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. 1998 Oct;228(4):479–490. doi: 10.1097/00000658-199810000-00005

Liver transplantation for hepatocellular carcinoma: a registry report of the impact of tumor characteristics on outcome.

G B Klintmalm 1
PMCID: PMC1191521  PMID: 9790338

Abstract

OBJECTIVE: The objective of this study from the International Registry of Hepatic Tumors in Liver Transplantation is to analyze the impact of tumor characteristics on tumor recurrence and patient survival. SUMMARY BACKGROUND DATA: Many attempts have been made to identify patients with hepatocellular carcinoma who can be treated successfully with liver transplantation. Studies presented to date lack enough patients to make reported findings universally accepted. In lieu of a prospective, randomized multicenter trial, in 1992 an International Registry of Hepatic Tumors in Liver Transplantation was established to collect data on these patients, their tumors, and their treatment. METHODS: The registry mails out new patient registration forms and patient follow-up forms twice yearly to all known liver transplant programs. Fifty-three programs in 21 countries have supplied information on 553 patients with tumors. Four hundred ten patients had hepatocellular carcinoma (HCC), and 12 had the fibrolamellar variant of HCC (FLL-HCC). These 422 patients were investigated for this study. One hundred sixty-nine of these (40.0%) were classified as "incidental tumors." For the remaining patients, the tumor was known before the transplant. Twenty-six and eight tenths percent of the patients had a history of hepatitis B and 32.7% had a history of hepatitis C. RESULTS: One hundred ninety patients (46.7%) have died, 99 free of tumor and 91 with tumor. Death was tumor related in 90 patients. Of the 232 patients now living, 215 are free of tumor and 17 have tumor. The most common sites for recurrence are the transplanted liver (41.7%) and the lungs (28.7%). The overall patient survival was 72.2% at 1 year, 63.4% at 2 years, 47.4% at 4 years, and 44.4% at 5 years. Using univariate analysis, incidental tumors (p = 0.3107), FLL-HCC (p = 0.0704), multifocal tumor (p = 0.5464), and bilobar tumor (p = 0.1024) were not found to have an influence on patient survival. Four factors, tumor size greater than 5 cm (p = 0.0221), vascular invasion (p = 0.0005), positive nodes (p = 0.0014), and histologic grade (p = 0.0001) had a profound impact on patient survival. Using Cox multiple regression analysis, only histologic grade had a negative impact on overall patient survival (p = 0.0009) and for patients with known tumors (p = 0.0003). For incidental tumors, patient survival was negatively influenced by multifocality (p = 0.0021) and an age older than 60 years (p = 0.0008). Tumor histologic grade (p = 0.0134) and size (>5 cm) (p = 0.0133) were significantly linked to recurrence-free patient survival. CONCLUSIONS: This analysis has documented three tumor characteristics that strongly impact patient survival after transplantation for HCC. In addition to tumor size greater than 5 cm and the presence of vascular invasion (which confirm several, single-center studies), this registry notes that a poorly differentiated HCC may be a contraindication for transplantation. A liver tumor's histologic grade may be important information to have when these patients are considered for liver transplantation.

