Evaluation of hyperbilirubinemia as a new diagnostic marker for acute appendicitis and its role in the prediction of complicated appendicitis

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1 ORIGINAL ARTICLE and its role in the prediction of complicated appendicitis Dipen Patel 1 *, Nimish J. Shah 2, Bhavin Patel 3,Mital Parikh 4, Digant Patel 5, Chirag Dalal 6 1,4 Senior Resident, Dept of Surgery, SSGH, Baroda Medical College, 2 Associate Professor and Head of Unit, Dept of Surgery, SSGH, Baroda Medical College, 3 Assistant Professor, Dept of Surgery, GMERS, Gotri, 5,6 Assistant Professor, Dept of Surgery, SSGH, Baroda Medical College ABSTRACT BACKGROUND: The diagnosis of Appendicitis still remains a dilemma inspite of advances in the radiological and laboratory investigations. Delay in diagnosis leads to perforation and peritonitis thereby increasing morbidity and mortality. Recently, elevation in serum bilirubin is reported to have a predictive potential for the diagnosis of complicated appendicitis, the pro inflammatory mediators tend to reach liver via superior mesenteric vein and may directly or indirectly produce liver dysfunction thus implying a credibility of serum bilirubin as the biological marker to predict and differentiate Appendicitis.The aims of the study are to study the relationship between hyperbilirubinemia and acute appendicitis and evaluate whether elevated bilirubin levels have a predictive potential for the diagnosis of complicated appendicitis. MATERIALS AND METHODS: A cross sectional study was conducted in the Department of General Surgery, SSGH, Baroda in which a total of 100 patients with clinical diagnosis of acute appendicitis were studied. Data collected included laboratory and histological results.all patients diagnosed as acute uncomplicated or complicated appendicitis clinically on admission, were operated upon and confirmed by histopathological examination. RESULTS: Hyperbilirubinaemiahad a sensitivity of 65.33% for acute uncomplicated appendicitis and 92 % for complicated appendicitis. Patients with complicated appendicitis (perforated or gangrenous appendix) had higher mean bilirubin levels (p<0.001). The sensitivity of white cell count was less than hyperbilirubinaemia. The prevalence was highest in 2 nd and 3 rd decade ( 62%). 71% were males and 29% were females. CONCLUSION: The level of serum bilirubin can be a credible aid in diagnosis of acute uncomplicated appendicitis and a helpful investigation in decision making. Serum bilirubin levels have a predictive potential for the diagnosis of complicated appendicitis. Keywords: Serum Bilirubin (SB), Total Serum Bilirubin (TSB), Ultrasonography (USG), White Blood Cell (WBC), Computed Tomography (CT) INTRODUCTION Acute appendicitis comes under one of the most frequently encountered cause of Acute abdomen. 1,2 Appendicectomy is the most frequently performed emergency abdominal operation and is often the first major procedure performed by a surgeon in training 1. Experienced clinicians accurately diagnose appendicitis based on a combination of history, physical examination and laboratory studies about 80% of the time 3. *Corresponding Author Dr. Dipen patel Senior Resident, Department of Surgery, S.S.G. Hospital and Medical College Baroda, Gujarat - dipen23patelr@gmail.com In spite of advances in the radiological and laboratory investigationsthe diagnosis of Appendicitis still remains a dilemma. Although most patients with Acute Appendicitis can be easily diagnosed, in some cases the sign and symptoms are variable and a firm diagnosis can be difficult. This is particularly true where the appendix is retrocaecal or retroileal. The percentage of appendicectomies performed where appendix subsequently found to be normal varies 15-50%, and postoperative complications can occur in up to 50% of these patients. Delay in diagnosis of Acute Appendicitis leads to perforation and peritonitis and increased mortality. Perforation ranges 50-90% in various series. To supplement the clinical diagnosis and to reduce the frequency of unnecessary 28 Int J Res Med. 2014; 3(3);28-33 e ISSN: p ISSN:

2 Appendicectomy, the importance of laboratory investigations like White Blood Cell (WBC) counts and C-reactive protein (CRP) values has been stressed. 4 The use of Ultrasonography (USG) as a diagnostic tool for appendicitis has been widely known and studied. 5 However up to date there is no confirmatory laboratory marker for the pre-operative diagnosis of acute appendicitis and appendicular perforation. Recently, elevation in serum bilirubin was reported, but the importance of the raised total bilirubin has not been stressed in appendicitis. 6 It is well established that when microbes invade the body, leukocytes defend it. This leads to increase in the leukocyte count. Bacterial invasion in the appendix leads to transmigration of bacteria and the release of proinflammatory cytokines such as TNFalpha, IL6 and cytokines. These reach the liver via Superior mesenteric vein (SMV) and may produce inflammation, abscess or dysfunction of liver either directly or indirectly by altering the hepatic blood flow. 7 In view of the above context, the present study was undertaken to assess relationship between hyperbilirubinemia and acute appendicitis and to evaluate its credibility as a diagnostic marker for acute uncomplicated appendicitis and also, to see whether elevated bilirubin levels have a predictive potential for the diagnosis of complicated ( necrotising and perforated ) appendicitis. MATERIALS AND METHODS This is a cross sectional study conducted in the Department of General Surgery, S.S.G.Hospital, Baroda during the period of January 2013 to October Sampling method The sample size was calculated based on the following formula. Z 2 x p x q n = d 2 Where, n = Sample size Z = (considering confidence as 95%) p = prevalence (prevalence is taken as 50% as exact prevalence is not known) q = 100 p that is, 50% d = Absolute error which was 10% A total of 100 patients with clinical diagnosis of acute uncomplicated appendicitis or complicated appendicitis were studied based on the following criteria. Inclusion Criteria All patients diagnosed as acute uncomplicated or complicated appendicitis clinically on admission, operated upon and confirmed by histopathological examination were included. Exclusion Patients documented to have a past history of Jaundice or Liver disease. Chronic alcoholism (that is intake of alcohol of > 40 g/day formen and > 20 g/day in Women for 10 years). Hemolytic disease. Acquired or congenital biliary disease. Patients with positive HBsAg. 29 Int J Res Med. 2014; 3(3);28-33 e ISSN: p ISSN: Patients with cholelithiasis. Patients with cancer of hepato-biliary system. The serum bilirubin and LFTs were carried out using the Semi Auto Analyser ( erbachem V2 ) machine available in the hospital and HbsAg was tested by ELISA The patients were operated, intraoperative findings were noted and the specimen was sent to the department of Pathology for Histopathological examination Histopathological diagnosis of either acute appendicitis or necrotising appendicitis was noted. Ethics Ethical clearance was obtained from The Scientific And Ethical Review Committee of the institution for the study. Based on the selection criteria patients admitted with clinical diagnosis of acute appendicitis or complicated appendicitis under Department of General Surgery, SSGH, Baroda during the study period were screened for eligibility. STATISTICAL ANALYSIS The data obtained was tabulated on Microsoft excel spreadsheet and analysed

3 as below. Patients with clinical diagnosis of acute uncomplicated appendicitis having hyperbilirubinemia were expressed in percentage as: Patients with clinical diagnosis of acute uncomplicated appendicitis with elevated Serum bilirubin level All patients with clinical diagnosis of acute uncomplicated appendicitis Mean of the level of elevation of Serum bilirubin was calculated for patients with clinical diagnosis of acute appendicitis. Patients with clinical diagnosis of complicated appendicitis having hyperbilirubinemia were expressed in percentage as; Patients with clinical diagnosis of complicated appendicitis with elevated Serum bilirubin All patients with clinical diagnosis of complicated appendicitis Mean of the level of elevation of serum bilirubin were calculated for patients with clinical diagnosis of.complicated appendicitis A hypothesis was made based on the observation of the level of the two means. RESULTS Out of 100 patients enrolled for the study, 71 patients (71%) were males while the remaining 29 patients (29%) were females.the overall mean age of all 100 patients