No abstract

Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty-eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan-NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long-term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow-up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time-to-progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4-23.0; p = 0.001). Adjusted transplant-related survival benefit was 6.82 months (95% CI: 1.10-12.54; p = 0.019) and 38.43 months (95% CI: 21.41-55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long-term outcome. Transplant-related survival benefit increases over time and maximizes after 10 years.

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.

Heat shock proteins (HSPs) are a large family of proteins with different molecular weights and different intracellular localizations. These proteins undertake crucial functions in maintaining cell homeostasis, and therefore they have been conserved during evolution. Hsp70 and Grp94/gp96, due to their peptide chaperone capacity and their ability to actively interact with professional antigen-presenting cells (APCs), are also endowed with crucial immunological functions. The immunological properties of these proteins and their implications for vaccine in human cancer will be discussed. Immunological and clinical data of phase I/II studies in melanoma and colorectal cancer patients will be reviewed.