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ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 4  |  Page : 167-171

Correlation of serum C-reactive protein, white blood count, and neutrophil percentage with histopathological findings in acute appendicitis


1 Department of Pediatrics, King Fahad Medical City, Riyadh, Saudi Arabia
2 Department of Otolaryngology, King Abdulaziz Medical City, Jeddah, Saudi Arabia
3 Department of Surgery, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
4 Preventive Medicine and Public Health Resident, Ministry of Health, Jeddah, Saudi Arabia
5 Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
6 Department of Surgery, University of Jeddah, Jeddah, Saudi Arabia

Date of Submission12-Nov-2019
Date of Acceptance13-Aug-2021
Date of Web Publication30-Dec-2021

Correspondence Address:
Wisam H Jamal
Department of Surgery, University of Jeddah, Jeddah
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ssj.ssj_43_19

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  Abstract 


Background: Acute appendicitis is still known as one of the most common abdominal emergencies, one of the challenges encountered by the emergency physician is accurate diagnosis of acute appendicitis. In a trial to overcome these difficulties, this study aimed to assess the diagnostic accuracy of readily available and inexpensive inflammatory markers serum C-reactive protein (CRP) levels, white blood cells (WBCs), and neutrophils count in the diagnosis of acute appendicitis.
Methods: This is a retrospective study. Two hundred and forty-one participants who performed appendectomy in King Abdulaziz University Hospital from January 1, 2013, to December 31, 2017, were included in this study, of which 148 (61.4%) were males and 93 (38.6%) were females. Chi-square and t-test were used for statistical analysis.
Results: The study included 241 patients; the median CRP, WBCs, and neutrophils were significantly higher in patients who underwent open surgery and in complicated appendicitis compared to noncomplicated ones. Receiver operating characteristic curve analysis revealed higher accuracy of CRP in discrimination of acute appendicitis with a sensitivity and specificity of 94% and 57%, respectively.
Conclusion: The diagnostic accuracy of the CRP is greater than the WBCs and neutrophil count. Thus, high serum CRP levels support the surgeon's clinical diagnosis. However, none of the studied markers is 100% diagnostic for acute appendicitis. It is recommended to include CRP measurement as a routine laboratory test in patients with suspected diagnosis of acute appendicitis.

Keywords: Acute appendicitis, C-reactive protein, diagnosis, neutrophils, receiver operating characteristic curve, white blood cells


How to cite this article:
Aldhafiri FM, Aldhafiri FM, Alshahrani M, Almaymuni AD, Algethami MR, Maghrabi AA, Rizk HA, Jamal WH. Correlation of serum C-reactive protein, white blood count, and neutrophil percentage with histopathological findings in acute appendicitis. Saudi Surg J 2020;8:167-71

How to cite this URL:
Aldhafiri FM, Aldhafiri FM, Alshahrani M, Almaymuni AD, Algethami MR, Maghrabi AA, Rizk HA, Jamal WH. Correlation of serum C-reactive protein, white blood count, and neutrophil percentage with histopathological findings in acute appendicitis. Saudi Surg J [serial online] 2020 [cited 2022 Jan 21];8:167-71. Available from: https://www.saudisurgj.org/text.asp?2020/8/4/167/334508




  Introduction Top


Acute appendicitis is still known as one of the most common abdominal emergencies, and the overall lifetime risk of having surgery is high with a percentage of 12% and 23% in male and female, respectively. Furthermore, it has been shown that appendicitis is the most frequent source of community-acquired intra-abdominal infections.[1],[2],[3]

Based on presenting history and clinical examination, the diagnosis of appendicitis is usually made but the accuracy is only between 76% and 92%.[4],[5] Therefore, there is a need for laboratory investigations to support the diagnosis, such as white blood cells (WBCs), differential counts (the percentage of neutrophil [PN] granulocytes), and C-reactive protein (CRP).[4],[6],[7]

The rate of negative appendectomy is still high, as well as perforation due to the difficulty for reaching the accurate diagnosis.[4],[8],[9] After using ultrasound and computed tomography, the rate of negative appendectomies has decreased, while the perforation rate has remained high (22%–62%).[10],[11],[12]

Negative appendectomy is considered an unnecessary surgery that comes with risk of complications and even death. Moreover, it comes at high financial cost for the patient and national economy. Hence, reducing unnecessary appendectomies and complicated appendicitis rate improves the patient's health and national economy.[13]

Although the radiological modalities such as ultrasound, computed tomography, and magnetic resonance imaging are helpful and accurate in diagnosing acute appendicitis, they are not easy to apply in most primary health-care centers and some hospitals because of high costs.[14],[15],[16]

In contrast, laboratory investigations are easy, fast, sensitive, and not expensive in diagnosing acute appendicitis. CRP has been considered as important nonspecific inflammatory marker. Its value has been investigated and was assumed to be a good predictor of appendicitis.[4],[17],[18],[19]

Our aim in this study was to investigate the accuracy of CRP, WBCs, and neutrophils in diagnosing acute appendicitis by comparing it to the histopathological examination.


