Early Versus Delayed Cholecystectomy in Mild Gallstone Pancreatitis: An Updated Meta-Analysis of Randomized Controlled Trials

Introduction

Gallstone pancreatitis remains one of the most common causes of acute pancreatitis worldwide and accounts for a substantial proportion of gastrointestinal hospitalizations. While most cases are mild and improve with supportive care, patients remain at risk for recurrent biliary events until definitive gallbladder removal is performed. Recurrent pancreatitis, biliary colic, acute cholecystitis, and cholangitis can occur during the waiting period if surgery is delayed, often leading to repeat emergency department visits, readmissions, and increased healthcare utilization. For many years, surgeons traditionally delayed cholecystectomy because of concerns regarding active inflammation, technical difficulty, increased adhesions, and possible perioperative complications. However, growing evidence suggests that these concerns may be overstated in patients with mild disease. Multiple randomized studies have demonstrated that early laparoscopic cholecystectomy during the index admission is both feasible and safe, while also reducing recurrent biliary complications [1]. Despite this evidence, practice patterns remain variable [2]. Definitions of “early” surgery differ across studies and institutions, ranging from surgery within 24 hours to surgery later during the same admission. This variability has contributed to ongoing uncertainty regarding the ideal timing of intervention. The aim of this updated meta-analysis was to evaluate outcomes of early cholecystectomy performed within 72 hours of admission compared with delayed cholecystectomy in patients with mild gallstone pancreatitis. Outcomes of interest included recurrent biliary complications, operative outcomes, perioperative morbidity, and updated evidence from recently published studies [3,4].

Methods

Search Strategy and Eligibility

A systematic search was performed using MEDLINE, PubMed, and the Cochrane Library. The search was updated with recently indexed literature through online database searches. Search terms included gallstone pancreatitis, acute biliary pancreatitis, mild acute pancreatitis, early cholecystectomy, delayed cholecystectomy, laparoscopic cholecystectomy, randomized controlled trial, and meta-analysis. Studies were eligible for the quantitative RCT synthesis if they: (1) enrolled adult patients with mild gallstone or biliary pancreatitis; (2) compared early cholecystectomy within 72 hours of admission with delayed cholecystectomy; (3) were randomized controlled trials; and (4) reported at least one outcome of interest. Severe pancreatitis, necrotizing pancreatitis, pediatric studies, case reports, editorials, reviews, and studies without extractable timing or outcome data were excluded from quantitative pooling. Recently published prospective or observational studies were not combined with the RCT meta-analysis, but were included in an updated narrative evidence table when clinically relevant [59].

Outcomes

The primary outcome was recurrent biliary complications, including recurrent pancreatitis, biliary colic, acute cholecystitis, cholangitis, jaundice, or recurrent biliary obstruction. Secondary outcomes included conversion to open cholecystectomy, intraoperative complications, postoperative complications, readmission, reoperation, mortality, operative time, and hospital length of stay..

Statistical Analysis

The original pooled analysis used Review Manager (RevMan) version 5.4. Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were calculated using Mantel-Haenszel methods.

Heterogeneity was assessed using the I2 statistic. In the updated search, newly identified randomized trials were reviewed for event-level data. Trials with zero events in both study arms were retained in the qualitative RCT synthesis but do not contribute to pooled OR estimation for that outcome using standard MantelHaenszel methods.

Results

Study Selection and Updated Evidence Base

The original search identified 163 references, of which 45 were selected for full review. Nine randomized trials met inclusion criteria for the initial analysis. The original manuscript reported 1,046 patients; for the primary biliary-complication outcome, 993 patients contributed analyzable event-level data. An updated search identified one additional randomized trial published online in HPB by Zhou et al., which randomized 120 patients with mild acute biliary pancreatitis to early laparoscopic cholecystectomy within 72 hours versus delayed surgery. Several newer prospective or observational studies were also identified and are summarized narratively [5].

Primary Outcome

Recurrent Biliary Complications

In the original event-level RCT analysis, early cholecystectomy significantly reduced recurrent biliary complications. There were 15 events among 500 patients in the early group and 80 events among 493 patients in the delayed group. The pooled OR was 0.17 (95% CI 0.10-0.29; p<0.00001), favoring early cholecystectomy. Heterogeneity was low-to-moderate (Chi2=11.51, df=7, p=0.12; I2=39%).The newly identified Zhou et al. RCT reported no recurrent biliary events in either arm. Therefore, it supports the safety of early surgery but does not mathematically change the pooled OR for recurrent biliary complications under standard Mantel-Haenszel methods because zero-event studies in both arms are non-informative for relative odds estimation [5].

Secondary Outcomes

Early cholecystectomy was not associated with a statistically significant increase in conversion to open cholecystectomy, intraoperative complications, or postoperative complications. In the original analysis, conversion to open cholecystectomy was similar between groups (OR 1.27, 95% CI 0.63-2.58; p=0.50). Intraoperative complications were also similar (OR 0.64, 95% CI 0.18-2.28; p=0.49), as were postoperative complications (OR 0.73, 95% CI 0.40-1.32; p=0.30).Zhou et al. reported no increase in overall complication rate with early surgery (10.0% vs 8.3%; p=0.752), no significant difference in conversion to open surgery (3.3% vs 5.0%; p=1.00), no postoperative readmissions, no reoperations, and no deaths. Early surgery was associated with shorter procedure time and shorter hospital length of stay (Tables 1-3) (Figure 1).

The original pooled RCT analysis demonstrated significantly fewer biliary complications with early cholecystectomy within 72 hours.

Figure 1: Original Forest Plot for Biliary Complications.