ganglion cyst in the scapho-lunate site where the
motion and force is concentrated. The repeated minor injuries and
mechanical stress cause intramedullary vascular disturbance leading
to aseptic bone necrosis. This is followed by proliferation of fibroblasts and histocytes and production of hyaluronic acid with mucoid
degeneration leading to the formation of the cyst.

Figure 5: Post-operative radiograph of scaphoid.

Discussion
Intraosseous ganglion may develop either within the bone near but
not directly communicating with a joint or from adjacent joint tissues
with secondary penetration into bone [2]. The first type is more commonly reported [3-5]. Intraosseous ganglion was described by Fisk in
1949 as a periosteal ganglion-like lesion developing a cystic bony
defect through intraosseous penetration [6]. In 1966, Crabbe named

Mainstay of treatment for the interosseous ganglion is by curettage


of lesion and bone graft [4]. We also performed curettage and bone
grafting, via volar approach. Patient was symptom free at three
months follow up and occurrence of trabeculations within 6 months
was noted radiologically. Complications due to intraosseous ganglion cyst are fracture and repeated erosion leading to rupture of
tendon mainly flexor tendon of finger. Re-occurrence of cyst can occur after bone graft. Castellanos reported a case of pathological fracture of the scaphoid due to intraosseous ganglion followed by regression of the cyst after healing of the fracture [13]. Regression of

http://www.mednifico.com/index.php/elmedj/article/view/347

410

scaphoid ganglion can occur with uneventful healing of the fracture


[14].

Conclusion
Cases of intraosseous ganglions are reported in literature mostly in
lower limbs and lunate among carpals, with scaphoid being a rare
site of the involvement. In this report, we described a symptomatic
case which was successfully treated by intralesional curettage, and
autogenous bone grafting.
Competing interests: The authors declare that no competing interests exist.
Received: 1 August 2014
Accepted: 3 January 2015
Published Online: 3 January 2015

References
1. Schajowicz F, Sainz MC, Slullitel JA. Juxta-articular bone cysts (intra-osseous
ganglia): a clinicopathological study of eighty-eight cases. J Bone Joint Surg
Br. 1979;61(1):107-116
2. Fealy MJ, Lineaweaver W. Intraosseous ganglion cyst of the scaphoid. Ann Plast
Surg 1995;34:2157

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Intraosseous ganglion cyst of scaphoid: A case report

3. Uriburu IJ, Levy VD. Intraosseous ganglia of the scaphoid and lunate bones:
report of 15 cases in 13 patients. J Hand Surg 1999;24:66770
4. Iwahara T, Hirayama T, Takemitu Y. Intraosseous ganglion of the lunate. The
Hand 1983;15:2979
5. Bowers WH, Hurst LC. An intraarticular-intraosseous carpal ganglion. J Hand
Surg 1979;4:3757
6. Fisk GR. Bone concavity caused by a ganglion. J Bone Joint Surg Br.
1949;31B(2):220
7. Crabbe WA. Intra-osseous ganglia of bone. Br J Surg. 1966;53(1):15-7.
8. Feldman F, Johnston A. Intraosseous ganglion. Am J Roentgenol Radium Ther
Nucl Med 1973;118:32843
9. Schajowicz F, Sainz MC, Slullitel JA. Juxta-articular bone cysts (intraosseous
ganglia). J Bone Joint Surg 1979;61b:10716.
10. Sim FH, Dahlin DC. Ganglion cysts of bone. Mayo Clin Proc 1971;46:4848.
11. Schajowicz F, Clavel Sainz M, Slullitel JA. Juxta-articular bone cysts (intraosseous ganglia): a clinicopathological study of eighty-eight cases. J Bone
Joint Surg Br. 1979;61(1):107-16
12. Bennett DC, Hauck RM. Intraosseous ganglion of the lunate. Ann Plast Surg.
2002;48(4):439-42
13. Castellanos J, Bertran C, Perez R, Roca J. Pathological fracture of the scaphoid
caused by intraosseous ganglion followed by regression after the healing of
the fracture. J Trauma; 2001; 51; 1; 141-3.
14. De Smet L, Fabry G. Regression of an intraosseous ganglion of the scaphoid
following fracture. Acta Orthop Belg 1994; 60; 4; 434-5.

http://www.mednifico.com/index.php/elmedj/article/view/346

411

Open Access

Case Report

Half annular pancreas - a cadaveric case report


B Satheesha Nayak1, Naveen Kumar1, Srinivasa Rao Sirasanagandla1, Ravindra S Swamy1, S Sudarshan1

Abstract
Background: Annular pancreas is an unusual and not often reported congenital anomaly of the pancreas. Thus, it is rarely suspected when
the patient is asymptomatic. However, the condition may be occasionally associated with other clinical complications of the abdomen.
Case Presentation: We report here a case of partial or incomplete annular pancreas detected during cadaveric dissection. A triangular
projection from the head of the pancreas extended over the anterior surface of the second part of the duodenum and covered its major
portion. As a possible compression effect, the first part of the duodenum was dilated.
Conclusion: Prior knowledge of existence of incomplete annular pancreas helps in the diagnostic approach of radiological procedures. As
annular pancreas may predispose to other congenital or morphological abnormalities, its timely diagnosis is warranted. (El Med J 2:4; 2014)
Keywords: Pancreas, Annular Pancreas, Duodenum

Introduction
Annular pancreas (AP) is an uncommon congenital anomaly in which
the second part of the duodenum is usually, either completely or
partially, encircled by a ring of pancreatic tissue, which eventually
becomes continuous with the head of the pancreas [1]. Embryologically, the pancreas exhibits dual or combined source of embryogenesis by the ventral and dorsal endodermal pancreatic buds at the
junction of foregut and midgut. Both the buds lie in relation to the
corresponding surfaces of developing duodenum. With the deferential development of duodenum as to rotate to right side, ventral pancreatic bud moves dorsally and lies caudal to dorsal pancreatic bud,
with the subsequent fusion along with its parenchyma and duct [2].
Faulty migration process results in congenital complete or incomplete annulations of the pancreas surrounding the 2nd part of the
duodenum. The pathogenesis of AP is debatable as there are several
differences in the opinions among the researchers. However, one of
the oldest hypotheses, popularly known as Leccos theory being acceptable to many researchers states that, adherence of distal tip of
ventral pancreatic bud to duodenum before its migration results in
the formation of obstructive pancreatic ring [3].
Overall incidence of AP is reported to be one in 20,000 newborns
with higher frequency among males. It has been associated with polyhydramnios [4]. The occurrence of AP in the form of complete and
incomplete ring is reported to be 25% and 75% respectively [5]. Although the AP commonly affects the 2nd part of the duodenum, occasionally 1st and 3rd part of the duodenum may also be victimized
by the annulations. Thus, it has been estimated that, in 74% of cases
AP is confined to 2nd part, whereas in 21% cases it affects the 1st and
3rd part of the duodenum [6].Rarely, AP can be associated with other
congenital abnormalities such as Downs syndrome, tracheo-esophageal fistula, atresia of the intestine and pancreaticobiliary malrotation [7]. Therefore, it becomes compulsory for clinicians to look for
AP in patients with symptoms of acute pancreatitis and other congenital disorders, in order to prevent undue delay in the treatment
which might lead to irreversible clinical complications.

Case Report
During routine dissection classes for medical undergraduates, we
found a rare case of half annular pancreas. The head of the pancreas
Melaka Manipal Medical College (Manipal Campus), Manipal University, Madhav
Nagar, Manipal, Karnataka State, India

had a triangular projection towards the right that covered the anterior surface of 2nd part of the duodenum almost completely (Figures
1 and 2). This was found in a South Indian male cadaver, approximately aged 65 years. During life, this half annulus formed by the
head of the pancreas would have had a compressive effect on the
second part of the duodenum. As a possible result of this the 1st part
of duodenum was dilated. The half annulus measured 3 inches vertically and 2 inches transversely and was apparently normal. The histology of this projection did not indicate any tumorous changes (Figure 3). Slight autolysis of pancreatic acini was evident and this was
possibly because of the delay in embalming the cadaver. Other parts
of the pancreas were also normal.

Figure 1: Dissection of the upper abdomen showing the half


annular pancreas. (HP head of pancreas; 2D second part of
duodenum; 3D third part of duodenum; SMA superior
mesenteric artery; SMV superior mesenteric vein; MCA middle
colic artery; TMC transverse mesocolon; AC ascending colon).

Discussion
The major risk of AP is that it may constrict the duodenum and therefore impair the flow of its contents. However, this risk is not evident
in all cases of AP [8]. The existence of complete AP is generally encountered during the neonatal stage, whereas incomplete or partial
annular pancreas may not present till adulthood [9]. At times, AP
may remain asymptomatic in adults, but congenital AP is frequently
characterized by severe duodenal obstruction which necessitates instantaneous surgical intervention in the infants. However, in adults
when it becomes symptomatic it is usually associated with peptic
ulcer, inflammation of the pancreas and or obstructive jaundice [10].

Correspondence: Naveen Kumar


Email: naveentonse@gmail.com

2014 Nayak et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Nayak BS, Kumar N, Sirasanagandla SR, Swamy RS, Sudarshan S: Half annular pancreas - a cadaveric case report. El Mednifico Journal 2014, 2(4).

412

Half annular pancreas - a cadaveric case report

agnosis as tumors of duodenum. According to Maker et al., enteroenterostomy may be considered successful interventional therapeutic tool over the conventional ERCP in the diagnostic approach
of AP [17].

Figure 2: Dissection of the upper abdomen showing


the half annular pancreas and associated dilation of
the first part of duodenum. (HP head of pancreas; 1D
first part of duodenum; 2D second part of duodenum;
3D third part of duodenum; S stomach; P pylorus;
SMA superior mesenteric artery; SMV superior
mesenteric vein; GDA gastroduodenal artery)

The current case, presenting a half annular pancreas is remarkable,


because it might mislead the clinicians as neoplasmic growth. To rule
out possibility of any neoplasm, we examined the extended mass of
pancreatic tissue histologically. The microscopic anatomy revealed
the normal pancreatic tissue morphology except for the slight postmortem changes of the cell structure. This is possibly because of delay in the process of embalming the cadaver that might have led to
autolytic effects of pancreatic acini.

Conclusion
In conclusion, unusual case of partial annular pancreas that we report here might not be a congenital malformation. However, its presence might lead to misinterpretation in the conventional radiologic
procedures which in turn might cause superfluous trouble to the patients.
Competing interests: The authors declare that no competing interests exist.
Received: 21 July 2014
Accepted: 3 January 2015
Published Online: 3 January 2015

Figure 3: Microscopic anatomy of the half annulus of


pancreatic tissue under low power magnification of a
light microscope. There is no evidence of any neoplasia.
However, slight autolysis of the parenchyma is evident.

Yogy et al, in their study of AP by endoscopic retrograde cholangiopanreaticography (ERCP), categorized its pattern based on the duct
system [11]. According to the authors, the most frequent type of AP
will have annular duct arising from main pancreatic duct. The main
pancreatic duct itself encircling the duodenum makes next highest
frequency of AP. AP may rarely be associated with the cases such as
pancreatolithiasis or malignancy of the pancreas [9, 12]. In such
cases, the differential diagnosis becomes difficult for the clinicians
and pathologists [13]. Therefore, it is advisable to rule out AP as a
coexistence of pancreatic malignancy, pancreaticolithiasis, as AP may
predispose these complications.
A rare case of acute pancreatitis localized in an annulus of AP in a
child of 6 years old has been reported by Ohino and Kanematsu [14].
Rarely, portal annular pancreas can be encountered. Such a case of
incomplete annular pancreas around the contents of right free margin of lesser omentum has been reported by Srinivasa et al [15]. This
phenomenon is vulnerable to cause duodenopancreatic reflux during pancreatic resection procedures, if overlooked. Extremely rare
case of double AP, in which the uncinate process of the pancreas
surrounded the 3rd part of the duodenum completely and pancreatic
tissue extending from the head of the pancreas encircling junction
of 1st and 2nd part of the duodenum incompletely was reported by
Satheesha et al. [16].
Prior knowledge of rare occurrence of AP, particularly partial AP is
necessary to the clinician before performing conventional radiography, CT and MR pancreatography procedures to rule out faulty di-

Vol 2, No 4

References
1. Miyazawa M, Muto A, Sato M, Koyama K, Endo H, Ashino Y. A case of annular
pancreas in a male adult. Fukushima J Med Sci 2004,50(2):75-81
2. Langman J. Medical embryology. 6th ed. Baltimore, Md: Williams & Wilkins,
1989: pp. 245-247.
3. Lecco TM. Zur morphologie des pankreas annulare.Sitzungsberichte der
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4. Jarry J, Wagner T, Rault A, Sa Cunha A, Collet D. Annular pancreas: A rare cause
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adults. American Journal of Roentgenology 2009, 193(2):455460.
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von Alllgower M, Harder F, Hollender F, Peiper J (eds) Chirurgische
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9. Sharma AK, Mishra PK, Chibber S. Annular pancreas: MR and MR
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pancreas derived from pair ventral pancreata, supporting Balwins hypothesis.
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11. Yogi Y, Shibue T, Hashimoto S: Annular pancreas detected in adults diagnosed
by ERCP: report of four cases. Gastroenterol Jpn 1987; 22:92-99.
12. Yogi Y, Kosai S, Higashi S, Iwamuara T, Setoguchi T. Annular pancreas
associated with pancreatolithiasis: a case report. Hepatogastroenterology
1999,46(25):527-31
13. Gilinsky NH, Lewis JW, Flueck JA, Fried AM. Annular pancreas associated with
diffuse chronic ancreatitis. Am. J Gastroenterology 1987; 82:681-684.
14. Ohino Y, Kanematsu T. Annular pancreas causing localized recurrent
pancreatitis in a child: report of a case. Surg Today 2008, 38(11):1052-5
15. Srinivasa R S, Satheesha B N, Kumar MR Bhat. A Rare Congenital Anomaly of
the Pancreas:A Cadaveric Case Report. J. Pancreas 2013,10; 14(4):454-457.
16. Satheesha N, Narendra P, Bincy M G, Anitha G. A Strange Case of Double
Annular Pancreas. J Pancreas (Online) 2013, 10; 14(1):96-98.
17. Maker V, Gerzenshtein J, Lerner T. Annular pancreas in the adult: two case
reports and review of more than a century of literature. Am Surg 2003,
69(5):404-410.

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413

Open Access

Case Report

Treatment option for deficient maxilla by bone expansion using D-shaped bone expander for implant
restorations
Satheesh B Haralur1, Farhan K Shah2, Nausheen Khan2

Abstract
Background: Researchers are continuously developing various implant site development techniques to improve the predictability of
implant restoration. The bone expansion from osteotome is a simple technique to improve the bone width, and is mainly applied to
maxillary bone. It enables the dentist to select the optimum implant location and orientation for better functional and aesthetic
rehabilitation.
Case Presentation: A male patient of 30 years of age with history of tooth extraction nine weeks before due to non-restorable carious
tooth destruction, reported to our department of Prosthodontics wanting to replace missing 11 and 16. Clinical examination of the
extracted site with digital palpation, bone mapping showed the deficient bone width in both the region for the adequate implant size and
buccal soft tissue concavity in the lateral incisor region. Bone mapping revealed the underlying bone was deficient in width by 1-1.5 mm
for 3.4-3.8 mm diameter implant placement. Following conventional Panoramic, peri-apical radiographs, initial clinical examinations dental
implants were advised with bone expansion by osteotomes.
Conclusion: The osteotome techniques are a predictable, simple alternative to complex augmentation techniques to place an implant in
case of bone atrophy. The bone expansion technique is limited to maxillary the bone, with bone width deficient less than 3 mm. Since it
is a single stage surgical procedure, it is advantageous for the patient for early prosthetic replacement. (El Med J 2:4; 2014)
Keywords: Maxillary Dentures, Implant Supported Prosthesis, Ridge Augmentation

Introduction
The implant supported prosthesis has multiple advantages over the
conventional denture. It is advantageous over conventional prosthesis due to its better support, retention, phonetics and improved masticatory efficiency. The aesthetic satisfaction is very essential for the
success of the prosthesis especially in the anterior region [1]. The
healthy peri-implant tissue contours in harmony with adjacent teeth
is critical for the positive aesthetic outcome of the prosthesis [2].
Subsequent to tooth extraction, the overlying tissue contours are
changed due to resultant bone loss in both horizontal and vertical
direction [3, 4]. The change in underlying bone morphology leads to
loss of papillae and gingival contour. The deficient bone volume also
compromises the optimal implant positioning [5]. Lack of proper position and orientation of the implant will impede the restoration of
function and aesthetics by prosthesis [6]. Other deleterious consequences of bone are the insufficient osseo-integration, loss of initial
stability, and support for the prosthesis [7, 8]. The efficiency of the
oral hygiene measures also compromised due deficient soft tissue
contours and crestal bone loss [9]. Satisfactory bone density and volume is decisive in the implant treatment prognosis. Deficient bone
should not encourage the dentist to place the implant in the ineffective area for a prosthesis.
Since the ridge grafting becomes more and more problematic as
time passes, efficient alternative techniques are explored by the researchers. The osteotome technique is one such method dentists can
efficiently apply for atrophic maxillae to prepare the implant bed [10,
11]. The maxillary bone atrophy in anterior region results in compromised osseo-integration and un-aesthetic concavity [12]. Bone expanders are hand instruments used to separate the labial and palatal
cortical lamellae by applying a controlled force using surgical mallet.