was 26 ± 13.4 years (range, years). The average age in males and females was 26.9 ± 13.0 years (range, years) and 24.9 ± 14.3 years (range, years) respectively.32 patients (32%) had Total Leukocyte count less than 11,000/mm 3 while 68 patients (68%) counts above 11,000/mm 3.The mean of TLC count in all patients was 12467± /mm 3 (range, /mm 3 ). The diferential count shows predominance of neutrophils with mean of ± 6.94.The mean Total bilirubin of all 100 patients was 1.3 ± 0.45 mg/dl (range, mg/dl) while the Direct bilirubin was 0.7 ± 0.3 mg/dl (range, mg/dl) and indirect bilirubin was 0.6 ± 0.28 range ( )The mean SGPT was 19.8 ± 5.95 U/L (range, U/L).18 patients (18%) of all 100 patients were found to have normal bilirubin levels ( 1.0 mg/dl), while 82 patients (82%) had raised bilirubin levels (> 1.0 mg/dl).out of 25 patients diagnosed as complicated appendicitis 23 patients (92%) had raised bilirubin levels (> 1.0 mg/dl), while the remaining 02 patients (8%) had normal levels ( 1.0 mg/dl).histopathologically,75 patients (75%) were confirmed as Acute Uncomplicated appendicitis while 25 patients (25%) were diagnosed as complicated appendicitis.the mean bilirubin levels in patients diagnosed with Acute uncomplicated appendicitis was 1.19 ±0.33 mg/dl (range, mg/dl) while in patients diagnosed with complicated appendicitis was 1.78 ±0.48 mg/dl (range, mg/dl). The Direct bilirubin and Indirect bilirubin in patients diagnosed with Acute uncomplicated appendicitis were 0.64 ± 0.26 mg/dl and 0.54 ± 0.20 respectively. The Direct bilirubin and Indirect bilirubin in patients diagnosed with complicated Appendicitis were 0.94 ±0.33 mg/dl and 0.79 ± 0.39 mg/dl respectively.49 patients (65.33%) of the total patients diagnosed with Acute uncomplicated appendicitis (n=75) were found to have elevated bilirubin levels (> 1.0 mg/dl) while 26 patients (34.67%) had normal bilirubin levels ( 1.0 mg/dl). Similarly, 23 patients (92%) of the total patients diagnosed with complicated Appendicitis (n=25) were found to have elevated bilirubin levels (> 1.0 mg/dl) while 02 patients (8%) had normal bilirubin levels ( 1.0 mg/dl). DISCUSSION Obstruction of the lumen is believed to be the major cause of acute appendicitis. Faecoliths are the usual cause of obstruction. Less- common causes are hypertrophy of lymphoid tissue, tumors, intestinal parasites.the bacteriology of normal appendix is similar to that of 30 Int J Res Med. 2014; 3(3);28-33 e ISSN: p ISSN:

4 normal colon. The principal organism seen in normal appendix, in acute appendicitis, and in perforated appendicitis areescherichiacoliandbacteroidsfragilis. However a wide variety of both facultative and anaerobic bacteria may be present. Table No.13. COMPARISON FOR SEX INCIDENCE IN VARIOUS STUDIES Various studies M:F Present study (2013) 2.4 : 1 n=100 Marudanayagam et al : 1 (2006) n=2660 Samsi et al 26 (1969) 2 : 1 n=100 In the present study of the 100 patients enrolled for the study, 71 patients (71%) were males while the remaining 29 patients (29%) were females.this correlates with the male preponderance seen in other studies. Table No.14 COMPARISON FOR AGE INCIDENCE IN VARIOUS STUDIES Age in years Marudanayagamet al 12 (2006)in % ( n = 2660 ) Present study in % Up to Over The mean age in our study population (100 patients) was 26.4 ± years (range, years). Majority of the patients ( 62 %) in present study were in 2 nd and 3 rd decades of life.this is consistent with other studies as well as with the quoted incidence in literature. Table 15: COMPARISON FOR TOTAL COUNT IN VARIOUS STUDIES STUDIES WBC COUNT ( > 11,000/cmm ) 68% Present Study ( n=100 ) Emmanuel et al 28 93% ( n=472 ) Ghimire et al 20 55% ( n=141 ) The total leukocyte count was found elevated(>11,000/cmm) in 68 patients (68%) of the total 100 patients. The mean of TLC count in all patients was ± /mm3 (range, /mm3). This correlates with other studies. Table No. 16 COMPARISON FOR SERUM BILIRUBIN IN VARIOUS STUDIES References Total Bilirubin > 1.0 mg/dl complicated appendicitis Present study 65.33% 92% (n=100) Khan et al 6 (n=110) Emmanuel et al 28 (n=472) Young Hong etal 21 (n=1195) 56.36% 80.6% 29% 60% 62% 90% Hyperbilirubinemia (> 1.0 mg/dl) in our study was found in 82 patients (82%) of all the 100 patients (n=100) enrolled in the study, while 18 patients (18%) had normal bilirubin