  Methods Top


This is a retrospective study, conducted from December 2017 to May 2018 at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. KAUH is one of the biggest tertiary referral and teaching centers in the western region of Saudi Arabia with a capacity of 800 beds. The Institutional Review Board of KAUH approved the study.

Population and setting

All patients admitted for appendectomy in KAUH from January 1, 2013, to December 31, 2017, were included in our study; patients with incomplete data were excluded from our study.

Data source and data extraction

The data was extracted from the hospital record. The studied variables were as following: (1) demographic data (age, gender); (2) type of operation (open vs. laparoscopy); (3) blood samples for routine laboratory tests (WBCs, neutrophil, and CRP) which were obtained at admission; (4) doctor's inspection of the appendix during operation and histopathological results.

The acceptable WBCs value in our laboratory is 0–10 × 109/L. Therefore, levels above 10 × 109/L were considered as elevated WBCs. The PNs were counted elevated when it is more than 75% of WBCs. The normal CRP level in our laboratory is <3.0 mg/L; levels above 6 mg/L were considered as high. Doctor's inspection of the appendix during operation is written by the surgeon in the operation notes as the following (normal, inflamed, inflamed with abscess, phlegmon, inflamed with fecalith material, perforated, perforated with gangrene). Then, appendices were removed, fixed in 4% formalin, and histopathologically studied. Shoshtari et al. described criteria for the histopathological results of the removed appendix, patients were classified into three groups: Group A (normal appendix); Group B (inflamed appendix-simple appendicitis); and Group C (perforated/gangrenous/malignant appendix-complicated appendicitis).[20]

Statistical analysis

Categorical variables were described using a frequency and associated percentages. While continuous variables for normally distributed were described using mean and standard deviation. If continuous variables did not follow a normal distribution, they were given as median with the interquartile range. Comparison between groups was carried using t-test and Chi-square test for continuous and categorical data, respectively. For all statistical tests, P < 0.05 was deemed significant.


  Results Top


A total of 241 who performed appendectomy were included in this study, of which 148 (61.4%) were males and 93 (38.6%) were females. The median age score was 17 years as shown in [Table 1].
Table 1: Demographic data

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Most of the cases 228 (94.6%) had open surgery, and only 13 (5.4%) performed laparoscopic surgery. The median scores of WBCs, neutrophils, CRP, and ALP were 13.5, 77.0, 25.6, and 121, respectively [Table 2].
Table 2: Medical characteristics

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[Table 3] represents doctor's inspection of the appendix, which revealed that more than half of the sample 132 (55.6%) reported either inflammation alone or inflammation associated with other problems (abscess, fecalith material), followed by perforation 50 (20.8%) and 42 (17.4%) were not reported in the operation notes.
Table 3: Doctor inspection of the appendix

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On the other hand, the histopathological results showed that the majority of cases 211 (87.6%) had simple appendicitis, while the rest were divided equally between normal and complicated appendicitis (perforated, gangrenous, or malignant) 15 (6.2%) as shown in [Table 4].
Table 4: Histopathology

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To facilitate the comparison between doctor's inspection and histopathological results, we divided each variable into three categories (normal, complicated, and noncomplicated) after analyzing each variable separately. Noncomplicated cases included all appendicitis except perforated, gangrenous, and malignant. The results revealed no significant relation between type of surgery and histopathological results, even that most of the cases had open surgery. However, there was a significant relation between doctor's inspection and histopathological results, where two-thirds of noncomplicated cases from doctor's inspection were noncomplicated regarding histopathology, as well as complicated cases (P = 0.008) [Table 5].
Table 5: Relation between complication and doctor inspection of the appendix and operation type

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Regarding laboratory results, we found that neutrophils count and CRP were higher among those who had open surgery (78.2 vs. 35.1, P = 0.030) and (35.0 vs. 3.02, P = 0.028), respectively [Table 6].
Table 6: Comparing the laboratory investigation regarding type of surgery