Department of Prosthodontics, College Of Dentistry, King Khalid University, Abha,


Kingdom of Saudi Arabia
2Integrative Medical Biology, Umea University, Umea, Sweden
1

Along with widening the narrow residual ridges, they are also utilized for bone condensation and maxillary sinus elevation. The objective of this case report is to highlight the improvement in aesthetics and osseo-integration by the simple process of bone expansion.

Case Presentation
A male patient of 30 years of age reported to our Department of
Prosthodontics wanting to replace missing 11 and 16. The patient
presented the history of tooth extraction nine weeks before, due to
non-restorable carious tooth destruction. The patient desired to have
fixed prosthetic option, but was not inclined for the required abutment tooth preparation for conventional tooth supported fixed partial denture. The patient had a high lip line, and his both posterior
maxillary segments were visible during a smile. The upper and lower
lip contours were satisfactory during the test. The patient's past medical history had no significant findings to negatively impact the dental implant treatment. The patient reported to be non-smoker and
wanted to replace the missing teeth in a relatively short time due to
his marriage.
Clinical examination of the extracted site with digital palpation, bone
mapping showed the deficient bone width in both the region for the
adequate implant size and buccal soft tissue concavity in the lateral
incisor region. Bone mapping revealed the underlying bone was deficient in width by 1-1.5 mm for 3.4-3.8 mm diameter implant placement. The patients economic constraints prevented the digital radiography evaluations and conventional bone augmentation with
graft techniques. Following conventional panoramic, peri-apical radiographs and initial clinical examinations, dental implants were advised with bone expansion by osteotomes. In addition to being a
simple procedure, bone expansion by osteotome is more economical and allows the simultaneous implant placement.

Correspondence: Satheesh B Haralur


Email: hb_satheesh@yahoo.com

2014 Haralur et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Haralur SB, Shah FK, Khan N: Treatment option for deficient maxilla by bone expansion using D-shaped bone expander for implant restorations. El Mednifico Journal 2014, 2(4).

414

Treatment option for deficient maxilla by bone expansion

The treatment objective was to replace the missing maxillary teeth


with implant supported fixed prosthesis following implant site augmentation. The treatment options to augment the implant site was
discussed with the patient. Owing to time and economic constraints,
the bone expansion with osteotome was finalized. Clinical examination showed the bone width was deficient by 1-1.5, favoring the
bone expansion technique.
A full thickness muco-periosteal flap was elevated to completely expose the residual ridge. This enables the clinician to evaluate the
ridge and make the osteotomy with direct vision. Bony spicules and
sharp bone of the crestal bone was trimmed with bone files and a
small round bur was used to penetrate the crestal bone slightly. A
small diameter pilot drill (2 mm) was used for initial insertion and
creating a trench. The pilot drill was placed in the center of the crest
or slightly palatal to avoid the expansion of the atrophic ridge predominantly at the expense of the labial plate. The pilot drill guided
the subsequent osteotomes to the predetermined direction and
depth for planned 13 mm implants.
ANKYLOS D (DENTSPLY, Waltham, MA,USA) shape bone expanders
were used in gradually greater diameter starting from No 1 (2 mm)
till 02 (3.5 mm) slowly malleting them deeper. The force was directed
over the long axis of the bone expander. The convex shape of the Dshaped profile of the instrument should face towards the labial side
and the flat side towards the palatal bone lamella to prevent the
extreme tension in the labial cortical plate. The periodic pausing during bone expansion was allowed for the viscoelastic bone to adapt
to the expansion. The bone expander was rotated with a gentle pulling force to allow a traumatic removal of the instrument. Digital pressure on the labial plate was applied to help support the bone during
the preparation and detect apical perforation.
Implant site preparation was completed using the implant drills sequentially till 3.4 mm diameter and 13 mm length followed by crestal
widening drill of the same diameter. A XiVE implant (DENTSPLY Implants, Waltham, MA, USA) of the diameter of 3.4 mm and length 13
mm was hand ratcheted in an osteotomy site for the lateral incisor
region; this allowed the final expansion of the ridge. Consequently,
a second implant of 3.8 mm diameter and 13 mm length was placed
in the missing first molar (Figures 1 and 2). Following implant placement healing cap was placed, and the patient was discharged with
required postoperative instructions.

Figure 1: Implant with abutment for lateral incisor after bone expansion.

Vol 2, No 4

Figure 2: Final prosthesis with good aesthetic appearance.

The patient was recalled after 48 hours to evaluate the post-operative signs and symptoms. He reported minimal postoperative discomfort. He was reviewed and monitored for eight weeks with inbetween two-week interval. The patient was advised for prosthetic
part of the treatment after eight weeks with evaluation of pre and
post-operative radiographs and clinical examinations. The missing
teeth were replaced with cemented porcelain fused to metal crowns
using standard prosthodontic procedures. The patient was recalled
after three months and six months to evaluate the implant supported prosthesis. The patient was satisfied with functional and aesthetic rehabilitation.

Discussion
Alveolar bone is developed in conjunction with tooth eruption and
depends on the tooth. Tooth extraction leads to drastic changes in
bone anatomy and its volume [13]. Post extraction accelerated ridge
resorption is observed both in horizontal and vertical directions in
first 3-6 months, and it is continued at a slower rate throughout the
life [14].
The divergent alveolar bone, thin facial alveolar bone in the maxilla
make it susceptible for higher resorption following tooth extraction.
Post extraction atrophy patterns necessitate implant site development to achieve the optimum implant position and direction [15].
The implant should be orientated in harmony with the coronal tooth
form. Implant restorations to be considered as successful should totally satisfy the functional and the aesthetic demand of the patient.
The important aesthetic parameter is the soft tissue profile identical
to the contralateral natural healthy teeth [16, 17]. Insufficient bone
volume also compromises the osseo-integration and oral hygiene
measures.
Implant restoration in the esthetic zone requires meticulous treatment plan to decide on the implant size, position, soft and hard tissue management [18]. The pre-operative bone volumes are evaluated by palpation, bone mapping and computed radiography. Bone
volume evaluation will help the clinician to make a decision on surgical or nonsurgical bone augmentation technique to make implant
position prosthetically feasible. Numerous surgical bone augmentation techniques are proposed to deal with inadequate dental implant
site bone volume. Bone expansion with expanders methods is advised for the situation of deficient bone width. Bone expansion with
osteotome is utilized for the atrophic bone to enhance the bone
width and to secure the ideal dental implant placement.

Haralur SB, Shah FK, Khan N

Summers in 1994 proposed the first cylindrical-conical expansion osteotomes for the preparation of implant site in the maxillary bone
[19]. The angled designs are available for posterior segments to enhance access. Researchers have modified osteotomes into different
variants, to be used as chisels, expansion screws and surgical techniques [20]. The instruments are designed to compress the bone laterally to increase the trabecular density adjacent to the site and improve the primary implant stability. Bone expansion by osteotomes
are advised for maxillary bone only due to its spongy, cancellous
bone content [21]. This nature of the bone allows the lateral compression and expansion of adjacent area. Bone expansion with expander is discouraged for mandibular sites due to increased density
and reduced bone plasticity.
Osteotome technique is advantageous over other techniques. The
procedure is a single stage surgical placement of dental implant and
does not require extended surgical time. Assessment of the bone
volume is critical for case selection, since bone width deficient more
than 3 mm is not recommended for bone expansion. Large bone
deficiency requires the additional complimentary bone grafts. Osteotome is inserted into the bone by the precise application of force.
Uncontrolled percussion force leads to patient discomfort, labyrinthine concussion, and benign paroxysmal positional vertigo [22, 23].
This method is also utilized for indirect maxillary sinus lift by fracturing the cortical layer and separating the sinus membrane [24]. Osteotome bone expansion if carefully applied to maxilla, is highly predictable surgical procedure to improve the implant site.

Conclusion
The success of implant restorations in the anterior region predominantly depends on the aesthetic satisfaction of the patient. The osteotome techniques are a predictable, simple alternative to complex
augmentation techniques to place an implant in case of bone atrophy. Bone expansion technique is limited to maxillary the bone, with
bone width deficient less than 3 mm. Since it is a single stage surgical
procedure, it is advantageous for the patient for early prosthetic replacement.
Competing interests: The authors declare that no competing interests exist.
Received: 5 September 2014
Accepted: 3 January 2015
Published Online: 3 January 2015

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http://www.mednifico.com/index.php/elmedj/article/view/344

Open Access

Case Report

Coexistence of a normal thyroid with a non-functional ectopic thyroid tissue: a case report with review
Sunder Goyal1, Snigdha Goyal2, Shveta Narang1, Isha Saini3

Abstract
Background: Ectopic thyroid is not uncommon but presence of non-functional ectopic thyroid tissue in the neck with a coexisting normal
thyroid is quiet rare.
Case Presentation: A 10-year-old female presented with a mass in the anterior upper neck. The thyroid function tests of the patient were
within normal limits. Ultrasonography revealed a normal thyroid gland and a solid mass in the midline of upper half of neck. Fine needle
aspiration cytology (FNAC) of swelling revealed thyroid tissue. Scintigraphy showed a normal thyroid and the mass didnt show any uptake
of 99mTcO4. The mass was excised. Histopathology proved it as ectopic thyroid tissue. The patient had an uneventful recovery.
Conclusion: Diagnosis of ectopic thyroid tissue poses dilemma to treating physician. In order to prevent misdiagnosis and mismanagement,
it is mandatory to prove presence of normal thyroid tissue in lower neck with the help of 99mTcO4 scintigraphy. (El Med J 2:4; 2014)
Keywords: Ectopic Thyroid, Coexisting Normal Thyroid, Scintigraphy

Introduction
Ectopic thyroid tissue is a congenital disease caused by the abnormal
migration of thyroid tissue in the embryonic stage [1]. It is relatively
uncommon and is defined as thyroid tissue not located anterio-laterally to the second and fourth tracheal cartilages. Commonly, ectopic thyroid is located in the midline, between the foramen caecum
and the normal location of the thyroid gland, and most often it is
located in the base of the tongue.
It can be asymptomatic neck mass or can present with dysphagia,
dysphonia or dyspnea, according to the size and location of ectopic
tissue. In the majority of cases, ectopic thyroid is the only thyroid
tissue present [1]. But in our case there was coexistence of ectopic
thyroid tissue with normal thyroid gland. This is an uncommon condition, hence, we report this 12 years girl who presented with asymptomatic midline upper neck mass.

Thyroid function tests, as well as the thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels of the patient were normal. Blood
serum calcitonin, calcium and parathyroid hormone (PTH) levels
were normal. A neck ultrasound revealed a normal thyroid gland at
its normal location in lower neck and a solid mass of heterogeneous
echotexture in the midline of upper neck. Ultrasound guided fine
needle aspiration (FNA) was done. Aspirated fluid was thick brownish in color. Smears prepared were air dried and wet fixed and were
stained with May Grunwald Giemsa and papanicolaou stain. Smears
showed abundant thick as well as thin colloid with a few clusters of
benign follicular epithelial cells. There were no squamous or columnar epithelial cells which ruled out thyroglossal cyst (Figure 2). Diagnosis of ectopic thyroid tissue was made.

Case Report
A 12-year-old female child presented with a painless mass in the middle of the upper neck for the last 6 months. The patient was asymptomatic. Physical examination revealed a 2.5 x 2 cm non-tender mass
in the midline (Figure 1). It was moving with deglutition and with
tongue protrusion. Considering the age and location a provisional
diagnosis of thyroglossal cyst was made.

Figure 2: Abundant thick as well as thin colloid with a few clusters of benign
follicular epithelial cells.
99m

Figure 1: Midline upper neck swelling.

Department of Surgery, Kalpana Chawla Govt Medical College, Karnal, Haryana,


India
2Department of Pathology, Dr RML Postgraduate institute of Medical sciences,
New Delhi, India
1

TcO4 scintigraphy of the patients neck revealed the normal thyroid gland at its normal site; the upper midline upper neck swelling
did not show any uptake of 99mTcO4.The mass was resected and it
was well encapsulated separate structure from the normal thyroid
gland. Histopathological examination revealed follicles lined with cuboidal epithelium and distended with colloid material. Postoperatively the patient was euthyroid and had normal calcium levels.

Ex Physician, Life Line Clinical & diagnostic Centre, Karnal, Haryana, India
Correspondence: Sunder Goyal
Email: goyal.sunder@yahoo.in

2014 Goyal et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Goyal S, Goyal S, Narang S, Saini I: Coexistence of a normal thyroid with a non-functional ectopic thyroid tissue: a case report with review. El Mednifico Journal 2014, 2(4).

Goyal S, Goyal S, Narang S et al.

Discussion
Ectopic thyroid tissue, defined as thyroid tissue not located anteriolaterally to the second and fourth tracheal cartilages, is uncommon.
It is a congenital disease caused by abnormal migration of thyroid
tissue in the embryonic stage. During embryogenesis, the descent of
the thyroid does not proceed normally, leading to various possible
anomalous locations of the gland. According to the timing of the
embryonic development, thyroid descent may stop at various sites,
from the base of the tongue to any site of the thyroglossal duct. In
the majority of cases it is located in the midline, between the foramen caecum and the proper location of the thyroid gland, and most
often it is located in the base of the tongue. It was first described by
Hickman in 1869 in a newborn baby who died after birth due to suffocation caused by a lingual thyroid [2].
The commonest form of ectopic thyroid is lingual thyroid, which may
cause dysphonia. Next common site is midline of neck along the path
of the thyroglossal duct. In the patient in the present study, it was
located in midline in the upper neck. Other uncommon sites of ectopic thyroid are the submandibular region, lower neck, parotid salivary gland, trachea, lateral to the carotid arteries and jugular veins,
mediastinum, heart, lung, duodenum, adrenal gland and uterus [38].
The exact incidence of ectopic thyroid is not known. Post-mortem
studies proposed that incidence of asymptomatic thyroid tissue may
be about 710% of adults. Mostly, ectopic thyroid tissue may be the
only functioning tissue and rarely may be affected with thyrotoxicosis [9]. Rarely, it may coexist with a normal thyroid gland, as in the
present case [3, 4].
Clinical presentation can be as asymptomatic neck mass or with dysphagia, dysphonia or dyspnea, according to the size and location of
ectopic tissue like over trachea or in mediastinum. Diagnostic modalities are ultrasound, color Doppler ultrasonography (CDU), grayscale ultrasonography (GSU), computerized tomography and magnetic resonance imaging (MRI) [10]. Radionuclide imaging (RI) is considered the definitive diagnostic test method for detecting ectopic
thyroid tissue. FNAC is mandatory for tissue diagnosis.
Ectopic thyroid tissue may undergo pathological changes such as
thyrotoxicosis and malignancy like normal thyroid gland. Malignant
changes in ectopic thyroid tissue are rare but if thyroid tissue is

417

found in the lateral cervical lymph nodes, then metastasis of a malignant thyroid tumor should be excluded.
Treatment is excision of ectopic thyroid mass if it is non-functional
and normal thyroid gland is present and functional. Treatment of ectopic thyroid tissue depends on factors such as mass size, local symptoms, age of the patient, the functional status of the thyroid gland
and complications, including ulceration, hemorrhage and neoplasia.

