Appendicitis with Positive Ultrasound and its Relation to Total and Differential Leucocytic Count

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1 Appendicitis with Positive Ultrasound and its Relation to Total and Differential Leucocytic Count G. M. Saleh*, E.A. Sh. Sabek*, E. S. Elessiely* and E. M. Ibrahim** Radiation Health Research Department, National Center for Radiation Research and Technology Atomic Energy Authority, Cairo, Egypt Received: 19/11/2015 Accepted: 16/12/2015 ABSTRACT Background: The most common cause of acute surgical abdomen is acute appendicitis and the most commonly done emergency surgery is appendectomy. Although a battery of tests and different scoring methods are available for diagnosis of acute appendicitis, it is very difficult to prevent negative explorations for appendicectomy (15-30%). None of the tests has satisfactory Sensitivity and specificity that can be relied upon. Objectives: The aim of the present study was to evaluate the role of total and differential leukocyte count, and ultrasonography (USG) of abdomen in diagnosing acute appendicitis and reducing the rates of negative appendicectomies and to prevent complications like perforation, peritonitis, and the longer the delay between diagnosis and surgery, the more likely is the perforation leading to peritonitis. In addition, emphasis was given to whether combining the investigations for the same patient would improve the diagnostic accuracy. Materials and Methods: A total of 76 clinically diagnosed patients of acute appendicitis, posted for emergency appendicectomy were included in the study in General Surgery Department of EL-Salam Hospital. This study was conducted in the period October 2012 to September Preoperatively blood tests for, total leukocyte count, differential leukocyte count (DLC) and USG abdomen were done. All patients were subjected to histological examination postoperatively, which was taken as the gold standard. The three investigations results were correlated with histo-pathological examination reports to evaluate their role in diagnosis of acute appendicitis. Results: In the present study, the US has the highest sensitivity and specificity (90%, 80%) followed by Total leucocytic count (87.5%, 90%), white Neutrophil count (78.75%, 80%). Combining US and WBC count increases the sensitivity and specificity of the tests (96.25%, 80%). Conclusion: US contains important diagnostic information and hence should always be included in the diagnostic workup of acute appendicitis. The sensitivity of WBC count and DLC are low individually, but when combined with US the sensitivity and specificity increases. When all three tests are negative acute appendicitis is very unlikely and surgery can be safely deferred in these patients thereby reducing the negative appendicectomy rates. Keywords: Appendicitis, Total leucocytic count, Neutrophil count, Ultrasonography. INTRODUCTION Acute appendicitis is known to be one of the common causes of right iliac fossa pain and often the cause of surgical emergencies (1). Acute appendicitis with its varied manifestations maysimulate almost any other acute abdominal conditions and can also be mimicked by a variety of conditions (2).It is estimated that the accuracy of clinical diagnosis of acute appendicitis ranges from 76% and 92% (3). Appendicectomy for suspected acute appendicitis is one of the most common procedures. The rate of 100

2 normal appendices unnecessarily removed remains high (15-30%) (4) Despite several techniques. On one hand, a normal appendix at appendicectomy represents a misdiagnosis; on the other hand, a delayed diagnosis may lead to perforation and peritonitis. Equally distressing is the fact that perforation may occur in up to 35% of cases. (5) So traditionally; surgeons have accepted a high incidence of unnecessary appendicectomiesin order to decrease the incidence of perforation. This approach is increasingly questioned in today s era of evidence-based medicine. The high rate of negative explorations for appendicitis is a burden faced not only by the general surgeons, but also the patient and society as a whole, since appendicectomy, like any other operations, results in socioeconomic impacts in the form of hospital expenses, lost working days, and declined productivity. (6) The goal of surgical treatment is removal of an inflame dappendix before perforation with a minimal numbers of negative appendicectomies. The question does this patient have appendicitis? Is an important question for the following reasons:- 1. Appendicitis is one of the most common causes of abdominal pain. 2. Western literatures reports that 6% of population have risk of suffering from appendicitis during their lifetime (7) 3. Although the overall mortality from appendicitis has dropped from about 26% to less than 1% with advent of antibiotics and early surgical intervention, however in elderly it is approximately 5-15% 4. The morbidity due to appendiceal perforation ranges from 17% to 40%. The perforation rate is higher in elderly and children (8) 5. Further, if it remains untreated it may lead to appendicular lump, appendicular abscess, gangrenous appendix and finally appendicular perforation 6. Failure to make an early diagnosis converts acute appendicitis to perforated appendicitis, a disease with potential complications including intra- abdominalabscesses, wound infection and death (9) 7. The negative laparotomy ranges from 15% to 30% and is associated with significant morbidity. (4, 5) The negative laparotomy rate is significantly higher in young women (up to 45%) because of prevalence of pelvic inflammatory disease and other common obstetrical and gynecological disorders.(8,10). In conclusion, acute appendicitis may simulate many other acute abdominal conditions/illnesses, and despite intensive clinical research and discussion, the diagnosis of acute appendicitis still remains a challenge. Moreover, the exactdiagnosis is important for proper management. This study aims to compare the few known and proven investigations for appendicitis such as leukocyte count, neutrophil count and ultrasonography (USG). Comparing how specific and sensitive each one is, which is the best and has maximum positive predictive value. This would be carried out by comparing it with histo-pathological examination (HPE) report. The need for study is to find out, which is most accurate and sensitive investigation to improve diagnosis of appendicitis and decision-making and hence decrease negative and unnecessary appendicectomies. We would also like to know whether a normal white blood cells (WBC) count and raised neutrophil count would exclude the presence of acute appendicitis. Aims and Objectives 1. To find out the specificity, sensitivity, predictive value of positive test and predictive value of negative test of CRP, total leukocyte count, neutrophil count and USG in diagnosis of acute appendicitis 2. To correlate HPE report with the blood investigations reports (CRP, total leukocyte count, neutrophil count) and USG in clinically diagnosed cases of acute appendicitis. 3. To establish the effect of combining all the investigation in same patients. 4. To interpret the efficacy to improve the diagnosis and decision making of acute appendicitis and hence reduce negative appendicectomies with the help of these investigations. 101

