J Korean Surg Soc 2012;83:237-241

http://dx.doi.org/10.4174/jkss.2012.83.4.237
JKSS
Journal of the Korean Surgical Society
pISSN 2233-7903ㆍeISSN 2093-0488

ORIGINAL ARTICLE

The diagnostic values of preoperative laboratory

markers in children with complicated appendicitis

Hany Noh, Sei-Jin Chang1, Airi Han

Departments of General Surgery and 1Preventive Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

Purpose: Accurate diagnosis and optimal management of acute appendicitis, despite being the most common surgical emer-
gency encountered in emergency departments, is often delayed in pediatric patients due to nonspecific symptoms and com-
munication barriers, often leading to more complicated cases. The aim of this study is to investigate the diagnostic sig-
nificance of common laboratory markers. Methods: A total of 421 patients aged 15 and younger underwent surgical treat-
ment for acute appendicitis. We conducted a retrospective analysis for white blood cell (WBC), C-reactive protein (CRP) and
bilirubin. All patients were classified into simple or complicated appendicitis groups based on postoperative histology.
Results: The mean age of the patients in the complicated appendicitis group was younger than that in the simple group (P =
0.005). WBC, CRP and bilirubin levels were significantly higher in the complicated appendicitis group (P ＜ 0.001, ＜0.001,
0.002). The relative risk for complicated appendicitis was calculated using age, WBC, CRP and bilirubin. Elevated CRP levels
were associated with the highest risk for complicated appendicitis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.38
to 4.65) followed by WBC (HR, 2.42; 95% CI, 1.07 to 5.46) and bilirubin (HR, 2.04; 95% CI, 1.09 to 3.82). The most sensitive
markers for diagnosing complicated appendicitis were WBC (95.2%) and CRP (86.3%). Bilirubin levels showed the highest
specificity at 74.8%. Conclusion: The risk of complicated appendicitis was significantly higher in patients younger than 10
years old. Preoperative WBC, CRP and bilirubin have clinical value in diagnosing complicated appendicitis with a HR of 2.0
to 2.5. Our results suggest that the utilization of WBC, CRP, and bilirubin can assist in the diagnosis of complicated appendi-
citis in pediatric patients, allowing prompt diagnosis and optimal management.

Key Words: Appendicitis, Child, Leukocytes, C-reactive protein, Bilirubin

INTRODUCTION their inability to provide accurate histories and typically

low indexes of suspicion that lead to misdiagnosis [2].
Appendicitis remains the most common acute surgical Complicated appendicitis is closely related to wound
condition of the abdomen and is also the most commonly infection, intraabdominal abscess formation, postopera-
misdiagnosed [1]. About one third of patients with appen- tive intestinal obstruction, prolonged ileus and rarely, en-
dicitis are younger than 18 years of age. Younger children terocutaneous fistula. In females, it has been associated
typically present with complicated appendicitis due to with fallopian tube dysfunction, leading to infertility [3].

Received May 24, 2012, Revised July 23, 2012, Accepted August 5, 2012

Correspondence to: Airi Han

Department of General Surgery, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 220-701, Korea
Tel: ＋82-33-741-0571, Fax: ＋82-33-742-1815, E-mail: [email protected]

cc Journal of the Korean Surgical Society is an Open Access Journal. All articles are distributed under the terms of the Creative Commons
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Copyright © 2012, the Korean Surgical Society

Hany Noh, et al

Because of high morbidity of complicated appendicitis, CRP, bilirubin levels, AST and ALT with Pearson’s
careful diagnosis and prompt treatment is imperative. chi-square test. Sensitivity, specificity, positive predictive
The accuracy of diagnosing acute appendicitis has value and negative predictive value were calculated for
greatly improved with the introduction of computed to- WBC, CRP, bilirubin and age at operation. Hazard ratios
mography [4]. However, physicians should be cautious in (HRs) were calculated for WBC, CRP, bilirubin and age at
the use of computed tomography (CT) for pediatric pa- operation through binary logistic regression after multi-
tients due to reports of long term adverse effects [5,6]. variate data analysis. A P-value ≤ 0.05 was used to in-
We conducted this study to investigate the diagnostic dicate statistical significance.
significance of common laboratory markers in children
with complicated appendicitis.
RESULTS

