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p53 alterations are considered to be predictive of poor prognosis in hepatocellular carcinoma (HCC) and may induce a humoral response. Anti-p53 serum antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human p53 on 130 European HCC patients before treatment and during the clinical course of the disease. p53 immunohistochemistry was performed on tumours from the 52 patients who underwent surgery, and DNA sequencing analysis was initiated when circulating anti-p53 antibodies were detected. Nine (7%) HCC patients had anti-p53 serum antibodies before treatment. During a mean period of 30 months of follow-up, all the negative patients remained negative, even when recurrence was observed. Of the nine positive patients, eight were still positive 12-30 months after surgery. The presence of anti-p53 serum antibodies was correlated neither with mutation of thep53 gene nor the serum alpha-fetoprotein levels and clinicopathological characterics of the tumours. However, a greater incidence of vascular invasion and accumulation of p53 protein were observed in the tumours of these patients (P < 0.03 and P < 0.01 respectively) as well as a better survival rate without recurrence (P = 0.05). In conclusion, as was recently shown in pancreatic cancer, anti-p53 serum antibodies may constitute a marker of relative 'good prognosis' in a subgroup of patients exhibiting one or several markers traditionally thought to be of bad prognosis. [ABSTRACT FROM AUTHOR]

Background: Appropriate risk stratification for the difficulty of liver transplantation (LT) is essential to guide the selection and acceptance of grafts and avoid morbidity and mortality., Methods: Based on 987 LTs collected from 5 centers, perioperative outcomes were analyzed across the 3 difficulty levels. Each LT was retrospectively scored from 0 to 10. Scores of 0-2, 3-5 and 6-10 were then translated into respective difficulty levels: low, moderate and high. Complications were reported according to the comprehensive complication index (CCI)., Results: The difficulty level of LT in 524 (53%), 323 (32%), and 140 (14%) patients was classified as low, moderate and high, respectively. The values of major intraoperative outcomes, such as cold ischemia time (p = 0.04) and operative time (p < 0.0001) increased gradually with statistically significant values among difficulty levels. There was a corresponding increase in CCI (p = 0.04), severe complication rates (p = 0.05) and length of ICU (p = 0.01) and hospital (p = 0.004) stays across the different difficulty levels., Conclusion: The LT difficulty classification has been validated., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience., (© 2018 Steunstichting ESOT.)

Background/aims: To externally validate the predictive mathematical model of survival designed by Linhares et al. (2006)., Methodology: This retrospective study was conducted on 217 individuals submitted to liver retransplantation from January 2000 to December 2008 in four European centers. The following variables were obtained on the recipient: age, creatinine, urgency of retransplantation and time between transplantation and retransplantation. The Kaplan-Meier survival curve and ROC curve were used to validate the mathematical model., Results: The present results showed a similar pattern of survival compared to the study of Linhares et al. (2006) concerning the biological variations, when survival curves were compared for each of the four variables analyzed between both samples. When compared, the areas below the ROC curve (aROC) of derivation (0.733) and validation samples (0.593) presented significant difference (p = 0.005), revealing low relationship of sensitivity and specificity between the two curves. Similarity was observed in Kaplan-Meier survival curves., Conclusion: This study allowed external validation by the Kaplan-Meier survival curves of the predictive mathematical model of survival in liver retransplantation proposed by Linhares et al. (2006). However, validation through the ROC curve, the aROC, evidenced weak discrimination ability.

Objective: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period., Background: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases., Methods: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1-149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures., Results: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT., Conclusions: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

Background: The platelet count varies considerably between individuals, but within an individual the platelet count is remarkably stable over time. Mechanisms controlling the platelet count are not yet established., Objective: In the present study, we tested the hypothesis that the liver is important in controlling the circulating platelet count, as the liver is the main producer of thrombopoietin., Methods: We compared the platelet count prior to and after liver transplantation in >250 patients transplanted for familial amyloidotic polyneuropathy (FAP). In contrast to most patients undergoing liver transplantation, patients with FAP have normal liver function before transplantation. Furthermore, we compared platelet counts in 89 living liver donors with the platelet count in the recipients of these grafts. Finally we compared platelet counts in donor-recipient pairs of hematopoietic stem cells., Results and Conclusions: The platelet count prior to transplantation correlated with the platelet count at 3 or 12 months after transplantation in patients with FAP (r=0.48, P<0.0001 at 3 months, r=0.39, P<0.0001 at 12 months), whereas the platelet count in a living liver donor did not correlate with the platelet count in the recipient at 3 or 12 months after transplantation (r=0.16, P=0.26 at 3 months, r=0.11, P=0.30 at 12 months). The platelet count of related donors of hematopoietic stem cells correlated with the platelet count in the recipient after transplantation (r=0.25, P=0.011)., Conclusions: These results suggest that the liver, in spite of being the prime producer of thrombopoietin, does not dictate the circulating platelet count, whereas the bone marrow does appear to play a role., (© 2012 International Society on Thrombosis and Haemostasis.)

Genetic instability has been detected in many types of cancers but poorly investigated in hepatocellular carcinoma (HCC). We have studied the incidence of microsatellite instability (MI) at eight highly polymorphic microsatellite markers and the poly A tract BAT26 and tested for mutations at two sites of repetitive sequence (poly-A nucleotides 709-718 and GT repeat-nucleotides 1931-1936) in the Transforming Growth Factor beta (TGFbeta) type II receptor (RII) gene, in a group of 46 European HCCs and the surrounding nontumour tissue. This analysis showed that 63% of HCCs exhibit MI in at least one chromosome locus and 41% in two or more loci. No mutations of the TGFbetaRII gene were found in the MI positive tumours. No correlation was found with clinicopathological characteristics of the tumours such as cirrhosis, etiology, number of nodules, Edmondson's grade and vascular invasion. However, in patients who had a rearranged D16S402 microsatellite in their tumour, the recurrent disease and the number of nodules were significantly higher than in the others (P<0.005 and P<0.02, respectively). We propose to consider D16S402 rearrangement in HCC as a prognostic factor to identify patients presenting a higher risk of recurrence.