Risk Avoidance and Liver Transplantation: A Single-center Experience in a National Network.

OBJECTIVES: To evaluate the risk avoidance policy at liver transplant centers. BACKGROUND: Transplant center improvements have extended the indications for the sickest patients and the use of extended criteria donors (ECD). This may result in lower survival, perhaps paradoxically discouraging transplant centers from these procedures. We evaluated the outcome of recipients or donors refused by other transplant centers and transplanted by our transplant unit without risk avoidance policy. METHODS: Between 2007 and 2015, 616 patients underwent liver transplantation at our Unit; 142 patients (23%) had been rejected by other Italian centers, because of recipient selection (70 patients, 11%) or because of donor selection (78 patients, 12%), group A. Recipient and donor features were analyzed and compared with 474 patients transplanted in the same period, group B. RESULTS: Recipients were mainly rejected for comorbidity (19%), portal vein thrombosis (16%), previous surgery (9%), obesity (9%), and hepatocellular carcinoma (6%). Donors were rejected for HBcAb+ (33%), HCV+ (18%), liver biopsy (9%), HBsAg+ (6%), neoplastic (6%), or infective risk (5%).Most recipient and donor features were comparable between groups A and B.The 1- and 3-year overall graft and patient survival rates were similar in groups A and B and were comparable with national data. CONCLUSIONS: Recipients and donor grafts were rejected for reasons not accepted by scientific literature. They did not differ from control group patients and their postoperative outcome was comparable. These results highlight the discrepancy among transplant centers and the relevance of risk avoidance in LT policy.

Liver metastases from non-gastrointestinal non-neuroendocrine tumours: review of the literature.

Liver resection is integrated in the oncological surgical management of metastatic gastrointestinal and neuroendocrine tumours. However, the good prognosis reached in these cases has not been obtained for metastatic tumours of other histological types. In this review, we analysed the published case reports and series of hepatectomies in patients with metastatic breast cancer, melanoma, sarcoma, genitourinary tumours, pulmonary and adrenocortical tumours. From the reported data the surgical resection of oligometastases yields good results in terms of improved survival, in particular when the disease-free time period is longer than 1 year. Hepatic resection can be a valid surgical strategy to obtain a survival benefit in patients with liver metastases from non-gastrointestinal, non-neuroendocrine tumours. However, a careful patient selection is needed in order to obtain a real survival benefit; patients with a good performance status, with a disease-free period longer than 1 year and with oligometastases may obtain the best advantage from this approach.

Immunosuppression Modifications Based on an Immune Response Assay: Results of a Randomized, Controlled Trial.

BACKGROUND: An immune function assay shows promise for identifying solid organ recipients at risk for infection or rejection. The following randomized prospective study was designed to assess the clinical benefits of adjusting immunosuppressive therapy in liver recipients based on immune function assay results. METHODS: Adult liver recipients were randomized to standard practice (control group; n = 102) or serial immune function testing (interventional group; n = 100) performed with a commercially available in vitro diagnostic assay (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation, immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to 6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed rejection/infection and within 1 week after event resolution. RESULTS: Based on immune function values, tacrolimus doses were reduced 25% when values were less than 130 ng/mL adenosine triphosphate (low immune cell response) and increased 25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune cell response). The 1-year patient survival was significantly higher in the interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer than 14 days after transplantation was significantly lower among patients in the interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs 11%; P < 0.05). Among recipients without adverse events, the study group had lower tacrolimus dosages and blood levels. CONCLUSIONS: Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes.

Laparoscopic major hepatectomies: clinical outcomes and classification.

BACKGROUND: According to the Louisville Statement, laparoscopic major hepatectomy is a heterogeneous category that includes "traditional" trisectionectomies/hemi-hepatectomies and the technically challenging resection of segments 4a, 7, and 8. The aims of this study were to assess differences in clinical outcomes between laparoscopic "traditional" major hepatectomy and resection of "difficult-to-access" posterosuperior segments and to define whether the current classification is clinically valid or needs revision. METHODS: We reviewed a prospectively collected single-center database of 390 patients undergoing pure laparoscopic liver resection. A total of 156 patients who had undergone laparoscopic major hepatectomy according to the Louisville Statement were divided into two subcategories: laparoscopic "traditional" major hepatectomy (LTMH), including hemi-hepatectomies and trisegmentectomies, and laparoscopic "posterosuperior" major hepatectomy (LPMH), including resection of posterosuperior segments 4a, 7, and 8. LTMH and LPMH subgroups were compared with respect to demographics, intraoperative variables, and postoperative outcomes. RESULTS: LTMH was performed in 127 patients (81 %) and LPMH in 29 (19 %). Operation time was a median 330 min for LTMH and 210 min for LPMH (p < 0.0001). Blood loss was a median 500 ml for LTMH and 300 ml for LPMH (p = 0.005). Conversion rate was 9 % for LTMH and nil for LPMH (p = 0.219). In all, 28 patients (22 %) developed postoperative complications after LTMH and 5 (17 %) after LPMH (p = 0.801). Mortality rate was 1.6 % after LTMH and nil after LPMH. Hospital stay was a median 5 days after LTMH and 4 days after LPMH (p = 0.026). CONCLUSIONS: The creation of two subcategories of laparoscopic major hepatectomy seems appropriate to reflect differences in intraoperative and postoperative outcomes between LTMH and LPMH.

Long-term antiviral treatment for recurrent hepatitis C after liver transplantation.

