Current Evidence on Laparoscopic Lavage for Perforated Diverticulitis The College of Surgeons of Hong Kong Joint Hospital Grand Round 15 Dec 2018

Background Diverticulosis: about 25% of Hong Kong population1 In western countries: 60% by the age of 60, 80% by the age of 802 4% of these patients develop acute divericulitis3 up to 25% of these patients requires emergency surgery4 Traditionally, for left sided disease, Hartmann’s procedure is the most commonly performed procedure High morbidity (39% - 67%) and mortality rate (7.7% - 13%)4,5 Around 50% stoma reversal rate4,5 2. Due to the high morbidity and low and often difficult reversal procedure  PRA; which has its own well documented complications Lower morbidity, similar mortality and higher stoma reversal rate4,5 3. While it seems that we are adopting a more aggressive approaches, it LLD the next step to take? Well documented complications result in frequent admissions6 Chan CC et al. Colonic diverticulosis in Hong Kong: distribution pattern and clinical significance. Clin Radiol. 1998 Nov;53(11):842-4 Delvaux M. Diverticular disease of the colon I Europe: epidemiology, impact on citizen health and prevention. Aliment Pharmacol Ther 2003; 18 (supple 3): 71-74 Shahedi K et al. Long-term risk of acute diverticulitis among patients with incidental diverticulosis found during colonoscopy. Clin Gastroenterol Hepatol. 2013 Dec;11(12):1609-13. Li D et al. Evolving practice patterns in the management of acute colonic diverticulitis: a population-based analysis. Dis Colon Rectum. 2014 Dec;57(12):1397-405

Hinchey Classification Grading system for diverticular disease with abscess formation or free perforation Grade I Pericolic abscess or phlegmon (Modified classification) 1a: confined pericolic inflammation or Phlegmon 1b: confined pericolic abscess Grade II Distant intrabdominal, pelvic, retroperitoneal abscess Grade III Generalized purulent peritonitis Grade IV Generalized feculent peritonitis Hinchey EJ, Schaal PG, Richards GK. Treatment of perforated diverticular disease of the colon. Adv Surg. 1978;12:85-109.

Left Sided Perforated Diverticulitis - current treatment options Hartmann’s procedure High morbidity (39% - 67%) and mortality rate (7.7% - 13%)1,2 Around 50% stoma reversal rate1,2 Colonic resection with primary anastomosis Rate of reversal after ileostomy is higher (80-90%)3 Well documented complications result in frequent admissions4 Laparoscopic Peritoneal Lavage (LPL) Recent retrospective study showed increased use of primary anastomosis in emergency surgery for acute diverticulitis by 7% in the United States4 Masoomi H, Buchberg BS, Magno C, Mills SD, Stamos MJ. Trends in diverticulitis management in the United States from 2002 to 2007. Arch Surg 2011; 146: 400–6 Oberkofler CE et al. A multicenter randomized clinical trial of primary anastomosis or Hartmann's procedure for perforated left colonic diverticulitis with purulent or fecal peritonitis. Ann Surg. 2012 Nov;256(5):819-26; discussion 826-7. Bridoux V et al. Hartmann's Procedure or Primary Anastomosis for Generalized Peritonitis due to Perforated Diverticulitis: A Prospective Multicenter Randomized Trial (DIVERTI). J Am Coll Surg. 2017 Dec;225(6):798-805. doi: 10.1016/j.jamcollsurg.2017.09.004. Epub 2017 Sep 22. Salem L, flum DR. Primary anastomosis or Hartmann’s procedure for patients with diverticular abscess? A systemic review. Dis Colon Rectum. 2004; 47: 1953-1964 Paquette IM et al. Readmission for dehydration or renal failure after ileostomy creation. Dis Colon Rectum. 2013 Aug;56(8):974-9