METHODS Of the 421 patients included in our study, there were 256
males (61%) and 165 females (39%). Of these, 270 patients
A total of 421 patients aged 15 or younger underwent (64%) were diagnosed with complicated appendicitis.
surgical treatment for acute appendicitis from September There were no significant differences between sexes (P =
2003 to October 2011 at Wonju Christian Hospital. A retro- 0.869).
spective analysis was completed by reviewing medical The mean ages at operation were 10.3 years (SD, ±3.1; 2
records. to 15 years) and 9.2 years (SD, ±3.3; 2 to 15 years) for the
Patient sex, age at surgery, and preoperative laboratory simple and complicated groups, respectively. The ages of
markers (white blood cell [WBC], C-reactive protein the patients in the complicated appendicitis group were
[CRP], bilirubin, aspartate aminotransferase [AST], and significantly lower than in the simple group (P = 0.005).
alanine aminotransferase [ALT]) were recorded. Hyperbi- Mean bilirubin levels were 0.9 mg/dL (SD, ±0.6; 0.1 to 4.0
lirubinemia was defined as total bilirubin ＞1.0 mg/dL. mg/dL). Bilirubin levels were 0.8 mg/dL (SD, ±0.5; 0.1 to 3.8
Normal values were defined as follows: WBC 4.4 to 10.0 × mg/dL) and 0.9 mg/dL (SD, ±0.6; 0.1 to 4.0 mg/dL), in the
3
10 /μL, CRP ＜ 0.5 mg/dL and AST, ALT ＜40 U/L. simple and complicated groups, respectively, with the
All patients were classified into either simple or compli- complicated group exhibiting significantly higher levels
cated appendicitis groups based on postoperative histo- (P = 0.002). Bilirubin showed the highest specificity in di-
logy. Complicated appendicitis was defined as a gan- agnosing complicated cases at 75% compared to WBC
grenous and/or perforated appendicitis. Many terms have (19%) and CRP (35%).
3
been used to describe the varying stages of appendicitis, Mean WBC was 16.4 × 10 /μL (SD, ±5.2; 3.1 to 32.0 ×
3
including acute appendicitis, suppurative appendicitis, 10 /μL) for all patients. Mean WBCs in the simple and com-
3
gangrenous appendicitis, and perforated appendicitis. plicated groups were 14.6 × 10 /μL (SD, ±4.9; 3.1 to 30.7 ×
3 3 3
These distinctions are vague, and only the clinically rele- 10 /μL) and 17.4 × 10 /μL (SD, ±5.1; 3.3 to 32.0 × 10 /μL), re-
vant distinction of simple and complicated appendicitis spectively, with significantly higher levels in the compli-
should be used. We use the term ‘complicated’ appendici- cated group (P ＜ 0.001).
tis to describe both gangrenous and perforated appendici- CRP levels were assessed preoperatively in 307 patients.
tis [7]. The mean CRP was 6.2 mg/dL (SD, ±7.9; 0 to 47.5 mg/dL).
For the simple and complicated groups, the mean CRPs
Statistical analysis were 3.2 mg/dL (SD, ±4.9; 0 to 24.0 mg/dL) and 7.7 mg/dL
We conducted all analyses using SPSS ver. 18.0 (SPSS (SD, ±8.7; 0 to 47.5 mg/dL), respectively. CRP levels were
Inc., Chicago, IL, USA). The mean values, SDs, ranges, and significantly higher in the complicated group (P ＜ 0.001).
P-values were calculated for sex, age at operation, WBC, The sensitivity for CRP in the diagnosis of complicated ap-

238 thesurgery.or.kr
 The markers in children with appendicitis

Table 1. Details of laboratory values, epidemiology of the two groups

Total Non-complicated Complicated

P-value
(n = 421, 100%) (n = 151, 36%) (n = 270, 64%)
Female/male 165 (39%)/256 (61%) 58 (38%)/93 (62%) 107 (40%)/163 (60%) 0.869
Age (yr) 9.6 ± 3.3 (2-15) 10.3 ± 3.1 (2-15) 9.2 ± 3.3 (2-15) 0.005
3
WBC (×10 /µL) 16.4 ± 5.2 (3.1-32.0) 14.6 ± 4.9 (3.1-30.7) 17.4 ± 5.1 (3.3-32.0) ＜0.001
CRP (mg/dL) 6.2 ± 7.9 (0-47.5) 3.2 ± 4.9 (0-24.0) 7.7 ± 8.7 (0-47.5) ＜0.001
Bilirubin (mg/dL) 0.9 ± 0.6 (0.1-4.0) 0.8 ± 0.5 (0.1-3.8) 0.9 ± 0.6 (0.1-4.0) 0.002
AST (U/L) 27.7 ± 10.1 (11-100) 27.4 ± 8.7 (11-59) 27.9 ± 10.8 (14-100) 0.396
ALT (U/L) 18.4 ± 12.4 (4-162) 18.6 ± 13.9 (4-162) 18.2 ± 11.4 (4-97) 0.558

Values are presented as mean ± standard deviation (range).