3 MATERIALS AND METHODS Source of Data: This study was performed on76 patients who have been clinically diagnosed of having acute appendicitis and who were posted for emergency appendicectomy in General Surgery Department Institute of Kasr ELeiny hospital. During the period from October 2012 to September 2013, consent was taken from every patient. Method of Collecting Data Sample size: - 76 cases of acute appendicitis. Sampling method: Simple random sampling Inclusion Criteria: All patients above the age of 6 years diagnosed clinically to have acute appendicitis and subjected for appendectomy. Exclusion Criteria: 1. Patients with co-morbid conditions were not included in the study 2. Patients who were managed conservatively were also excluded from the study 3. Patients admitted for interval appendicectomy following recurrent appendicitis or appendicular mass previously treated conservatively, were also excluded 4. Concomitant conditions where leukocyte count/ neutrophil count is elevated in acute appendicitis patients with associated diseases like: a. Rheumatoid arthritis b. Systemic lupus erythematosis c. Glomerular nephritis d. Gout e. Inflammatory bowel disease f. Any other conditions where Total and Differential leucocytic count was raised. Clinical diagnosis of acute appendicitis was done by in the Department of Surgery, based on symptoms of pain, migration, nausea and vomiting, anorexia, fever and signs of peritoneal inflammation such as right iliac fossa tenderness, rebound tenderness and guarding. Once acute appendicitis was suspected, the patient was subjected to routine investigations as per the hospital protocol. Urine microscopy was performed in all cases. Elderly patients were subjected to further investigations as part of pre-anesthetic workup including X-ray chest, electrocardiogram etc. Total leucocyte count and differential count was done in all cases. WBC count of more than 10,000 cells/mm3 was considered as positive and neutrophil count of more than 75% was considered positive. USG of abdomen was done in all our cases to confirm diagnosis and rule out other causes of pain abdomen. No special preparation of the patient was required prior to sample collection by approved techniques. When there was delay, the sample was stored at 2-8 C. Maximum period of storage was 72 h. Ultrasound examinations were performed by a radiology resident, using graded compression with 5-7 MHz transducers on 500 Logic GE Spectra (GE, Milwaukee, Wisconsin).The assistance of a consultant radiologist was requested in performing the examination if this was deemed necessary. A consultant radiologist issued reports on all examinations, having either supervised the study or reported on the films. The diagnostic criteria for appendicitis on ultrasound were those suggested by Birnbaum and Wilson (8) : identification in the right iliac fossa of an echogenic mass and/or a noncompressible aperistaltic, tubular, laminated structure measuring at least 6mm in anteroposterior diameter. Increased flow in the wall on color doppler was regarded as confirmatory but not essential for diagnosis Total and differential leukocytic counts were done as follows: A phlebotomist collects the sample through venipuncture, drawing the blood into a test tube containing an anticoagulant (EDTA) to stop it from clotting. This process is automated by use of an automated analyzer (Sysmex auto analyzer), differential leukocytic counting (DLC) was also done; a blood film is made and a large number of white blood cells (WBC) (at least 100) are counted. This gives the percentage of cells that are of each WBC type such as neutrophils, eosinophils, basophils, 102

RESULTS Seventy-six patients with positive ultrasound evaluations after a clinical diagnosis of appendicitis underwent appendectomy. Pathology reports were available for 76patients.

