ORIGINAL�ARTICLE ABSTRACT Objective: To assess the outcome of laparoscopic cholecystectomy (LC) in the treatment of acute cholecystitis. Study Design: Quasi experimental study. Place and Duration of Study: The study was conducted at Surgical Unit I, Department of General Surgery, st st Pakistan Institute of Medical Sciences, Islamabad from 1 Jan 2013 to 31 Dec 2018. Materials and Methods: All those patients who reported within 72 hours of onset of symptoms of acute calculus cholecystitis were included. Patients of acute pancreatitis, choledocholithiasis, with comorbids and previous abdominal surgery were excluded. Three port LC was performed in patients of acute cholecystitis after diagnosis by consultant skilled surgeon. Data were collected in a proforma that included demographics of the patient, operative findings, operating time, intra- or post-operative complications and duration of hospital stay. Data was collected and SPSS version 20 was used for analysis. Results: Total 143 patients of acute calculous cholecystitis were studied with 38 males and 105 females. The mean age of patients was 46.23 years ranged from 22 to 76 years. The mean operative time was 68.1 ± 25.31 minutes with conversion rate of 2.1%. The overall rate of complication was 24.5 per cent and no serious bile duct injury was noted in any patient. Bleeding (5.6%) and biliary injury (2.1%) were intraoperative complications. Port site infection (6.3%), chest infection (3.5%) and biliary leak (2.8%) were major postoperative complications. The mean total hospital stay was 4.16 (3–8 days). Conclusion: Laparoscopic Cholecystectomy can be performed safely in patients with acute calculous cholecystitis within 72 hours of the onset of symptoms. Key Words: Acute Cholecystitis, Biliary injury, Cholelithiasis, Laparoscopic Cholecystectomy, Post site infection. cholecystectomy was performed in selected cases, but with advances in instrumentation, improved visualization due to new cameras, increased knowledge of the hepato-biliary anatomy and improved surgical skills, surgeons began performing laparoscopic cholecystectomy even in acute cholecystitis, which was initially considered a 3 relative contraindication. LC for the surgical treatment of patients with acute 4, 5 cholecystitis remains debatable, in particular the timing of LC with respect to inflammation, oedema and Calot's triangle adhesions. More complications like excessive bleeding, increased chance of common bile duct injury and conversion are known to be associated with LC for the treatment of acute 6 cholecystitis. Nevertheless, some surgeons recommended early LC as preferred treatment for acute cholecystitis, with increased experience and 7 improvement of the instruments. Several randomized controlled trials Comparison of early LC (performed within 7 days of symptoms onset) with delayed LC (usually performed 4 to 6 weeks after symptoms onset) reported benefits with early LC of Introduction Gall stone disease has a worldwide prevalence of 10 – 15% and around 20 percent of patients with cholelithiasis present with acute calculus 1 cholecystitis. Laparoscopic cholecystectomy (LC) has been accepted as the gold standard in treating chronic symptomatic cholecystitis calculus since 2 1992. However LC was not previously considered as a preferred treatment in patients with acute cholecystitis. Conservative management was done followed by elective cholecystectomy after 6 – 8 weeks of interval time. Surgeons had concerns regarding increased complication rate and high chances of conversion. Initially laparoscopic Outcome of Laparoscopic Cholecystectomy in Patients of Acute Cholecystitis 1 2 3 4 5 S H Waqar , Muhammad Tariq Abdullah , Sajid Ali Shah , Zafar Iqbal Malik , Fatima Shahzad Correspondence: Dr. S H Waqar Department of General Surgery Pakistan Institute of Medical Sciences, Islamabad E-mail: waqardr@yahoo.com 1,2,3,4 Department of General Surgery Pakistan Institute of Medical Sciences, Islamabad 5 Al Nafees Medical College, Islamabad Funding Source: NIL; Conflict of Interest: NIL Received: May 18, 2020; Revised: July 15, 2020 Accepted: July 22, 2020 Outcome of Laparoscopic CholecystectomyJIIMC 2020 Vol. 15, No.3 149 positive Murphy's sign, leukocytosis, oedematous distended and/or thickened gall bladder, presence of stones and pericholecystic fluid on ultrasound examination were the criteria considered for acute cholecystitis. Patients with choledocholithiasis, previous abdominal surgery, acute pancreatitis and comorbid like hypertension, heart disease, diabetes were excluded from the study. Patients underwent LC on first available list within 72 hours by consultant