Antibiotic prophylaxis for acute cholecystectomy: PEANUTS II multicentre randomized non-inferiority clinical trial.

BACKGROUND: Guidelines recommending antibiotic prophylaxis at emergency cholecystectomy for cholecystitis were based on low-quality evidence. The aim of this trial was to demonstrate that omitting antibiotics is not inferior to their prophylactic use. METHODS: This multicentre, randomized, open-label, non-inferiority clinical trial randomly assigned adults with mild-to-moderate acute calculous cholecystitis (immediate cholecystectomy indicated) to 2 g cefazolin administered before incision or no antibiotic prophylaxis. The primary endpoint was a composite of all postoperative infectious complications in the first 30 days after surgery. Secondary endpoints included all individual components of the primary endpoint, other morbidity, and duration of hospital stay. RESULTS: Sixteen of 226 patients (7.1 per cent) in the single-dose prophylaxis group and 29 of 231 (12.6 per cent) in the no-prophylaxis group developed postoperative infectious complications (absolute difference 5.5 (95 per cent c.i. -0.4 to 11.3) per cent). With a non-inferiority margin of 10 per cent, non-inferiority of no prophylaxis was not proven. The number of surgical-site infections was significantly higher in the no-prophylaxis group (5.3 versus 12.1 per cent; P = 0.010). No differences were observed in the number of other complications, or duration of hospital stay. CONCLUSION: Omitting antibiotic prophylaxis is not recommended.

Conservative treatment of acute cholecystitis: a systematic review and pooled analysis.

BACKGROUND: In medical practice, the tendency to remove an inflamed gallbladder is deeply rooted. Cholecystectomy, however, is associated with relatively high complication rates, and therefore the decision whether or not to perform surgery should be well considered. For some patients, the surgical risk-benefit profile may favour conservative treatment. The objective of this study was to examine the short- and long-term outcome of conservative treatment of patients with acute calculous cholecystitis. METHODS: A systematic search of MEDLINE, Embase and Cochrane Library databases was performed. Prospective studies reporting on the success rate of conservative treatment (i.e. non-invasive treatment) of acute cholecystitis during index admission were included, as well as prospective and retrospective studies reporting on the recurrence rate of gallstone-related disease during long-term follow-up (i.e. ≥12 months) after initial non-surgical management. Study selection was undertaken independently by two reviewers using predefined criteria. The risk of bias was assessed. The pooled success and mortality rate during index admission and the pooled recurrence rate of gallstone-related disease during long-term follow-up were calculated using a random-effects model. RESULTS: A total of 1841 patients were included in 10 randomized controlled trials and 14 non-randomized studies. Conservative treatment during index admission was successful in 87 % of patients with acute calculous cholecystitis and in 96 % of patients with mild disease. In the long term, 22 % of the patients developed recurrent gallstone-related disease. Pooled analysis showed a success rate of 86 % (95 % CI 0.8-0.9), a mortality rate of 0.5 % (95 % CI 0.001-0.009) and a recurrence rate of 20 % (95 % CI 0.1-0.3). DISCUSSION: Conservative treatment of acute calculous cholecystitis during index admission seems feasible and safe, especially in patients with mild disease. During long-term follow-up, less than a quarter of the patients appear to develop recurrent gallstone-related disease, although this outcome is based on limited data.

The optimal treatment of patients with mild and moderate acute cholecystitis: time for a revision of the Tokyo Guidelines.

INTRODUCTION: According to the Tokyo Guidelines, severity of acute cholecystitis is divided into three grades based on the degree of inflammation and the presence of organ dysfunction. These guidelines recommend grade I (mild) acute cholecystitis to be treated with early laparoscopic cholecystectomy and grade II (moderate) acute cholecystitis with delayed cholecystectomy. Yet, several studies have shown that, for acute cholecystitis in general, early cholecystectomy is superior to delayed cholecystectomy in terms of complication rate, duration of hospital stay and costs. The aim of this study was to determine the clinical outcomes of emergency cholecystectomy in patients with grade II acute cholecystitis. Based on our findings, we propose a revision of the Tokyo Guidelines. METHODS: We performed a retrospective observational cohort study of 589 consecutive patients undergoing emergency cholecystectomy for acute calculous cholecystitis in a large teaching hospital between January 2002 and January 2015. Patients were classified according to the severity assessment criteria of the Tokyo Guidelines. Patients with grade I and grade II acute cholecystitis were compared for perioperative outcomes. RESULTS: Emergency cholecystectomy was performed in 270 patients with grade I acute cholecystitis and 187 patients with grade II acute cholecystitis. There was no difference in conversion rate (6 vs. 6%, p = 0.985) and operating time (60 min [25-255] vs. 70 min [30-255], p = 0.421). Also the perioperative complication rate (7 vs. 9%, p = 0.517), 30-day mortality (1 vs. 1%, p = 0.648) and length of hospital stay (4 days [1-42] vs. 4 days [1-62], p = 0.327) were similar between grade I and grade II acute cholecystitis. CONCLUSION: The clinical outcomes of emergency cholecystectomy did not differ between patients with grade I and grade II acute cholecystitis. The findings support a revision of the Tokyo Guidelines with respect to the recommendation of performing emergency cholecystectomy in both grade I and grade II acute cholecystitis.