4 monocytes and lymphocytes. By multiplying the percentage with the total number of WBCs, the absolute number of each type of WBCs can be obtained. DLC is done by specialist physician and verified by a clinical pathology consultant. RESULTS Seventy-six patients with positive ultrasound evaluations after a clinical diagnosis of appendicitis underwent appendectomy. Pathology reports were available for 76patients. Table (1): sex and age distribution Age Sex Mean ± SD ± Range 6 63 Female 20 (26.3%) Male 56 (73.7%) Sex Female Male 26% 74% Table (2): Diagnosis by ultrasound Diameter Diameter groups Compresability/Tend. Intraluminal Fluid Cecal Wall Thickening LN/M/Applith Peritionel Fluid Mean ± SD 9.66 ± 3.20 Range 3 16 < % > % Negative % Lack % Tend 4 5.3% Lack/Tend % Negative % Fluid % Negative % Thick % Negative % Applith 2 2.6% RT Aden mass 2 2.6% Mesentric in 6 7.9% Negative % Fluid % 103

Table (3): Diagnosis by TLC and Differential LC Mean ± SD Range TLC 10.55 ± 3.55 5.9 18.3 Neutrophills 71.18 ± 12.10 40 91 Lymphocytes 21.38 ± 10.96 4 53 Monocytes 5.11 ± 1.

5 Table (3): Diagnosis by TLC and Differential LC Mean ± SD Range TLC ± Neutrophills ± Lymphocytes ± Monocytes 5.11 ± Table (4): T- test value Diameter <11 Diameter > 11 TLC Mean ± SD 9.96 ± ± 4.18 Range Neutrophills Mean ± SD ± ± Range Lymphocytes Mean ± SD ± ± Range Monocytes Mean ± SD 4.78 ± ± 2.30 Range Independent t-test T P-value <11 >11 Mono cytes 104

Table (5): Ultrasound versus total and differential leucocytic count Compressibility/Tend. Negative Lack Tend Lack/Tend Mean ± SD 9.35 ± 3.55 11.39 ± 3.73 9.80 ± 0.00 10.46 ± 3.45 TLC Range 5.9 17.

6 Table (5): Ultrasound versus total and differential leucocytic count Compressibility/Tend. Negative Lack Tend Lack/Tend Mean ± SD 9.35 ± ± ± ± 3.45 TLC Range One Way ANOVA Test F P-value Neutrophills Mean ± SD ± ± ± ± Range Lymphocytes Mean ± SD ± ± ± ± Range Monocytes Mean ± SD 4.50 ± ± ± ± 1.69 Range Negative Lack Tend Lack/Tend Neutrophills Lympho Cytes Negative Lack Tend Lack/Tend 105

7 Table (6): TLC and Diff. LC versus Intraluminal Fluid TLC Neutrophills Lymphocytes Monocytes Intraluminal Fluid Negative Intraluminal Fluid Positive Mean ± SD 9.96 ± ± 3.88 Range Mean ± SD ± ± Range Mean ± SD ± ± Range Mean ± SD 5.02 ± ± 2.23 Range Independent t-test T P-value Table (7): TLC and Diff. LC versuscecal Wall Thickening TLC Neutrophills Lymphocyte s Monocytes Cecal Wall Thickening Negative Cecal Wall Thickening Thick Mean ± SD ± ± 3.68 Range Mean ± SD ± ± Range Mean ± SD ± ± Range Mean ± SD 5.43 ± ± 1.84 Range Independent t- test T P-value Table (8): TLC and Diff. LC versus LN/Mass and Applith LN/M/Applith Negative Applith RT aden mass Mesentric in TLC Mean ± SD ± ± 0 11± ± 5.45 Range Neutrophills Mean ± SD ± ± 0 79 ± ± Range One Way ANOVA Test F P-value Lymphocytes Mean ± SD ± ± 0 18 ± ± Range Monocytes Mean ± SD 5.31 ± ± 0 3 ± ± 0.89 Range

Table (9): TLC and Diff. LC versus Peritonel Fluid TLC Neutrophills Lymphocytes Monocytes Peritionel Fluid Negative Peritionel Fluid Fluid Mean ± SD 10.10 ± 3.45 11.67 ± 3.63 Range 5.9 18.3 5.9 17.