Laparoscopic Peritoneal Lavage vs. Resectional Surgery

Background and Guidelines First described in 19961 Diagnostic laparoscopy: to exclude other causes and Hinchey IV diverticulitis Thorough irrigation of peritoneal cavity with saline Non resection ; No planned 2nd look/elective surgery Applications in Hinchey III diverticulitis Current guidelines: No general recommendation for perforated diverticulitis1-4 In 2008, Myers et al5 produced a prospective multi-institutional studies showing an encouraging result of Laparoscopic peritoneal lavage (LPL) Myer’s In 2008, Myers et al.12 reported the best series to date. Of 1,257 patients admitted for diverticulitis within 7 years, 100 (7%) had peritonitis, with evidence of free air on roentgenogram or CT scan. These patients were resuscitated, given a third-generation cephalosporin and flagyl, and then taken emergently to the operating room (OR) for laparoscopy. Of the 100 patients who underwent laparoscopy, eight were found to have Hinchey IV disease and underwent the HP. The remaining 92 Hinchey II and III patients underwent lavage and drainage. Three of these patients died (much lower than reported for PRA or the HP) = 3% An additional two patients had nonresolution, one went on to have the HP performed and the other one had further percutaneous drainage. Overall, 88 of the 92 lavage patients had resolution of their symptoms. During the 36 months of follow-up, there were only two recurrences. This series challenges our basic understanding of the natural history of diverticulitis. It is surmised with resolution of an acute perforation; local fibrosis prevents the recurrent perforation of the diverticulum. Jasim M Radhi*, Jennifer A Ramsay and Odette Boutross-Tadross. Diverticular disease of the right colon. Radhi et al. BMC Research Notes 2011, 4:383 Chan CC et al. Colonic diverticulosis in Hong Kong: distribution pattern and clinical significance. Clin Radiol. 1998 Nov;53(11):842-4 Ma Ru Kim et al. Treatment of Right Colonic Diverticulitis: The Role of Nonoperative Treatment. J Korean Soc Coloproctol 2010:26(6);402-406 N I Markham, A K C Li. Diverticulitis of the right colon- experience from Hong Kong. Gut, 1992, 33, 547-549 Myers E, Hurley M, O’Sullivan GC, Kavanagh D, Wilson I, Winter DC. Laparoscopic peritoneal lavage for generalized peritonitis due to perforated diverticulitis. Br J Surg. 2008;95:97Y101

Current Evidence Randomized Controlled Trials

The Ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis7 Sandra Vennix et al. Lancet 2015; 386:1269-77 34 teaching hospitals and 8 academic hospitals in Italy/Belgium/the Netherlands Inclusions criteria: signs of general peritonitis + free gas/free fluid on imaging First diagnostic laparoscopy then randomization Laparoscopic Lavage group versus sigmoidectomy (Hartmann operation: primary anastomosis = 1:1) Calculated sample size: 132 for each arm - First randomized controlled trial

Results Ended prematurely due to significantly higher rate of In-hospital major morbidity or mortality in the LLD group Only 45 in the LLD group and 42 in the Sigmoidectomy group respectively Adverse events: 37 events (LLD) vs. 10 events (Sigmoidectomy group) (P=0.0005) Surgical interventions: 18 (LLD) vs. 2 (Sigmoidectomy) (P=0.0011) Among the adverse events, in-hospital surgical interventions account for most

Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis The SCANDIV Randomized Clinical Trial8 Schultz JK et al. JAMA. 2015 Oct 6;314(13):1364-75 21 surgical units (9 in Sweden and 12 in Norway), ranging from small community hospitals to tertiary referral centres. Randomisation before diagnostic laparoscopy Laparoscopic Lavage versus Resectional surgeries Primary outcome: Severe postoperative complications (Clavien-Dindo score >IIIa) within 90 days. Sample size: 101 (laparoscopic lavage group) versus 98 (Primary resection group) 2-group, open-labeled, pragmatic, superiority, multicenter RCT 21 surgical units were included in the trial (9 in Sweden and 12 in Norway), ranging from small community hospitals to tertiary referral centers. These units covered a catchment population of approximately 5 million CT: Colonic wall thickening and pericolic inflammation Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life.

Results - at 90 days (primary outcome)

Results - secondary outcome at 1 year10 Laparoscopic lavage group Resection group P-value Patients with stoma 14% 42% <0.001 Mortality At index admission 2(3%) 3 (4%) 0.68 At 90days 12 (13.5%) 7 (8.4%) 0.34 At 12 months 14 (13.9%) 11 (11.5%) 0.67 Tow sided Fisher Exact test All severe adverse events (>/=Grade IIIa) within 90days of index operations and all diverticulitis-related adverse events within 1 year of index operations, including those related to stoma reversal, but not stoma reversal itself or elective sigmoid resection

Results - at Index admission Re-operations at index admission 12 (16%) in laparoscopic lavage group vs. 3 (4%) in Sigmoidectomy group P=0.03

The DILALA trial: Laparoscopic Lavage for Perforated Diverticulitis With Purulent Peritonitis: A Randomized, Controlled Trial 9,10 9 surgical departments in Sweden and Denmark Randomization after Diagnostic laparoscopy Laparoscopic Peritoneal Lavage versus Hartmann’s Operation Primary end-point: Reoperations within 12 months Sample size: 43 (laparoscopic lavage group) vs. 40 (Hartmann’s group)

