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research-article2014
ORIGINAL ARTICLE
Abstract
Correspondence:
Waqas Farooqui
Lundtoftegrdsvej 27, st th
2800 Lyngby
Denmark
Email: waqas.farooqui@regionh.dk
73
Introduction
Statistical Analysis
Method
During a 3-year study period from May 2009 to May
2012, we retrospectively included all patients suspected of or suffering from appendicitis, who underwent an acute diagnostic laparoscopy, laparoscopic
appendectomy, or conventional (open) appendectomy in a surgical department. Data was extracted
from the electronic patient journal system and
included patient demographics, histological findings, results of blood tests (liver function test, WBC,
bilirubin, and CRP), and clinical symptoms on admission. Patients were excluded if one of the following
criteria were present: appendectomy or laparotomy
for other reasons than appendicitis; known liver, biliary, or hematologic diseases; recent severe illness
(defined as any illness resulting in an increased CRP
and WBC count); pregnancy at the time of admission;
missing results from relevant blood tests; or an age
below 16 years.
Patients were divided into two groups consisting of
patients with histologically verified appendicitis and
patients with other differential diagnoses. Patients
with a histologically verified appendicitis were further divided into two subgroups depending on
whether they had a perforated or non-perforated
appendicitis. Perforation was defined as the presence
of one of the following criteria: visible perforation at
operation, documented presence of a periappendicular abscess, or histologically verified perforation (a
break of the serosa layer).
Results
A total of 1656 patients were initially included. Out of
those, 39% were excluded due to the presence of one
or more of the exclusion criteria. A total of 1008
patients were operated with a preoperative suspicion
of appendicitis. Of these, 700 patients had a pathologically verified inflamed appendix. Of the patients with
an inflamed appendix, 27% had a perforated appendix
(Fig. 1). A total of 698 patients had their appendix
removed through laparoscopy, 24 patients through
open surgery, and 286 patients underwent a diagnostic laparoscopy. Patient demographics are shown in
Table 1.
In the univariate analysis, patients with acute
appendicitis had significantly higher blood levels of
WBC (p < 0.001), bilirubin (p < 0.001), CRP (p < 0.001),
and ALAT (p = 0.001) than patients without appendicitis. Levels of ASAT were not significantly different
between the two groups (p = 0.818). Patients with perforated appendicitis had significantly higher levels of
WBC count (p = 0.004), bilirubin (p < 0.001), and CRP
(p < 0.001) than patients with a non-perforated appendicitis. No differences in levels of ASAT (p = 0.331)
and ALAT (p = 0.178) were seen between the two
groups.
In the multivariate analysis for detecting markers
that predicted appendicitis versus non-appendicitis,
we found that the WBC count, bilirubin, and ALAT
74
W. Farooqui, et al.
Age (years)
Gender
Male
Female
WBC
Bilirubin
CRP
ALAT
ASAT
Non
appendicitis
(n = 308)
Appendicitis
(n = 700)
33 (1691)
40 (1697)
84 (27.3%)
224 (72.7%)
10.4 (3.2027.6)
9 (163)
25.50 (3427)
17 (3455)
26 (13607)
343 (49%)
357 (51%)
13.5 (3.7033.40)
12 (291)
39.50 (3486)
19 (3828)
27 (9326)
Statistical
significance
p < 0.001
p < 0.001
p < 0.001
p = .002
p = 0.001
p = 0.818
Non-perforated
appendicitis
(n = 510)
37 (1697)
246 (48.2%)
264 (51.8%)
13.2 (3.730.3)
12 (278)
26.5 (3486)
19 20.82 (3203)
27 (9166)
Perforated
appendicitis (n = 190)
51 (1695)
97 (51.1%)
93 (49.9%)
13.85 (5.433.4)
15.5 (291)
86 (3379)
17.5 75.43 (3828)
27 (12326)
Statistical
significance
p < 0.001
p = 0.004
p < 0.001
p < 0.001
p = 0.331
p = 0.178
WBC: white blood count; CRP: C-reactive protein; ALAT: alanine transaminase; ASAT: aspartate transaminase.
Data are presented as median (range).
levels were all significant factors (Table 2). In the multivariate analysis, discriminating perforated from
non-perforated appendicitis, we found that blood levels of WBC, bilirubin, and CRP were significant
parameters for predicting appendiceal perforation
(Table 2).
A linear regression model, including the WBC
count, bilirubin, and ALAT (y = 4.624 logWBC +
1.378 log Bilirubin + 0.684 log ALAT) had the highest
PPV to discriminate between acute appendicitis and
non-appendicitis (Table 3). In order to discriminate
between perforated and non-perforated appendicitis
level of CRP, a linear regression model, including
WBC count and level of bilirubin and CRP as variables (y = 1.842logWBC + 0.815log Bilirubin + 1.091log
CRP), had the highest negative predictive value
(NPV) (Table 4). A comparison of the ROC curves is
shown in Figs 2 and 3.
Discussion
This study found that the WBC count, levels of bilirubin, CRP, and ALAT levels were all significantly
75
Logistic regression
coefficient (B)
SE
Statistical
significancea
Exp (B)
0.522
0.263
0.118
0.257
p < 0.001
p < 0.001
p = 0.191
p = 0.008
101.930
3.966
1.166
1.981
0.673
0.342
0.162
p = 0.006
p = 0.017
p < 0.001
6.311
2.158
2.977
95% confidence
interval
36.7283.3
2.46.6
0.91.5
1.23.3
1.68823.602
1.1554.417
1.1674.090
WBC: white blood count; CRP, C-reactive protein; ALAT: alanine transaminase; ASAT: aspartate transaminase.
Parameters were analyzed using their logarithmic value.
aLogistic regression analysis.