BACKGROUND AND AIMS: The management of patients treated for hepatitis C recurrence after liver transplantation and not achieving virological response following treatment with interferon plus ribavirin is controversial. METHODS: A retrospective analysis of the outcomes of 70 patients non-responders to antiviral treatment after liver transplantation was performed. Twenty-one patients (30.0%; Group A) were treated for ≤ 12 months and 49 (70.0%; Group B) for more than 12 months. RESULTS: The 2 groups were comparable for main demographic, clinical and pathological variables. Median duration of antiviral treatment was 8.2 months in Group A and 33.4 months in Group B. No patient achieved a complete virological response. The 5-year patient hepatitis C-related survival rate was 49.2% in Group A and 88.3% in Group B (P=0.002), while the 5-year graft survival rate was 49.2% in Group A and 85.9% in Group B (P=0.007). The median yearly fibrosis progression rate was 1.21 per year in Group A and 0.40 per year in Group B (P=0.001). CONCLUSIONS: Prolonged antiviral treatment showed an overall beneficial effect in transplanted patients with a recurrent hepatitis C infection and not responding to conventional therapy. The treatment should be continued as long as it is permitted, in order to improve clinical and histological outcomes.

Safety of hepatic resection for colorectal metastases in the era of neo-adjuvant chemotherapy.

PURPOSE: The relationship between neo-adjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases and post-operative morbidity still has to be clarified. METHODS: Data from 242 patients undergoing hepatectomy for colorectal liver metastases, judged resectable at first observation, were reviewed and their clinical outcome was related to neo-adjuvant chemotherapy (125 patients). Selection biases were outlined and properly handled by means of propensity score analysis. RESULTS: Post-operative death was 1.2% and morbidity 40.9%. Pre-operative chemotherapy was only apparently related to higher morbidity (P = 0.021): multivariate analysis identified extension of hepatectomy and intra-operative blood loss as independent prognostic variables (P < 0.05). Patients receiving and not receiving neo-adjuvant chemotherapy were significantly different for several covariates, including extension of hepatectomy (P = 0.049). After propensity score adjustment, 94 patients were identified as having similar covariate distribution (standardized differences <|0.1|) except for neo-adjuvant treatment (47 patients for each group). In this matched sample, mortality was similar and post-operative complications were only slightly higher (hazard ratio = 1.38) in treated patients. A significantly higher need for fluid replacement was only observed in patients receiving neo-adjuvant chemotherapy (P = 0.038). CONCLUSIONS: Neo-adjuvant chemotherapy showed a limited role in determining post-operative morbidity after hepatic resection and did not modify mortality.

Anatomic variations of intrahepatic bile ducts in a European series and meta-analysis of the literature.

BACKGROUND: Accurate knowledge of biliary anatomy and its variants is essential to ensure successful hepatic surgery; however, data from European countries are lacking. METHODS: Two hundred cholangiograms obtained from patients submitted to whole liver transplantation were reviewed; donors' characteristics were related to the prevalence of typical biliary anatomy and its variants. A comprehensive literature search was performed with MEDLINE and EMBASE from 1980 to 2010 to investigate whether geographical origin could be related to biliary abnormalities. RESULTS: Typical biliary anatomy was observed in 64.5% of cases, but female donors more frequently presented an anatomic variation; typical anatomy was present in 55.0% of females and in 74.0% of males (P = 0.005). Twenty-two reports were identified by the literature search with a total of 7,559 cases, including the present series; heterogeneity was low (Q = 14.60; I2 < 5.0%) after exclusion of three outlier reports. Prevalence of typical biliary anatomy was similar in Europeans and Americans (∼60%); a slightly higher prevalence was observed in Asiatics (∼65%). CONCLUSIONS: Anatomic variants seem to be more frequent in females, probably as a consequence of different embryologic development. Available data suggest that typical biliary anatomy can be more frequent in Asiatics, but an accurate means of classification is essential to making comparison realistic.

Prognostic factors for tumor recurrence after a 12-year, single-center experience of liver transplantations in patients with hepatocellular carcinoma.

Background. Factors affecting outcomes after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS) in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12%) patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP) levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Cox's proportional hazard model showed that only elevated AFP levels (Odds Ratio = 2.88; 95% C.I. = 1.43-5.80; P = .003), preoperative tumor treatments (Odds Ratio = 4.84; 95% C.I. = 1.42-16.42; P = .01), and microvascular invasion (Odds Ratio = 4.82; 95% C.I. = 1.87-12.41; P = .001) were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.

Liver transplantations with donors aged 60 years and above: the low liver damage strategy.

According to transplant registries, grafts from elderly donors have lower survival rates. During 1999-2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged > or = 60 years and managed with the low liver-damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D > or = 60-LLDS). Group D > or = 60-LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60-no-LLDS and 89 donors aged > or =60 years, group D > or = 60-no-LLDS). In the donors proposed from the age group of > or =60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end-stage liver disease score) were comparable among groups, but group D > or = 60-LLDS had a lower mean ischemia time: 415 +/- 106 min vs. 465 +/- 111 (D < 60-no-LLDS), P < 0.05 and vs. 476 +/- 94 (D > or = 60-no-LLDS), P < 0.05. After a median follow-up of 3 years, the 1- and 3-year graft survival rates of group D > or = 60-LLDS (84% and 76%) were comparable with group D < 60-no-LLDS (89% and 76%) and were significantly higher than group D > or = 60-no-LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.