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Abstract: Background:: The use of orthotopic liver transplantation (OLT) for the treatment of patients with hepatocellular carcinoma (HCC) remains controversial because of the risk of both exclusion from the waiting list due to tumor progression and post OLT HCC recurrence. The aim of the present study was to evaluate the effect of an aggressive HCC treatment during the waiting list time on overall and recurrence-free survival of HCC transplanted patients in a single institutional study. Methods:: Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. In all, 90% of the study group had HCC treatment while on the waiting list (transarterial chemoembolization, percutaneous therapies, chemotherapy). Results:: Only one patient (2.5%) was removed from the waiting list after developing neoplastic portal thrombosis 3 months after listing, while 33 (82.5%) underwent to OLT after a median waiting list time of 11 months (range 3–16 months). On histological examination, 42% of the group did not meet the “Milan criteria” and 42% were pTNM stages III and IV. The median follow-up was 42 months. The 5-year actuarial survival rate was 64% and recurrence-free survival was 91%. HCC recurred in only two patients (6%). Conclusions:: The use of routine pre-OLT tumor grading and of an aggressive HCC treatment during the waiting list, in our experience, resulted in a very low risk of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence. [Copyright &y& Elsevier]

Aim: To explore the potential prognostic role of preoperative tumor grade and blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC) eligible for radical therapies according to a well-defined treatment algorithm not including nodule size and number as absolute selection criteria., Methods: Fifty patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (1) histological assessment of tumor grade by means of percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3) patient's eligibility for radical therapies., Results: At preoperative evaluation, 54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery (resection or liver transplantation) was performed in 29 patients, while 21 had percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-, and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy, performance status and three tumor-related variables (AFP mRNA, HCC grade and gross vascular invasion) resulted as significant survival predictors at univariate analysis. Nodule size and number did not perform as significant prognosticators. Multivariate study selected only surgical therapy and a biologically early HCC profile (AFP mRNA negative and well-differentiated tumor without gross vascular invasion) as independent survival variables., Conclusion: The preoperative determination of tumor grade and blood AFP mRNA status may potentially refine the prognostic evaluation of HCC patients and improve the selection process for radical therapies.

Background: There are few studies evaluating the prognostic impact on survival of treatment strategy in patients with hepatocellular carcinoma (HCC). The aim of this study was to analyse whether a multimodal approach, that represents a synergic association of different therapeutic procedures, may improve survival of patients with HCC., Patients and Methods: Two hundred and fourteen patients with HCC were enrolled in the study. The multimodal approach was chosen for 27 out of 106 (25%) non surgical patients, 42 out of 81 (52%) patients who underwent liver resection and 19 out of 27 (70%) patients who underwent liver transplantation., Results: The long-term survival of patients who underwent the multimodal approach improved significantly with respect to patients treated by both resection and other therapies alone. The 5-year survival rates were 52% vs. 11% (p < 0.05) in the non surgical group and 40% vs. 24% (p < 0.05) in the resection group when a multimodal approach was used for the treatment of recurrences. In patients with advanced HCC undergoing liver transplantation, multimodal treatment resulted in long-term survival comparable to that of patients with early HCC., Conclusion: A multimodal approach should be suggested in all patients with HCC, since a careful integration of surgical and non surgical treatments may improve long-term survival in such patients.

Thermal homeostasis represents the major issue during liver transplantation (OLT) since severe hypothermia may have a deleterious effect on both liver recipient organism and postoperative graft functioning. Because of the known negative influence of hypothermia on intraoperative cardiovascular activity and coagulation system, numerous methods have been suggested to reduce intraoperative heat loss and promote active warming (continuous temperature monitoring, external heat sources, improvement in surgical technique and technologies). A good intraoperative OLT course has an obvious influence on post OLT graft function recovery, but thermal homeostasis has also an essential direct effect on the graft as a constitutive component of conventional cold preservation methods. Hypothermia, however, contributes directly to the graft ischemia-reperfusion injury particularly in marginal and partial organs by several angiogenic mechanisms. For these reasons, on the light of the development of new strategies to increase the donor pool, clinical research is focusing on new preservation methods such as extracorporeal circuits with normothermic oxygenated perfusion.