Results - primary outcome Laparoscopic lavage Hartmann’s group P-value Reoperations within 12 months ≧ 1 reoperations 12 (27.9%) 25 (62.5%) 0.004 Mean reoperations per patient 0.35 0.8 0.010

Results - Mortality and stoma rate Laparoscopic Lavage Hartmann’s Group P-value Mortality At 30days 3 (7.7%) 0 (0%) 0.094 At 12months 6 (14%) 6 (15%) Stoma rate at 12months 3 (7%) 11 (28%) 90-day mortality in the laparoscopic lavage group was 13.5% (12 of 89 patients) vs 8.4% (7 of 83 patients) in the resection group (difference, 5.1% [95% CI, −4.7% to 14.7%]; P = .34

Results Adverse events at 12months Intra-abdominal abscess: 14 in laparoscopic lavage group vs. 4 in Hartmann group

Summary SCANDIV DILALA LADIES Sample size 199 83 87 Problems with Laparoscopic lavage Significantly higher early intervention rate Higher rate of intra-abdominal abscess Prematurely ended due to high early intervention rate Mortality Insignificant Morbidity Stoma Rate Significantly less

Conclusions Alternative to patients Save a stoma and related complications (of stoma itself/reversal surgery) Yet mandatory close clinical monitoring for timely intervention in case failed to control sepsis Result in no difference in short term and 1-year morbidity and mortality rate

O’Sullivan GC, Murphy D, O’Brien MG, Ireland A O’Sullivan GC, Murphy D, O’Brien MG, Ireland A. Laparoscopic management of generalized peritonitis due to perforated colonic diverticula. Am J Surg 1996; 171: 432–34. Myers E, Hurley M, O’Sullivan GC, Kavanagh D, Wilson I, Winter DC. Laparoscopic peritoneal lavage for generalized peritonitis due to perforated diverticulitis. Br J Surg. 2008;95:97Y101 ASCRS 2014 Practice Parameters for the Treatment of Sigmoid Diverticulitis ACPGBI and RCS 2014 2014 Commissioning guide: Colonic diverticular disease WSES 2016 Guidelines for the management of acute left sided colonic diverticulitis in the emergency setting Caroline S. Andeweg et al. Guidelines of Diagnostics and Treatment of Acute Left-Sided Colonic Diverticulitis. Dig Surg 2013;30:278– 292 Sandra Vennix et al. laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis. Lancet 2015; 386:1269-77 Schultz JK et al. Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis The SCANDIV Randomized Clinical Trial. JAMA. 2015 Oct 6;314(13):1364-75 A. Thornellet al. Laparoscopic Lavage for Perforated Diverticulitis With Purulent Peritonitis: A Randomized Trial. Ann Intern Med. 2016 Feb 2;164(3):137-45 Angenete E. et al. Laparoscopic Lavage Is Feasible and Safe for the Treatment of Perforated Diverticulitis With Purulent Peritonitis: The First Results From the Randomized Controlled Trial DILALA. Ann Surg. 2016 Jan;263(1):117-22

A. Thornellet al. Laparoscopic Lavage for Perforated Diverticulitis With Purulent Peritonitis: A Randomized Trial. Ann Intern Med. 2016 Feb 2;164(3):137-45 Angenete E. et al. Laparoscopic Lavage Is Feasible and Safe for the Treatment of Perforated Diverticulitis With Purulent Peritonitis: The First Results From the Randomized Controlled Trial DILALA. Ann Surg. 2016 Jan;263(1):117-22 Cirocchi R et al. Laparoscopic lavage versus surgical resection for acute diverticulitis with generalised peritonitis: a systematic review and meta-analysis. Tech Coloproctol. 2017 Feb;21(2):93- 110 Ceresoli M, Coccolini F, Montori G, Catena F, Sartelli M, Ansaloni L (2016) Laparoscopic lavage versus resection in perforated diverticulitis with purulent peritonitis: a meta-analysis of randomized controlled trials. World J Emerg Surg 11:42 Angenete E, Bock D, Rosenberg J, Haglind E (2016) Laparoscopic lavage is superior to colon resection for perforated purulent diverticulitis-a meta-analysis. Int J Colorectal Dis. doi: 10.1007/s00384-016-2636-0 Marshall JR, Buchwald PL, Gandhi J et al (2016) Laparoscopic lavage in the management of Hinchey grade III diverticulitis: a systematic review. Ann Surg. doi: 10.1097/SLA.0000000000002005 ClinicalTrials.gov. LapLAND laparoscopic lavage for acute non-feculent diverticulitis. http://clinicaltrials.gov/show/NCT01019239. Accessed 19 June 2016