Conclusion
Diagnosis of ectopic thyroid tissue poses dilemma to treating physician. In order to prevent misdiagnosis and mismanagement, it is
mandatory to prove presence of normal thyroid tissue in lower neck
with the help of 99mTcO4 scintigraphy.
Competing interests: The authors declare that no competing interests exist.
Received: 31 August 2014
Accepted: 3 January 2015
Published Online: 3 January 2015

References
1. Noussios G, Anagnostis P, Goulis DG, Lappas D, Natsis K. Ectopic thyroid tissue:
anatomical, clinical, and surgical implications of a rare entity. Eur J Endocrinol.
2011;165:375382.
2. Kumar Choudhury B, Kaimal Saikia U, Sarma D, et al. Dual ectopic thyroid with
normally located thyroid: a case report. J Thyroid Res. 2011;2011:159703.
3. Feller KU, Mavros A, Gaertner HJ. Ectopic submandibular thyroid tissue with a
coexisting active and normally located thyroid gland: case report and review
of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:618
623.
4. Wei Zheng, Jian Tan, Tong Liu. Coexistence of non-functional ectopic thyroid
tissue and a normal thyroid: A case report Exp Ther Med. Oct 2013; 6(4): 1059
1061.
5. Mysorekar VV, Dandekar CP, Sreevathsa MR. Ectopic thyroid tissue in the
parotid salivary gland. Singapore Med J. 2004;45:437438.
6. Casanova JB, Daly RC, Edwards BS, Tazelaar HD, Thompson GB. Intracardiac
ectopic thyroid. Ann Thorac Surg. 2000;70: 16941696.
7. Shiraishi T, Imai H, Fukutome K, Watanabe M, Yatani R. Ectopic thyroid in the
adrenal gland. Hum Pathol. 1999;30:105108.
8. Yilmaz F, Uzunlar AK, Sgt N. Ectopic thyroid tissue in the uterus. Acta
Obstet Gynecol Scand. 2005;84:201202.
9. Kumar R, Gupta R, Bal CS, Khullar S, Malhotra A. Thyrotoxicosis in a patient with
submandibular thyroid. Thyroid. 2000;10:363365.
10. Ohnishi H, Sato H, Noda H, Inomata H, Sasaki N. Color Doppler
ultrasonography: diagnosis of ectopic thyroid gland in patients with
congenital hypothyroidism caused by thyroid dysgenesis. J Clin Endocrinol
Metab. 2003;88:51455149.

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Open Access

Case Report

Literature evaluation of a case with endometrial cancer and primary cutaneous anaplastic large cell
lymphoma
Feryal Karaca1, Fatma Sert2, Elif Cals3, Emine Bagr4, Erkut Erkut5

Abstract
Background: Radiotherapy (RT) is used as an indispensable treatment approach for cancer therapy as an adjuvant or alone for definitive
option. For early stage endometrial cancer, RT is applied after operation as an adjuvant. Primary cutaneous anaplastic large cell lymphoma
(PCALCL) is a type of lymphoma which is seen rarely and has excellent prognosis with accurate treatment. It is another indication for RT.
Developments in the diagnosis and the treatment of PCALCL have improved the disease prognosis and outcomes.
Case Presentation: We present a case of a 55-years-old patient who had endometrial cancer and PCALCL, whose 9 years follow-up period
was excellent with no recurrences and no metastasis. The outcome was achieved with the combination of surgery and RT.
Conclusion: The presented case is important for long follow-up duration with no metastasis and/or no recurrences with single RT usage in
both primary cancers. Single RT applications may be considered as an initial treatment option for surgically excised PCALCL with excellent
outcome. (El Med J 2:4; 2014)
Keywords: Radiotherapy, Endometrial Carcinoma, Primary Cutaneous Anaplastic Large Cell Lymphoma

Introduction
Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a type
of lymphoma which is seen rarely and has excellent prognosis with
accurate treatment [1]. The differential diagnosis from carcinoma
metastasis, malignant melanoma or malignant histiocytosis must be
done carefully. Recent developments in the diagnosis and treatment
of PCALCL have improved the disease prognosis and outcomes.
We present a case of a patient, who was followed for 9 years without
any relapse and/or metastasis, with two primary cancer diagnoses
(PCALCL and endometrial carcinoma) and discuss new literature regarding PCALCL treatment.

excision was applied to the lesion due to not obtaining any response
to medical therapy. T-cell lymphoblastic disease, CD30+, lymphomatoid papulosis type C was reported in pathologic report and diagnosis was given as CD30+, CD3+, CD4+, CD5+ (Figure 3-7). Beta-2 microglobulin level of the patient was detected high (2.06; range: 0.8-1.8).
Thereafter, bone marrow biopsy and whole body Positron Emission
Tomography-Computed Tomography (PET-CT) screening were done.
Neither bone marrow biopsy nor PET-CT results showed any pathological finding. Only, minimal FDG uptake was seen in excision area
(Figure 8). Electron beam irradiation to the excision bed was performed by using 200 cGy per fraction daily doses to 4000 cGy total
doses as a result of the diagnosis.

Case Presentation
Fifty five years-old woman with postmenopausal bleeding was evaluated for endometrial malignancy and no radiological dissemination
was found in her screening. She was operated in gynecologic oncology department with total abdominal hysterectomy and bilateral salpingo-oophorectomy operation. She was staged as 1B Grade 1 endometrial adenocarcinoma pathologically (Figure 1). Pelvic radiotherapy (RT) was planned to be applied to the patient in our gynecological oncology consult. Conformal RT with four fields (anteriorposterior, posterior-anterior, right and left side) including pelvic
lymph nodes, parametrium and operation bed was given by using
18 MV photon energy and 200 cGy daily doses in 25 fraction. 50 Gy
total dose was applied to the patient. The patient was followed for 5
years without any recurrences and metastatic disease in terms of endometrial carcinoma.
A non-healing, ulcero-vegetant lesion, macroscopically 5 x 3 x 2 cm
sized lesion located in posterior of the left thigh, was detected in her
routine policlinic control after 5 years (Figure 2). No response was
seen despite use of oral and topical antibiotic treatment. Surgical

Department of Radiation Oncology, Van Regional Training and Research Hospital,


Van, Turkey
2Department of Radiation Oncology, Denizli State Hospital, Denizli, Turkey
3Department of Pathology, Kilis State Hospital, Kilis, Turkey
1

Figure 1: Grade 1 endometrial adenocarcinoma with >50% myometrial invasion and including
glandular and papillary tissues (H&E x40).

After 48 months from the treatment of second primary diagnosis, the


routine control of the patient was excellent; there was no recurrence
or metastatic lesion.

Department of Pathology, Cukurova University Hospital, Adana, Turkey


Department of Radiation Oncology, Cukurova University Hospital, Adana, Turkey
Correspondence: Fatma Sert
Email: gracilis81@yahoo.com

4
5

2014 Karaca et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Karaca F, Sert F, Cals E, Bagr E, Erkut E: Literature evaluation of a case with endometrial cancer and primary cutaneous anaplastic large cell lymphoma. El Mednifico Journal 2014, 2(4).

Karaca F, Sert F, Cals E et al.

Figure 2: Ulcerative and vegetan lesion


seen before treatment.

Figure 3: The neoplastic lymphoid cells infiltrating into the dermis


(H&E x40).

Figure 4: The lymphoid cells showing nuclear pleomorphisim (H&E x400).

419

Figure 6: The neoplastic cells straining positive with CD4 (x400).

Figure 7: The neoplastic cells straining positive in focal areas with CD2 (x400).

Figure 8: Hypermetabolic area in PET/CT scanning obtained after excision of


skin lesion.

Discussion
Extracutaneous involvement and lymph node metastasis are seen
rarely in localized PCALCL. PCALCL with extracutaneous involvement
shows worse prognosis than the others [2]. Ki-1 is an antigen which
activates CD30 and it is a member of tumor necrosis factor family
located in cell membrane. The patients with CD30+ disease show better response to the treatment than the ones without CD30 [1].
PCALCL consists of large, atypical cells resembling Reed Sternberg
cells histologically. These anaplastic cells can grow rapidly in inflammatory process [3].

Figure 5: The neoplastic cells straining strong positive with CD30 (x400).

PCALCL is a disease with indolent course and multidisciplinary management is required for the diagnosis and the treatment. Dissemination, multifocality, visceral organ involvement and lymph node me-

http://www.mednifico.com/index.php/elmedj/article/view/343

420

tastasis are of importance in prognosis of PCALCL. The given favorable factors in terms of overall survival are unifocality and local lymph
node metastasis. However, it is reported that multifocality and visceral organ involvement are unfavorable prognostic factors [4]. Local
surgical excision is the first and the most important management
step for unifocal PCALCL and it is reported that local surgical excision
is used for 19%-57% of patients in literature [2, 4, 5]. On the other
hand, the rate of recurrences is high after surgery alone [6].
Chemotherapy applications are preferred for multifocal lesions and
recurrent disease. Multiple agent combined chemotherapy has been
examined. As a choice for multi agent treatment, the use of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has
been evaluated for initial therapy in many researches [7-10]. Methotrexate, etoposide and gemcitabine are the agents used for single
agent chemotherapy applications [5, 11]. Monoclonal antibodies are
used for CD 30+ patients.
Surgical excision and RT are the most common and best documented therapies for solitary or localized PCALCL [6}. Cutaneous T
cell variants are quite radiosensitive [12]. Short plaques can be
treated perfectly by using low dose superficial orthovoltage therapy
or electron beams [13]. Irradiation doses change between 30-46 Gy
with a median diameter of the lesional region of 3 cm and a 2- to 3cm margin of uninvolved perilesional skin. RT with a dose of 40 Gy
in 2-Gy fractions has been reported to be well tolerated with only
mild and transient side effects [13].
A review of the literature reveals that RT alone has been preferred as
a local therapy option for 48% of patients [6]. Complete response
was obtained for 95% of these included patients with RT. After median 22 months follow-up (range: 5-95 month), 41% of them recurred with RT alone. Beljaards et al. reported a disease free duration
to first relapse of 14 months (range, 2-59 months) in 4 patients with
skin-limited relapses [14]. In our presented case, there was no recurrence in terms of both primaries after follow-up for 9 year from endometrium adenocarcinoma and 4 year from PCALCL.

Conclusion
The presented case is important for long follow-up duration with no
metastasis and/or no recurrences with single RT usage in both primary cancer diseases. Single RT applications may be considered as
an initial treatment option for surgically excised PCALCL with excellent outcome.
Competing interests: The authors declare that no competing interests exist.
Received: 20 August 2014
Accepted: 5 January 2015
Published Online: 5 January 2015

Vol 2, No 4

Endometrial cancer and primary cutaneous lymphoma

References
1. Droc, C., Cualing, H.D., Kadin, M.E. Need for an improved molecular/genetic
classification for CD30+ lymphomas involving the skin. Cancer Control.
2007;14(2):124-32.
2. N. Yamane, N. Kato, M. Nishimura, M. Ito, T. Yanagi, R. Osawa. Primary
cutaneous CD30+ anaplastic large-cell lymphoma with generalized skin
involvement and involvement of one peripheral lymph node, successfully
treated with low-dose oral etoposide. Clin Exp Dermatol. 2009;34(5):e56-9.
3. Kumar S, Pittaluga S, Raffeld M, Guerrera M, Seibel NL, Jaffe ES. Primary
cutaneous CD-30 positive anaplastic large cell lymphoma in childhood: report
of 4 cases and review of the literature. Pediatr Dev Pathol. 2005;8(1):52-60.
4. Kadin M.E. Current management of primary cutaneous CD30+T-cell
lymphoproliferative disorders. Oncology (Williston Park). 2009:30;23(13):115864.
5. Yamane N, Kato N, Nishimura M, Ito M, Yanagi T, Osawa R. Primary cutaneous
CD30_ anaplastic large-cell lymphoma with generalized skin involvement and
involvement of one peripherallymph node, successfully treated with low-dose
oral etoposide. ClinExpDermatol. 2009;34(5):e56-e59.
6. Kempf W, Pfaltz K, Vermeer MH, Cozzio A, Ortiz-Romero PL, Bagot M, et al.
EORTC, ISCL, and USCLC consensus recommendations for the treatment of
primary cutaneous CD30-positive lymphoproliferative disorders:
lymphomatoidpapulosis and primary cutaneous anaplastic large-cell
lymphoma. Blood. 2011;118(15):4024-35.
7. Liu HL, Hoppe RT, Kohler S, Harvell JD, Reddy S, Kim YH. CD30_ cutaneous
lymphoproliferative disorders: the Stanford experience in lymphomatoid
papulosis and primary cutaneous anaplastic large cell lymphoma. J Am Acad
Dermatol. 2003;49(6):1049-58.
8. Asha LK, Thomas D, Binitha MP, Nandakumar G. Primary cutaneous multifocal
CD30_ anaplastic large cell lymphoma. Indian J Dermatol Venereol Leprol.
2006;72(5):376-378.
9. Sheehy O, Catherwood M, Pettengell R, Morris TC. Sustained response of
primary cutaneousCD30 positive anaplastic large cell lymphoma to
bexarotene and photopheresis. Leuk Lymphoma. 2009;50(8):1389-1391
10. Diamantidis MD, Papadopoulos A, Kaiafa G, Ntaios G, Karayannopoulou G,
Kostopoulos I,et al. Differential diagnosis and treatment of primary, cutaneous,
anaplastic large cell lymphoma: not always an easy task. Int J Hematol.
2009;90(2): 226-229.
11. Duvic M, Reddy SA, Pinter-Brown L, Korman NJ, Zic J, Kennedy DA, et al. A
phase II studyof SGN-30 in cutaneous anaplasticlarge cell lymphoma and
related lymphoproliferative disorders. Clin Cancer Res. 2009;15(19):6217-6224.
12. Whittaker SJ, Marsden JR, Spittle M, Russel Jones R; British Association of
Dermatologists, UK. Cutaneus Lymphoma Group. Joint British Association of
Dermatologists and U.K Cutaneous Lymphoma Group guidelenes for the
management of primary cutaneos T cell lymphomas. Br J Dermatol.
2003;149(6):1095-1107.
13. Yu JB, McNiff JM, Lund MW, Wilson LD. Treatment of primary cutaneous CD30_
anaplasticlarge-cell lymphoma with radiation therapy. Int J RadiatOncolBiol
Phys. 2008;70(5):1542-1545.
14. Beljaards RC, Kaudewitz P, Berti E, Gianotti R, Neumann C, Rosso R, et al.
Primary cutaneous CD30-positive large cell lymphoma: definition of a new
type of cutaneous lymphoma with a favorable prognosis. A European
Multicenter Study of 47 patients. Cancer. 1993:15;71(6):2097-104.

