Surgery and Hepatocellular Carcinoma.

The optimal surgical strategy for hepatocellular carcinoma (HCC) is under active debate. Bio-markers of the liver functional reserve as well as volumetric analysis of the future liver remnant are essential for safe liver resection of HCC. The present algorithms applied to surgical strategies for HCC are not ideal because many patients who could potentially undergo safe resection are deemed liver transplant candidates in Western countries, whereas the opposite is the case in Eastern countries.

Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest.

Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors.

Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC.

Background & Aims: The AFP model was shown to be superior to the Milan criteria for predicting hepatocellular carcinoma (HCC) recurrence after liver transplantation in a French population. Our aim was to test the AFP model in a non-French, post-hepatitic cirrhosis-based population of HCC candidates.

Methods: 574 patients transplanted for HCC in four Italian centers were studied.

Use of Everolimus in Liver Transplantation: Recommendations From a Working Group.

Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking.

The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies.

Inflammatory bowel diseases are an increasing phenomenon in western countries and in growing populations. The physiopathology of these conditions is linked to intestinal stem cells homeostasis and regenerative potential in a chronic inflammatory microenvironment. Patients with IBD present an increased risk of developing colorectal cancer (CRC), or colitis associated cancer (CAC).

Importance of primary indication and liver function between stages: results of a multicenter Italian audit of ALPPS 2012-2014.

Background: Posthepatectomy liver failure is one of the most feared complications in extended hepatic resections. In 2012, a novel two-stage liver resection was developed, able to induce rapid and extensive hypertrophy by portal vein ligation and in situ liver splitting - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). The technique became more widely employed but its use remained controversial due to reporting of high complication and mortality rates.

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma.

Background: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.

From Inflammation to Cancer in Inflammatory Bowel Disease: Molecular Perspectives.

Inflammatory bowel diseases (IBD) are associated with an increased risk of colitis-associated colorectal carcinoma (CAC). CAC is one of the most important causes of morbidity and mortality in patients with Crohn's disease and ulcerative colitis. The aim of the present review was to discuss the most important signaling pathways and genetic alterations involved in carcinogenesis related to IBD, focusing on the molecular aspects of cancer stem cell physiology and the impact of the inflammatory microenvironment.

Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study.

Background: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented.

Methods: In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy.

Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma - The SHELTER study.

Background & Aims: No established therapies for patients with hepatocellular carcinoma (HCC) and progression on first-line sorafenib treatment currently exist. This phase I/II trial investigated safety, pharmacokinetics and potential biomarkers of the histone deacetylase inhibitor resminostat and a combination therapy with resminostat and sorafenib.

Methods: Patients with HCC and radiologically confirmed progression on sorafenib were treated in an exploratory, multi-center, open-label, uncontrolled, non-randomized, parallel group phase I/II study.

Defining the possible therapeutic benefit of lymphadenectomy among patients undergoing hepatic resection for intrahepatic cholangiocarcinoma.

Background: The aim of the study was to investigate the therapeutic role of lymphadenectomy (LND) in patients with intrahepatic cholangiocarcinoma.

Methods: 826 patients who underwent liver resection were identified using the SEER database from 1988 to 2011. Two groups of patients were defined: 201 (24%) undergoing potentially therapeutic LND (group A, >3 lymph nodes (LN) removed), and 625 (76%) not receiving therapeutic LND (group B, ≤3 LNs removed).

Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation.

Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor's biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes.

Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study.

Unlabelled: In patients with cirrhosis and hepatorenal syndrome (HRS), terlipressin has been used either as continuous intravenous infusion or as intravenous boluses. To date, these two approaches have never been compared. The goal of this study was to compare the administration of terlipressin as continuous intravenous infusion versus intravenous boluses in the treatment of type 1 HRS.

SerpinB3 and Yap Interplay Increases Myc Oncogenic Activity.

SerpinB3 has been recently described as an early marker of liver carcinogenesis, but the potential mechanistic role of this serpin in tumor development is still poorly understood. Overexpression of Myc often correlates with more aggressive tumour forms, supporting its involvement in carcinogenesis. Yes-associated protein (Yap), the main effector of the Hippo pathway, is a central regulator of proliferation and it has been found up-regulated in hepatocellular carcinomas.

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

Background: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC).

Methods: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years.

Differential timing of oxidative DNA damage and telomere shortening in hepatitis C and B virus-related liver carcinogenesis.

In viral hepatitis, inflammation is correlated with chronic oxidative stress, one of the biological events leading to DNA damage and hepatocellular carcinoma (HCC) development. Aim of this study was to investigate the complex molecular network linking oxidative damage to telomere length and telomerase activity and regulation in hepatitis C and B virus-related liver carcinogenesis. We investigated 142 patients: 21 with HCC (in both tumor and peritumor tissues) and 121 with chronic viral hepatitis in different stages.

Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects?

Cholangiocarcinoma (CCAs) may be defined as tumors that derived from the biliary tree with the differentiation in the biliary epithelial cells. This tumor is malignant, extremely aggressive with a poor prognosis. It can be treated surgically and its pathogenesis is poorly understood.

A Multistep, Consensus-Based Approach to Organ Allocation in Liver Transplantation: Toward a "Blended Principle Model".

Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD-based system for governing organ allocation.

Salvage liver transplantation after laparoscopic resection for hepatocellular carcinoma: a multicenter experience.

Liver transplantation is the ideal treatment for patients affected by early stage hepatocellular carcinoma and chronic liver disease. Considering organs shortage, alternative treatments have to be adopted to minimize the waitlist drop-out, and in case of recurrence within the accepted criteria, salvage transplantation can be considered. Surgical resection is one of the most effective treatments, with the possibility of oncological radicality and pathological analysis of the specimen.

Perioperative thrombotic complications in liver transplantation.

Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation (OLT), the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival. Thromboembolism during OLT is characterized not only by a complex aetiology, but also by unpredictable onset and evolution of the disease. The initiation of a procoagulant process may be triggered by various factors, such as inflammation, venous stasis, ischemia-reperfusion injury, vascular clamping, anatomical and technical abnormalities, genetic factors, deficiency of profibrinolytic activity, and platelet activation.