Diverticular disease is a common disorder ranging from 10% in those younger than 40 years to between 50% and 70% in those older than 80 years.¹ The most frequent complication, acute diverticulitis, can range from mild uncomplicated diverticulitis, which requires no antibiotics,^2-4 to life-threatening peritonitis.⁵

Pancreatic surgery carries a high risk for complications, and pancreatic fistula remains the main cause of most of the serious complications. Several methods have been introduced during the past decades to address the problem and reduce the incidence of pancreatic fistula and overall complication burden after pancreatic surgery. For pancreaticoduodenectomy, these methods include different types of pancreaticoenteric anastomoses, different drainage strategies, and various stenting methods of the pancreatic duct.^1-4 For distal pancreatectomies, different cutting methods and pancreatic stump sealing strategies have been used.^5,6 Somatostatin analogs, especially octreotide, have also been used for both pancreaticoduodenectomy and distal pancreatectomy. Although the use of octreotide is widespread in some countries, octreotide has not gained full acceptance globally, as meta-analyses have not shown consistent benefit.^7,8 Despite rigorous research, postoperative pancreatic fistula remains a significant challenge: up to every third patient at high risk will develop a clinically significant pancreatic fistula.^6,9

Background: Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested. Methods: A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work. Results: From May 2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 were assigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i. −0.9 to 21) per cent was not statistically different for the primary outcome (1-sided P = 0.142), and secondary outcomes were similar. Conclusion: The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https://eudract.ema.europa.eu/eudract-web/index.faces), NCT03234296 (http://www.clinicaltrials.gov).