Pattern and management of recurrent hepatocellular carcinoma after liver transplantation

Abstract

A series of 132 patients who underwent liver transplantation for primary liver cancer was collected from three different Italian hospitals and studied for recurrence of hepatocellular carcinoma after liver replacement. Twenty-one patients (15.9%) had a neoplastic recurrence after an average follow-up period of 7.8 months after transplantation (range, 1-25 months); 15 (71%) occurred within the first 18 months after transplant and only two recurred later than 2 years. The sites of recurrence were grafted liver (19%), lung (19%), bone (14%), and other (5%). Eight patients (38%) had multiple organ involvement at the onset. After 1, 2, 3, and 4 years the overall survival rates were 62%, 43%, 29%, and 23%, respectively. The tumor factors related to early cancer recurrence after transplantation were diameter of nodules more than 3 cm (P < 0.05), tumor stage not meeting the "Milan criteria" (P < 0.03), and presence of peri-tumoral capsule (P < 0.05); the number of nodules, TNM stage, presence of vascular invasion, alpha-fetoprotein level more than 150 UI/l, pre-transplant chemoembolization and resectability of cancer deposits did not seem to be related to early recurrence. The prognosis differed in the 7 patients with resectable recurrences (57% 4-year survival) and the 14 patients with unresectable disease (14% 4-year survival) (P < 0.02). Better patient selection and new combined medical strategies could reduce the incidence of and mortality from liver cancer recurrence after transplantation. The role of surgical resection of recurrence should be further investigated.

Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: Clinical patterns and outcome variables

“…Many of them may, nevertheless, benefit from LT by achieving long-term survival (7-11). Our outcome results in patients with advanced HCC are even better than results of other well-experienced transplant centers (2,(15)(16)(17). About 30% of our overall study population would have been excluded from curative LT, if Milan criteria were used strictly for decision making about patient drop-out from the transplant list.…”

“…Several transplant groups have demonstrated that, apart from number and size of tumor nodules, parameters of tumor biology, such as differentiation and microvascular tumor invasion (MVI) play an important role for predicting patient prognosis, and should be, therefore, incorporated in the pretransplant selection process (4,8,9,10,11). However, since expanding the selection criteria may increase the risk of tumor relapse, its justification will very much depend on outcome of posttransplant HCC recurrence (13)(14)(15)(16)(17)(18)(19) …”

Milan criteria in liver transplantation for hepatocellular carcinoma: An evidence-based analysis of 15 years of experience

“…In this respect, the MC remain the benchmark for any other prognostic criteria proposed for expanding the use of LT in patients with cirrhosis and HCC. 24,40,80 or >1000 ng/mL 12,18,51 Up-to-7 criteria met 21,26 Tumor size >3 cm, 36 12,30,33 Total tumor volume >28 cm 3 35 or >115 cm 3 24 Total tumor diameter >8 cm 12,42 Bilobar nodules 66 Multiple nodules 52,71,76 Nodule number >3 25,26 and 13 level 2b studies 27,30,33,34,36,39,40,42,47,48,[51][52][53] have confirmed the likelihood of detecting mVI, grade 3 tumors, and microsatellites as the tumor size and number increase beyond the MC. In patients with HCCs meeting the MC, mVI is detected at a rate of 10% to 15%, poorly differentiated tumors are detected at a rate of 13% to 33%, and microsatellites are detected at a rate of 7% to 28%.…”

Role of Surveillance in Prevention of Hepatocellular Carcinoma

“…[45][46][47][48] If explant pathology is within the currently accepted criteria for transplantation then rate of recurrence is low (8%) but on the other hand If pathology is outside of the criteria then chance of recurrence is as high as 50%. 45 In two of above mentioned studies majority of patients had recurrence within 12 and 18 months respectively.…”

“…In a study conducted by regalia et al HCC recurrence was detected in 71% patients within 18 months after orthotopic liver transplantation. 47 A Japanese study has suggested that frequent measurement of AFP and des-g-carboxy-prothrombin was useful for detecting recurrent HCC. This may be useful for long-term follow-up markers for post-transplant surveillance.…”