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In addition, the WBCs count and CRP were higher among those in histopathological complicated group than noncomplicated and normal groups (16.5 vs. 13.5 vs. 7, P = 0.005) and (88 vs. 35 vs. 2.9, P = 0.008), respectively [Table 7].
Table 7: Comparing the laboratory investigation regarding histopathological results

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[Table 8] shows the accuracy, sensitivity, and specificity of CRP, WBC, and neutrophils. We found that CRP is the most accurate and sensitive test (82.9%–94%), respectively, in predicting acute appendicitis. The receiver operating characteristic (ROC) curve was drawn to define the optimum diagnostic accuracy, sensitivity, specificity, and positive predictive value (PPV), determined by the area under the ROC curve of the studied CRP and WBCs values.
Table 8: Diagnostic accuracy, sensitivity, specificity, and positive predictive value of white blood cell count, C-reactive protein, and percentage of neutrophil in diagnosing acute appendicitis

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[Table 8] shows diagnostic accuracy, sensitivity, specificity, and positive (PPV) of WBC count, CRP, and PN in diagnosing acute appendicitis.


  Discussion Top


One of the challenges encountered by the emergency physician is accurate diagnosis of acute appendicitis. The main reasons are frequent atypical presentations and nonspecific findings, which either cause delayed diagnosis with complications or misdiagnosis.[10]

In a trial to overcome these difficulties, this study aimed to assess the diagnostic accuracy of readily available and inexpensive inflammatory markers serum CRP levels, WBCs, and neutrophils count in the diagnosis of acute appendicitis.

Overall, 77.2% and 93.8% of the studied cases had intraoperative and histopathological confirmation of acute appendicitis, respectively. This agrees with the reported negative appendectomy rate in surgical literature that varies from 15% to 30%.[22] Similar studies reported lower percentages (85.55%, 83.64%, and 872.2%) of histopathologically confirmed acute appendicitis.[23],[24],[25]

Moreover, this study revealed a significant association between gross examination of the appendix by the surgeon during operation and the histopathological findings; two-thirds of histopathologically diagnosed cases as noncomplicated appendicitis were truly diagnosed by the surgeon. In addition, 78.6% of cases were correctly diagnosed as complicated both by the gross and the histopathological examination.

In this study, median serum CRP levels and WBCs count were significantly higher in patients with complicated appendicitis than in those with normal or only inflamed appendix. Furthermore, median serum CRP levels and neutrophils count were significantly higher in patients who underwent open surgery compared to laparoscopy due to higher numbers of open surgeries compared to laparoscopic surgeries. In agreement with these findings, a prospective study investigated five hundred patients with suspected appendicitis reported higher mean CRP levels and WBCs count at admission in patients with acute appendicitis.[26]

Shafi et al.[25] and Xharra et al.[24] reported significantly higher values of CRP in complicated acute appendicitis than in cases of simple acute appendicitis.

The diagnostic accuracy of the studied markers in the diagnosis of acute appendicitis was assessed by ROC curve analysis. Serum CRP levels showed the highest accuracy in discriminating acute appendicitis compared to WBCs and neutrophils counts (82.9%, 65.0%, and 54.0%, respectively) with a sensitivity and specificity of 94% and 57%, respectively. Likewise, Xharra et al.[24] reported a higher accuracy, sensitivity, and specificity of the CRP than the WBCs and the neutrophils in predicting acute appendicitis. They concluded that elevated serum CRP levels support the surgeon's clinical diagnosis and its combination with the WBCs and the neutrophils increases the diagnostic accuracy and significantly decreases misdiagnosis. In addition, Erkasap et al.[27] reported a more higher sensitivity and specificity (96% and 78%, respectively) of the CRP in discriminating acute appendicitis. An earlier study by Asfar et al.[9] reported a higher specificity of CRP of 93.6% than in our study and concluded that a normal CRP value probably excludes the diagnosis of acute appendicitis. The role of CRP in minimizing the rate of negative appendectomy was recommended by Shogilev et al.[28]


  Conclusion Top


The diagnostic accuracy of the CRP is greater than the WBCs and neutrophil count. Thus, high serum CRP levels support the surgeon's clinical diagnosis. However, none of the studied markers is 100% diagnostic for acute appendicitis. It is recommended to include CRP measurement as a routine laboratory test in patients with suspected diagnosis of acute appendicitis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Asfar S, Safar H, Khoursheed M, Dashti H, Al-bader A. Would measurement of C-reactive protein reduce the rate of negative exploration for acute appendicitis? J R Coll Surg Edinb 2000;45:21-4.  Back to cited text no. 9
    