8 Table (9): TLC and Diff. LC versus Peritonel Fluid TLC Neutrophills Lymphocytes Monocytes Peritionel Fluid Negative Peritionel Fluid Fluid Mean ± SD ± ± 3.63 Range Mean ± SD ± ± 8.52 Range Mean ± SD ± ± 6.63 Range Mean ± SD 5.31 ± ± 1.33 Range Independent t-test T P-value Lympho Cytes Negative Fluid 107

9 Cases Case 1: Male patient 45 years with appendicular diameter =12 mm with lack of compressibility and tenderness and with intraluminal fluid. 108

10 Case 2: Female patient 19 years with appendicular diameter =16 mm with lack of compressibility and tenderness and with intraluminal fluid and cecal wall thickening. 109

11 Case3: Male patient 16 years with appendicular diameter =14 mm with lack of compressibility and tenderness and with intraluminal fluid, cecal wall thickening and peritoneal Fluid. 110

12 DISCUSSION The cause of right iliac fossa pain continues to elude surgeons for more than a century. The cause may be acute appendicitis which requires surgery or something else that may not require intervention. To resolve the dilemma, a study was conducted in the SKIMS to determine the role of investigations (TLC, NP, CRP and USG) in patients operated for suspected appendicitis. A study sample was formed by 76 subjects operated for appendicitis on the basis of suggestive clinical and/or paraclinical parameters. A similar study was conducted by Singh et al. (15), where they concluded that these investigations should be interpreted in the light of clinical findings. The majority of patients with acute appendicitis have an elevated total leukocyte count of more than ten thousand. It was observed in this study that the initial leucocyte count was elevated in 46 out of a total of 76 patients proved pathologically. Higher mean TLC values were observed in gangrenous and perforated appendices which are summed up in a different article in order not to make the present study too large. Lau et al. (17) found an elevated leucocyte count in 81.4% of patients with a specificity of 77.3%. Most of the studies reveal that >60% of patients with acute appendicitis have a TLC of over ( 20, 21). Since the white cell count is raised in 25-70% of patients with other causes of acute right iliac fossa pain (5), the investigation is rendered almost useless by its low specificity and has little diagnostic value (2,5). It was observed in this study that raised NP was less sensitive (58.52%) and specific (61.90%) with higher mean values in gangrenous/perforated appendicitis. The sensitivity of raised NP ranges from 60 to 84% in various studies (22, 23, and 24). The sensitivity improved to 87% while the specificity continued to be low when raised TLC and raised NP was combined by the or rule. Similarly, comparable results of 90.5% (sensitivity) and 58.8% (specificity) were observed by Lau et al. (17). Ultrasonography, besides being highly specific in diagnosis acute appendicitis, accurately excludes diseases that do not require surgery. Most of the American and European studies give high sensitivities of 80-90% and specificities of % (24). Less accurate results in another study (23) and low values obtained in the present study could be due to the fact that the probe used was 5MHz in contrast to 7.5MHz used by these invistegators. Poorer results are also observed for retro-caecal appendices (24) which, in the present study, were seen in 29 patients and only 12 of them were picked up by USG. Also, it is technically difficult to detect an inflamed appendix in obese or distended patients. We would also like to remark that the results are operator-expertise dependent. The present study revealed that 18 of the total of 19 gangrenous/perforated appendices were picked up by USG (>94%), though the sonologist did not make the diagnosis of perforated or gangrenous appendicitis. Takeda et al. observed a sensitivity of 100% in such cases. Combining the previous three investigations to USG by the or rule raises the sensitivity to >90%, but the specificity continued to be low (47%). In contrast, sensitivity decreased and specificity increased markedly when all the 4 suggestive investigations were used together. CONCLUSION It must be emphasized that the total and the differential cell counts should be interpreted in the light of physical findings as normal counts do not exclude appendicitis and raised counts and raised NP can occur even in normal patients. The CRP is a better indicator of appendicitis than TLC and NP. In view of its high sensitivity and specificity, USG promises to be the investigation of choice. This test is non-invasive and can be of particular help in pregnancy (5) but its main disadvantage lies in the fact that it requires special equipment and special expertise. Hence, the decision against laparotomy, however, must always be based on the clinical findings which are the mainstay of the diagnosis. In the present era of laparoscopic surgery, ruling out appendicitis may not be a major problem (25), but we understand that if the patient undergoes anesthesia and laparoscopy with the diagnosis not being appendicitis, it does not mount to anything less than laparotomy. Another aspect is that others may 111