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421

Open Access

Case Report

Occult medullary carcinoma of thyroid - an unusual clinical and pathologic presentation


Khalid S Aljabri1, Samia A Bokhari1, M Haq1, A Durani2, A Altayeb3, S J Alzahrani4, M Alshareef1

Abstract
Background: Medullary thyroid cancer is a neuroendocrine tumor originating from the parafollicular C cells of the thyroid which secrete
calcitonin. MTC accounts for approximately 4% of all clinically detected thyroid malignancies. The prevalence of occult MTC in the general
population is not well established.
Case Presentation: We describe a rare patient with occult sporadic MTC who presented with cervical lymphadenopathy and an
asymptomatic mediastinal mass and elevation of calcitonin and carcinoembryonic antigen levels.
Conclusion: Our practice is to recommend basal calcitonin testing for thyroid nodule patients with increased risk of MTC, including those
with a family history of MTC, with a diagnosis of hyperparathyroidism or pheochromocytoma, or symptoms of flushing or diarrhea. (El Med
J 2:4; 2014)
Keywords: Medullary Carcinoma, Thyroid Cancer, Occult, Neuroendocrine Tumor

Introduction
Approximately 10% of patients with thyroid cancer have the histopathologic subtype termed medullary thyroid cancer (MTC) [1]. An
occult primary in MTC is recognized in familial cases. It is rare, and
even rarer in sporadic cases. Recognition and diagnosis of the primary lesion is difficult and usually is made only with secondary
changes - evidence of local extension or metastases, or from evidence of involvement with other systems associated with this lesion.
Metastatic dissemination to both the central and lateral cervical
lymph node compartments, including the mediastinum, is a common occurrence in patients with clinically apparent MTC [2, 3].
Medullary carcinoma grows with a very slow but progressive indolent course; the growth of the primary tumor locally is usually imperceptible compared with its spread and invasion into neck structures
and metastasis to cervical lymph nodes and distant nodes. In this
report we describe a rare patient with occult sporadic MTC who presented with cervical lymphadenopathy and an asymptomatic mediastinal mass and elevation of calcitonin and carcinoembryonic antigen (CEA) levels.

with contrast. The surrounding fat planes were preserved. No abnormal cervical lymph nodes could be identified elsewhere.
The thyroid gland is normal in size, shape and attenuation (Figure 1).
Left cervical lymph node fine needle aspiration (FNA) cytology revealed metastatic carcinoma probably medullary carcinoma of the
thyroid or nasopharyngeal carcinoma. Right and left ventricular of
the larynx, lingual and laryngeal surface of epiglottis, right and left
vallecular of the hypopharynx, pyriform fossa of the hypopharynx,
base of the tongue and nasopharynx biopsies were obtained and
found to be negative for cancer. Ultrasound of the thyroid showed
multiple tiny ill-defined nodules in the left thyroid lobe (Figure 2).
FNA of the left thyroid lobe showed chronic thyroiditis and benign
cystic colloid nodule.

Case Report
A 29 years old Saudi male patient was evaluated for neck swelling
for two years prior to presentation on May 2012. The swelling was
small, and gave the patient no discomfort initially. The swelling increased very slowly in size over two years, until May 2012 it had become noticeable enough to seek medical advice. It remained painless and there were no pressure symptoms. The patient was clinically
euthyroid and had unremarkable medical history. The family history
was negative for thyroid diseases or endocrinopathies.
There was no goiter or palpable thyroid nodules. There was enlargement of the left upper anterior cervical lymph node. Ultrasound and
CT scan neck and chest with intravenous contrast revealed a solitary
enlarged left upper deep cervical lymphadenopathy just beneath the
sternomastoid muscle, showing intense heterogenous enhancement
Department of Endocrinology, King Fahad Armed Forces Hospital. Jeddah,
Kingdom of Saudi Arabia
2Department of Internal Medicine, King Fahad Armed Forces Hospital. Jeddah,
Kingdom of Saudi Arabia
3Department of Pathology, King Fahad Armed Forces Hospital. Jeddah,
Kingdom of Saudi Arabia
1

Figure 1(a): Ultrasound of the posterior triangle of die neck shows enlarged
posterior triangle lymph node (white arrow}. Figure 1(b): Contrast enhanced
CT scan of the neck shows enlarged lymph node with significant enhancement
(white arrow). Figure 1(c): Mediastinal lymphadenopathy.

Serum calcium: 2.21 mmol/L (normal=2.15-2.55), parathyroid hormone: 4.09 pmol/L (normal=1.6-6.9), TSH: 7.21 mIU/L (normal= 0.274.2), Free T4: 20.18 pmol/L (normal=12-22), 25-hydroxyvitamin D:
25.4 nmol/l, CEA: 35 ng/ml (normal=0-3.4), calcitonin: 445 ng/L (normal=0-12). The patient was further investigated for pheochromocytoma in order to exclude MEN 2 syndrome and carcinoid syndrome;
24 hours urine collection showed creatinine: 15.2 nmol (normal=7.0Department of Radiology, King Fahad Armed Forces Hospital. Jeddah,
Kingdom of Saudi Arabia
Correspondence: Khalid S Aljabri
Email: khalidsaljabri@yahoo.com

2014 Aljabri et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Aljabri KS, Bokhari SA, Haq M, Durani A, Altayeb A, Alzahrani SJ, Alshareef M: Occult medullary carcinoma of thyroid - an unusual clinical and pathologic presentation. El Mednifico Journal 2014,
2(4).

422

18.0), adrenalin: 4 nmol (normal=0-22), noreadrenalin: 52 nmol (normal=12-85), metanephrine: 698 nmol (normal=337-1509), nor-metanephrine: 1854 nmol (normal=566-1930), 5-hydroxyindilacetate: 4
mg (2-7).

Figure 2: Ultrasound of the right and left thyroid lobes show heterogeneity
of the parenchyma with multiple tiny ill-defined nodules (white arrow).

The possibility of primary hyperparathyroidism was also considered.


The laboratory tests showed normal serum calcium and serum parathyroid. Thus, a diagnosis of primary hyperparathyroisism was excluded. CT scan of the abdomen and pelvis utilizing adrenal mass
protocol showed the liver demonstrates homogeneous density with
regular outline and no focal lesion, the pancreas demonstrates homogeneous density with no pancreatic mass lesion. Both adrenal
gland appear unremarkable with no adrenal mass, no retroperitoneal
mass lesion.
The patient underwent total thyroidectomy and dissection of the
central compartment lymph nodes. Thirty nine cervical and four
pretracheal lymph nodes were examined histologically and immunohistochemically. Histopathology confirmed the diagnosis of MTC
with metastases to cervical and pretracheal lymph nodes (Figure 3a).
Metastases to 5 of 39 resected cervical lymph nodes and one of four
pretracheal lymph nodes were found. The thyroid gland showed thyroid follicles of variable sizes and extensive hurthle cells metaplasia.
A single focus showed two nests of atypical cells of MTC within the
thyroid follicles and where positive for calcitonin and chromogranin
(Figure 3b). Mutation for proto-oncogen was not detected. The patient recovered uneventfully.

Figure 3(a): Metastatic medullary carcinoma in a lymph node (x100, Black arrow).
Figure 3(b): Calcitonin immunostaining showing follicles of medullary carcinoma
stained brown in patchy areas {x100 Black arrow).

Discussion
MTC is a neuroendocrine tumor originating from the parafollicular C
cells of the thyroid which secrete calcitonin. MTC accounts for approximately 4% of all clinically detected thyroid malignancies [4].
The prevalence of occult MTC in the general population is not well
Vol 2, No 4

Occult medullary carcinoma of thyroid

established. A systematic review of 24 autopsy series reported a


prevalence of 0.14% of occult MTC in unselected autopsies [5]. This
prevalence may be an underestimate because of the variability between the series in terms of slice thickness, calcitonin immunostaining, and extent of the pathological exam of the thyroid [5]. Whereas
autopsy series report a very low, prevalence of undiagnosed MTC,
patients undergoing thyroidectomy for nodular thyroid disease have
a rate of approximately 1015% of cases [5]. The prevalence of MTC
in nodular goiter can be estimated from several prospective and retrospective series. For series with more than 100 patients, MTC prevalence ranges from 0.1 to 1.3%. The composite prevalence of MTC is
0.31% across 15,992 patients [5, 6].
MTC is more often located at the junction of the upper third and the
lower two-thirds of the thyroid lobes. Metastatic dissemination to
both central and lateral cervical lymph nodes occurs frequently like
in our case. Cervical lymph node metastases are found in 20-30% of
patients with MTC <1 cm in diameter, in 50% of patients with a tumor 1-4cm in diameter and in up to 90% of patients with a tumor
>4cm in diameter [7, 8].
Our patient could be spared the nasopharyngeal and hypopharyngeal biopsies if serum calcitonin and CEA were done earlier knowing
the limitations of fine-needle aspiration of the thyroid gland to accurately diagnose MTC. Serum CEA, a glycoprotein involved in cell adhesion, is usually elevated when MTC is diffuse and distant metastases are present, but not in preclinical MTC [9]. CEA is a tumor marker
in colorectal carcinoma, gastric carcinoma, pancreatic carcinoma,
lung carcinoma and breast carcinoma [10].
Serum calcitonin levels are elevated in C-cell disorders, thus making
it a sensitive clinical marker for MTC. There has been interest in the
routine use of serum calcitonin level screening in the evaluation of
nodular thyroid disease [11]. Routine serum calcitonin screening is
standard in the initial evaluation of thyroid nodules in Europe based
on the 2006 European Thyroid Association guidelines and the 2010
American Association of Clinical Endocrinologists [12, 13]. Conversely, the 2009 American Thyroid Association guidelines for the
management of thyroid nodules could not recommend for or against
the routine measurement of calcitonin in the initial evaluation of thyroid nodules [14]. This decision was based, in part, on a lack of convincing evidence that screening with serum calcitonin levels decreased MTC-related mortality, improved overall patient outcomes,
or demonstrated cost-effectiveness.
There is controversy regarding the sensitivity of FNA for MTC; the
diagnostic accuracy of the technique may vary widely in clinical practice. A German study reported that the accuracy of diagnosing MTC
by FNA was 89% by experienced cytopathologists; furthermore, in
98.9% of patients, the cytopathology findings indicated a need for
thyroidectomy. Combined data for the three largest cytopathology
series with surgical ascertainment indicate that 79% of the patients
had FNA positive for MTC, and 96% indicated some form of thyroid
neoplasm prompting surgery. Variation in sensitivity has been attributed to inconsistent use of calcitonin immunohistochemistry, difficulty in recognizing typical and variant MTC cytomorphology, and
especially problems stemming from multiplicity of nodules and the
challenges of selecting appropriate nodules for FNA [15]. In a small

Aljabri KS, Bokhari SA, Haq M et al.

fraction of MTC cases, familial inheritance is occult but discoverable.


Thus, in 56% of cases, a germline RET mutation is present even
when the family history is initially judged negative [16]. Subsequent
genetic testing typically reveals the presence of less penetrant RET
mutations. Very careful attention to family history is sometimes useful in detecting these situations, including an appreciation of when
the family history has low information content due to small family
size, early death, or lack of contact with biological parents and sibs.
In addition to family history, the presence of systemic symptoms
pointing to MTC can be informativeespecially diarrhea, flushing,
and bone pain. 10% of MTC patients had such systemic symptoms
at presentation, usually in the setting of widespread metastatic disease.
Given the limitations of history and ultrasound clues to MTC and the
potential shortcomings of FNA, preoperative diagnosis can be difficult. In the majority of cases, to reduce the rate of MTC cases diagnosed postoperatively, the preoperative diagnosis could be based
on the results of thyroid fine-needle aspiration (FNA), serum calcitonin level, and RET proto-oncogene testing. In the 2009 American
Thyroid Association (ATA) guidelines for the surgical management
of known MTC, the extent of calcitonin preoperative elevation guides
the selection of preoperative imaging studies, which in turn influence the extent of surgery.

Conclusion
Consistent with the above literature review, our practice is to recommend basal calcitonin testing for thyroid nodule patients with increased risk of MTC, including those with a family history of MTC,
with a diagnosis of hyperparathyroidism or pheochromocytoma, or
symptoms of flushing or diarrhea. We also consider calcitonin testing
in patients with FNA results suspicious for malignancy that lack typical features of papillary or follicular neoplasms, and in patients with
a metastatic pattern typical of MTC. On the other hand, patients with
benign FNA results from a solitary nodule are rarely offered calcitonin testing. If the basal calcitonin level is greater than 80 pg/ml in
males or at a lower threshold in females, we generally offer total thyroidectomy, including central neck dissection in patients with
marked calcitonin elevation.
Competing interests: The authors declare that no competing interests exist.
Received: 17 July 2014
Accepted: 5 January 2015
Published Online: 5 January 2015

423

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1. Hazard JB, Hawk WA, Crile G., Jr Medullary (solid) carcinoma of the thyroid; a
clinicopathologic entity. J Clin Endocrinol Metab. 1959 Jan;19(1):152161.
2. Russell CF, Van Heerden JA, Sizemore GW, The surgical management of
medullary thyroid carcinoma. Ann Surg. 1983;197: 42-84.
3. Fleming JB, Lee JE, Bouvet M. Surgical strategy for the treatment of medullary
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4. Leboulleux S, Baudin E, Travagli JP, Schlumberger M. Medullary thyroid
carcinoma. Clin Endocrinol . 2004; 61:299310
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Thyroid Carcinoma at Autopsy. JCEM, 2011; 96: E109-E113
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10. Thomas SN, Zhu F, Schnaar RL, 2008 Carcinoembryonic antigen and CD44
variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and
L-selectin in shear flow. J Biol Chem 283: 15647-15655.
11. Elisei R, Bottici V, Luchetti F, Di Coscio G, Romei C, Grasso L, Miccoli P, Iacconi
P, Basolo F, Pinchera A, Pacini F. Impact of routine measurement of serum
calcitonin on the diagnosis and outcome of medullary thyroid cancer:
experience in 10,864 patients with nodular thyroid disorders. J Clin Endocrinol
Metab. 2004; 89:163168
12. Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W. European
consensus for the management of patients with differentiated thyroid
carcinoma of the follicular epithelium. Eur J Endocrinol. 2006;154:787803
13. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedus L, Vitti P;
AACE/AME/ETA Task Force on Thyroid Nodules. American Association of
Clinical Endocrinologists, Associazione Medici Endocrinologi, and European
Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis
and Management of Thyroid Nodules. Endocr Pract.2010; 16(Suppl 1):143
14. Cooper DS, Doherty GM, Haugen BR, Hauger BR, Kloos RT, Lee SL, Mandel SJ,
Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL,
Tuttle. Revised American Thyroid Association management guidelines for
patients with thyroid nodules and differentiated thyroid cancer.
Thyroid.2009;19:11671214
15. Wohllk N, Cote GJ,Bugalho MM,Ordonez N, Evans DB, Goepfert H, Khorana
S,Schultz P,Richards CS, Gagel RF. Relevance of RET proto-oncogene mutations
in sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab.1996;
81:37403745
16. Kebebew E, Ituarte PH, Siperstein AE, Duh QY, Clark OH. Medullary thyroid
carcinoma: clinical characteristics, treatment, prognostic factors, and a
comparison of staging systems. Cancer. 2000; 88:11391148.

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Open Access

Case Report

Florid squamous and focal mucinous metaplasia in Warthins tumor mimicking low grade
mucoepidermoid carcinoma: A diagnostic dilemma on fine needle aspiration cytology
Debjani Mallick1, Sonia Gon1, Riti Tushar Kanti Sinha1, Gayatri Ghosh1

Abstract
Background: Lack of typical cytological features of Warthins tumor (WT) on fine needle aspiration cytology (FNAC) added by presence of
atypical features in the form of metaplastic or atypical squamous cells on a necrotic background may mimic carcinoma leading to preoperative diagnostic dilemma.
Case Presentation: An interesting case of WT in a 53 year old female is being reported with a history of sudden increase in the size, along
with evidence of level I and II lymph nodes on CT scan. FNAC prompted a diagnosis of WT with florid squamous metaplasia with low grade
mucoepidermoid carcinoma as a differential diagnosis. Histopathology confirmed the diagnoses of WT with vast areas of florid squamous
metaplasia and focal areas showing mucinous metaplasia.
Conclusion: Awareness of potential source of erroneous diagnoses, especially the squamous component of the lesion coupled with
awareness of typical features of the lesion may result in higher accuracy rate thereby helping in proper management. (El Med J 2:4; 2014)
Keywords: Warthins Tumor, Papillary Cystadenolymphoma, Squamous Metaplasia, Mucinous Metaplasia, FNAC

Introduction
Papillary cystadenolymphoma, or Warthin's tumor (WT) is the second
most common benign salivary gland tumor and represents 5% to
14% of all parotid tumors [1]. Metaplasia to squamous or goblet cells
may occur in the epithelial components of WT and accounts for 7.5%
of the cases [2]. Sometimes, such metaplastic changes or infarction
in the tumor may be confused with false positive diagnosis of malignancy on FNAC, especially, squamous cell or mucoepidermoid carcinoma (MEC) [3].
Here, a case of WT with florid squamous and focal mucinous metaplasia, mimicking low grade MEC on cytomorphology is reported for
its rarity as well as uncommon presentation and cytomorphological
variation from the typical characteristic features making it a potential
source of diagnostic dilemma. An interesting history of sudden
growth of the tumor added with florid squamous metaplasia on cytomorphology posed a diagnostic dilemma for the cytopathologists.