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Selected References

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  1. Bismuth H., Morino M., Sherlock D., Castaing D., Miglietta C., Cauquil P., Roche A. Primary treatment of hepatocellular carcinoma by arterial chemoembolization. Am J Surg. 1992 Apr;163(4):387–394. doi: 10.1016/0002-9610(92)90039-t. [DOI] [PubMed] [Google Scholar]
  2. Colella G., Rondinara G. F., De Carlis L., Sansalone C. V., Slim A. O., Aseni P., Rossetti O., De Gasperi A., Minola E., Bottelli R. Liver transplantation for hepatocellular carcinoma: prognostic factors associated long-term survival. Transpl Int. 1996;9 (Suppl 1):S109–S111. doi: 10.1007/978-3-662-00818-8_28. [DOI] [PubMed] [Google Scholar]
  3. Crafa F., Gugenheim J., Ruggiero A., Pepe S., Mouiel J. DNA flow cytometry in patients undergoing liver transplantation for hepatocellular carcinoma. Transpl Int. 1996;9 (Suppl 1):S112–S114. doi: 10.1007/978-3-662-00818-8_29. [DOI] [PubMed] [Google Scholar]
  4. Farmer D. G., Rosove M. H., Shaked A., Busuttil R. W. Current treatment modalities for hepatocellular carcinoma. Ann Surg. 1994 Mar;219(3):236–247. doi: 10.1097/00000658-199403000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Figueras J., Jaurrieta E., Valls C., Benasco C., Rafecas A., Xiol X., Fabregat J., Casanovas T., Torras J., Baliellas C. Survival after liver transplantation in cirrhotic patients with and without hepatocellular carcinoma: a comparative study. Hepatology. 1997 Jun;25(6):1485–1489. doi: 10.1002/hep.510250629. [DOI] [PubMed] [Google Scholar]
  6. Hart J., Busuttil R. W., Lewin K. J. Disease recurrence following liver transplantation. Am J Surg Pathol. 1990;14 (Suppl 1):79–91. [PubMed] [Google Scholar]
  7. Iwatsuki S., Gordon R. D., Shaw B. W., Jr, Starzl T. E. Role of liver transplantation in cancer therapy. Ann Surg. 1985 Oct;202(4):401–407. doi: 10.1097/00000658-198510000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kar S., Carr B. I. Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma. Hepatology. 1995 Feb;21(2):403–407. [PubMed] [Google Scholar]
  9. Ko S., Nakajima Y., Kanehiro H., Aomatsu Y., Yoshimura A., Taki J., Kin T., Yagura K., Oyama T., Yagi M. Liver transplantation for hepatocellular carcinoma: consideration from the findings on autopsy. Transplant Proc. 1996 Jun;28(3):1691–1692. [PubMed] [Google Scholar]
  10. Lemoine A., Le Bricon T., Salvucci M., Azoulay D., Pham P., Raccuia J., Bismuth H., Debuire B. Prospective evaluation of circulating hepatocytes by alpha-fetoprotein mRNA in humans during liver surgery. Ann Surg. 1997 Jul;226(1):43–50. doi: 10.1097/00000658-199707000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Majno P. E., Adam R., Bismuth H., Castaing D., Ariche A., Krissat J., Perrin H., Azoulay D. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg. 1997 Dec;226(6):688–703. doi: 10.1097/00000658-199712000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Marsh J. W., Dvorchik I., Subotin M., Balan V., Rakela J., Popechitelev E. P., Subbotin V., Casavilla A., Carr B. I., Fung J. J. The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: a pilot study. Hepatology. 1997 Aug;26(2):444–450. doi: 10.1002/hep.510260227. [DOI] [PubMed] [Google Scholar]
  13. Michel J., Suc B., Montpeyroux F., Hachemanne S., Blanc P., Domergue J., Mouiel J., Gouillat C., Ducerf C., Saric J. Liver resection or transplantation for hepatocellular carcinoma? Retrospective analysis of 215 patients with cirrhosis. J Hepatol. 1997 Jun;26(6):1274–1280. doi: 10.1016/s0168-8278(97)80462-x. [DOI] [PubMed] [Google Scholar]
  14. O'Grady J. G., Polson R. J., Rolles K., Calne R. Y., Williams R. Liver transplantation for malignant disease. Results in 93 consecutive patients. Ann Surg. 1988 Apr;207(4):373–379. doi: 10.1097/00000658-198804000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ojogho O. N., So S. K., Keeffe E. B., Berquist W., Concepcion W., Garcia-Kennedy R., Imperial J., Esquivel C. O. Orthotopic liver transplantation for hepatocellular carcinoma. Factors affecting long-term patient survival. Arch Surg. 1996 Sep;131(9):935–941. doi: 10.1001/archsurg.1996.01430210033007. [DOI] [PubMed] [Google Scholar]