surgeon skilled in laparoscopy and was performed using three ports. The study parameters in terms of difficulty in dissection during surgery, operating time, intraoperative and postop complications, postoperative hospital stay, and need to convert to open cholecystectomy were studied. Data were collected and entered in a pre-designed proforma that included demographics of the patient, operative findings, operative time, intra- or post- operative complications and hospital duration. The Social Sciences Statistical Package (SPSS version 20) was used for the entry and analysis of the collected data. Descriptive statistics for both qualitative and quantitative data was determined. The mean and standard deviation was determined for quantitative factors, such as age and gender. We estimated the frequency and percentages of qualitative data such as gender, difficulties in dissection and the need for open surgery conversion. Results Among 143 patients with acute calculous cholecystitis, 38 were males and 105 were females with a ratio of males and females of 1:3.1. The mean age of patients was 46.23 years, ranged from 22 to 76 years. Majority of patients belonged to fourth and fifth decade. Patients' demographics and preoperative clinical data is presented in table I. Ultrasound findings are shown in table II. The mean operative time was 68.1 ± 25.31 minutes. Laparoscopy was successful in 140 cases, and three cases were converted into open cholecystectomy. The reasons for conversion were unclear and distorted anatomy of Calot's triangle due to thick dense adhesions, edema and exudates, bile leakage from cystic duct with suspicion of injury to common bile duct, and unexplained bleeding. Three patients had biliary injury, two to common hepatic duct and one to accessary duct in gall bladder fossa, during surgery and were managed preoperatively. shorter hospital stay, decreased cost and same level of clinical safety with no major morbidity or mortality 8 discrepancy. However sample size of the trials was not big except Gutt et al who recently reported a randomized controlled multicenter trial of 618 9 patients. With this emerging supportive data, still only a minority of surgeons are performing early LC in patients with acute cholecystitis. Once the surgeons had experience in laparoscopic surgery, early LC for acute cholecystitis in the western countries became popular in the 1990's. Tokyo Guidelines 2018 (TG13) of Japanese Society of Hepato-Biliary-Pancreatic Surgery stated that the ideal management for acute cholecystitis due to cholelithiasis is early LC, mainly before 72�h of the 10 symptom onset. Few studies showed that urgent LC should be the first choice therapy for AC in patients 11,12 who are fit for operative intervention. The purpose of this study is to evaluate the surgical outcomes of LC for acute calculous cholecystitis within 72 h of symptom onset, as this subject is less addressed in our local setup. Keeping in consideration the results of recent research favouring early LC in acute cholecystitis, this trial is planned with the purpose of evaluating the outcome of LC in patients with acute cholecystitis. The objective of the study is to assess the outcome of LC in the treatment of acute cholecystitis in terms of difficulty of procedure, operative time, duration of hospital stay and incidence of complications. Materials and Methods This interventional Quasi experimental study was conducted in Surgical Unit I, department of General st st Surgery, PIMS, Islamabad from 1 Jan 2013 to 31 Dec 2018. Sample size of 143 patients with acute cholecystitis due to cholelithiasis was calculated by using WHO formula taking power of study = 80 and selected by convenient sampling. Study was conducted after taking approval from hospital ethical committee. Patients were included for inclusion after having written informed consent. Patients who presented within 72 hours of symptoms of acute cholecystitis in emergency department were included in the study. Diagnosis of acute calculus cholelithiasis was made by either senior postgraduate, senior registrar or assistant professor using clinical, laboratory and radiological findings. Right hypochondrium tenderness with JIIMC 2020 Vol. 15, No.3 150 Outcome of Laparoscopic Cholecystectomy Discussion The application and timing of LC in patients of acute cholecystitis is still controversial, despite of guidelines published that advocate early LC during 13 same hospital admission. Recently, few studies indicate that LC is feasible and considered safe for acute cholecystitis with various complications and 14,16 conversion rates. But are these complications and