Long-Term Results With Multimodal Adjuvant Therapy and Liver Transplantation for the Treatment of Hepatocellular Carcinomas Larger Than 5 Centimeters

Abstract

ObjectiveTo determine the long-term results of liver transplantation for hepatocellular carcinoma (HCC) measuring 5 cm or larger treated in a multimodality adjuvant protocol. Summary Background DataTransplant has been established as a viable treatment of HCC measuring less than 5 cm, but the results for larger tumors have been disappointing. Several studies have shown promising preliminary results when combining transplant with preoperative transarterial chemoembolization and/or perioperative systemic chemotherapy in the treatment of advanced HCC that is not amenable to resection. However, follow-up in the studies has been limited and the number of patients has been small. MethodsBeginning in October 1991, all patients with unresectable HCC measuring 5 cm or larger, as measured by computed tomography, were considered for enrollment in the authors' multimodality protocol. Entry criteria required that all patients be free of extrahepatic disease based on computed tomography scans of the chest and abdomen and bone scan and have a patent main portal vein and major hepatic veins on duplex ultrasonography. Patients received subselective arterial chemoembolization with mitomycin C, doxorubicin, and cisplatin at the time of diagnosis, repeated as necessary based on tumor response. Patients received a single systemic intraoperative dose of doxorubicin (10 mg/m 2 ) before revascularization of the new liver and systemic doxorubicin (50 mg/m 2 ) every 3 weeks as tolerated, for a total of six cycles, beginning on the sixth postoperative week. ResultsEighty patients were enrolled; 37 were eventually excluded, due mainly to disease progression while on the waiting list, and 43 underwent liver transplant. Mean pathologic tumor diameter was 5.8 Ϯ 2.7 cm. Median follow-up of surviving transplanted patients was 55.1 Ϯ 24.9 months. There were two (4.7%) perioperative deaths. Median overall survival was significantly longer in transplanted patients (49.9 Ϯ 10.42 months) than in those who were excluded (6.83 Ϯ 1.34 months). Overall and recurrence-free survival rates in transplanted patients at 5 years were 44% and 48%, respectively. A tumor size larger than 7 cm and the presence of vascular invasion correlated significantly with recurrence. Recurrencefree survival at 5 years was significantly higher for the 32 patients with tumors measuring 5 to 7 cm (55%) than the 12 patients with tumors larger than 7 cm (34%). ConclusionsA significant proportion of patients with HCC measuring 5 cm or larger can achieve long-term survival after liver transplantation in the context of multimodal adjuvant therapy. Patients with tumors measuring 5 to 7 cm have significantly longer recurrence-free survival compared with those with larger tumors.

IL-12 Gene Therapy Is an Effective Therapeutic Strategy for Hepatocellular Carcinoma in Immunosuppressed Mice

“…However, it is a serious problem that immunosuppressants increase the incidence of skin cancer and sarcoma and induce cancer progression causing incremental fatality of transplant recipients (1-3), because malignant tumors in transplant recipients are frequently more aggressive than similar malignancy in the general population (4). In the field of liver transplantation, it has been accepted that liver transplantation is an effective treatment for small, unresectable hepatocellular carcinoma (HCC) 3 in patients with cirrhosis (5) and it was recently reported that a significant proportion of patients with HCC measuring 5 cm or larger can achieve long-term survival after liver transplantation in the context of multimodal adjuvant therapy (6). Therefore, as the indications for liver transplantation have gradually included the advanced HCC, such liver transplant patients have been especially exposed to the greater risk of HCC recurrence in addition to the incidental risk of other types of malignancy, such as skin cancer (7).…”

Toward optimizing the indications for orthotopic liver transplantation in hepatocellular carcinoma

“…Even if a particular patient in this subgroup might benefit from liver transplantation, the overall 5-year survival rate of 50% for the entire subgroup is not acceptable in the current era of donor organ shortages. 34,35 Several groups have proposed extensions of the Milan criteria for liver transplantation, but most studies that are cited in support of these proposals have been retrospective and have been based on analyses of explanted livers (ie, information not available before surgery). 24,[35][36][37][38][39] Recently, Mazzaferro et al 25 made an interesting contribution to this controversy in their retrospective review of pathology after liver transplantation for HCC in 1556 patients; 1112 of these patients had tumors that did not fulfill the Milan criteria.…”

“…34,35 Several groups have proposed extensions of the Milan criteria for liver transplantation, but most studies that are cited in support of these proposals have been retrospective and have been based on analyses of explanted livers (ie, information not available before surgery). 24,[35][36][37][38][39] Recently, Mazzaferro et al 25 made an interesting contribution to this controversy in their retrospective review of pathology after liver transplantation for HCC in 1556 patients; 1112 of these patients had tumors that did not fulfill the Milan criteria. In a subgroup of 283 patients not meeting the Milan criteria whose tumors were within the up-to-7 criteria (ie, HCCs with a maximum score of 7, with the score being the sum of the size of the largest tumor and the total number of tumors) and were not characterized by microvascular invasion, the overall 5-year survival rate was 71.2%.…”

Inappropriate inferences from registry data: Pitfalls of inaccurate data handling?

“…Even the best preoperative imaging techniques can underestimate tumor burden in as many as 20% and significant progression in tumor size and number between imaging and LT after waiting period is not uncommon [9,10]. Additionally 10% to 15% nodules suspected to harbor HCC on pre-transplant imaging are reported benign following microscopic scrutiny of resection specimens by histopathologists [11].…”