Early Cholecystectomy for Acute Cholecystitis in the Elderly Population: A Systematic Review and Meta-Analysis.

BACKGROUND: In the era of advanced surgical techniques and improved perioperative care, the willingness to perform emergency operations in elderly patients continues to increase. This systematic review aimed at assessing the clinical outcomes of early cholecystectomy in elderly patients with acute cholecystitis. METHODS: Medline, Embase, and Cochrane Library databases were systematically searched for studies reporting on early cholecystectomy for acute cholecystitis in patients aged ≥70 years. The conversion rate, perioperative morbidity, and mortality were calculated using a random-effects model. RESULTS: Eight articles fell within the scope of this study. In total, 592 patients were identified. The mean age was 81 years. Early cholecystectomy was performed laparoscopically in 316 patients (53%) and open in 276 patients (47%). The procedure was associated with a conversion rate of 23% (95% CI 18.6-28.3), a perioperative morbidity of 24% (95% CI 20.5-27.5), and a mortality of 3.5% (95% CI 2.3-5.4). CONCLUSION: Early cholecystectomy seems to be a feasible treatment in elderly patients with acute cholecystitis. To reduce morbidity, patients who may benefit from surgery ought to be selected carefully. Future prospective studies should compare early cholecystectomy with alternative treatments to select the treatment that is most appropriate for elderly patients.

Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial.

OBJECTIVE: To assess whether laparoscopic cholecystectomy is superior to percutaneous catheter drainage in high risk patients with acute calculous cholecystitis. DESIGN: Multicentre, randomised controlled, superiority trial. SETTING: 11 hospitals in the Netherlands, February 2011 to January 2016. PARTICIPANTS: 142 high risk patients with acute calculous cholecystitis were randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous catheter drainage (n=68). High risk was defined as an acute physiological assessment and chronic health evaluation II (APACHE II) score of 7 or more. MAIN OUTCOME MEASURES: The primary endpoints were death within one year and the occurrence of major complications, defined as infectious and cardiopulmonary complications within one month, need for reintervention (surgical, radiological, or endoscopic that had to be related to acute cholecystitis) within one year, or recurrent biliary disease within one year. RESULTS: The trial was concluded early after a planned interim analysis. The rate of death did not differ between the laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v 9%, P=0.27), but major complications occurred in eight of 66 patients (12%) assigned to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the drainage group 45 patients (66%) required a reintervention compared with eight patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease occurred more often in the percutaneous drainage group (53% v 5%, P<0.001), and the median length of hospital stay was longer (9 days v 5 days, P<0.001). CONCLUSION: Laparoscopic cholecystectomy compared with percutaneous catheter drainage reduced the rate of major complications in high risk patients with acute cholecystitis. TRIAL REGISTRATION: Dutch Trial Register NTR2666.

Perioperative antibiotic prophylaxis in the treatment of acute cholecystitis (PEANUTS II trial): study protocol for a randomized controlled trial.

BACKGROUND: The additional value of perioperative antibiotic prophylaxis in preventing infectious complications after emergency cholecystectomy for acute cholecystitis is a much-debated subject in the surgical community. Evidence-based guidelines are lacking, and consequently the use of antibiotic prophylaxis varies greatly among surgeons and hospitals. Recently, high-level evidence became available demonstrating that postoperative antibiotic prophylaxis in patients with acute cholecystitis does not reduce the risk of infectious complications. Preoperative antibiotic prophylaxis in relation to the risk of infectious complications, however, has never been studied. METHODS: The PEANUTS II trial is a randomized, controlled, multicenter, open-label noninferiority trial whose aim is to determine the utility of preoperative antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis. Patients with mild or moderate acute cholecystitis, as defined according the Tokyo Guidelines, will be randomly assigned to a single preoperative dose of antibiotic prophylaxis (2000 mg of first-generation cephalosporin delivered intravenously) or no antibiotic prophylaxis before emergency cholecystectomy. The primary endpoint is a composite endpoint consisting of all postoperative infectious complications occurring during the first 30 days after surgery. Secondary endpoints include all the individual components of the primary endpoint, all other complications, duration of hospital stay, and total costs. The hypothesis is that the absence of antibiotic prophylaxis is noninferior to the presence of antibiotic prophylaxis. A noninferiority margin of 10% is assumed. With a 1-sided risk of 2.5% and a power of 80%, a total of 454 subjects will have to be included. Analysis will be performed according to the intention-to-treat principle. DISCUSSION: The PEANUTS II trial will provide evidence-based advice concerning the utility of antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis. TRIAL REGISTRATION: Netherlands Trial Register, NTR5802 . Registered on 4 June 2016.