Liver Transplantation Beyond Milan Criteria

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, being the fifth most common cancer and the third most common cause of cancer-related mortality. The incidence of HCC has been rising in the USA over the last 20 years. Liver transplantation is an optimal treatment option, as it eliminates HCC as well as the underlying liver disease. The Milan criteria (1 lesion greater than or equal to 2 cm and less than or equal to 5 cm, or up to 3 lesions, each greater than or equal to 1 cm and less than or equal to 3 cm) have been adopted by many transplant societies worldwide as the criteria to determine whether patients with HCC can move forward with liver transplantation. However, many believe that the Milan criteria may be too strict in regard to its size requirements for lesions. This has led to a number of expanded criteria for liver transplantation, concerning both overall size and number of lesions, as well as incorporation of other markers of tumor biology. Tumor markers, such as alphafetoprotein, can also be used to follow treatment of HCC and possibly exclude patients from transplant. HCC presenting beyond Milan criteria can also be down-staged with locoregional therapy. Monitoring response to locoregional therapy and longer wait times after locoregional therapy prior to transplant can serve as surrogate markers of tumor biology as well.

Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: case report and review of literature

“…And in contrast to deceased donor LT, recipient selection for LDLT is not limited by organ allocation systems. Subsequently, many centers have developed expanded center-specific criteria with acceptable results, including the University of California San Francisco criteria, Extended Toronto criteria, Kyoto criteria, and others [18][19][20][21][22][23][24].…”

Optimizing the management of intermediate-stage hepatocellular carcinoma: Current trends and prospects

“…The advancement of surgical techniques made it possible for liver transplantation beyond the Milan criteria. Five-year survival rates within the Asan criteria (nodule ≤5 cm, number of nodules ≤6), University of California San Francisco criteria (single nodule ≤6.5 cm, or 3 nodules ≤4.5 cm with total tumor diameter ≤8 cm), up-to-7 criteria (the sum of maximum tumor diameter and number <7) were 70.9% [ 13 , 14 ], 80.9% [ 15 ], and 71.2% [ 13 ], respectively. These findings imply that liver transplantation is a treatment option for selected patients with BCLC stage B HCC.…”

Locoregional Therapies for Bridging and Downstaging Hepatocellular Carcinoma Prior to Liver Transplant

“…In the initial study of over 1,500 patients, 5-year survival rates in patients that met Up-to-Seven criteria were similar (71.2%) to those that met the Milan criteria (73.3%) (7). This lead to the creation of the "Metro Ticket Calculator", which provides 3-and 5-year overall survival probabilities based on characteristics of HCC lesions (8). In 2016, the Toronto criteria was proposed, which do not include size or tumor number restrictions, but based candidacy on absence of extrahepatic disease, venous thrombi, cancer-related symptoms, and high-risk features on biopsy.…”

“…The options for locoregional therapies in downstaging are discussed in detail below. The decision on optimal locoregional therapy is contingent on multiple factors, but the Barcelona Clinic Liver Cancer (BCLC) staging system is often used to help make this decision (8). BCLC staging factors tumor burden, liver function and patient performance status to stratify patients by risk.…”