ELSEVIER Is Hepatocellular Carcinoma in Cirrhosis an Actual Indication for Liver Transplantation? G. Colella, L. De Carlis, G.F. Rondinara, C.V. Sansalone, L.S. Belli, P. Aseni, A.O. Slim, F. Gelosa, G.M. lamoni, A. Cot-h, E. Mazza, K. Arcieri, A. Giacomoni, E. Minola, G. Ideo, and D. Fot-ti zyxwvutsrqponmlkjihg P RIMARY hepatocellular carcinoma (HCC) remains one of the most common tumors in the world and is becoming an increasingly clinical problem in the manage- ment of cirrhotic patients also in Europe.‘,2 In recent years with the advent of modern imaging techniques and of early diagnostic programs for patients at risk we are able to define more accurately the extension of HCC and to select patients for treatment. Several options including alcohol- ization, trans-arterial chemoembolization, resective sur- gery, and liver transplantation (OLT) are available in the treatment of HCC. A complete surgical excision is generally considered the treatment of choice if extrahepatic tumor spread is excluded.‘-” Resective surgery has limitations imposed on the degree of resecability due to the reduced hepatic functional reserve and the decreased hepatic regen- erative ability in patients with HCC in cirrhosis. OLT offers the advantage to remove the entire liver allowing to cure theoretically both advanced cirrhosis and HCC in accor- dance to the principles of surgical oncology with total removal of primary disease and resection of lymph nodes and vascular structures. According to a limited supply of donor organs, OLT has been considered a controversial indication for HCC because of high rates of perioperative mortality and tumor recurrence reported in early results’-9 but up to now a consistent number of OLT has been performed for HCC in cirrhosis. Recently, a critical review of previous experience demonstrates a significant relation- ship between tumor stage and patient survival after OLT for HCC in cirrhosis.33”“7 Furthermore, hepatic resection appears to have a poor long-term survival while OLT has recently improved outcome.33’“-‘7 We report a retrospec- tive analysis on 71 patients with HCC who were trans- planted between 1985 and 1996 to define indication to OLT. Several variables were investigated and related to post-OLT tumor-related survival to evaluate the prognostic factors implicated on tumor recurrence and to define selection and management of patients undergoing OLT for HCC. PATIENTS AND METHODS Between December 1985 and June 1996 316 OLT were performed in 287 patients at the Department of General Surgery and Abdom- inal Organ Transplantation, Niguarda Hospital, Milan, Italy. 0041-1315/97/$17.00 PII SOO41-1345(96)00221-7 492 Among them 71 patients (61 male 10 female, median age 51 years, range 22 to 61) had an HCC at time of OLT. In 18 patients HCC was an incidental finding, HCC was discovered in a cirrhotic liver after OLT for end stage liver disease. No tumor were fibrolamellar. Two patients out of 71 were not cirrhotic. No patients had extrahepatic tumor spread at time of OLT except one patient who had lymph nodes tumor invasion in the hepatic hilum at patholog- ical examination after total hepatectomy. According to Child-Pugh classification 15 patients were Child A, 31 Child B e 23 Child C. HBsAg was positive in the serum of 22 patients and in 10 patients was associated to Delta virus infection. Thirty-three patients had HCVAb and HCVRNA positive serology. Ethiology of cirrhosis was viral in 41 patients (58%) alcoholic in 11 patients (1.5%) mixed in 9 patients (13%) and criptogenic in 10 patients (14%). In 4.5 patients HCC was monofocal and in 26 patients multifocal. The median diameter of HCC was 2,5 cm (range 0,5-16 cm). HCC was monolobar in 55 patients (77%) and bilobar in 16 patients (23%). A peritumoral not invaded capsule was demonstrated in 16 patients out of 61 patients evaluable (26%) vascular tumor invasion was discovered in 15 patients (20%): in 12 patients there was a microscopic neoplastic vascular invasion, in 3 patients there was tumor invasion of segmental portal branches. According to pTNM classification (18) 21 patients were stage I, 21 patients stage II, 15 patients stage III and 14 patients stage IVa. PreOLT trans-arterial chemoembolization (TAB) was performed in 26 patients. In 7 out of 29 patients treated with TAE a complete necrosis of HCC was documented by histology of total hepatectomy specimen. All patients underwent primary quadruple immunosuppression ther- apy with steroids, anti-thymocyte globulin, cyclosporine (CyA) and azathioprine. Monotherapy with CyA was utilized for chronic immunosuppression in absence of clinical contraindication or rejection episodes. Perioperative mortality rate within 3 months was 25% (18 patients). Actuarial survival curves were calculated in the remaining 53 patients (median follow up 57 months range 4-109) as cumulative survival rates by Kaplan-Meier method and analyzed by Log Rank and Mantel-Haenszel Tests, P 5 .05 was considered to be significant. Survival curves were compared for sex, age (150, >50 yr), tumor location (mono-bilateral), diameter (s-3, From the Department of Surgery and Abdominal Organ Trans- plantation (G.C., L.D.C., G.F.R., C.V.S., P.A., A.O.S., K.A., A.G., D.F.), Department of Medicine and Hepatology (L.S.B., F.G., G.M.I., G.I.), Department of Pathology (E.M.); and Department of Anestesiology and Abdominal Organ Transplantation (A.C., E.M.), Niguarda Hospital, Milan Italy. Address reprint requests to Dott. Giovanni Colella, Pizzamiglio II; Ospedale Niguarda, 20162 Milano, Italy. 0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 29, 492-494 (1997)