Table 3
Sensitivities, specificities, positive predictive values, and negative predictive values of parameters used in the early diagnosis of acute appendicitis.
Parameters
Sensitivity
Specificity
Positive
predictive value
Negative
predictive value
WBC count
Bilirubin
CRP
ALAT
ASAT
Linear model
0.68
0.69
0.81
0.73
0.52
0.64
0.64
0.56
0.32
0.39
0.51
0.75
0.81
0.78
0.73
0.73
0.71
0.86
0.46
0.45
0.42
0.39
0.32
0.49
WBC: white blood cell; CRP: C-reactive protein; ALAT: alanine transaminase; ASAT: aspartate transaminase.
Parameters significant in the multivariate analysisWBC, bilirubin, and ALAT. Linear model is a combination of the significant
parameters in the multivariate analysis.
Table 4
Sensitivities, specificities, positive predictive values, and negative predictive values of parameters used as indicators for identifying patients with a
perforated appendix among patients with acute appendicitis.
Parameters
Sensitivity
Specificity
Positive
predictive value
Negative
predictive value
WBC
Bilirubin
CRP
ALAT
ASAT
Linear model
0.34
0.50
0.54
0.03
0.61
0.60
0.77
0.71
0.79
0.99
0.43
0.76
0.35
0.39
0.49
0.46
0.28
0.48
0.76
0.79
0.82
0.73
0.75
0.83
WBC: white blood cell; CRP: C-reactive protein; ALAT: alanine transaminase; ASAT: aspartate transaminase.
Parameters significant in the multivariate analysisWBC, bilirubin, and CRP. Linear model is a combination of the significant parameters
in the multivariate analysis.
An explanation could be that CRP reacts slower compared to, for example, WBC (15). Thus, in the patient
with appendicitis, who normally has a short and
acute symptomatic history, the CRP may not react
until later. In contrast, the patients with perforated
appendicitis may have a more severe disease and a
longer duration of inflammation. This may result in
the significant elevation of CRP levels for perforated
disease.
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W. Farooqui, et al.
Fig.2. ROC curve analysis for patients with appendicitis versus patients with a differential diagnosis. Top left: WBC count (AUC = 0.707);
top right: bilirubin (AUC = 0.661); bottom left: ALAT (AUC = 0.569); and bottom right: linear model (AUC = 0.745).
ROC: receiving operating characteristics; WBC: white blood cell; AUC: area under curve; ALAT: alanine transaminase.
77
Fig.3. ROC curve analysis for patients with non-perforated appendicitis versus patients with perforated appendicitis. Top left: WBC count
(AUC = 0.565); top right: bilirubin (AUC = 0.617); bottom left: CRP (AUC = 0.700); and bottom right: linear model (AUC = 0.715).
ROC: receiving operating characteristics; WBC: white blood cell; AUC: area under curve; CRP: C-reactive protein.
diagnostically to differentiate between patients suffering from appendicitis and differential diagnoses
and thereby reduce the number of patients undergoing surgical treatment. The similar has been
attempted for patients suffering from perforated
and non-perforated appendicitis. As stated above,
many biomarkers have indeed been identified as
being related to appendicitis and appendiceal perforation, the most important and well documented
being WBC, CRP, and bilirubin. These biomarkers
have generally had a high specificity, but low
sensitivity (22, 23). Combining biomarkers increases
the specificity without a great change in sensitivity.
Therefore, relevant biomarkers, alone or in
combination, cannot be used as a differential tool
but rather as a supportive tool along side
the patients clinical appearance and symptomatic
history.
78
W. Farooqui, et al.
Conclusion
WBC count and bilirubin, CRP, and ALAT levels are
useful biomarkers in predicting appendicitis and
appendiceal perforation. Combining the biomarkers
increases the predictive values. Therefore, blood levels
of bilirubin, CRP, and ALAT should be taken in consideration when predicting appendicitis.
References
1. Lau WY, Teoh-Chan CH, Fan ST et al: The bacteriology and
septic complication of patients with appendicitis. Ann Surg
1984;200:576581.
2. Bennion RS, Baron EJ, Thompson JE Jr et al: The bacteriology of gangrenous and perforated appendicitis. Ann Surg
1990;211:165171.
3. Chen C-Y, Chen Y-C, Pu H-N etal: Bacteriology of acute appendicitis and its implication for the use of prophylactic antibiotics.
Surg Infect 2012;13(6):383390.
4.
Humes DJ, Simpson J: Acute appendicitis. BMJ
2006;333(7567):530534.
5. Andersson RE: Meta-analysis of the clinical and laboratory
diagnosis of appendicitis. Br J Surg 2004;91(1): 2837.
6. Lintula H, Kokki H, Pulkkinen J etal: Diagnostic score in acute
appendicitis. Validation of a diagnostic score (Lintula score) for
adults with suspected appendicitis. Langenbecks Arch Surg
2010;395:495500.
7. Sitter H, Hoffmann S, Hassan I etal: Diagnostic score in appendicitis. Validation of a diagnostic score (Eskelinen score) in
patients in whom acute appendicitis is suspected. Langenbecks
Arch Surg 2004;389:213218.
8. Anielski R, Kunierz-Cabala B, Szafraniec K: An evaluation of
the utility of additional tests in the preoperative diagnostics of
acute appendicitis. Langenbecks Arch Surg 2010;395:10611068.
9. Tan WJ, Pek W, Kabir T etal: Alvarado score: a guide to computed tomography utilization in appendicitis. ANZ J Surg
2013;83:748752.
10. Estrada JJ, Petrosyan M, Barnhart J etal: Hyperbilirubinemia in
appendicitis: a new predictor of perforation. J Gastrointest Surg
2007;11(6):714718.