Background: As colorectal cancer (CRC) patients with peritoneal metastases (PM) have a poor prognosis, new treatment options are currently being investigated for CRC patients. Specific biomarkers in the primary tumor could serve as a prediction tool to estimate the risk of distant metastatic spread. This would help identify patients eligible for early treatment. Aim: To give an overview of previously studied DNA and RNA alterations in the primary tumor correlated to colorectal PM and investigate which gene mutations should be further studied. Methods: A systematic review of all published studies reporting genomic analyses on the primary tissue of CRC tumors in relation to PM was undertaken according to PRISMA guidelines. Results: Overall, 32 studies with 18,906 patients were included. BRAF mutations were analyzed in 17 articles, of which 10 found a significant association with PM. For all other reported genes, no association with PM was found. Two analyses with broader cancer panels did not reveal any new biomarkers. Conclusion: An association of specific biomarkers in the primary tumors of CRC patients with metastatic spread into peritoneum could not be proven. The role of BRAF mutations should be further investigated. In addition, studies searching for potential novel biomarkers are still required.

Background: There is no consensus on the use of preoperative biliary drainage for resectable perihilar cholangiocarcinoma. This retrospective cohort study aimed to explore the association of biliary drainage with postoperative mortality and morbidity. Methods: This retrospective observational cohort study included patients who underwent resection of histologically confirmed perihilar cholangiocarcinoma from the Perihilar Cholangiocarcinoma Collaboration Group database across 27 Western hepatobiliary centres (2000–2022). To correct for baseline differences between patients who did or did not undergo drainage, propensity score weighting was applied. Outcomes were compared using propensity score-weighted regression and multivariable analysis. Results: Overall, 2067 patients were included, of whom 350 (16.9%) did not undergo biliary drainage. Before propensity score weighting, patients who did not undergo drainage were less likely to have Bismuth III–IV disease (297 (78.9%) versus 1448 (84.3%); P < 0.001), had lower median bilirubin levels (12.0 versus 85.5 µmol/l; P < 0.001), and a higher proportion had left hepatectomies (150 (42.9%) versus 454 (26.4%); P < 0.001). After propensity score-weighted regression analysis, patients in the drainage group were more likely to experience major postoperative complications (odds ratio 1.43, 95% confidence interval 1.04 to 1.95; P = 0.027) and posthepatectomy liver failure (odds ratio 2.12, 1.25 to 3.58; P = 0.005). In multivariable analysis, only posthepatectomy liver failure remained significant (odds ratio 2.13, 1.29 to 3.54; P = 0.003). Conclusion: In this retrospective propensity score weighting analysis, preoperative biliary drainage was associated with a higher incidence of posthepatectomy liver failure in resectable perihilar cholangiocarcinoma. These findings suggest that a subgroup of patients with perihilar cholangiocarcinoma can be operated safely without biliary drainage. The indication for preoperative biliary drainage should be considered on an individual basis.

Definitive assessment of resectability in perihilar cholangiocarcinoma (pCCA) often requires surgical exploration. Limited data exist on whether surgical exploration without resection affects the chance of receiving subsequent systemic therapy and survival. This nationwide analysis aims to address this question. Patients diagnosed with non-metastatic pCCA between 2012 and 2023 were selected from the Netherlands Cancer Registry and categorized as resected, explored (surgical exploration without resection), or non-explored (non-metastatic tumours without exploration or resection). Overall survival data was stratified by systemic therapy use. The cohort included 2014 patients of which 490 patients (24.3 %) underwent resection, 258 patients (12.8 %) underwent surgical exploration without resection, and 1266 patients (62.9 %) were not explored. Overall, 90-day mortality following exploration was 19.5 %. Among explored patients, 38.0 % (98/258) received systemic therapy compared to 10.6 % (134/1266) of non-explored patients (p < 0.001). With systemic therapy, explored patients had a median overall survival (mOS) of 14.3 months (95 % CI 12.7-18.2) from diagnosis compared to 12.8 months (95 % CI 11.6-15.8) for non-explored patients (p = 0.350). With best supportive care, explored patients had a mOS of 8.1 months (95 % CI 6.5-10.3) compared to 3.2 months (95 % CI 2.8-3.7) for non-explored patients (p ≤ 0.001). Among patients with non-metastatic pCCA receiving systemic therapy, survival outcomes are comparable between those who undergo surgical exploration and those who do not. Despite a possible impact on quality of life, these findings suggest that surgical exploration does not hinder access to systemic therapy or negatively affect survival.