O rthotopic liver transplantation (OLT) is the ideal treatment for hepatocellular carcinoma (HCC) emerging in liver cirrhosis since both the tumor and the underlying cirrhosis can be cured. 1 According to Mazzaferro et al., 2 OLT should be restricted to patients with single HCC lower than 5 cm or with no more than 3 nodules, each smaller than 3 cm, in order to achieve an acceptable rate of tumor recurrence. Several studies confirmed a 5-year survival of 57 to 74% if these selection criteria are taken into account. 3 -8 However, progressive tumor enlargement, occurrence of new nodules or of vascular invasion may take place precluding transplantation in HCC patients awaiting for OLT. Adjuvant treatments such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) have been used to prevent tumor progression in HCC patients listed for OLT, but a clear confirmation of their usefulness is still lacking. 1 The efficacy evaluation of percutaneous ablation techniques is usually made using imaging techniques such as multiphasic computed tomography (CT) and magnetic resonance imaging, assessing the presence of residual arterial vascularization within the nodule. Based upon imaging techniques, the rate of short-term complete necrosis of small HCCs lower than 3 cm has been shown to be 70 to 80% after PEI 9,10 and 90 to 93% after RFA. 10,11 The model of the explanted liver provides an unique opportunity to validate the ablation techniques allowing to evaluate their efficacy result from a pathological point of view. However, there are
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.
A specific split liver transplantation (SLT) program has been pursued in the North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449 liver transplants were performed in 7 transplant centers, using 1,304 cadaveric donors. Whole liver transplantation (WLT) and SLT were performed in 1,126 and 323 cases, respectively. SLTs were performed in situ as 147 left lateral segments (LLS), 154 right trisegment liver (RTL) grafts, and 22 modified split livers (MSL), used for couples of adult recipients. After a median posttransplant follow-up of 22 months, SLTs achieved a 3-yr patient and graft survival not significantly different from the entire series of transplants (79.4 and 72.2% vs. 80.6 and 74.9%, respectively). Recipients receiving a WLT or a LLS showed significantly better outcomes than patients receiving RTL and MSL (P Ͻ 0.03 for patients and P Ͻ 0.04 for graft survival). At the multivariate analysis, donor age of Ͼ60 yr, RTL transplant, Ͻ50 annual transplants volume, urgent transplantation (United Network for Organ Sharing (UNOS) status I and IIA), ischemia time of Ͼ7 hours, and retransplantation were factors independently related to graft failure and to significantly worst patient survival. Right grafts procured from RTL and either split procured as MSL had a similar outcome of marginal whole livers. In conclusion, in 5 yr, the increased number of pediatric transplants due to split liver donation reduced to 3% the in-list children mortality, and a decrease in the adult patient dropout rate from 27.2 to 16.2% was observed. Such results justify a more widespread adoption of SLT protocols, organizational difficulties not being a limit for the application of such technique. Liver Transpl 12: 402-410, 2006.
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