13 argue that this is an era of CT imaging and CT would give better diagnostic accuracy (26), but in a developing country like ours we understand that doing CT scan is not very cost effective. We conclude that these simple investigations, if simultaneously not suggestive of the diagnosis, rule out appendicitis and in such a situation surgeons should rather choose a conservative approach than a negative laparotomy. REFERENCES (1) Peranteau WH, Smink DS. Appendix, Meckel s and other small bowel diverticula. In: Zinner MJ, Ashley W. Stanley, editors. Maingot s Abdominal Operation. 12th ed. New York: The McGraw- Hill Companies; p (2) Brown SP. Acute appendicitis. In: Ellis BW, Brown SP, editors. Hamilton Bailey s Emergency Surgery. 13th ed. New York: Arnold; p (3) John H, Neff U, Kelemen M. Appendicitis diagnosis today: clinical and ultrasonic deductions. World J Surg 1993;17: (4) O Connell PR. The vermiform appendix. In: Williams NS, Bulstrode CJ, O Connell PR, editors. Bailey and Love s Short Practice of Surgery. 26th ed. London: Arnold; p (5) Borushok KF, Jeffrey RB Jr, Laing FC, Townsend RR. Sonographic diagnosis of perforation in patients with acute appendicitis. AJR Am J Roentgenol 1990;154: (6) Shakhatreh HS. The accuracy of C-reactive protein in the diagnosis of acute appendicitis compared with that of clinical diagnosis. Med Arh 2000;54: (7) Balsano N, Cayten CG. Surgical emergencies of the abdomen. Emerg Med Clin North Am 1990;8: (8) Lewis FR, Holcroft JW, Boey J, Dunphy E. Appendicitis. A critical review of diagnosis and treatment in 1,000 cases. Arch Surg 1975;110: (9) Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990;132: (10) Mueller BA, Daling JR, Moore DE, Weiss NS, Spadoni LR, Stadel BV, et al. Appendectomy and the risk of tubal infertility. N Engl J Med 1986;315: (11) Sess P: Acute appendicitis. Epidemiology, diagnostic accuracy and complications. Scand J Gastroenterol; 1983; 18: (12) Hoffmann J, Rasmussen OO: Aids in the diagnosis of acute appendicitis. Br J Surg; 1989; 76: (13) Birnbaum BA, Wilson SR. Appendicitis at the millennium. Radiology 2000; 215: (14) Verma A, Mehta FS, Yas Y et al.: C-reactive protein in acute appendicitis. Ind J Surg; 1996; (15) Singh D, Garg P, Contra N, Sharma VK: Comparative evaluation of C-reactive protein, total leucocyte count and ultrasonography in acute appendicitis. Ind J ClinPract; 1996; 7: (16) Sabiston DC, Lyerly HK. In: Textbook of Surgery. WB Saunders, 15th ed, 1997; 1: (17) Lau WY, HO YC, Chu KW, Yeung C: Leucocyte count and neutrophil percentage in appendectomy for suspected appendicitis. NZ J Surg; 1989; 59: (18) English DC, Allen W, Coppola ED, Sher A: Excessive dependence on the leucocytosis in diagnosis appendicitis. Am Surgeon; 1977; 43: (19) Raffery AT: The value of leucocyte count in the diagnosis of acute appendicitis. Br J Surg; 1976; 63: (20) Bolton JP, Craven CR, Croft RJ, Menzies-Gow N: An assessment of the value of white cell count in the management of suspected acute appendicitis. Br J Surg; 1976; 62:

14 (21) Burns RP, Cochran JL, Russel WL, Bard RM: Appendicitis in mature patients. Ann Surg; 1985; 201: (22) Alvarado A: A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med; 1986; 15: (23) Niekel RA, Lampmann LE: Graded compression sonography in acute appendicitis. Rofo 1986; 145: (24) Adams DH, Fine C, Brooks DC: High resolution real-time ultrasonography: a new tool in the diagnosis of acute appendicitis. Am J Surg; 1988; 155: (25) Bijnen CL, van den Broek WT, Bijnen AB, de Ruiter P, Gouma DJ: Implications of removing a normal appendix. Dig Surg; 2003; 20: (26) Ujiki MB, Murayama KM et al.: CT scan in the management of acute appendicitis. J Surg Res 2002; 105(2):

Original Research Article A clinicopathological study of acute appendicitis in eastern India Ekka NMP 1, Singh PR 2, Kumar V 3

Original Research Article A clinicopathological study of acute appendicitis in eastern India Ekka NMP 1, Singh PR 2, Kumar V 3 1 Dr Nishith M Paul Ekka Senior Resident drnmpekka@gmail.com 2 Dr Pritesh