levels ( 1.0mg/dL) range, ( mg/dl), which was above the normal range ( 1.0mg/dL) considered for the study, hence indicating the occurrence of hyperbilirubinemia. The mean of Direct bilirubin was 0.7±0.3 mg/dl (range, mg/dl) while that of Indirect bilirubin was 0.6±0.28 mg/dl (range, mg/dl). Amongst the patients diagnosed with Acute uncomplicated appendicitis(n=75), 49 patients (65.33%) were found to have elevated bilirubin(>1.0 mg/dl) while only 26 patients (34.67%) had normal bilirubin levels ( 1.0 mg/dl). In patients diagnosed with complicated appendicitis (n=25), 23 patients (92%) had bilirubin elevated (>1.0 mg/dl), while only 2 patients (8%) had normal levels (<1.0 mg/dl). Thus, Hyperbilirubinemia was found in most of the patients diagnosed with acute uncomplicated appendicitis (65.33%) or complicated appendicitis ( 92 %). The mean bilirubin levels in patients diagnosed with Acute uncomplicated appendicitis was 1.3±0.45 mg/dl (range, mg/dl) while in patients 31 Int J Res Med. 2014; 3(3);28-33 e ISSN: p ISSN:

5 diagnosed with complicated appendicitis was 1.78±0.48 mg/dl (range, mg/dl). Hence, we see that patients with complicated appendicitis had higher levels of bilirubin as compared to that of acute appendicitis. So we infer that, patients with features suggestive of appendicitis with higher values of bilirubin, are more susceptible of having complicated appendicitis than those with normal or slightly elevated total serum bilirubin. Appendicitis were 0.7±0.3 mg/dl and 0.54±0.2 respectively. Similarly, direct bilirubin and indirect bilirubin in patients diagnosed with complicated appendicitis were 0.94±0.33 mg/dl and 0.79±0.39 mg/dl respectively.sensitivity of bilirubin in predicting acute uncomplicated appendicitis and complicated appendicitis was 65.33% and 92% respectively. REFERENCES : 1. O' Connel PR. The Vermiform Appendix. In: Williams NS, Bulstrode CJK, O'Connell PR (Ed.). Bailey and Love's - Short practice of surgery. 25 ed. London: Arnold: 2008; p Smink DS, Soybel DI. Appendix and Appendectomy. In: Zinner MJ, Stanely W (eds) Maingot s abdominal operations. 11 th ed. Ashely: McGraw Hill; p John Maa. The Appendix. In Townsend CM, Beauchamp RD, EversBM, Mattox KL, eds. Sabiston Textbook of Surgery. 18 th ed. Philadelphia, Pa: Saunders Elsevier; p: Grönroos JM, Grönroos P. A fertileaged woman with right lowerabdominal pain but unelevated leukocyte count and C-reactive protein: acute appendicitis is very unlikely. Langenbecks Arch Surg 1999; 384: Jeffrey RB, Laing FC, Lewis FR. Acute appendicitis: high-resolution real-time US findings. Radiology 1987; 163: Khan S. Evaluation of hyperbilirubinemia in acute inflammation of appendix: A prospective study of 45 cases. KUMJ 2006; 4(3) 15: Beg RB, Garlungton AW. Translocation of certain endogenous bacteria from the GI tract to mesenteric lymph node and other organ in Gonobiotic mouse model. Infect Immunol 1979;23: Bernard M. Jaffe and David H. Berger. The Appendix. In Brunicardi F, Andersen D, Billiar T, Dunn D, Hunter J, Matthews J, et al. Schwartz's Principles of Surgery. 9 th ed. New York: McGraw Hill; p Wolff H. Medical history aspects of appendicitis treatment. ZentralblChir 1998; 123 Suppl 4: Flum DR, Morris A, Koepsell T, Dellinger EP. Has misdiagnosis of appendicitis decreased over time? A population-based analysis. JAMA 2001; 286 (14): Bhajekar M.V.: Surgical Appendix. In British Journal of Surgery; Jan 1955 ; Vol-42 ; 174 ; p Marudanayagam R, Williams GT, Rees BI. Review of the pathological results of 2660 appendicectomy specimens. J Gastroenterol 2006; 41: Thompson MM, Underwood MJ, Dookeran KA, Lloyd DM, Bell PRF. Role of sequential leucocyte counts and C-reactive protein measurements in acute appendicitis. Br J Surg; 1992; 79: Thimsen DA, Tong GK, Gruenberg JC. Prospective evaluation of C- reactive protein in patients suspected to have acute appendicitis. Am Surg 1989; 55(7): DeCarvalho BR, Diogo-FilhoA, Fernandes C, Barra CB. Leukocyte count, C reactive protein, alpha-1 acid glycoprotein and erythrocyte sedimentation rate in acute appendicitis. ArqGastroenterol 2003; 40(1): Wise SW, Labuski MR, Kasales CJ, Blebea JS, Meilstrup JW, Holley GP, et al. Comparative assessment of CT and sonographic techniques for ap- 32 Int J Res Med. 2014; 3(3);28-33 e ISSN: p ISSN:

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