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Hollerbach 1, 2
J. Willert 1 Endoscopic Ultrasound-Guided Fine-Needle Aspiration
T. Topalidis 3
M. Reiser 1
Biopsy of Liver Lesions: Histological and Cytological
W. Schmiegel 1 Assessment
Original Article
Background and Study Aims: EUS-guided fine-needle aspira- Results: EUS-FNA provided appropriate biopsy specimens in 40/
tion biopsy (EUS-FNA) is used increasingly for the diagnosis of 41 patients. It was not possible to aspirate sufficient material in
mediastinal, biliopancreatic, and gastric tumors. However, little one patient. On average, 1.4 needle passes were necessary to ob-
is known about EUS-FNA in hepatic lesions and the best method tain sufficient amounts of tissue. With regard to malignancy, the
Institution
1
Department of Internal Medicine, Ruhr University Bochum, Knappschaftskrankenhaus, Germany
2
Department of Gastroenterology, Allgemeines Krankenhaus Celle, Celle, Germany
3
Institute of Cytology, Hannover, Germany
Corresponding Author
S. Hollerbach ´ Klinik für Gastroenterologie, Allgemeines Krankenhaus Celle ´ Academic Teaching Hospital ´
University of Hannover ´ Siemensplatz 4 ´ 29223 Celle ´ Germany ´ Fax: +49-5141-721209 ´
E-mail: stephan.hollerbach@akh-celle.de
the pancreas, and the biliary, retroperitoneal, and perirectal in these instances [8 ± 10], and little is known about the clinical
space. In recent years, several prospective controlled studies potential of EUS-FNA as an alternative route in these and other
have shown that EUS-FNA provides a safe way of obtaining rapid patient subgrups. Though it is not possible to visualize all of the
and reliable diagnoses in benign and malignant disease [1 ± 5]. liver by means of transgastric or transduodenal EUS, the entire
Improved accuracy and cost-effectiveness have been demon- left lobe and most central segments of the liver (i. e., segments
strated in comparisons with other imaging techniques [1 ± 7]. I±V) are usually accessible, as schematically outlined in Figure 1.
In some instances, suspicious lesions in the liver may cause a di- To evaluate the feasibility, safety, and reliability of EUS-FNA in
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
All patients completed a standard questionnaire regarding the phy, as carefully listed and documented in the final report of the
performance and safety of endoscopy, EUS, and FNA, including a physician, were used as reference.
standard written informed consent sheet.
Statistical Analysis
Endoscopy and Investigational Techniques A prospective analysis was carried out of the number of needle
Patients fasted overnight. EUS was then carried out with the pa- passes (mean values) needed to obtain sufficient amounts of tis-
tient in a left lateral decubitus position or supine, and by means sue for both histological and cytological examinations, and of the
of a longitudinal scanner echo endoscope (FG-34 UX; Hitachi Ul- number of any complications.
trasound, Wiesbaden, Germany), equipped with a 7.5-MHz
curved-array linear ultrasound transducer. A standard Hancke± The sensitivity, specificity, positive predictive value (PPV), and
Vilmann aspiration biopsy needle (22 G), distributed by GIP negative predictive value (NPV) of the histological and cytologi-
MediGlobe, was used in all instances. All patients received seda- cal findings, compared with the results of the reference methods,
tion with intravenously administered midazolam (0.1 ± 0.25 mg/ were analyzed using appropriate 2 2 tables. The sensitivity and
kg body weight) and/or disoprivan (60 ± 380 mg) during the in- specificity were calculated in a combined fashion that included
Original Article
vestigation. both malignant and benign findings.
Sampling Protocol
Approximately half of the aspirated tissue cylinders were gently Results
pushed with the needle stylet onto glass slides for cytological a-
nalysis. Subsequently, slide smears were prepared and air-dried. General Assessment and Safety
The remaining half of the aspirated tissue cylinders were poured The diagnostic procedure (EUS-FNA) was well tolerated by a
in toto directly into a small plastic bottle containing formalin, to large majority of patients. No major complications requiring sur-
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
Original Article
Figure 2 a Endoscopic ultrasound (EUS) appearance of a small 1-cm Benign tumors (hemangioma, focal nodular hyperplasia (FNH),
nodule (arrow) that was found incidentally during an EUS examination benign cyst) were correctly diagnosed in five out of eight pa-
in the left lobe of the liver (segment II). b Transgastric EUS-FNA biopsy
tients, when the morphological EUS examination results were
of the tumor nodule shown in a, under direct ultrasound-guided visual-
ization. The tip of the 22-G puncture needle can clearly be seen as an combined with cytological and histological findings. However,
echogenic strand within the echo-reduced tumor nodule (arrow). c both histological and cytological investigation failed to establish
Histological examination revealed a single small metastasis of a well- the definite diagnosis in the two patients with FNH, in whom the
differentiated neuroendocrine tumor. The primary tumor was later final diagnosis was based on the scintigraphy findings and clini-
found to be located in the ileocecal region of the colon.
cal follow-up.