conversions appropriate to surgeons and especially patients who are at the end of suffering? Therefore, further studies are required to obtain definitive results. With this background and intent, we studied the outcome of LC in acute cholecystitis as well as evaluating feasibility and safety in our local setting. Mean age of patients in this study was 43.26 ± 11.28 (22 – 76 years), which is in consistent with the 8,17 regional studies but less than the European studies 18,19 (58 years). In the present study, the mean operating time was 68.1min (35 – 116) that is comparable to 2,20 other studies. we started LC in patients of acute cholecystitis after many years of experience of LC in cholelithiasis; so less operative time is possibly due to increase in skills and gaining more confidence. Jarrar M S et al stated that the length of the operation for delayed LC group was significantly longer than for the early LC group (97 minutes versus 82.17 minutes, 21 p=0.003). LC was successfully completed in 140 patients and only three cases were converted to open cholecystectomy. This conversion rate of 2.1% is in 22 consistent with Rehman et al (2.4%) and 1 Abdelkader M et al (2%) but less than reported by 2 Farooq A et al (5%). Reasons for conversion to open were difficult anatomy and bleeding. The inflammation associated with acute cholecystitis results in an oedematous plane around the gall bladder, which promotes the dissection. This feature was observed in almost all cases therefore, Operative and postoperative data was shown in table III. There was no death in this study. The overall complication rate was 24.5 per cent and no major bile duct injury occurred in any patient. Postoperative pain was experienced with variable degree of intensity. Visual analog scale (VAS) was used to measure pain intensities. 81 (56.6%) patients had mild pain, 54 (37.8%) had moderate pain, and eight (5.6%) had severe pain as calculated by VAS. The average duration of hospital stay was 4.16 (3–8 days). Table I: Pa�ent’s Demographics and Preopera�ve Clinical Data (N=143) Table II: Pre-Opera�ve Ultrasound Findings Table III: Opera�ve and Post-Opera�ve Data (n=143) JIIMC 2020 Vol. 15, No.3 151 Outcome of Laparoscopic Cholecystectomy Sign REFERENCES 1. Abdelkader AM, Ali HE. Laparoscopic cholecystectomy for management of acute calculus cholecystitis within and after 3 days of symptom beginning: a retrospective study. Egypt J Surg 2018; 37:46-52. 21. 2. Farooq A, Zia L, Khalid M. Outcome of Same Admission Laparoscopic Cholecystectomy for Acute Cholecystitis in a District Hospital. Annals of King Edward Medical University 2019; 25(1): 81-5. 3. Chhajed R, Dumbre R, Fernandes A, Phalgune D. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a comparative study. International Surgery Journal 2018; 5(10): 3381-85. 4. Rajcok M, Bak V, Danihel L, Kukucka M, Schnorrer M. Early versus delayed laparoscopic cholecystectomy in treatment of acute cholecystitis. Bratisl Lek Listy. 2016; 117(6):328-31. 5. Thangavelu A, Rosenbaum S, Thangavelu D. Timing of Cholecystectomy in Acute Cholecystitis. J Emerg Med. 2018; 54(6):892-7. 6. Song GM, Bian W, Zeng XT, Zhou JG, Luo YQ, Tian X. Laparoscopic cholecystectomy for acute cholecystitis: early or delayed?: Evidence from a systematic review of discordant meta-analyses. Medicine (Baltimore). 2016; 95(23):e3835. 7. Wakabayashi G, Iwashita Y, Hibi T, Takada T, Strasberg SM, Asbun HJ et al. Tokyo Guidelines 2018: surgical management of acute cholecystitis: safe steps in laparoscopic cholecystectomy for acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci. 2018; 25(1):73-86. 8. Tayeb M, Rauf F, Bakhtiar N. Safety and Feasibility of Laparoscopic Cholecystectomy in Acute Cholecystitis. J Coll Physicians Surg Pak. 2018; 28(10):798-800. 9. Gutt CN, Encke J, K¨oninger J, Harnoss JC, and Weigand K, Kipfmülleret K al. acute cholecystitis: early versus delayed cholecystectomy, a multicenter randomized trial (ACDC study, NCT00447304). Annals of Surgery 2013; 258(3): 385–93. 10. Okamoto K, Suzuki K, Takada T, Strasberg SM, Asbun HJ, Endo I et al. Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis [published correction appears in J Hepatobiliary Pancreat Sci. 2019; 26(11):534]. 11. Roulin D, Saadi A, Di Mare L, Demartines N, Halkic N. Early Versus Delayed Cholecystectomy for Acute Cholecystitis, Are the 72 hours Still the Rule? A Randomized Trial. Ann Surg 2016; 264(5): 717-22. 12. Arslan Onuk ZA, Gündüz UR, Koç Ü, Kızılateş E, Gömceli İ, Akbaş SH, Bülbüller N et al. Same-admission laparoscopic cholecystectomy in acute cholecystitis: the importance of 72 hours and oxidative stress markers. Ulus Travma Acil Cerrahi Derg. 2019; 25(5):440-6. 