COMMENT & RESPONSEIn Reply We appreciate the valuable correspondence from Robertson et al and Zhu and Wei regarding our article, which has allowed us to further clarify the strengths and limitations of our findings.The primary goal of cholecystectomy in acute biliary pancreatitis (ABP) is to prevent recurrent attacks. While early cholecystectomy (EC) is established as safe for mild ABP, its safety for moderately severe and severe ABP lacks robust evidence. 1 Our study is a post hoc analysis of the MANCTRA-1, originally designed to assess guideline compliance and related outcomes. 2 Our analysis reveals that EC in patients with moderately severe and severe ABP should be approached cautiously.As noted by our colleagues, significant differences in baseline characteristics between the study and control groups were apparent. These differences were highlighted through the analysis of specific patient-related comorbidities, including cardiac, pulmonary, kidney, or endocrinological disorders, and composite outcomes such as the Charlson Comorbidity Index. Given the intrinsic relationship between these differences and the nature of ABP, achieving perfectly balanced study and control groups with sufficient statistical power is unlikely. To address these limitations, we conducted subgroup and adjusted statistical analyses using multivariable regression models.We agree that, despite the inclusion of several international centers, our cohort may be inconsistent with earlier reports on acute pancreatitis, with only 108 patients having moderately severe or severe ABP. 3 A possible explanation may be found in the fact that we enrolled only patients with ABP. Another important limitation also highlighted in the article is that some EC procedures may have coincided with other interventional procedures in patients with unresolved organ dysfunction, making it impossible to draw firm conclusions about the specific cause of death in those cases. Therefore, we concur that the nature of the study does not permit us to make strong definitive statements regarding the causal relationship between EC and postoperative complications.Nevertheless, it is important to note that patients with moderately severe and severe ABP exhibited not only i n c re a s e d m o r b i d it y a n d m o r t a l it y b u t a l s o m o re cholecystectomy-related complications, such as bile leakage (2.4%), when compared with patients with mild ABP. This indicated an elevated postoperative risk for the study group. Additionally, we conducted subgroup analyses for patients with both moderately severe and severe ABP and adjusted analyses aimed at providing insights into patients at higher risk of complications. These analyses indicated that patients with more complex cases and a pronounced inflammatory