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Rosengren D, Brown AF, Chu K. Radiological imaging to improve the emergency department diagnosis of acute appendicitis. Emerg Med Australas 2004;16:410-6.  Back to cited text no. 10
    
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Jones K, Peña AA, Dunn EL, Nadalo L, Mangram AJ. Are negative appendectomies still acceptable? Am J Surg 2004;188:748-54.  Back to cited text no. 11
    
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Ponsky TA, Huang ZJ, Kittle K, Eichelberger MR, Gilbert JC, Brody F, et al. Hospital- and patient-level characteristics and the risk of appendiceal rupture and negative appendectomy in children. JAMA 2004;292:1977-82.  Back to cited text no. 12
    
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Alkire BC, Shrime MG, Dare AJ, Vincent JR, Meara JG. Global economic consequences of selected surgical diseases: A modelling study. Lancet Glob Health 2015;3 Suppl 2:S21-7.  Back to cited text no. 13
    
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Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg 2004;91:28-37.  Back to cited text no. 14
    
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Paajanen H, Mansikka A, Laato M, Ristamäki R, Pulkki K, Kostiainen S. Novel serum inflammatory markers in acute appendicitis. Scand J Clin Lab Invest 2002;62:579-84.  Back to cited text no. 15
    
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Mohammed AA, Daghman NA, Aboud SM, Oshibi HO. The diagnostic value of C-reactive protein, white blood cell count and neutrophil percentage in childhood appendicitis. Saudi Med J 2004;25:1212-5.  Back to cited text no. 17
    
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Wu HP, Chang CF, Lin CY. Predictive inflammatory parameters in the diagnosis of acute appendicitis in children. Acta Paediatr Taiwan 2003;44:227-31.  Back to cited text no. 18
    
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Paajanen H, Mansikka A, Laato M, Kettunen J, Kostiainen S. Are serum inflammatory markers age dependent in acute appendicitis? J Am Coll Surg 1997;184:303-8.  Back to cited text no. 19
    
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Shoshtari MH, Askarpour S, Alamshah M, Elahi A. Diagnostic value of quantitative CRP measurement in patients with acute appendicitis. Pak J Med Sci 2006;22:300-3.  Back to cited text no. 20
    
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Pal KM, Khan A. Appendicitis: A continuing challenge. J Pak Med Assoc 1998;48:189-92.  Back to cited text no. 21
    
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Joshi MK, Joshi R, Alam SE, Agarwal S, Kumar S. Negative appendectomy: An audit of resident-performed surgery. How can its incidence be minimized? Indian J Surg 2015;77:913-7.  Back to cited text no. 22
    
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Thirumallai S, Wijesuriya SR, Mitchell A, Delriviere L. Predictive value of C-reactive protein with Alvarado score in acute appendicitis. ANZ J Surg 2014;84:335-6.  Back to cited text no. 23
    
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Xharra S, Gashi-Luci L, Xharra K, Veselaj F, Bicaj B, Sada F, et al. Correlation of serum C-reactive protein, white blood count and neutrophil percentage with histopathology findings in acute appendicitis. World J Emerg Surg 2012;7:27.  Back to cited text no. 24
    
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Shafi SM, Afsheen M, Reshi FA. Total leucocyte count, C-reactive protein and neutrophil count: Diagnostic aid in acute appendicitis. Saudi J Gastroenterol 2009;15:117-20.  Back to cited text no. 25
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Msolli MA, Beltaief K, Bouida W, Jerbi N, Grissa MH, Boubaker H, et al. Value of early change of serum C reactive protein combined to modified Alvarado score in the diagnosis of acute appendicitis. BMC Emerg Med 2018;18:15.  Back to cited text no. 26
    
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Erkasap S, Ates E, Ustuner Z, Sahin A, Yilmaz S, Yasar B, et al. Diagnostic value of interleukin-6 and C-reactive protein in acute appendicitis. Swiss Surg 2000;6:169-72.  Back to cited text no. 27
    
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Shogilev DJ, Duus N, Odom SR, Shapiro NI. Diagnosing appendicitis: Evidence-based review of the diagnostic approach in 2014. West J Emerg Med 2014;15:859-71.  Back to cited text no. 28
    



 
 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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