13. Patel PP, Daly SC, Velasco JM. Training vs practice: A tale of opposition in acute cholecystitis. World J Hepatol 2015; 7(23): 2470-3. 14. Lyu Y, Cheng Y, Wang B, Zhao S, Chen L. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: an up-to-date meta-analysis of randomized controlled trials. Surg Endosc 2018; 32(12):4728- 41. 15. Kohga A, Suzuki K, Okumura T, Yamashita K, Isogaki J, dissection in majority of these cases was easy, associated with lesser needs to convert to open cholecystectomy. The ease of dissection also resulted lesser mean operative time and low morbidity. The patients had lesser severity of postoperative pain and nausea/vomiting episodes. Laparoscopic cholecystectomy is more likely to be successful within the 72 hours following the onset of symptoms and operation in the next available elective list. This approach is associated with lesser 23 incidence of major complications. We agree that several main technical aspects need to be taken into account when conducting laparoscopic surgery for acute cholecystitis. We used some modifications to handle these technical difficulties, like decompression of the gall bladder, use of retrieval bag, subhepatic drain and widening of epigastric wound. The overall complication rate was 24.5% that is comparable to rate reported by other 16,18 researchers. Intraoperative two patients with bleeding and one with bile duct injury were converted to open cholecystectomy. Limitations of the study are less sample size and single centered study. Future studies are recommended as randomized control trials for outcome of early versus late LC in patients of acute calculus cholecystitis to strengthen the evidence of beneficial effect of LC in acute cholecystitis. In summary, recent literature favors laparoscopic cholecystectomy in acute cholecystitis, although the timing of operation is debatable. Evidence suggests that LC within 72 hours of onset of symptoms is both 24 safe and cost effective. Patients with acute cholecystitis who are discharged without undergoing surgery may have a high risk of presenting with gall stone complications. So early LC in patients of acute cholecystitis is a favorable option in experienced hands. Conclusion Laparoscopic Cholecystectomy can be performed safely in patients with acute calculus cholecystitis in expert hands and should be done within 72 hours of the onset of symptoms. It is more effective in terms of patient safety, less operative time, and less duration of hospital stay without increase in morbidity or mortality. JIIMC 2020 Vol. 15, No.3 152 Outcome of Laparoscopic Cholecystectomy 21. Jarrar MS, Chouchène I, Fadhl H, Ghrissi R, Elghali A, Ferhi F, et al. Early versus delayed laparoscopic cholecystectomy for lithiasic acute cholecystitis during emergency admissions. Results of a monocentric experience and review of the literature. Tunis Med 2016; 94: 519-24. 22. Rehman S, Afzal M, Butt QM. Outcomes of laparoscopic cholecystectomy in acute cholecystitis. Pakistan Armed Forces Medical Journal 2017; 67(1): 58-61. 23. Griniatsos J. Factors predisposing to conversion from laparoscopic to open cholecystectomy. Ann Laparosc Endosc Surg 2018; 3: 12. 24. SAGE's guideline for the clinical application of laparoscopic biliary tract surgery. January 9, 2019. (Accessed June 14, 2020) Available at https://www.sages.org/publications/ guidelines/guidelines-for-the-clinical-application-of- laparoscopic-biliarytract-surgery/. Sanaka MR. Nationwide trends of hospital admissions for acute cholecystitis in the United States. Gastroenterol Rep (Oxf) 2017; 5(1): 36-42. Kawabe A, Kimura T. Outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis performed at a single institution. Asian J Endosc Surg 2019; 12(1): 74-80. 16. Khalid S, Iqbal Z, Bhatti AA. Early Versus Delayed Laparoscopic Cholecystectomy for Acute Cholecystitis. J Ayub Med Coll Abbottabad 2017; 29(4): 570-3. 17. Yokota Y, Tomimaru Y, Noguchi K, Noda T, Hatano H, Nagase H, et al. Surgical outcomes of laparoscopic cholecystectomy for acute cholecystitis in elderly patients. Asian J Endosc Surg. 2019; 12(2):157-161. 18. Jensen KK, Roth NO, Krarup PM, Bardram L. Surgical management of acute cholecystitis in a nationwide Danish cohort. Langenbecks Arch Surg. 2019; 404(5):589-597. 19. Terho PM, Leppäniemi AK, Mentula PJ. Laparoscopic cholecystectomy for acute calculous cholecystitis: a retrospective study assessing risk factors for conversion and complications. World J Emerg Surg. 2016; 11:54. 20. Wadhwa V, Jobanputra Y, Garg SK, Patwardhan S, Mehta D, JIIMC 2020 Vol. 15, No.3 153 Outcome of Laparoscopic Cholecystectomy