Impact and clinical usefulness of genetic data in the surgical management of colorectal cancer liver metastasis: a narrative review

Importance:In patients who undergo surgery for colorectal cancer liver metastases(CRLM),a number of somatic mutations have been associated with worse overall(OS)and recurrence-free survival(RFS).Although useful,an association with prognosis does not necessarily equate to an impact on surgical management.Objective:The aim of this review was to investigate whether the best-studied somatic mutations impact surgical management of CRLM by informing:(I)post-hepatectomy surveillance;(II)selection of surgical technique;(III)selection of optimal margin width;and(IV)selection of patients for surgery.Lastly,we discuss the refinement of genetic data from overall mutation status to specific variants,as well as lesser studied somatic mutations.Evidence Review:We conducted a computerized search using PubMed and Google Scholar for reports published so far,using mesh headings and keywords related to genetic data and CRLM.Findings:Genetic data may impact surgical management of CRLM in three ways.Firstly,KRAS mutations can predict lung recurrences.Secondly,KRAS mutations may help tailor margin width.Thirdly,KRAS mutations may help tailor surgical technique.Conclusions:Although genetic data may impact post-hepatectomy surveillance,selection of surgical technique and optimal margin width,their use to guide surgical selection remains elusive,as the data cannot support denying surgery to patients according to their somatic mutation profile.

Lessons learned from hepatocellular carcinoma may cause a paradigm shift in intraductal papillary mucinous neoplasms:a narrative review and discussion of conceptual similarities in tumor progression and recurrence

Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality ( "field defect" ) in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic "field defect" may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression;thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.