The patient was subjected to FNAC to know the exact nature of the
tumor. Aspirated material was mucoid, murky fluid. The MGG stained
smears revealed many lymphoid cells in various stages of maturation
on a background of amorphous and granular debris. Many scattered
as well as clusters of squamoid cells and few macrophages were also
present (Figure 1). Cytomorphology prompted a diagnosis of WT
with florid squamous metaplasia. However, as there was sudden increase in size of the tumor and presence of level I and II lymph nodes,
low grade MEC was kept as a differential diagnosis. Superficial parotidectomy was done and the specimen was sent for histopathological examination.

Case Report
A 53 year old female presented in the OPD of Surgery department,
with chief complaint of a slowly growing mass in front of the right
ear since 1 year. There was history of sudden increase in size for 1
month. The mass was completely asymptomatic and was not associated with history of fever, hoarseness, dysphagia, or weight loss. On
physical examination, a 5 2 cm non tender, mobile mass was seen
at the angle of the right mandible, predominantly cystic in consistency. Oral cavity examination was normal. Signs of facial nerve
palsy were absent. No cervical nodes were palpable. Her routine hematological and biochemical tests were within normal limit.
Contrast enhanced CT scan of neck was done in which an exophytic
lesion in lower part of superficial lobe of right parotid gland with
irregular thick peripheral enhancement was noted. Deep lobe of
right parotid was normal. Multiple bilateral level I and II lymph nodes
were also seen.

Figure 1: Sheets of squamous metaplastic cells (a, b) and chunks of mucoid


material (c). Note the presence of epithelial cells in cluster and lymphoid cells
in the background (d); (MGG and H&E, 400x).

Pathological Examination
On gross examination, the mass was brownish in color, soft in consistency and measured 5.6 x 2.5 x 1.2 cm. Cut surface showed encapsulated multicystic tumor measuring 5.6 cm in greatest dimension
with greyish brown cut surface and brownish granular debris filling
the cysts. Surrounding normal salivary gland tissue was identified.
Representative sections were taken. The hematoxylin and eosin
stained sections revealed an encapsulated tumor composed of bilayered oncocytic and basaloid epithelium forming cystic structures,
papillae and glands that were accompanied by a dense lymphoid

Department of Pathology, ESI-PGIMSR, ESIC Medical College, Joka, Kolkata, India


Correspondence: Sonia Gon
Email: drsgon9@gmail.com

2014 Mallick et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Mallick D, Gon S, Sinha RTK, Ghosh G: Florid squamous and focal mucinous metaplasia in Warthins tumor mimicking low grade mucoepidermoid carcinoma: A diagnostic dilemma on fine
needle aspiration cytology. El Mednifico Journal 2014, 2(4).

Mallick D, Gon S, Sinha RTK et al.

425

stroma with secondary follicles and germinal centers formation.


Some of the cysts were lined by metaplastic squamous epithelium.
Vast areas of florid squamous metaplasia and focal areas showing
mucinous metaplasia collaborating with cytological diagnosis were
also noted (Figure 2). The cavity show inspissated proteinaceous material and evidence of infarction necrosis. No significant anaplasia,
tumor necrosis, increased mitoses or perineural invasion was noted.
Final diagnosis of WT with florid squamous metaplasia and focal mucinous metaplasia was offered.

usually not seen in case of MEC [9]. The present case had metaplastic
cells in sheets along with plenty of mucinous material and there was
prominent absence of oncocytic cells; hence low grade MEC was
kept as differential diagnosis.

Figure 2: Florid squamous metaplasia of the lining epithelium (a, b, d) and


focal mucinous metaplasia in Warthins tumor; (H&E, 400X). Note the
presence of lymphoid cells.

FNAC of a parotid swelling is very useful in distinguishing neoplastic


from inflammatory lesions, thus helping a clinician to plan management of the patient accordingly. Awareness of potential source of
erroneous diagnoses, especially the squamous component of the lesion coupled with awareness of typical features of the lesion may
result in higher accuracy rate, allowing clinicians to make more appropriate therapeutic decisions.

Cytomorphological distinction between the two is also important as


there is a propensity to malignant transformation into adenocarcinoma (not otherwise specified), undifferentiated carcinoma, MEC,
squamous cell carcinoma and oncocytic carcinoma at a rate of 0.03%
for all WT [10]. A malignant change in a WT is suggested clinically by
a recent history of a rapid enlargement of a longstanding mass [11].
Also, to be noted is that the malignant transformation of its lymphoid component into malignant lymphoma is relatively common,
whereas, an epithelial malignancy in WT is extremely rare. The present case had a history of sudden increase in the size of the tumor,
along with evidence of level II lymph nodes on CT scan. Also on cytomorphology, florid squamous metaplasia and focal mucinous metaplasia forced the cytopathologist to keep low grade MEC as a differential diagnosis.

Conclusion

Discussion
FNAC continues to be a reliable diagnostic technique in hands of an
experienced cytopathologist for the diagnosis of salivary gland neoplasm. The sensitivity of diagnosis of malignant lesions is high,
though the rate of tumor type-specific characterization is lower, due
to variable cytomorphology. Distinct cytomorphological elements of
oncocytic epithelial cells amidst variable population of lymphoid
cells are the most important criteria for a correct diagnosis of WT on
FNAC. In the absence of any one, as many as 26% of WT may be
misclassified as malignant on FNAC [4, 5]. Relative lack of these classic features and presence of atypical or metaplastic cells may lead to
an erroneous cytopathologic interpretation.
As such, squamous cells are often seen in a variety of neoplastic and
non-neoplastic salivary gland lesions, such lymphoepithelial cysts, sialadenitis, pleomorphic adenomas, MECs, and primary and metastatic squamous cell carcinomas [5]. WT may show squamous or goblet cell metaplasia in 7.5% cases [2]. The etiology of metaplastic
changes in WT is still unknown but it has been hypothesized that
extravasation of oncocytic and/or mucinous secretions or cyst contents may result in these changes [6]. These metaplastic changes to
squamous, mucous cells or even ciliated cells, can also occur in response to inflammation or infarction. The transition from cylindrical
cells to squamous cells may be due to infection or ischemia and necrosis in a large tumor. Ischemia was thought to be the most probable etiology for squamous metaplasia [7].
In WT, lack of typical cytological features added by presence of atypical features in the form of metaplastic or atypical squamous cells on
a necrotic background may lead to diagnostic error of carcinoma [8].
The most common misinterpretation is squamous cell carcinoma followed by MEC [3]. Hence, the squamous component of the lesion
must be examined carefully, along with other cellular and background components, to arrive at an accurate diagnosis. Presence of
plenty of oncocytes, dirty cystic background and lymphocytes are

Competing interests: The authors declare that no competing interests exist.


Received: 29 August 2014
Accepted: 5 January 2015
Published Online: 5 January 2015

References
1. Monk JS, Church JS. Warthin's Tumor-A High Incidence and No Sex
Predominance in Central Pennsylvania. Arch Otolaryngol Head Neck Surg
1992;118(5):477-8.
2. Seifert G, Bull HG, Donath K. Histologic subclassification of the
cystadenolymphoma of the parotid gland. Analysis of 275 cases. Virchows Arch
A Pathol Anat Histol 1980; 388:13-38.
3. Lee K, Jung CK, Lee A, Lee KY, Kang CS. Fine Needle Aspiration Cytology of the
Warthin's Tumor Misinterpretated as Squamous Cell Carcinoma: A Case Report.
Korean J Cytopathol 2005; 16(2):106-9.
4. Batsakis JG. Carcinoma ex papillary cystadenoma lymphomatosum malignant
Warthins tumor. Ann Otol Rhinol Laryngol 1987; 96: 2345.
5. Parwani AV, Ali SZ. Diagnostic accuracy and pitfalls in the fine-needle
aspiration interpretation of Warthins tumor. Cancer Cytopathology 2003; 99:
16671
6. Taxy JB. Necrotizing squamous/mucinous metaplasia in oncocytic salivary
gland tumors. A potential diagnostic problem. Am J Clin Pathol 1992;97(1):405.
7. Gunduz M, Yamanaka N, Hotomi M, Kuki K, Yokoyama M, Nakamine H.
Squamous cell carcinoma arising in Warthins tumour. Auris Nasus Larynx
1999;26:35560.
8. Ballo MS. Sources of diagnostic error in the fine-needle aspiration diagnosis of
Warthin's tumor and clues to a correct diagnosis. Diagn Cytopathol
1997;17(3):230-4
9. Perkins M. Review of Fine-Needle Aspiration Cytology of Salivary Gland
Neoplasms, With Emphasis on Differential Diagnosis. Am J Clin Pathol
2002;118(Suppl 1):S100-15.
10. Bell D, Luna MA. Warthin adenocarcinoma: analysis of 2 cases of a distinct
salivary neoplasm. Ann Diagn Pathol 2009,13:201-7.
11. Cob CJ, Greaves TS, Raza AS. Fine needle aspiration cytology and the
diagnostic pitfalls in Warthins tumour with necrotizing granulomatous
inflammation and facial nerve paralysis. Acta Cytol 2009;53:4314.
http://www.mednifico.com/index.php/elmedj/article/view/268

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Open Access

Case Report

Massive upper and lower gastrointestinal bleeding due to intra-abdominal gossypiboma


Muharrem Karaoglan1, Fuat Ipekci1, Ismail Sert2, Safak Ozturk1, Azad Gazi Sahin1

Abstract
Background: Gossybipoma is defined as surgical material such as compresses or sponges forgotten at the operation site following surgical
procedures. The incidence of gossypiboma is generally underreported due to medico-legal causes and being asymptomatic in many patients
for months or years.
Case Presentation: This case report presents the massive upper and lower gastrointestinal bleeding due to intra-abdominal gossypiboma
in a patient with Hartmann colostomy.
Conclusion: The possible surgical materials should be kept in mind for all patients with history of surgical operations. In patients with
gastrointestinal bleeding and history of previous operation, the diagnosis of the gossypiboma should not be overlooked. (El Med J 2:4; 2014)
Keywords: Gossypiboma, Gastrointestinal Bleeding, Hartmann Colostomy

Introduction
Gossybipoma is defined as surgical material such as compresses or
sponges forgotten at the operation site following surgical procedures. They can be encountered in all kinds of surgery whether intraabdominal or extra-abdominal. The incidence of gossybipoma is
generally underreported due to medico-legal causes and being
asymptomatic in many patients [1]. In clinical assessments they can
be misdiagnosed as recurrence of tumor, mass, cyst, etc. Clinical
presentation is variable and dependent on the location and size of
the foreign body and the type of inflammatory reaction presented
by the host.
Gossypibomas in the abdomen may present as abscess, mass, cyst
formations, internal or external fistula, and gastrointestinal obstruction or generalized peritonitis. Patients may be asymptomatic. Nonspecific clinical symptoms or serious complications may be encountered. Gastrointestinal bleeding due to gossypiboma is not common
and, here in, we present a case with gossypiboma who underwent
surgical intervention due to massive upper and lower gastrointestinal bleeding.

gent explorative laparotomy. In the operation, a fibrin covered inflammatory mass (with dimension of 15x15x13 cm) invading jejunum segment of the intestine at about 10 cm-distance from the
Treitz ligament was observed. This mass had invaded both the proximal part of the jejunum and sigmoid stump and had caused mucosal destruction, perforation and bleeding sites. The inflammatory
mass was totally removed with 15 cm segment of the jejunum and
end-to-end anastomosis was performed. 20 cm segment of the sigmoid stump that was invaded by the inflammatory mass was removed and stump was redone. In pathology report, perforation sites
of the intestinal wall, localized peritonitis and giant-cell inflammatory
responses at various sites were observed. A surgical sponge (gossypiboma), 16x15x15 cm in diameter was reported.

Case Report
A 33-year-old man presented with fatigue, vomiting, abdominal pain
and gastrointestinal bleeding. He had a history of urgent operation
due to gunshot injury three months ago. In his previous operation,
owing to having injury of spleen, kidney and colon, splenectomy, left
nephrectomy, left hemi-colectomy and Hartmann type temporary
end colostomy was performed.
After resuscitative treatment, the laboratory, imaging and endoscopy testing were performed to determine the bleeding site (Figure
1 and 2). Massive bleeding was observed from both colostomy
mouth and anus. Moreover, hematemesis existed. Upper gastrointestinal endoscopy did not reveal any bleeding site and colonoscopy
from both colostomy and rectum did not detect any cause of bleeding. Due to deterioration of the patients condition, need of more
blood transfusion and acute abdomen signs, we performed an ur-

Department of General Surgery, Tepecik Training and Research Hospital, Izmir,


Turkey
2Department of Transplantation and General Surgery, Tepecik Training and
Research Hospital, Izmir, Turkey
1

Figure 1: X-ray image shows a


suspicious mass formation.

Figure 2: CT scan revealed a mass formation including air and liquid and invading
the psoas muscle in the upper left abdominal area (in both intra and retroperitoneal
area). The radiological preliminary diagnosis was abscess in the field of operation.

Correspondence: Ismail Sert


Email: drismailsertege@yahoo.com

2014 Karaoglan et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Karaoglan M, Ipekci F, Sert I, Ozturk S, Sahin AG: Massive upper and lower gastrointestinal bleeding due to intra-abdominal gossypiboma. El Mednifico Journal 2014, 2(4).

Karaoglan M, Ipekci F, Sert I et al.

During postoperative period, wound detachment occurred and it


was treated with secondary healing process and resulted in incisional
hernia. Temporary colostomy was closed and hernia repair was performed six months after the second operation. The follow up of the
patient was uneventful.

Discussion
Gossypibomas are encountered in every kind of surgery, the rates
are as follows: 52% in general surgery, 22% in gynecological surgery,
10% in vascular and urological surgery and 6% in orthopedic surgery
[2]. The incidence of gossypiboma after intra-abdominal operations
varies between 1 in 1000 to 1 in 1500 [3]. Risk factors are emergency
operations, high body mass index, unplanned changes in the procedure, long operation time, inexperienced and inadequate staff and
unstable condition of the patient [4, 5]. In our case, patient previously underwent emergency operation due to gunshot injury, the
patient was in unstable condition owing to massive blood loss and
the operation time was over 4 hours.
Patients with abdominal gossypiboma may be asymptomatic or may
present with non-specific symptoms like abdominal pain, vomiting,
diarrhea, weight loss, tenesmus or palpable mass etc [4]. Gastrointestinal bleeding due to gossypiboma is uncommon and only a few
reports are present in literature. Erdil at al. reported a case with upper gastrointestinal bleeding due to retained surgical sponge in the
bulbus [6]. In another case report, rectal bleeding due to gossypiboma treated with colonoscopy was presented [7]. Campos at al. reported a case with refractory iron deficiency anemia due to gossypiboma [8]. Our case is unique because of the having massive both
upper and lower gastrointestinal bleeding due to gossypiboma. In
our case, upper and lower gastrointestinal endoscopy did not reveal
any pathological findings.
Two types of foreign body reaction may occur as a result of gossypiboma. One of them is an aseptic fibrous response and other one is
exudative reaction [3]. The first one leads to adhesions and encapsulation, and has generally a long silent clinical course. The second
one leads to abscess formation, and generally occurs in early postoperative period [3]. In some cases, migration of the gossypiboma
into the gut may be seen. The most common migration part of the
intestine is the small bowel [3]. The migration can cause perforation,
fistula formation, abscess formation, obstruction or bleeding. In our
case, because of the invasion of the surgical sponge into the jejunum
and sigmoid stump, massive gastrointestinal bleeding and perforation was observed.
Diagnosis of the gossypiboma can be made by using imaging methods such as x-ray, ultrasonography (US), computed tomography (CT)
or magnetic resonance imaging. X-ray imaging may easily reveal the
sponges that contain a radiopaque marker. In our case, there was no
radiopaque marker but it showed a suspicious mass image (Figure
1). A mass formation with wavy hyperechoic area and dense acoustic
shadow may be found in US imaging [4]. In early postoperative period, US may not be effective for diagnosis because of the intestinal

427

gas distension and incision pain [4]. Well bordered masses with hyperdense material inside, capsular enhancement and calcification of
the wall of the mass are the findings of CT imaging [4]. And in some
cases, especially for intraluminal gossypibomas, endoscopy has
played important role for diagnosis. Although improvement in imaging methods, correct diagnosis cannot be made in all cases. Suspicion of the gossypiboma may be the key point for the diagnosis. In
our case, both CT scan and endoscopy were performed. CT scan revealed a mass formation including air and liquid, invading the psoas
mussels in the upper left abdominal area (in both intra and retroperitoneal area) (Figure 2). The radiological preliminary diagnosis was
abscess in the field of operation.
Because of their medico-legal problems, mortality and morbidity potentials, prevention of gossypibomas are of great importance and
require great responsibility for surgeons and the team of the operation. For this reason, all tools of operation, materials, sponges, compresses must be counted before and after the operation and strict
protocols should be applied in material-counting for every operation
in surgical clinics.