  16. Olthoff K. M., Millis J. M., Rosove M. H., Goldstein L. I., Ramming K. P., Busuttil R. W. Is liver transplantation justified for the treatment of hepatic malignancies? Arch Surg. 1990 Oct;125(10):1261–1268. doi: 10.1001/archsurg.1990.01410220045007. [DOI] [PubMed] [Google Scholar]
  17. Olthoff K. M., Rosove M. H., Shackleton C. R., Imagawa D. K., Farmer D. G., Northcross P., Pakrasi A. L., Martin P., Goldstein L. I., Shaked A. Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma. Ann Surg. 1995 Jun;221(6):734–743. doi: 10.1097/00000658-199506000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Penn I. Hepatic transplantation for primary and metastatic cancers of the liver. Surgery. 1991 Oct;110(4):726–735. [PubMed] [Google Scholar]
  19. Pichlmayr R. Is there a place for liver grafting for malignancy? Transplant Proc. 1988 Feb;20(1 Suppl 1):478–482. [PubMed] [Google Scholar]
  20. Pinna A. D., Iwatsuki S., Lee R. G., Todo S., Madariaga J. R., Marsh J. W., Casavilla A., Dvorchik I., Fung J. J., Starzl T. E. Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation. Hepatology. 1997 Oct;26(4):877–883. doi: 10.1002/hep.510260412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ravikumar T. S., Steele G. D., Jr Hepatic cryosurgery. Surg Clin North Am. 1989 Apr;69(2):433–440. doi: 10.1016/s0039-6109(16)44798-5. [DOI] [PubMed] [Google Scholar]
  22. Ringe B., Wittekind C., Bechstein W. O., Bunzendahl H., Pichlmayr R. The role of liver transplantation in hepatobiliary malignancy. A retrospective analysis of 95 patients with particular regard to tumor stage and recurrence. Ann Surg. 1989 Jan;209(1):88–98. doi: 10.1097/00000658-198901000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schwartz M. E., Sung M., Mor E., Fisher A., Popescu I., Fiel I., Sheiner P., Emre S., Guy S., Miller C. M. A multidisciplinary approach to hepatocellular carcinoma in patients with cirrhosis. J Am Coll Surg. 1995 May;180(5):596–603. [PubMed] [Google Scholar]
  24. Spreafico C., Marchianò A., Regalia E., Frigerio L. F., Garbagnati F., Andreola S., Milella M., Lanocita R., Mazzaferro V. Chemoembolization of hepatocellular carcinoma in patients who undergo liver transplantation. Radiology. 1994 Sep;192(3):687–690. doi: 10.1148/radiology.192.3.8058934. [DOI] [PubMed] [Google Scholar]
  25. Stone M. J., Klintmalm G. B., Polter D., Husberg B. S., Mennel R. G., Ramsay M. A., Flemens E. R., Goldstein R. M. Neoadjuvant chemotherapy and liver transplantation for hepatocellular carcinoma: a pilot study in 20 patients. Gastroenterology. 1993 Jan;104(1):196–202. doi: 10.1016/0016-5085(93)90852-4. [DOI] [PubMed] [Google Scholar]
  26. Venook A. P., Ferrell L. D., Roberts J. P., Emond J., Frye J. W., Ring E., Ascher N. L., Lake J. R. Liver transplantation for hepatocellular carcinoma: results with preoperative chemoembolization. Liver Transpl Surg. 1995 Jul;1(4):242–248. doi: 10.1002/lt.500010409. [DOI] [PubMed] [Google Scholar]
  27. Wong P. Y., McPeake J. R., Portmann B., Tan K. C., Naoumov N. V., Williams R. Clinical course and survival after liver transplantation for hepatitis B virus infection complicated by hepatocellular carcinoma. Am J Gastroenterol. 1995 Jan;90(1):29–34. [PubMed] [Google Scholar]
  28. Yamanaka N., Okamoto E., Fujihara S., Kato T., Fujimoto J., Oriyama T., Mitsunobu M., Toyosaka A., Uematsu K., Yamamoto K. Do the tumor cells of hepatocellular carcinomas dislodge into the portal venous stream during hepatic resection? Cancer. 1992 Nov 1;70(9):2263–2267. doi: 10.1002/1097-0142(19921101)70:9<2263::aid-cncr2820700909>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]

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