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
Original Article
Figure 4 a Transgastric endosonographic image of an echo-bright tu-
mor nodule measuring 2.5 cm in diameter, which was located in seg-
ment II of the left lobe of the liver in a patient with severe coagulopa-
thy due to decompensated cirrhosis. The tumor had previously been
detected by abdominal ultrasound as arising from a cirrhotic liver,
and confirmed by CT scanning. Percutaneous biopsy appeared to be a
747
Table 1 Agreement between histological and/or cytological re- Table 2 Summary of the statistical analysis of the subgroup of pa-
sults and tumor type, in patients with hepatic tumor le- tients with malignancies (n = 33), and of all patients enrol-
sions (n = 41), as proven by reference methods led (n = 41) in the study
Tumor type n EUS-FNA diag- Histological Cytological Sensitivity, % Specificity, % PPV, % NPV, %
nosis correct diagnosis diagnosis
(histological correct correct EUS-FNA in malignant
and cytological) disease 94 100 100 78
EUS-FNA in all conditions,
Colorectal cancer 8 7/8 7 6 including benign lesions 92 100 100 72
Lung cancer 9 9/9 8 9
Pancreatic cancer 6 6/6 4 5 EUS, endoscopic ultrasonography; FNA, fine-needle aspiration cytology; PPV, pos-
itive predictive value; NPV, negative predictive value.
Breast cancer 4 4/4 4 2
HCC 3 3/3 2 2
CCC 2 1/2 1 0
NHL 1 1/1 1 0
Hemangioma 3 2/3 2 0 Hence, we considered the FNA diagnosis to be incorrect in both
Benign cyst 3 3/3 0 3 cases (Table 1).
Focal nodular
hyperplasia 2 0/2 0 0 In the 15 patients with lesions arising within a cirrhotic liver, the
HCC, hepatocellular carcinoma; CCC, cholangiocellular carcinoma; NHL, Non- biopsy results did not substantially differ from those obtained in
Hodgkin's lymphoma. patients without chronic liver disease.
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
Discussion Taking the previous and present study together [8 ± 10], EUS-FNA
of liver lesions compares favourably with the diagnostic accuracy
This prospective controlled study shows that EUS-FNA is a feasi- of EUS-FNA in other diseases, particularly with respect to pan-
ble, safe, and powerful technique for obtaining a definite tissue- creatic malignancies [2,12]. In a large international multicenter
based diagnosis in patients with focal liver lesions, particularly trial, Wiersema et al. report similar results for EUS-FNA in the di-
those of cancerous origin. In addition, it can be performed as an agnosis of other accessible extraluminal masses [1], suggesting
alternative method in patients who present with an enhanced that EUS-FNA of liver lesions can now be considered to be an in-
risk for complications during percutaneous biopsy, and even in tegral part of the EUS repertoire in selected patients, which has
very small accessible lesions in the liver (< 1 cm). The best diag- already emerged as routine procedure in specialized EUS centers.
nostic results are achieved when tissue analysis is performed One of the major advantages of EUS-FNA is the ability to simulta-
both by histological and cytological assessment of specimens. neously offer diagnostic ultrasound assessment and interven-
Negative FNA results, however, do not rule out malignant disease tional procedures, such as tissue sampling, and even therapeutic
and the procedure should be repeated, if clinically feasible. To procedures such as celiac plexus neurolysis. Hence, EUS-guided
the best of our knowledge, this is the first study that assesses in FNA of liver lesions should be used particularly in those patients
Original Article
a prospective fashion the diagnostic performance of EUS-FNA to- in whom an endoscopic ªone-stop shopº procedure, including si-
gether with an optimization of tissue sampling from liver le- multaneous diagnosis, staging, and sometimes even palliative
sions. From our data we conclude that EUS-FNA has certain ad- therapy [13], is desirable. In the future, it seems possible that
vantages in selected patients, if performed by an expert, but we EUS-guided fine-needle injection therapy (EUS-FNI) for pallia-
acknowledge that we certainly need more data on this subject tive therapy of malignant diseases such as liver metastasis may
before EUS-FNA can be recommended to a broad readership as a play an important role if integrated into a multimodal therapeu-
ªstandardº procedure in this clinical setting. Hence, our data tic concept, as described recently [13].
open a new avenue of investigational endoscopy. Comparative
Hollerbach S et al. EUS-Guided Biopsy of Liver Lesions ´ Endoscopy 2003; 35: 743 ± 749
cal with histological assessment. Negative results do not rule out 5
Gress FG, Hawes RH, Savides TJ et al. Endoscopic ultrasound-guided
malignant disease and the procedures should be repeated, as fine-needle aspiration biopsy using linear array and radial scanning
endosonography. Gastrointest Endosc 1997; 45: 243 ± 250
clinically required. EUS-FNA can also be simultaneously used for 6
Giovannini M, Seitz JF, Monges G, Terrier H et al. Fine-needle aspira-
the diagnosis and staging of malignancies (ªone-stopº proce- tion cytology guided by endoscopic ultrasonography: results in 141
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7
peutic potential of EUS-guided therapy in some of these instan- Pfau PR, Chak A. Endoscopic ultrasonography. Endoscopy 2002; 34:
21 ± 28
ces. 8
Hollerbach S, Wilhelms I, Willert J et al. EUS-guided fine needle biopsy
(FNA) of liver tumors a is highly accurate and safe diagnostic proce-
dure in high-risk patients. Gastrointest Endosc 2001; 76: A1425
9
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