Expanding indications for liver transplantation in the era of liver transplant oncology.

Despite numerous advances and emerging data, liver transplantation in the setting of gastrointestinal malignancies remains controversial outside of certain accepted indications. In an era of persistent organ shortage and increasing organ demand, allocation of liver grafts must be considered carefully. While hepatocellular carcinoma and hilar cholangiocarcinoma have become accepted indications for transplantation, tumor size and standardized multi-disciplinary treatment protocols are necessary to ensure optimal patient outcomes. As more studies seeking to expand the oncologic indications for liver transplantation are emerging, it is becoming increasingly clear that tumor biology and response to therapy are key factors for optimal oncologic outcomes. In addition, time from diagnosis to transplantation appears to correlate with survival, as stable disease over time portends better outcomes post-operatively. Identifying aggressive disease pre-transplant remains difficult with current imaging and tissue sampling techniques. While tumor size and stage are important prognostic predictors for most malignancies, patient and tumor selection protocols are necessary. As the fields of medical and surgical oncology continue to evolve, it is clear that a protocolized interdisciplinary treatment approach is necessary for combatting any cancer effectively. Disease stability over time and response to neoadjuvant therapy may be the best predictors for successful patient outcomes and can be easily incorporated in our treatment paradigms. Current data evaluating liver transplantation for expanded oncologic indications such as: expanded criteria hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed tumors, and liver limited metastatic colorectal carcinomas, incorporate multi-modal therapies and evaluation of tumor treatment response. While further investigation is necessary, initial results suggest there is an expanded role for transplant surgery in malignancy in a new era of liver transplant oncology.

Hepatocellular carcinoma: a review of diagnostic challenges for the pathologist.

Histopathologists retain a critical role in the diagnosis and management of hepatocellular carcinoma (HCC). HCC arises usually but not exclusively in a background of advanced-stage chronic liver disease. The histological diagnosis of HCC poses many challenges particularly when dealing with liver biopsy specimens due to the heterogeneity of HCC and the difficulty to confirm hepatocellular differentiation in some instances. Primary liver tumors should be considered as a continuum with typical hepatocellular and cholangiocarcinoma at the two ends and a whole range of tumors showing both hepatocellular and cholangiocellular differentiation with or without an associated progenitor/stem cell component in the middle. Characterization of combined (or mixed) hepatocellular-cholangiocarcinoma can be very challenging. In advanced-stage chronic liver disease, the main challenge for the histopathologist is still to differentiate between HCC and its precursors, although this is rarely critical in the clinical setting at present. HCC originating in non-cirrhotic livers needs to be differentiated from other primary and extrahepatic tumors and from hepatocellular adenoma, bearing in mind that progression to malignancy is more through a continuum that watertight histological categories.