Conclusion
The possible forgotten surgical materials should be kept in mind for
all patients with history of surgical operations. This case report is
unique, because of being first report describing massive upper and
lower gastrointestinal bleeding in a patient with disintegrated gastrointestinal tract. In patients with gastrointestinal bleeding and history of previous operation, the diagnosis of the gossypiboma should
not be overlooked.
Competing interests: The authors declare that no competing interests exist.
Received: 19 August 2014
Accepted: 6 January 2015
Published Online: 6 January 2015

References
1. Silva SM, Souss JB. Gossypiboma after abdominal surgery is a challenging
clinical problem and a serious medicolegal issue, Arg Brass Cir Dig, 2013; 26:
140-3.
2. Sivrikoz ON, Karaarslan S, Budayc MH,kmez A,Solak A. Gastrointestinal
stromal tmr taklid eden gossipiboma(Tekstiloma): Olgu sunumu,Trk
Patoloji Derg. ,2014; 1:1-3.
3. Yun-Xiao Lv, Cheng-chan Yu, Chun-Fang Tung, Cheng-chung Wu. Intractable
duodenal ulcer caused by transmural migration of gossypiboma into the
duodenum-a case report and literature review. BMC Surgery. 2014; 14(36):
1471-82.
4. Yldrm S, Tarim A, Nursal T.Z, Yildirim T, Caliskan K,Torer N, et al. Retained
surgical sponges (gossypiboma) after intraabdominal or retroperitoneal
surgery: 14 cases treated at a single center. Langenbecks Arch Surg.2006; 391:
390-5.
5. Gawende AA,Stunder DM, Orav EJ, et al. Risk factors for retained instruments
and sponges after surgery. N Engl J Med.2003: 348; 229-235.
6. Erdil A, Kilciler G, Ates Y, Tuzun A,Gulsen M, Karaeren N, et al. Transgastric
migration of retained intraabdominal surgical sponge: Gossypiboma in the
bulbus. Inter Med.2008: 47; 613-5.
7. Hinrichs C,Methratta S,Ybasco AC. Gossypiboma treatedby colonoscopy.
Pediatr Radol 2003; 33:261-2.
8. Campos FF, Franco F, Maximiano LF, Martines JAS, Felipe-Silva AS, Kunitake TA.
An iron deficiency anemia of unknown cause: a case report involving
gossypiboma. Clinics. 2010; 65(5):555-8.

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Open Access

Case Report

Treacher Collins syndrome - a report of two cases with review of literature


Priyadharshini Alva1, Shishir Ram Shetty1, Subhas Babu G1, Ananya Madiyal1

Abstract
Background: Treacher Collins syndrome is congenital disorder characterized by developmental anomalies of the maxillofacial region. The
zygomatic complex and mandible are usually involved.
Case Presentation: We are hereby reporting the clinical and radiological features of two cases of Treacher Collins syndrome occurring in
different age groups. The extraoral and intraoral features of this syndrome are described in detail.
Conclusion: Multiple major reconstructive surgical procedures in severe form of TCS shown only marginal improvement. Therefore future
research should be directed towards preventive aspects and early prenatal detection of this condition. (El Med J 2:4; 2014)
Keywords: Treacher Collins syndrome, Malar Hypoplasia, Ear Malformation

Introduction
Treacher Collins syndrome (TCS) is a severe congenital disorder of
craniofacial development characterized by numerous developmental anomalies that are restricted to the head and face [1]. The syndrome is named after E Treacher Collins as he first described the essential features of the syndrome in 1900, although later in 1949,
Franceschetti and Klein carried out extensive review of this syndrome and coined the term mandibulofacial dysostosis [2].

Case Reports
Case Report 1
A 13-year-old male patient reported to our department with complaint of pain in the left back teeth region of the lower jaw since 3
months. On extraoral examination, bilateral downward slanting eyelids were observed. Malar hypoplasia, retrognathia and malformed
external ears were also observed (Figure 1). On intraoral examination
there was anterior open bite, narrow maxillary and mandibular
arches (Figure 2). There was a grossly decayed 36. Panoramic radiograph showed hypoplastic ramus and condyle. Lateral cephalogram
showed steep mandibular angle (Figure 3). Based on these clinical
and radiological features a diagnosis of Treacher Collins syndrome
was made. The patient was not willing for reconstructive therapy;
however, the endodontic treatment of 36 was completed.

Figure 1: Clinical photograph showing classical extraoral features in patient 1.

Figure 2: Clinical photograph showing open-bite and narrow dental arches in patient 1.

Case Report 2
A 32-year old male patient reported to us with decayed teeth in the
right and left back region of the upper jaw since 7 months. On examination of the patient, downward slanting of the eye, notching of
the lower eyelid, malar hypoplasia, retrognathia, and external ear
malformation were noticed (Figure 4). On intraoral examination, narrow maxillary and mandibular arches and high arched palate was
observed (Figure 5). Root stumps were present bilaterally in the maxillary posterior region. Panoramic radiograph revealed hypoplastic
ramus and condyle and accentuated masseteric notch. Lateral cephalogram showed convex facial profile. Based on these clinical and
radiological features, a diagnosis of Treacher Collins syndrome was
made. Extraction of root stumps was carried out followed by prosthetic rehabilitation.

Figure 3: Panoramic radiograph and lateral cephalogram showing radiographic


features of hypoplastic ramus, condyle and convex facial profile in patient 1.

Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of


Dental Sciences, Nitte University, Mangalore, India

Correspondence: Priyadharshini Alva


Email: alva.priya@gmail.com

Figure 4: Clinical photograph showing classical extraoral features in patient 2.

2014 Alva et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Alva P, Shetty SR, G SB, Madiyal A: Treacher Collins syndrome - a report of two cases with review of literature. El Mednifico Journal 2014, 2(4).

Alva P, Shetty SR, G SB, Madiyal A

Figure 5: Clinical intraoral photograph showing high ached palate and narrow dental
arches in patient 2.

429

5. Atypical hair growth in the form of tongue shaped processes of


the hair line extending towards the cheek in the pre-auricular
region. This feature was observed in only one of our case.
6. Association at times with other anomalies, such as obliteration
of the naso-frontal angle, pits or clefts between the mouth and
ear and skeletal deformities. Obliteration of the nasofrontal angle was observed in both our cases.
Some of the lesser important features were emphasized by Axelsson
et al (1963) [8]:
1. Antimongoloid palpebral fissures.
2. Anomaly of the lower lid: coloboma of the outer third, or deficient lashes, or both.
3. Hypoplasia of the malar bones and mandible

Figure 6: Panoramic radiograph and lateral cephalogram showing radiographic


features of hypoplastic ramus, condyle and convex facial profile in patient 2.

Discussion
Treacher Collins syndrome, or Franceschetti syndrome, is an autosomal dominant disorder of craniofacial development [3]. Pathogenesis of TCS has been postulated to be due to several factors like abnormal patterns of neural crest cell migration, abnormal domains of
cell death, improper cellular differentiation during development or
an abnormality of the extracellular matrix [1, 4].
TCS has an incidence of approximately 1 in 50,000 live births. It affects both genders equally and has a family history in 40% of cases
while the remaining 60% appear to arise as a result of a de novo
mutation [5, 6]. There was no family history in both of our cases.
Derivatives from the first and second pharyngeal arch, groove and
pouch are affected in TCS [7].
The typical characteristics of the TCS as stated by Franceschetti and
Klein in 1949 are as follows [8]:
1. Antimongloid palpebral fissures with either a notch or coloboma
of outer third of the lower lid and occasional absence or paucity
of lashes of lower eyelid. Antimongoloid palpebral fissure and
coloboma were observed in both the reported cases.
2. Hypoplasia of facial bones, especially the malar bones and mandible. These features were present in our cases
3. Malformation of the external ear and occasionally of middle and
inner ear, with low implantation of the auricle. Ear malformation
was observed in both our cases
4. Macrostomia, high palate, malocclusion and abnormal position
of the teeth. Although macrostomia was not observed, high
arched palate and malocclusion was observed in our cases.

Hypoplasia of the malar bones and mandible was observed in both


our cases. A multidisciplinary approach is required for the management of individuals affected by TCS involving craniofacial surgeons,
orthodontists, ophthalmologists, otolaryngologists and speech therapists [1, 4].

Conclusion
Some reports have suggested that multiple major reconstructive surgical procedures in severe form of TCS have shown only marginal
improvement and these patients are unlikely to benefit from stem
cell therapy [3]. Therefore future research is directed towards preventive aspects and early prenatal detection of this condition.
Competing interests: The authors declare that no competing interests exist.
Received: 3 July 2014
Accepted: 6 January 2015
Published Online: 6 January 2015

References
1. Agrawal SM, Parihar SS, Agrawal MG. Mandibulofacial Dysostosis (Treacher
Collins Syndrome) A Rare Case Report. Natl J Med Dent Res 2013;1(2): 34-37
2. Dixon MJ. Treacher Collins syndrome. J Med Genet 1995; 32: 806-8.
3. Kasat V, Baldawa R. Treacher Collins syndrome- a case report and review of
literature. J Clin Exp Dent. 2011;3(Suppl1):e395-9.
4. Trainor P, Dixon J, Dixon M. Treacher Collins syndrome: etiology, pathogenesis
and prevention. Eur J Hum Genet 2009; 17: 275-83.
5. Dixon MJ, Read AP, Donnai D, Colley A, Dixon J, Williamson R. The Gene for
Treacher Collins Syndrome Maps to the Long Arm of Chromosome 5. Am J
Hum Genet 1991; 49: 17-22.
6. Edwards S, Gladwin A, DixonM. The Mutational spectrum In Treacher Collins
Syndrome reveals a predominance of Mutations that Create a PrematureTermination Codon. Am J Hum Genet 1997; 60: 515-24.
7. Hertle R, Ziylan S, Katowitz J. Ophthalmic features and visual prognosis in
Treacher Collins Syndrome. Br J Ophthalmol 1993; 77: 642-5.
8. Farrar JE. Mandibulo-facial dysostosis a familial study. Br J Ophthalmol 1967;
51: 132-5.

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Open Access

Essay

Child sexual abuse leads to psychological disorders: Literature review


Savera Aziz Ali1, Sumera Aziz Ali1

Abstract
This scholarly paper explains the relationship between child sexual abuse and psychological disorders. Childhood sexual abuse (CSA) is a
forceful sexual contact with a child who is incapable of consenting. The impact of sexual abuse can range from physical to very severe
psychological effects. Psychological disorders caused by child sexual abuse include panic disorder, anxiety, depression, substance abuse,
low self-esteem and post-traumatic stress disorder. The phenomenon of child sexual abuse is shaped by some important theories like
behavioral, psychodynamic, attachment, cognitive and integrated theory. These theories may help to develop a sound empirical base
through which cost effective strategies can be made to prevent child sexual abuse. Although child sexual abuse is considered as an offensive
act in Pakistan, but it is usually hidden in our society. Approximately 3,861 and 1,204 child sexual abuse cases were reported in 2012 and
2013 respectively from Pakistan. A series of current cases of child sexual abuse has brought the issue to the limelight. Child sexual abuse
affects not only the individual but also the families and societies on large scale. Therefore, an integrated approach focusing on the parents,
teachers and medical professionals can be proposed to prevent this issue. Prevention programs such as parenting education, home-visiting
programs, public education, and training sessions can be developed. Therefore, it is highly important for the families and communities to
work together with the support of stakeholders, so that a voice can be raised against CSA and this will ultimately reduce psychological
problems in the society. (El Med J 2:4; 2014)
Keywords: Childhood Sexual Abuse, Psychological Disorders

Introduction
This world would be without love, if young children were endorsed
to feel pain. Young children are very important assets of our society
and investing in children means investing in our nations economic
success. It is the responsibility of the whole society to take care of
their children but unfortunately, society has failed to take an approach to the health of young children. As a result of this, children
suffer from multiple problems like substance abuse, unintentional
injury, mental health problems and child abuse, which pose serious
threats to the young childrens health [1].
There are various types of child abuse such as physical abuse, emotional abuse and sexual abuse. Although every type of problem is
equally important but child sexual abuse (CSA) is more serious and
underreported problem as compared to others [2]. Due to CSA, a
child not only suffers from physical but also from emotional, social
and psychological problems both in short and long term. Therefore
CSA should receive appropriate medical and public health attention
[3].

Definition
Child sexual abuse has been described as any sexual contact with a
child through the use of force, threat, or dishonesty to secure the
childs participation, or any sexual contact with a child who is incapable of consenting due to age, disability or power differential [4].

Burden of child sexual abuse

tings and objectives of the study. For example, with a broad denition of sexual abuse as any sexual involvement, prevalence rates of
CSA can go as high as 50% and a narrow denition of sexual abuse
as forced genital activity yields prevalence rates of about 5% [4].
An analysis from 21 countries found 7% to 36% of women and 3%
to 29% of men had suffered sexual abuse during childhood [5]. More
simply, it can be said that one in every four girls and one in every six
boys is abused sexually across the world [6].
According to a report, there were 3,861 child sexual abuse cases in
2012 in Pakistan, around 17% increase as compared to 2011 [7].
Moreover, approximately 1,204 cases of child sexual abuse were reported from January 2013 to June 2013, with 68% of the sufferers
being girls and 32% boys [8].
A series of current cases of child sexual abuse has brought the issue
to the attention and there are multiple painful stories of child sexual
abuse in Pakistani society. On September 14th, 2013, gang sexual
abuse of a 5-year-old girl in Lahore made headlines in Pakistani
newspapers. In the same month, five and six-year-old girls have been
sexually abused in Kasur and Gujranwala respectively, while a little
boy was sexually abused in Faisalabad [9]. Psychologists and social
scientists cite social factors as a major cause of increasing sexual
abuse of children in the country [10]. However, CSA has never received attention it deserves as a horrific crime in Pakistan.

Theories of Child Sexual Abuse

Child sexual abuse is highly prevalent in society but this problem is


underreported due to stigma associated with it and around 88% of
CSA is never reported. However, it has been found that globally 7.9%
of the males and 19.7% of females suffer from CSA [5]. Another research indicates the prevalence of CSA may vary from 5% to 50%.
These variations might be due to difference in definitions, study set-

Considering the burden and significance of CSA, it is highly important to focus on some cost effective preventive strategies, but
developing effective preventive strategies require a sound empirical
base which is based on some theories related to the CSA. Without
adequate understanding of these theories, the preventive strategies
would be more focused on the consequences of the CSA rather than
the causes [11].

Aga Khan University, School of Nursing and Midwifery and Department of


Community Health Sciences, Karachi, Pakistan

Correspondence: Sumera Aziz Ali


Email: sumera.ali@aku.edu

2014 Ali et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Ali SA, Ali SA: Child sexual abuse leads to psychological disorders: Literature review. El Mednifico Journal 2014, 2(4).

Ali SA, Ali SA

One of the important theories is the integrated theory that proposes that CSA occurs as a result of interactions between individual,
ecosystem and situational factors, which means that CSA cannot occur without interaction between biological, developmental, sociocultural and situational factors [12].
The other important theory is biological theory in which theorists
propose the organic explanations of human behavior. Biological theorists assume that physiological factors, such as hormone levels (androgens) and genetic makeup have an effect on the behavior [11].
Androgens increase sexuality and ejaculation and regulate aggression, cognition, emotion and personality [13]. Researchers have also
suggested a relationship between aggression and high testosterone
levels [14].
The third relevant theory is psychodynamic theory which explains
that sexual deviation is a manifestation of the unsettled problems
experienced during the developmental stages. Human psyche is
made up of three principal elements, id, ego and superego. According to psychodynamic theory, sexual deviance occurs when the id is
overactive [15]. The fourth important theory is behavioral theory, in
which behavioral theorists explain that sexual behavior is a learned
condition. A theoretical model of sexually deviant behavior states
that sexual deviancy may be learned through the same mechanisms
by which sexuality is learned [15]. The fifth important theory relevant
to CSA is attachment theory, according to which humans have a tendency to form solid emotional connections with others and when
individuals suffer emotionally, they act as a result of their loneliness
and isolation [16, 17].

Child sexual abuse and psychological disorders


Based on the literature review, it has been found that CSA is a traumatic childhood life event in which the negative consequences increase with increasing severity of abuse [18]. These disorders include
panic disorder, anxiety, anger, depression, substance abuse, phobias,
low self-esteem/self-hatred and post-traumatic stress disorder [4, 19,
20]. A longitudinal study of 30 years from New Zealand showed that
CSA was associated with increased rates of major depression, anxiety
disorder, alcohol dependence, suicidal ideation, suicide attempt and
drug dependence. Moreover, 47% of all childhood-onset psychological disorders and 26% to 32% of adult-onset disorders are attributed
to child sexual abuse [21].
In conservative societies like Pakistan, child sexual abuse is considered as an offensive act. Child sexual abuse and sexual maltreatment
are usually concealed in Pakistan [22]. Due to this conservative attitude, people do not talk about this issue in our society, including the
victims themselves. There is very limited and scarce research in Pakistan, related to CSA. No national survey or official statistics are available in Pakistan regarding CSA, and only limited kind of qualitative
reports are published by some private organizations [22]. Moreover,
multiple factors like izzat (honor), haya (modesty) and sharam
(shame) prevent the victims from disclosure of child sexual abuse
[23].
Child sexual abuse is a serious problem at individual, familial and
societal level. Therefore, prevention measures at different levels are
of paramount importance [22]. Numerous prevention programs such

431

as education of parents, home-visiting programs, public education


and training sessions for teachers can be developed [24]. Awareness
can be created about CSA through school-based domestic abuse
prevention programs and prevention campaigns [25]. In addition,
community empowerment and participation can also play an important role in prevention of CSA [26].
Currently, few NGOs like Sahil are working entirely on the subject of
child sexual abuse in collaboration with UNICEF. These private organizations are running different programs regarding child sexual
abuse such as Social Legal and Educational Program and Mass Media Awareness Program. These NGOs have developed some guidelines and education material for the children as well as for their parents to prevent their children from sexual abuse [27].

Recommendations
Considering the sensitivity and burden of the CSA, an integrated approach, focusing on the parents, teachers and medical professionals
can be proposed [28]. Moreover, Government should make some
laws and policies through which an immediate action can be taken
against the criminals and abusers. Strong political commitment and
specialized expertise on the subject, as well as special laws on CSA
should be developed. There should be some safety mechanisms
which enable the children to live freely in the society. Moreover, statistics regarding child sexual abuse need to be gathered and compiled at national and provincial levels to estimate the true burden of
problem in the society so that appropriate actions can be taken accordingly [22].

Conclusion
In short, child sexual abuse is an alarming issue which spoils the life
of children who have just started the journey of their life and are not
aware about such habits and behaviors. Despite the above mentioned series of cases and reports, the problem is not highlighted
much and gets ignored many times by higher authorities. Moreover,
there is lack of research in this area in developing world, and particularly in Pakistan.
Thus, it can be concluded that children are vulnerable group, whose
proper growth and development can decide the future of the society. The way we take care of our children today, will have a major
impact on the society tomorrow. Therefore, it is highly important for
the families and communities to work together with the support of
stakeholders, so that a voice can be made against CSA, as this will
ultimately reduce psychological problems and will improve the harmony in society.
Competing interests: The authors declare that no competing interests exist.
Received: 16 May 2014
Accepted: 25 November 2014
Published Online: 25 November 2014

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4. Gunnur Karakurta, Kristin E. Silver (2014). Therapy for Childhood Sexual Abuse
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12. Smallbone, S., Marshall, W. L., Wortley, R. (2008). Preventing child sexual abuse:
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15. Jennifer Tallon, Karen J. Terry (2013). Child Sexual Abuse: A Review of the
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Open Access

Essay

Mucopolysaccharidosis type III, Sanfilippo syndrome: What does coarse facies mean?
Avina Fierro1, Hernandez Avia2

Abstract
Background: The purpose of this study was to describe the peculiar facial dysmorphism of Sanfilippo syndrome, the most frequent type
of mucopolysaccharidosis with a progressive clinical course of nervous system degeneration.
Findings: We performed a retrospective study of the literature and reviewed clinical photographs of fifty published patients with Sanfilippo
syndrome, in order to review the principal features of craniofacial anomalies, while attempting to delineate the syndrome phenotype with
the specific dysmorphism previously described as coarse facies. The present study demonstrates the classical phenotype of the Sanfilippo
syndrome in the majority of patients with mild course. We observed that the most common dysmorphic facial features were: head with
mild macrocephaly, low anterior hairline, frontal bossing, periocular region with broad and thick eyebrows, eyes widely spaced, midface
with wide and depressed nasal bridge, wide nose with anteverted nares, broad, smooth philtrum, wide mouth with thick vermillion of
upper lip, and broad jaw.
Conclusion: Sanfilippo syndrome is characterized by normal phenotype at birth and at early infancy, when the patient has progressive
regression in capabilities by deterioration of gait, speech and behavior and shows a special facial dysmorphism associated with a specific
facial pattern. The dysmorphic scoring system may be used to classify patients and get an early, correct clinical diagnosis. (El Med J 2:4;
2014)
Keywords: Sanfilippo Syndrome, Mucopolysaccharidosis Type III, Facial Dysmorphism

Introduction
Mucopolysaccharidoses (MPS) are hereditary lysosomal storage diseases, a group of genetic metabolic disorders caused by an enzyme
deficiency specific to each type that results in the accumulation of
abnormal material of glycosaminoglycans. In the case of the type III,
the biochemical defect is in the breakdown of heparin sulphate that
is not properly metabolized and therefore accumulates or stores
within the cells [1].

12 (12q14.3). The mutations can be missense, nonsense, and insertion or deletion [9]. Neurological dysfunction and neurodegeneration, common to the Sanfilippo syndrome is, in part, due to the secondary metabolic perturbations induced by heparin sulfate accumulation. Cells show morphological changes due to lysosomal storage
[10]. Histopathologically, neuronal swelling and vacuolation cause
eventual progressive cerebral and systemic organ abnormalities [11].

Four separate enzyme defects have been recognized: type A (N-sulfoglucosamine sulfohydrolase), type B (N-acetyl alpha sulfoglucosamine sulfohydrolase), type C (acetyl-CoA Alpha-glusocamide Nacetyltransferase) and type D (N-acetylglusocamine 6-sulfatase) [2].
The deficiency of all these enzymes involves the breakdown of heparine sulfate, and the four biochemically heterogeneous types are
clinically indistinguishable because their clinical phenotype are similar [3].

Clinical course
SPS is the most common form of MPS that manifests primarily as a
neurologic disease with progressive mental deterioration, the most
pronounced symptom being severe neurocognitive deterioration of
the central nervous system. Course is characterized by rapid loss of
mental and motor abilities. Communication becomes impossible by
six years of age, then patients become increasingly unsteady on their
feet and most are unable to walk before teenage years [12]. Regression in capabilities by deterioration of gait, speech and behavior are
common. Some children may never learn to speak.

Sanfilippo syndrome (SPS), or MPS III, is a rare genetic disease characterized by mental retardation and somatic features, relatively mild,
including specific facial features. It was first described in 1963 by Sylvester Sanfilippo in eight children with mental retardation and heparin sulfate mucopolysacchariduria [4]. SPS is the most common type
of mucopolysaccharidoses, clinically with progressive neurological
deterioration, behavioral abnormalities and early mortality before
the twenty years of age [5]. Patients are often initially diagnosed with
developmental delay, attention deficit hyperactivity disorder and autism spectrum disorders [6].

The characteristic sleep disturbances are sometimes remaining


awake all night, body rocking and crying out due to prevalent inability to sleep for more than a few hours at a time [13]. Severely affected patient suffer serious hearing loss and neurologic degeneration at about the nine years of age, with rapid deterioration of social
and adaptive skills: progressive dementia, aggressive behavior, hyperactivity, attention deficit, seizures, temper tantrums and destructive behavior [14].

The frequency of the disease appears to be about one in 25,000 live


births [7]. The genetic inheritance is autosomal recessive with failure
to degrade heparin sulfate [8]. The first two subtypes are mapped to
chromosome 17: type A (17q25.3), type B (17q21.2). Type C has been
mapped to chromosome 8 (8p11.21), and the type D to chromosome

The clinical suspicion can be confirmed with a quantitative assay that


screens urine for the presence of glycosaminoglycan biomarkers using a spectrophotometric compound. Molecular genetic analysis reveals heparin sulfamidase (SGSH) gene mutations. Initial results
should be confirmed by a second enzyme assay and/or by molecular
genetic testing but the standard for diagnosis remains the enzyme

Dysmorphology Department, Pediatric Medical Center IMSS, Guadalajara, Mexico


Family Medicine Department, General Hospital 2 IMSS, Aguascalientes, Mexico
Correspondence: Avina Fierro
Email: avinafie@megared.net.mx

1
2

2014 Fierro et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Fierro A, Avia H: Mucopolysaccharidosis type III, Sanfilippo syndrome: What does coarse facies mean? El Mednifico Journal 2014, 2(4).

434

Mucopolysaccharidosis type III, Sanfilippo syndrome

activity assay in cultured skin fibroblasts or leukocytes [15]. Genetic


counseling is utilized to prevent the recurrence risk. Affected individuals inherit from parents, who must both carry the defective gene.
The next pregnancy has a one in four chance that the child will be
affected. Mutation analysis has enabled the detection of carriers in
affected families. Prenatal diagnosis is available through enzyme assay by levels of L-iduronidase or sulfate incorporation studies carried
out in cultured amniotic cells. A molecular genetic analysis is preferred for prenatal diagnosis. This is of particular concern when pregnancy is being considered. heparan sulfate and dermatan sulfate derived disaccharides are sensitive markers for newborn screening [16].
Phenotype and facial dysmorphism
The phenotype is normal at birth and in early infancy, with growth
standard or accelerated for one to three years, followed by slow
growth and then deteriorates progressively afterwards, when it manifests primarily as a neurologic disease with progressive mental deterioration [17]. Thickened skin and mild changes in bone and skeletal structures become noticeable with age, the effects on the musculoskeletal system are less severe than those caused by other forms
of MPS [18]. At age of two years, clinical symptoms start and facial
changes, previously defined as coarse facial features that are common to others inborn errors of metabolisms, occur [19]. Hunter described in 1917 the face of patients affected by mucopolisaccharidosis, with the term gargoylism. This is considered demeaning an insensitive and hence the term is no longer used and instead, the word
coarse is used. The problem with this is that it only vaguely describe the facial features in SPS [20].
The presence of a specific facial pattern in patients with a genetic
syndrome indicates that there is consistency in the phenotypic expression of the affected genes [21]. Facial appearance can be a significant clue in the identification of genetic diseases, but their low
incidence limits exposure during training and inhibits the development of skills in recognizing the facial gestalt characteristics [22].

Findings
A craniofacial dysmorphological examination was carried out, serial
photographs were reviewed, and a series of anthropometric craniofacial measurements were obtained. We observed variability in facial
dysmorphism, influenced by the different age of the patients, the
principal features are presented in Table 1. The head shows mild
macrocephaly, low anterior hairline and the face exhibits frontal
bossing. The ocular area is broad with thick eyebrows and eyes
widely spaced. The midface area is wide and has a depressed nasal
bridge and wide nose with anteverted nares. The philtrum is broad
and smooth; the mouth is wide with thick vermillion of upper lip
along with a broad jaw (Figure 1).
The present study demonstrates the classical phenotype of the Sanfilippo syndrome in the majority of patients with mild course. We
delineate the specific phenotype using the elements of morphology
compared to the standard terminology with the description of the
facial anomalies to facilitate reliable comparisons of findings among
patients [23]. The definition of each term is the Table 2.

Vol 2, No 4

Figure 1: Low anterior hairline, frontal bossing, broad and thick eye-brows, eyes
widely spaced, depressed nasal bridge, nose with anteverted nares; broad, smooth
philtrum and wide mouth with thick vermillion of upper lip.

Table 1: Facial features in Sanfilippo syndrome (MPS III)


Current nomenclature Previous description
%
Moderate enlargement of
84 %
Mild macrocephaly
the head
62 %
Low anterior hairline Short forehead
Prominent, protruding
88 %
Frontal bossing
forehead
98 %
Broad, thick eyebrows Bushy flared eyebrows
Ocular hypertelorism
98 %
Eyes widely spaced
92 %
Wide, depressed nasal Flat, sunken and low nasal
bridge
bridge
Pug nose with upturned
86 %
Wide nose with
nostrils
anteverted nares
Wide and flat philtrum
84 %
Broad, smooth
philtrum
Large broad mouth
94 %
Wide mouth
Full and broad thick lips
88 %
Thick vermillion of
upper lip
Strong, square jaw
64 %
Broad jaw

Discussion and conclusion


Patients with developmental or non-specific speech delay, behavioral abnormalities, and characteristic somatic mild dysmorphic feature should be screened for increased excretion of the heparan sulphate in urine characteristic of MPS III [24, 25]. The diagnosis is usually made between two to three years of age. Developmental milestones are near normal prior to this age after which the children have
unexplained speech delay and hyperactivity.