WBC, white blood cell; CRP, C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

Table 2. Sensitivity, specificity, PPV, NPV for WBC, CRP, bilirubin Table 3. Hazard ratio (HR) of age, CRP, bilirubin, WBC

Sensitivity Specificity PPV NPV HR (95% CI) P-value

(%) (%) (%) (%)
Age ≥ 10 (yr) 0.51 (0.30-0.86) 0.012
WBC ＞ 10.0 (×103/µL) 95 19 68 69 CRP ＞ 0.5 (mg/dL) 2.53 (1.38-4.65) 0.003
CRP ＞ 0.5 (mg/dL) 86 35 73 56 Bilirubin ≥ 1.0 vs. ≤ 0.6 (mg/dL) 2.04 (1.09-3.82) 0.026
3
Bilirubin ＞ 1.0 (mg/dL) 38 75 73 40 WBC ＞ 10.0 (×10 /µL) 2.42 (1.07-5.46) 0.034

PPV, positive predictive value; NPV, negative predictive value; CRP, C-reactive protein; WBC, white blood cell; CI, confidence
WBC, white blood cell; CRP, C-reactive protein. interval.

pendicitis was 86%, while the specificity was 35% (Tables DISCUSSION
1, 2).
No significant differences in AST or ALT levels were Despite being the most common surgical emergency,
seen between the two groups (P = 0.653, 0.742). acute appendicitis is often misdiagnosed, with negative
No correlations between elevated bilirubin levels and appendectomy rates reported between 10 to 30% [1].
AST or ALT levels was seen (P = 0.064, 0.111 by Pearson’s Morbidity following complicated appendicitis includes
correlation coefficient). bacterial peritonitis, urinary disorders, small bowel ob-
Binary multiple logistic regression analyses were con- struction and intra-abdominal abscesses, all of which are
ducted for age, WBC, CRP and bilirubin levels to assess the associated with poor postoperative outcomes. A careful
HR of these parameters. The risk of complicated appendi- history taking and thorough physical examination by a
citis is decreased to almost half for children ten years and physician are essential in diagnosing appendicitis. Our re-
older (HR, 0.51; 95% CI, 0.30 to 0.86). sults confirmed that the risk of complicated appendicitis
Patients with CRP levels higher than 0.5 mg/dL had a was nearly two times greater in patients younger than 10
2.53 times greater risk of complicated appendicitis than years old compared to patients 10 years and older.
patients with CRP levels less than 0.5 mg/dL (HR, 2.53; Evidently, there is a need for more objective and accurate
95% CI, 1.38 to 4.65). Patients with bilirubin levels greater measures for diagnosing appendicitis in children.
than 1.0 mg/dL had a HR of 2.04 compared with those with Even with recent advances in imaging, no single test can
bilirubin levels less than 0.6 mg/dL (HR, 2.04; 95% CI, 1.09 accurately diagnose perforation or gangrenous changes of
3
to 3.82). Patients with WBC greater than 10.0 × 10 /μL had the appendix. Common studies such as CT should also be
a HR of 2.42 compared with patients with WBC under 10.0 used with caution in children because of the potential risks
3
× 10 /μL (HR, 2.42; 95% CI, 1.07 to 5.46) (Table 3). of radiation [5,6]. There have been several studies of the di-
agnostic value of separate laboratory markers such as

thesurgery.or.kr 239
Hany Noh, et al

WBC [8], CRP [9] and bilirubin [10], but without definite plicated appendicitis. Bilirubin levels had the highest spe-
results. Our study is the first to evaluate different markers cificity for diagnosing complicated appendicitis, leading
together in a single study. to a 2.0 times greater chance for complicated appendicitis
Our results show that WBC and CRP are highly sensi- in patients with elevated levels.
tive markers in the diagnosis of complicated appendicitis We expect further studies to validate the use of these
in children and bilirubin is a marker with high specificity. markers in an appendicitis scoring system for children.
Patients with elevated WBC, CRP and bilirubin levels
were found to have a 2.0 to 2.5 times increased risk of com-
plicated appendicitis. CONFLICTS OF INTEREST
While WBC and CRP elevation are more common in-
dicators of inflammation, there has been new attention No potential conflict of interest relevant to this article
paid to bilirubin, which is often overlooked in the diag- was reported.
nosis of acute appendicitis [10]. Many studies have been
conducted on hyperbilirubinemia resulting from choles-
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