Advances in Molecular Pathology and Treatment of Periampullary Cancers.
OBJECTIVE
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.
From the *NHMRC Clinical Trials Centre; †Department of Surgery, The Prince Charles Hospital, Brisbane; ‡Department of Surgery, Flinders Medical Centre; §Queen Elizabeth Hospital, Adelaide; ∥University of Adelaide, South Australia; ¶School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne; #Cancer Care Centre, Department of Medical Oncology, St George Hospital; **Department of Surgery, Bankstown Hospital; and ††Division of Surgery, University of Western Sydney, Sydney, Australia.
Manju D
MD
Chandrasegaram
John W
JW
Chen
Timothy J
TJ
Price
John
J
Zalcberg
Katrin
K
Sjoquist
Neil D
ND
Merrett
D014670:Ampulla of Vater / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003138:Common Bile Duct Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004379:Duodenal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor