Liver Transplantation for Extended Criteria Hepatocellular Carcinoma Using Stable Response to Locoregional Therapy and Alpha-Fetoprotein as Selection Criteria.

INTRODUCTION: Current practice to only prioritize hepatocellular carcinoma (HCC) that fulfill the Milan criteria (INMC) is changing, since it causes the exclusion of patients who could benefit from liver transplantation. To select patients outside MC (OUTMC) for transplantation, we implemented extended selection criteria without up-front morphometric restrictions containing surrogate parameters of tumor biology. METHODS: OUTMC patients were considered without restrictions of morphometrics and received locoregional treatment after interdisciplinary consultation. Our dynamic selection criteria for OUTMC patients required (INMUC): (1) treatment response over (2) at least 6 months and (3) alpha-fetoprotein ≤400 ng/mL over the entire evaluation period. Patients with INMC tumors served as control and internal validation cohort. RESULTS: 31 of 170 liver transplant candidates were OUTMC. Of these, 8 dropped out. The remaining 23 patients met the selection criteria and underwent transplantation. Recurrence-free survival was higher in patients transplanted INMC compared to those OUTMC INMUC (92.2% vs. 70.8%; p = 0.026) after 5 years of follow-up. Overall survival showed no significant difference (p = 0.552). With dynamic selection of transplant candidates, recurrence could also be predicted for the INMC patients as internal validation cohort (c-index: 0.896; CI 0.588-0.981, p = 0.005). CONCLUSION: Dynamic selection criteria for the stratification of patients with OUTMC HCCs is feasible and allows for excellent long-term results and acceptable tumor recurrence rates comparable to INMC patients.

Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients.

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3⁺ (p = 0.016) and CD8⁺ (p = 0.028) independently predicted better OS and DFS, respectively. CD20⁺ showed a trend towards better DFS (p = 0.076). Scoring of CD3⁺, CD8⁺, and CD20⁺ independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3⁺ cells is an independent predictor of better OS, and CD8⁺ cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients.

Development of novel biological resection criteria for safe and oncologically satisfying resection of hepatocellular carcinoma.

OBJECTIVE: To develop criteria for safe and oncologically satisfying liver resection in case of early hepatocellular carcinoma with a 5-year overall survival (OS) similar to liver transplantation. SUMMARY BACKGROUND DATA: Liver resection (LR) and liver transplantation (LT) are potentially curative treatment options for hepatocellular carcinoma. Generally, LT achieves better OS. Due to organ shortage, however not all patients can receive a LT. METHODS: To decide which patients to resect and which to transplant we have developed biological resection criteria (BRC) as a compound out of mGPS (modified Glascow Prognostic Scale) and the Kings-Score (for HCV cirrhosis). These are based on routine clinical values that reflect both liver function and tumor biology/immunology. RESULTS: 276 patients were analyzed. Patients undergoing LR within BRC (inBRC) had a significantly better overall (73.6% vs. 35.4%, (p < 0.001)) and disease-free survival (54.7% vs. 17.2%, (p < 0.001)) as compared to patients outside the BRC (outBRC). The predictive value of BRC was independent of tumor burden. In a subgroup analysis outBRC patients had significantly worse outcome after major resection. In LT patients BRC had no predictive value. CONCLUSIONS: BRC may be a valuable tool to predict survival after LR for HCC. Patients resected inBRC may achieve comparable survival as LT. LR in outBRC patients are unlikely to be curative. All outBRC patients should be monitored closely for salvage LT.