Gallbladder cancer, treatment failure and relapses: the peritoneum in gallbladder cancer.

PURPOSE: This study aims to review gallbladder cancer (GBC) and present current management strategies, factors influencing prognosis, recurrence and areas of consideration.

METHODOLOGY: Literature search in PubMed was made and restricted to articles published from 2002 to 2013 using the following keywords: (GBC + peritoneum and GBC + surgery + metastasis/recurrence); abstract evaluation narrowed results to 53 articles. Twenty-six single-institution reports with 2,097 patients among 36 large-scale retrospective studies were obtained and focused on surgical outcomes.

RESULTS: GBC presents late and recurs early with a poor prognosis. There is no definitive time for curative re-resection following incidental diagnosis. Effective surgical strategies for each disease stage remain unclear. Management guidelines are not universally standardised, most institutions utilise protocols based on individual experiences and limitations. Early-stage GBC is curable with complete resection but invisible metastases at unobvious sites remain problematic. In this study, at least 450 patients relapsed, most had peritoneal metastasis. The peritoneum is a common metastatic site, its microenvironment is intrinsically hypoxic, well vascularized and lined with mesothelium overlaying immune aggregates, which express pro-angiogenic and adhesion molecules that are highly selective for tumour growth and evolution. There are no medical/molecular antagonists to inhibit peritoneal carcinomatosis. Peritonectomies have been successfully undertaken; furthermore, GBC responds to some chemotherapy combinations.

CONCLUSION: This review focused on GBC surgery. Peritoneal carcinomatosis is common. In carefully selected patients, the incorporation of peritoneal disease in cytoreductive surgery and intraperitoneal chemotherapy will inhibit a vehicle for dissemination, eliminate future relapse sites and improve survival. Areas for consideration include universally standardised protocols, clear management guidelines for each stage, effective re-resection timings with guidance on where or how to identify additional disease.