Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open‐label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6‐12 ng/mL. The primary endpoint was the proportion of treated biopsy‐proven acute rejection (tBPAR)–free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR‐free (P = 0.09); composite endpoint‐free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

Antioxidant agents have the potential to reduce ischemia/reperfusion damage to organs for liver transplantation (LT). In this prospective, randomized study, we tested the impact of an infusion of N-acetylcysteine (NAC) during liver procurement on post-LT outcomes. Between December 2006 and July 2009, 140 grafts were transplanted into adult candidates with chronic liver disease who were listed for first LT, and according to a sequential, closed-envelope, single-blinded procedure, these patients were randomly assigned in a 1/1 ratio to an NAC protocol (69 patients) or to the standard protocol without NAC [71 patients (the control group)]. The NAC protocol included a systemic NAC infusion (30 mg/kg) 1 hour before the beginning of liver procurement and a locoregional NAC infusion (300 mg through the portal vein) just before cross-clamping. The primary endpoint was graft survival. The graft survival rates at 3 and 12 months were 93% and 90%, respectively, in the NAC group and 82% and 70%, respectively, in the control group (P ¼ 0.02). An adjusted Cox analysis showed a significant NAC effect on graft survival at both 3 months [hazard ratio ¼ 1.65, 95% confidence interval (CI) ¼ 1.01-2.93, P ¼ 0.04] and 12 months (hazard ratio ¼ 1.73, 95% CI ¼ 1.14-2.76, P 0.01). The incidence of postoperative complications was lower in the NAC group (23%) versus the control group (51%, P < 0.01). In the subgroup of 61 patients (44%) receiving suboptimal grafts (donor risk index > 1.8), the incidence of primary dysfunction of the liver was lower (P ¼ 0.09) for the NAC group (15%) versus the control group (32%). In conclusion, the NAC harvesting protocol significantly improves graft survival. The effect of NAC on early graft function and survival seems higher when suboptimal grafts are used. Liver Transpl 19:135-144, 2013. V C 2012 AASLD.Received April 3, 2012; accepted July 7, 2012.Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; DRI, donor risk index; GSH, glutathione; ICU, intensive care unit; INR, international normalized ratio; IRI, ischemia/reperfusion injury; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; NAC, N-acetylcysteine; PDF, primary dysfunction; PNF, primary nonfunction; POD, postoperative day.Francesco D'Amico contributed to the study concept and design, the acquisition and analysis of data, and the supervision of the study and manuscript. Alessandro Vitale contributed to the analysis and interpretation of data, the drafting of the manuscript, and the statistical analysis. Anna Chiara Frigo contributed to the statistical analysis. Umberto Cillo contributed to the analysis and interpretation of data and the supervision of the study. Alessandra Bertacco contributed to the acquisition and analysis of data and the critical revision of the manuscript. Donatella Piovan, Domenico Bassi, Rafael Ramirez Morales, Pasquale Bonsignore, Enrico Gringeri, Michele Valmasoni, Greta Garbo, Enrico Lodo, Francesco Enrico D'Amico, Michele Scopelliti, Amedeo Carraro, ...

Background: Videolaparoscopic (VL) microwave ablation (MWA) is not included in most of the international guidelines as a therapeutic option for hepatocellular carcinoma (HCC). Aim of this study was to assess the safety of VL MWA in patients with HCC for whom resection or percutaneous ablation is unsuitable. Methods: A retrospective analysis was performed on a prospective database of patients with HCC treated with VL MWA at our institution from 2009 to 2016. Patient demographics, operational characteristics, and complications were recorded. Statistical analysis was performed to identify safety profile, overall survival and recurrence rate. Results: A total of 815 VL MWA were performed in 674 patients with a mean age of 64 years. Patients had a mean Model for End‐stage Liver Disease score of 10 (±3); 32.8% were Child B, 44.1% Barcelona Clinic Liver Cancer B‐C. Perioperative mortality was 0.4%. Overall morbidity was 30.8%, with Dindo‐Clavien complications ≥3 in 2%. The median length of stay was 2 days. In 43.1% VL MWA was the first‐line therapy. Overall 1‐, 3‐, and 5‐year survival rates were 81.9%, 54.9%, and 35.9%. Conclusions: The present is the largest series of VL ablation and the bigger number of patients with HCC treated with MW reported nowadays. It confirms the safety of a minimally invasive procedure for patients with HCC when resection or percutaneous ablation is not feasible.

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Sorafenib is acknowledged as the standard therapy for advanced hepatocellular carcinoma (HCC) but in the clinical practice the treatment of these patients is extremely complex and needs to be personalized. New evidence suggests that surgical resection-based multimodal treatments may improve outcome in these patients. There is no strong evidence supporting the ability of sorafenib in downstage HCC before surgery. We presented a case of a 53-year-old man with well-compensated HCV-cirrhosis complicated with HCC and neoplastic portal vein thrombosis. The patient was treated initially with sorafenib with optimal radiological and serological response and subsequently with liver resection. Pathological examination showed necrotic portal thrombosis and massive necrosis of a metastatic regional node confirming radiological evidence. This finding suggests that sorafenib exhibits a potential to downstage advanced HCC which is not irrelevant. A possible combination of different modalities has to be considered in the view of a personalized medicine.