Advances in molecular pathology and treatment of periampullary cancers

Objectives: Periampullary cancers (PACs) include the following 4 traditional anatomic subtypes: pancreatic, ampullary, biliary, or duodenal cancers. This review was performed to highlight recent advances in the genomic and molecular understanding of each PAC subtype and the advances in chemotherapeutic and molecular trials in these cancer subtypes. Results: Recent advances have highlighted differences in the genomic and molecular features within each PAC subtype. Ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. K-ras mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42%-52%), biliary (22%-23%), and duodenal cancers (32%-35%), suggesting crucial differences in targetable mutations in these cancer subtypes. Ampullary cancers of intestinal subtype and duodenal cancers seem to share similarities with colorectal cancer, given that they respond to similar chemotherapeutic regimens. This has potential implications for clinical trials and treatment selection, where PACs are often considered together. Conclusions: Future trials should be designed in view of our increased understanding of the different anatomic and histomolecularly profiled subtypes of PAC cancers, which respects their individual molecular characteristics, phenotype, and response to treatment.