Gallbladder Cancer, Treatment Failure and Relapses: the Peritoneum in Gallbladder Cancer

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

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.

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.

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.