Predictors of long-term outcome following liver transplantation for hepatocellular carcinoma: a single-center experience

Abstract

Summary Orthotopic liver transplantation (OLT) is increasingly being applied for cure in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC). In recipients with limited tumor burden, OLT achieves reasonable long‐term outcome. This study sought to identify clinical and pathologic variables predictive of long‐term disease‐free survival and the presence of vascular invasion. From 1992 to 2006, 130 patients underwent OLT for cirrhosis and HCC. Malignancy was diagnosed in 107 patients prior to OLT and in 23 patients on pathologic examination of the explant. Nine clinical and pathologic variables were considered including: TNM stage, nodularity, vascular invasion, Milan criteria, incidental lesion, differentiation, tumor size, preOLT transarterial chemoembolization (TACE), and administration of sirolimus‐based immunosuppression. The overall incidence of HCC recurrence was 17% with the majority (82%) being stage III. Cumulatively, tumor recurrence‐free survival (RFS) is 84, 74, and 67% at 1, 3, and 5 years respectively. Independent predictors of RFS included stage III and poorly differentiated lesions (P < 0.05). Furthermore, stage III tumors and those >3.5 cm in size were predictive of vascular invasion. Importantly, preOLT, TACE and postOLT sirolimus had no influence on survival. Pathologic variables including tumor stage and grade have a significant impact on outcome. Importantly, it seems that TACE and sirolimus had no beneficial effect.

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

“…The meta-analysis included 19 studies 2,15,16,19,26,33,35,39,40,42,46,48,[53][54][55]57,63,67,84 that used different methodologies to compare the overall survival of patients meeting the MC and patients exceeding the criteria at the time of the explant pathology examination; 3949 patients were also stratified by the graft origin (deceased or living donors).…”

“…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%.…”

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

“…Factors associated with tumor recurrence include tumor burden and vascular invasion. 4,5,7,9,[11][12][13][14][15][16][17] Recurrence tends to occur in 6.4% to 21.2% of patients 8,9,11,12 ( Table 1). The 5-year patient survival rate after HCC recurrence is only 22%.…”

Standards und neue Aspekte der Diagnostik und Therapie des hepatozellulären Karzinoms

“…Nachfolgend wurden viele prognostische Faktoren für das HCC-Rezidiv nach LTX beschrieben: TNM-Stadium/Tumorgröße [37,67,93,108], vaskuläre Invasion [36,44,83,114,120], schlechte Differenzierung [23,44,114], AFP-Spiegel vor LTX von > 200-1 000 ng/ml [29,83] und Tumorgenetik [26]. Die Anzahl und die Größe der Tumorherde sagen bis heute die Rezidivwahrscheinlichkeit am besten vorher.…”

“…Allerdings sind diese Daten nicht unumstritten, da die Patienten, die für eine TACE in Frage kamen, häufig eine bessere Leberfunktion und weniger fortgeschrittene Erkrankung hatten. Dementsprechend zeigte eine Studie unter Berück-sichtigung der zugrundeliegenden Lebererkrankung und Tumorlast keinen signifikanten Überlebensvorteil für eine TACE vor LTX [120]. Auch die Tumorrezidivrate war in der Gruppe, die vor LTX eine TACE erhalten hatte, nicht signifikant niedriger [83].…”