Fierro A, Avia H

SPS as mild somatic and dysmorphic features, with wide phenotypic


variability: severe in type A, intermediate in types B and C, and attenuated phenotype in type D. Differential diagnosis includes other
types of MPS: type I Hurler with severe facial features and gingival
hypertrophy, corneal opacity and hepatomegaly, type II Hunter with
short stature, frequent ear and respiratory infections, type IV Morquio with skeletal abnormalities, spinal manifestations and problems
in lower and upper extremities [26]. Diagnosing physicians should
consider Sanfilippo syndrome in children with mild dysmorphic features.
Table 2: Definition of dysmorphic features
Standard Term
Definition
Enhanced head circumference
Mild macrocephaly
Low anterior hairline Short distance between the hairline
or trichion and glabella
Bilateral bulging of lateral frontal
Frontal bossing
bone prominences with relative
sparing of the midline
Broad, thick eyebrows Regional increase in width of the
eyebrow with high density of hairs.
Augmented interpupillary distance
Eyes widely spaced
Wide, depressed nasal Increased breadth of the nasal
bridge, and posterior positioning of
bridge
the nasal root
Nose with enlarged interalar
Wide nose with
distance, and anteriorly-facing nostril
anteverted nares
Increased distance between ridges of
Broad, smooth
the philtrum, and flat skin surface in
philtrum
central region of the upper lip
Dilated distance between the oral
Wide mouth
commissures and enhanced width of
the oral aperture
Augmented height of the vermilion
Thick vermillion of
of the upper lip in the midline
upper lip
The use of the current standard terminology to describe the facial
dysmorphic features must replace the old fashion terms such as
coarse face: the goals are to standardize the delineation of the phenotype [27]. To date, no disease modifying treatment is available;
only supportive management and drug therapy is available to control hyperactivity and aggression. Early diagnosis may lead to therapy thereby offering the greatest clinical benefit when started prior
to the onset of significant neurologic sequelae [28]. New treatment
modalities for systemic manifestations include bone marrow transplant and enzyme replacement therapy, and have resulted in an improved prognosis in many cases [29]. This should be considered in
patients who have no evidence of neurological disease. Hematopoietic stem cell transplantation and substrate reduction therapy have
also been reported [30].
Competing interests: The authors declare that no competing interests exist.
Received: 22 August 2014
Accepted: 28 November 2014
Published Online: 28 November 2014

435

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Metab. 2012; 107: 705-10.
2. Wolfe BJ, Ghomashchi F, Kim T, Abam CA, Sadilek M, Jack R et al. New
substrates and enzyme assays for the detection of MPS III (Sanfil-ippo
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Identification of the gene encoding the enzyme deficient in
mucopolysaccharidosis IIIC (Sanfilippo disease type C). Am J Hum Genet. 2006;
79: 738-44.
9. Yoogalingam G1, Hopwood JJ. Molecular genetics of mucopolysaccha-ridosis
type IIIA and IIIB: Diagnostic, clinical, and biological im-plications. Hum Mutat.
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mucopolysaccharidosis IIID: clinical, biochemical, mor-phological and
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12. Valstar MJ, Neijs S, Bruggenwirth HT, Olmer R, Ruijter GJ, Wevers RA et al.
Mucopolysaccharidosis type IIIA: clinical spectrum and geno-type-phenotype
correlations. Ann Neurol. 2010; 68: 876-87.
13. Mahon LV, Lomax M, Grant S, Cross E, Hare DJ, Wraith JE et a al. Assessment
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syndrome type A. J Inherit Metab Dis 2014; 37: 431-7.
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http://www.mednifico.com/index.php/elmedj/article/view/220

437

Open Access

Letter to Editor

A conservative approach to reattach fractured anterior tooth fragment


Amit Chaudhari1, Priya Chaudhari2

Abstract
Dental trauma to the anterior maxillary teeth is common in children, which may result in fracture or tooth dislocation. One of the options for
managing coronal tooth fractures when the tooth fragment is available is reattachment, which can provide good and long-lasting aesthetics.
This article reports on coronal tooth fracture case that was successfully treated using tooth fragment reattachment. Reattachment of a tooth
fragment is a viable technique that restores function and aesthetics with a very conservative approach. (El Med J 2:4; 2014)
Keywords: Aesthetics, Dental Trauma, Tooth Fracture, Fragment Reattachment

Introduction

Case Description

Facial trauma that results in fractured, displaced, or lost teeth can


have significant negative functional, aesthetic, and psychological effects on children [1, 2]. Trauma to teeth has been, and continues to
be most common incidence occurring to children and adolescents.
The most common injuries to permanent teeth occur secondary to
falls, followed by traffic accidents, violence, and sports. All sporting
activities have an associated risk of orofacial injuries due to falls, collisions, and contact with hard surfaces [3, 4].

The patient, a thirteen year boy, reported to the private clinic with
chief complaint of broken front tooth while playing with his friend
on a playground. The patient was accompanied by his mother. The
fractured tooth fragment was recovered by the patient at the site of
the injury and he kept it in a plastic bottle. On complete clinical examination, it was observed that Upper right central incisor (11) was
fractured in enamel and dentin (Ellis Class II) 10 and upper left central incisor (21) was fractured on mesial aspect in enamel only (Ellis
Class I) 10 (Figure 1). Other soft tissue and hard tissue examination
showed no signs of trauma. Periapical radiographs were taken to determine extent of the fracture and to ensure that there were no other
injuries. Broken fragment of tooth was inspected carefully and
checked on broken surface for fit and stored in normal saline till the
procedure (Figure 2).

Effects of the trauma on the anterior teeth range from a simple crack
to complete avulsion, depending upon the force and nature of the
trauma [5]. Several factors influence the management of coronal
tooth fractures, including extent of fracture (biological width violation, endodontic involvement, alveolar bone fracture), pattern of
fracture and restorability of fractured tooth (associated root fracture), secondary trauma injuries (soft tissue status), presence/absence of fractured tooth fragment and its condition for use (fit between fragment and the remaining tooth structure), occlusion, aesthetics, finances, and prognosis [6].
If the trauma causes the tooth to become fractured and the fractured
fragment is retained, restoration of the tooth with the fractured fragment can be achieved with a beautiful aesthetic result [5, 6]. Reattachment of a fragment to the fractured tooth can provide good and
long-lasting aesthetics (because the tooths original anatomic form,
color, and surface texture are maintained), can restore function, can
result in a positive psychological response, and is a reasonably simple procedure [7].

Figure 1: Fractured Tooth.

In addition, tooth fragment reattachment allows restoration of the


tooth with minimal sacrifice of the remaining tooth structure. Furthermore, this technique is less time-consuming and provides a more
predictable long-term wear than when direct composite is used [8].
Long-term follow-ups have reported that reattachment using modern dentin-bonding agents or adhesive luting systems may achieve
functional and aesthetic success [9]. It is hoped that, with mature
dentition, ideal treatment will be received. Age is an important factor
in determining the best restoration. When options are available, children should receive conservative treatment until they are the appropriate age. This article reports successful reattachment of fractured
central incisor with required aesthetics.

On fractured upper right central incisor (11), patient had sensitivity


to blowing air or after moving probe. Hence, light cured calcium hydroxide (Septocal LC, Septodent, France) was applied and kept for
observation (Figure 3). Alternative treatment options and prognosis
were explained to patient and to his parents. After taking consent,
treatment option with fragment reattachment was decided as the
fragment was available.

Department of Public Health Dentistry, Kothiwal Dental College, Moradabad, India


Department of Prosthodontics, Guardian Dental Clinic, Thane, India

Correspondence: Amit Chaudhari


Email: dr.amit.chaudhari@gmail.com

1
2

Figure 2: Fractured tooth fragment.

2014 Chaudhari et al.; licensee El Mednifico Journal. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cite this article as: Chaudhari A, Chaudhari P: A conservative approach to reattach fractured anterior tooth fragment. El Mednifico Journal 2014, 2(4).

438

Conservative approach to reattach fractured tooth fragment

of the tooth. Polishing sequence was carried out in intervals of 24


hrs, 1 week and 2 weeks. Subsequent follow-up showed excellent
aesthetic result (Figure 5).

Figure 3: Calcium Hydroxide base to preserve dentine.

Treatment Plan
As there was no pain in the tooth, treatment was initiated without
using any anesthesia. The tooth and tooth fragment were cleaned
with pumice and washed and dried. 2% chlorhexidine gluconate was
used to clean tooth and tooth fragment followed by washing cleaning and drying with 5% sodium hypochlorite. Before starting procedure shade selection procedure were done and shade was selected
to be A2.
After this procedure, the operative area was isolated with cotton
rolls. Tooth and tooth fragment were etched using N-tech (Ivoclar
Vivadent, Schaan/Liechtenstein) 37% phosphoric acid gel, for 15 seconds and rinsed to enhance bond strength and minimize micro-leakage. After etching, dentin bonding agent N-Bond (Ivoclar Vivadent,
Schaan/Liechtenstein) was applied to tooth and fragment, thinned
with gentle air syringe, and light-cured for 15 seconds.
The adhesive system was then applied to the etched surface. Flowable composite resin Tetric N-Flow (Venus, Heraeus Kulzer, Dormagen,
Germany) was applied to both fragment and tooth surfaces. The fractured segment was then accurately placed on the tooth, paying special attention to the fit between the segments. When the original
position had been reestablished, excess resin was removed and the
area was light cured for 40 seconds on each surface, making sure
that no displacement of the fragment occurred before adhesive/resin polymerization was complete (Figure 4). To increase the
bonding strength and longevity of teeth restored by fragment reattachment, excess composite of few millimeters was placed lingually
on to the tooth surface.

Figure 4: Reattachment of tooth fragment.

After completion of fragment reattachment, the tooth was checked


for high point with keeping into occlusion. Facial and lingual aspect
of tooth were polished with sequential polishing disks Super-snap
(Shofu, Ratingen, Germany) followed by polishing paste shine N
smile (ICPA). After polishing, buffing was carried with SuperBuff Set
(Shofu, Ratingen, Germany) to achieve lifelike luster on facial aspect

Vol 2, No 4

Figure 5: After 2 week follow-up.

The technique used in this case report is reasonably simple, while


restoring function and aesthetics with a very conservative approach.
However, one has to keep in mind that a dry and clean working field
and the proper use of bonding protocol and materials is the key for
achieving success in adhesive dentistry.

Conclusion
With the materials available today, in conjunction with an appropriate technique, aesthetic results can be achieved with predictable
outcomes. Thus, the reattachment of a tooth fragment is a viable
technique that restores function and aesthetics with a very conservative approach, and it should be considered when treating patients
with coronal fractures of the anterior teeth, especially younger patients.
Competing interests: The authors declare that no competing interests exist.
Received: 22 July 2014
Accepted: 6 January 2015
Published Online: 6 January 2015

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published at the discretion of the Editorin-Chief and may undergo peer-review.
An abstract is not required for submission.

Corresponding author: The name, affiliation, mailing address and e-mail address
of the author responsible for correspondence about the manuscript on behalf of all authors. The corresponding authors e-mail address will be published.
The corresponding author is the guarantor for the integrity of the manuscript as
a whole.
Source(s) of support in the form of
grants, equipment, drugs, or all of these
(if applicable).
A statement of financial or other relationships that might lead to a conflict of
interest.
Word count for the text (including abstract, acknowledgments, figure legends,
and references).
Number of figures , Number of tables.

In all cases manuscripts should be written in


clear and concise English. Every manuscript
should preferably include discussion of
most relevant and recent (recent 5 years)
literature related to the topic. The manuscript should be written in font size 12-14,
double-spaced in all portions, abstract, text,
acknowledgments, references, individual
tables, and legends. Margins should be
about 2,5 cm (1 inch). All pages must be
numbered consecutively, beginning with
the title page. Please dont send the title
page as separate file.

Title Page: The title page should include


following information:

Abstract: An abstract should follow the title


page. It should not be longer than about
250 words and must reflect the content of
the article accurately. The abstract should
be structured as follows:
For original articles:
Background
Methods
Results
Conclusions

For short reports:


Background
Findings
Conclusions
For reviews:
A summary of the paper should be provided.
For case reports:

Article type: original article, short report,


review, case report, opinion, debate, essay, or letter to the editor.
Title of the article (bold letters, font size
14 or larger).
Authors list: Authors full names should
be given as first names followed by surnames, and should be clearly linked to
the respective institution by use upper
case Arabic numbers.
Affiliation(s)
Disclaimers (if applicable).

Background
Main observations
Conclusions
Key words: Following the abstract, provide
3 to 10 key words arranged in alphabetical
order. Terms from the Medical Subject
Headings (MeSH) list of Index Medicus
should be used; if suitable MeSH terms are
not yet available for recently introduced
terms, non-MESH terms may be used.

Manuscript structure:
For original articles:

Background
Objective
Patients/Materials and Methods
Results
Discussion
Conclusions
Recommendations

For short reports:

Background
Methods
Findings
Conclusions

For case reports:

Introduction
Case report(s)
Discussion
Conclusions

For reviews: Review articles should be divided into sections and sub-sections to
achieve highest possible text clarity.
References: References should be numbered consecutively in the order in which
they are first mentioned in the text. Identify
references in text, tables, and legends by
Arabic numerals in upper case. References
cited only in tables or figure legends should
be numbered in accordance with the sequence established by the first identification in the text of the particular table or
figure. References to articles and papers
should mention: (1) name(s) initials of all
author(s), (2) title of paper; (3) title of the
journal abbreviated in the standard manner
(see Index Medicus); (4) year of publication;
(5) volume; (6) first and final page numbers
of the article (references to online articles
should have the same structure and additionally the appropriate web address following page numbers). (7) PMID number
(these numbers appear under each abstract
in PubMed). References which are not
PubMed indexed do not require a PMID
number.
Example: Lima XT, Abuabara K, Kimball AB,
Lima HC. Briakinumab. Expert Opin Biol
Ther. 2009 Aug;9(8):1107-13. PMID:
19569977

References to books and monographs


should include: (1) name(s) followed by the
initials of the author(s) or editor (s); (2)
chapter (if relevant) and book title; (3)
edition, volume, etc.; (4) place; (5) publisher; (6) year; (7) page(s) referred to.
Example: MacKie RM. Lymphomas and
leukaemias. In: Textbook of Dermatology
(Champion RH, Burton JL, Ebling FJG, eds),
5th edn, Vol. 3. Oxford: Blackwell Scientific
Publications. 1992; 2107-2134
Figures: Figures may be inserted into the
text file or may be uploaded separately as
additional files as JPEG or TIFF files. Manuscripts with low quality images will not be
considered for publication. Drawn Figures
will not be redrawn by the EMJ. Letters,
numbers, and symbols on Figures should be
clear and even throughout and of sufficient
size, that when reduced for publication
each item will still be legible. Figures should
be made as self-explanatory as possible.
Please provide Figure legends on a separate
page with Arabic numerals corresponding
to the illustrations. If photographs of patients are used, either the subjects must not
be identifiable or their pictures must be
accompanied by written permission to use
the photograph for publication.
Sending the Manuscript to the Journal: The
manuscript should be uploaded directly
onto the EMJ website. If you have any difficulty with the above, the manuscript can be
sent by email to submit@mednifico.com.
Cover letter: Manuscripts submitted by email must be accompanied by a cover letter, which should include the following
information.
A statement that the same or very similar
work has not been published or submitted
for publication elsewhere. A conference
presentation with a published abstract is
not considered a publication in this regard.
A statement of financial or other relationships that might lead to a conflict of interest
A statement that the manuscript has been
read and approved by all the authors

xi

In the case of manuscripts uploaded directly


to the EMJ website these statements will be
required by the uploading system. Any
additional information for the editor may
be provided in the Comments for the Editor box in Step 1 of the uploading procedure.
Processing charges: There are no submission/per-page charges. However, the Board
may impose charges at a later point of time
in order to cover the fees associated with
open access publishing.
Submission Preparation Checklist: As part
of the submission process, authors are
required to check off their submission's
compliance with all of the following items,
and submissions may be returned to authors that do not adhere to these guidelines:
The submission has not been previously
published, nor is it before another journal for consideration (or an explanation
has been provided in Comments to the
Editor).
The submission file is in OpenOffice,
Microsoft Word, RTF, or WordPerfect
document file format.
Where available, URLs for the references
have been provided.
The text is single-spaced; uses a 12-point
font; employs italics, rather than underlining (except with URL addresses); and
all illustrations, figures, and tables are
placed within the text at the appropriate
points, rather than at the end.
The text adheres to the stylistic and
bibliographic requirements outlined in
the Author Guidelines, which is found in
About the Journal.
If submitting to a peer-reviewed section
of the journal, the instructions in Ensuring a Blind Review have been followed.
Copyright Notice
Authors who publish with this journal agree
to the following terms:
Authors retain copyright and grant the
journal right of first publication with the
work simultaneously licensed under a
Creative Commons Attribution License
that allows others to share the work with
an acknowledgement of the work's au-

thorship and initial publication in this


journal.
Authors are able to enter into separate,
additional contractual arrangements for
the non-exclusive distribution of the
journal's published version of the work
(e.g., post it to an institutional repository
or publish it in a book), with an acknowl-

edgement of its initial publication in this


journal.
Authors are permitted and encouraged
to post their work online (e.g., in institutional repositories or on their website)
prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater ci-

xii

tation of published work (See The Effect


of Open Access).
Privacy Statement: The names and email
addresses entered in this journal site will be
used exclusively for the stated purposes of
this journal and will not be made available
for any other purpose or to any other party.

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Gold Sponsors

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Results in a Gold Sponsors: followed by the sponsors logo on the homepage of the website, and on the
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_________________________
Asfandyar Sheikh,
Editor-in-Chief
El Mednifico Journal

_________________________
Syed Arsalan Ali,
Managing Editor
El Mednifico Journal

El Mednifico Journal
C2 Block R, North Nazimabad, Karachi 74700, Sindh, Pakistan
editorial@mednifico.com submit@mednifico.com
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We accept Original Articles, Review Articles, Case Reports, Opinions and Debates, Essays, Letters to the Editor. There are no paper submission charges.
Submit your articles via the online system or send as an email to: submit@mednifico.com
We require editors, programmers, layout designers and proofreaders for our editorial staff. We also require avid medical bloggers for our sister website,
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Address: El Mednifico Journal, Baba-e-Urdu Road, Karachi 74200 Pakistan. Email: editorial@mednifico.com. Phone: (92-334)2090696.

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