FEATURE Comparative Operative Outcomes of Early and Delayed Cholecystectomy for Acute Cholecystitis A Population-Based Propensity Score Analysis Charles de Mestral, MD, PhD, ∗ ‡ Ori D. Rotstein, MD, MSc,† Andreas Laupacis, MD, MSc,†‡ Jeffrey S. Hoch, MA, PhD,†‡ Brandon Zagorski, MS,‡ Aziz S. Alali, MD, ∗ and Avery B. Nathens, MD, PhD, MPH ∗ †‡ Objective: To compare the operative outcomes of early and delayed chole- cystectomy for acute cholecystitis. Background: Randomized trials comparing early to delayed cholecystectomy for acute cholecystitis have limited contemporary external validity. Further- more, no study to date has been large enough to assess the impact of timing of cholecystectomy on the frequency of serious rare complications including bile duct injury and death. Methods: This is a population-based retrospective cohort study of patients emergently admitted to hospital with acute cholecystitis and managed with cholecystectomy over the period of April 1, 2004, to March 31, 2011. We used administrative records for the province of Ontario, Canada. Patients were divided into 2 exposure groups: those who underwent cholecystectomy within 7 days of emergency department presentation on index admission (early cholecystectomy) and those whose cholecystectomy was delayed. The primary outcome was major bile duct injury requiring operative repair within 6 months of cholecystectomy. Secondary outcomes included major bile duct injury or death, 30-day postcholecystectomy mortality, completion of cholecystectomy with an open approach, conversion among laparoscopic cases, and total hospi- tal length of stay. Propensity score methods were used to address confounding by indication. Results: From 22,202 patients, a well-balanced matched cohort of 14,220 patients was defined. Early cholecystectomy was associated with a lower risk of major bile duct injury [0.28% vs 0.53%, relative risk (RR) = 0.53, 95% confidence interval [CI]: 0.31–0.90], of major bile duct injury or death (1.36% vs 1.88%, RR = 0.72, 95% CI: 0.56–0.94), and, albeit non-significant, of 30-day mortality (0.46% vs 0.64%, RR = 0.73, 95% CI: 0.47–1.15). Total hospital length of stay was shorter with early cholecystectomy (mean difference 1.9 days, 95% CI: 1.7–2.1). No significant differences were observed in terms, open cholecystectomy (15% vs 14%, RR = 1.07, 95% CI: 0.99–1.16) or in conversion among laparoscopic cases (11% vs 10%, RR = 1.02, 95% CI: 0.93–1.13). From the ∗ Sunnybrook Research Institute, Sunnybrook Health Sciences Center; †Li Ka Shing Knowledge Institute, St Michael’s Hospital; and ‡Institute for Clinical Evaluative Sciences, Toronto, Canada. Disclosure: No authors have conflicts of interest to declare. The project was funded by operating grants from the Canadian Surgical Research Fund and Physician Services, Inc, Foundation. In addition, this study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.annalsofsurgery.com). Reprints: Charles de Mestral, MD, PhD, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, D574, Toronto, ON, Canada M4N 3M5. E-mail: charles .demestral@mail.utoronto.ca. Copyright C  2013 by Lippincott Williams & Wilkins ISSN: 0003-4932/13/25901-0010 DOI: 10.1097/SLA.0b013e3182a5cf36 Conclusions: These results support the benefit of early overdelayed cholecys- tectomy for patients with acute cholecystitis. Keywords: acute cholecystitis, bile duct injury, delayed cholecystectomy, early cholecystectomy, laparoscopic cholecystectomy (Ann Surg 2014;259:10–15) A cute cholecystitis (AC) is the most common cause of hospital- ization for gastrointestinal disease. 1 Although cholecystectomy is the definitive management, the timing of surgery in relation to the first episode of AC remains an area of considerable practice variation. Operative intervention is either undertaken early on first presenting admission or, may be delayed some 6 to 12 weeks after initial nonoperative management to allow the acute inflammation to settle. Several randomized controlled trials have shown that early la- paroscopic cholecystectomy (within up to 7 days of symptom onset) is associated with a shorter total hospital length of stay and a sim- ilar rate of conversion to an open procedure, when compared with delayed cholecystectomy. 2–7 Furthermore, early surgery precludes the risk of recurrent gallstone-related symptoms, estimated to affect nearly 20% of patients. 7,8 However, despite this evidence and ex- pert consensus supporting early laparoscopic cholecystectomy, 7,9,10 rates of early surgery remain variable, ranging from 36% to 88% in recent reports from the United Kingdom, Japan, and the United States. 11–15 Practice patterns may not be consistent with best available evidence because concern remains that rare but devastating com- plications such as major bile duct injury or death may occur more frequently in the setting of emergency surgery on an acutely in- flamed gallbladder. 16 Major bile duct injury occurs in only 0.3% to 0.5% 17,18 of cholecystectomies but is a serious complication as- sociated with reduced long-term survival 17,19 and high litigation rates. 20 No study to date has been large enough to compare ma- jor bile duct injury or mortality rates between early and delayed cholecystectomy. Furthermore, the trials comparing early to delayed surgery were derived from single specialized centers and included patients recruited between 1993 and 2002. 2–6 Consequently, these data can- not be generalized to a broader range of hospitals or to current practice characterized by greater expertise with laparoscopic surgery. Under- standing comparative rates of open cholecystectomy and conversion in the laparoscopic era is important because, while conversion to an open approach is safe practice in the face of operative difficulty, open cholecystectomy is associated with greater postoperative pain, an increased incidence of surgical site infection, and a longer hospital stay. 21–23 To address these evidence gaps, we compared the operative outcomes of early and delayed cholecystectomy in a contemporary, population-based cohort of patients with acute cholecystitis. Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 10 | www.annalsofsurgery.com Annals of Surgery  Volume 259, Number 1, January 2014