Abstract
Background/Objectives: Cholecystectomy (CE) is among the most commonly performed surgical procedures worldwide. While it effectively treats gallstone disease, concerns have been raised about a potential long-term association with colorectal cancer (CRC), given overlapping risk factors and post-surgical physiological changes. Previous studies have reported inconsistent findings. This updated systematic review aimed to reassess the association between CE and CRC risk by incorporating the most recent evidence. Methods: In accordance with PRISMA 2020 guidelines, a systematic literature search was conducted in PubMed, Embase, Medline, Web of Science, and the Cochrane Library for studies published after May 2022. Eligible studies were observational cohort studies reporting relative risk estimates for CRC following CE. Data were extracted manually, and study quality was assessed using the NewcastleOttawa Scale (NOS). Only high-quality studies were included to update the systematic review. Publication bias was assessed using funnel plots and Egger's test. Results: Out of 156 identified records, three new high-quality cohort studies met the inclusion criteria and were added to the 18 studies from the previous review, resulting in a total of 21 studies. The findings were heterogeneous: while no consistent association with overall CRC risk was observed, several studies reported an elevated risk of proximal (right-sided) colon cancer following CE. Egger's test indicated no significant publication bias (p = 0.50). Conclusions: This updated systematic review suggests a potential association between CE and an increased risk of proximal colon cancer; however, the evidence remains inconclusive. Further prospective studies with robust confounder control and detailed tumor location-specific analyses are warranted to clarify causality and guide future screening strategies.