0000000001230487
AUTHOR
Fabrizio Di Francesco
Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection
Background: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. Methods: 124 HCC patients, who underwent a primary hepatic …
How important is the role of iterative liver direct surgery in patients with hepatocellular carcinoma for a transplant center located in an area with a low rate of deceased donation?
IntroductionHepatocellular carcinoma (HCC) accounts for nearly 90% of primary liver cancers, with estimates of over 1 million people affected by 2025. We aimed to explore the impacting role of an iterative surgical treatment approach in a cohort of HCC patients within the Milan criteria, associated with clinical risk factors for tumor recurrence (RHCC) after liver transplant (LT) and loco-regional therapies (LRT), as well as liver resection (LR) and/or microwave thermal ablation (MWTA).MethodsWe retrospectively analyzed our experience performed during an 8-year period between January 2013 and December 2021 in patients treated for HCC, focusing on describing the impact on preoperative end-st…
Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling
Simple Summary Intrahepatic cholangiocarcinoma is a rare disease with increasing incidence and mortality still characterized by an insufficient clinical outcome. Growing attention has recently surrounded this disease, and liver transplantation has emerged as a novel curative treatment for cholangiocarcinoma, along with a better understanding of genetic alterations potentially capable of driving tumorigenesis. The aim of this paper is to present a clinical description of our case series of patients affected by intrahepatic cholangiocarcinoma and by mixed forms of hepatocellular and cholangiocellular carcinoma, together with a genomic profiling of mutations occurring in a panel of genes relev…
Optimizing Liver Division Technique for Procuring Left Lateral Segment Grafts: New Anatomical Insights.
Left liver lobe (left lateral segment) grafts (LLG) is currently the most commonly used graft to transplant children (2/3 of cases currently in Europe); it is prepared by liver division (DL) in both living (LD) and deceased donors (DD) settings. Technically speaking, classical DL is through the parenchyma of segment IV - dividing the main left glissonean pedicle left to the main biliary confluence (trans-hilar (TH) approach): historically, this technique was introduced by Bismuth and Pichlmayr in 1988 in DD setting, and applied one year later for the first successful living donor transplantations by Strong (Figure 1).
Impact of Italian Score for Organ Allocation System on Deceased Donor Liver Transplantation: A Monocentric Competing Risk Time-to-Event Analysis
Background: Liver transplantation (LT) is the only definitive and curative treatment for patients with end-stage liver disease and hepatocellular carcinoma. We aimed to evaluate the impact of the Italian score for organ allocation (ISO) in terms of the waiting-list mortality, probability of LT, and patient survival after LT. Patient and methods: All of the adult patients on the waiting list for LT at our institute from January 2014 to December 2017 were included in the study. The probabilities of death while on the waiting list, dropout from the list, and LT were compared by means of cumulative incidence functions, in a competing risk time-to-event analysis setting. Uni- and multivariable l…
Complications in Immunosuppressive Therapy of Liver Transplant Recipients
BACKGROUND: In liver transplantation (LT), modern immunosuppressive protocol is focused on early corticosteroid (CS) weaning. The aim of the study was to investigate all early transplant-related complications using Clavien grading system, in order to identify a significant relation in two homogenous groups of consecutive liver transplanted patients, only different for steroid avoidance in immunosuppressive regimen. MATERIALS AND METHODS: One group was treated with a tacrolimus-based CS-free immunosuppressive protocol, the other one underwent tacrolimus plus low dose CS therapy. The preoperative continuous variables analyzed were age, gender, model for end-stage liver disease (MELD) score, a…
Laparoscopic Microwave Thermal Ablation for the Treatment of Hepatocellular Carcinoma in Chronic Hepatic Patients
Background: Laparoscopic microwave thermal ablation (LMWTA) is a well-established alternative treatment to liver resection for treatment of liver tumors. The aim of this study was to describe our experience in LMWTA for hepatocellular carcinoma (HCC) in chronic hepatic patients. Materials and Methods: A study group of 61 consecutive HCC patients treated with LMWTA from January, 2013 to May, 2020 were considered for this study. Patient characteristics, liver function test, operational characteristics, and complications were recorded. Results: Of the 61 patients who underwent LMWTA, median age was 64 (interquartile range [IQR]: 58-71) years, mean body mass index was 26.2 (IQR: 23.2-29.4); 44 …
Peri-Operative Liver Regeneration of the Remnant Liver Volume after Right Hepatectomy for Living Donation: A Multiple Regression Analysis
Early liver regeneration was studied in a series of 70 patients who underwent right hepatectomy for living donation from November 2004 to January 2010. Liver regeneration was evaluated by multidetector computed tomography at a mean time of 61.07 days after surgery. Pre-surgical variables such as age, weight, height, body mass index, liver function tests, creatinine, platelet count, international normalized ratio, glucose, and variables detected with preoperative multidetector computed tomography imaging, including diameter of main portal vein, steatosis, original liver volume and spleen volume, were investigated as potential predictors of liver regeneration. Future remnant liver volume was …
Adult to Adult Living Donor Liver Transplantation in Recipients with Low MELD: A Strategy Intended to Overcome Donor Shortage
Recent series have demonstrated advantages of living donor over deceased donor liver transplantation, with particular benefit for those with low model for end-stage liver disease score. The logic underlying the transplantation of patients before they become too sick is intuitive. It reduces mortality and drop outs from the waiting list and makes transplant surgery less demanding. Those principles have to be balanced with donor safety and transplant benefit for the recipient avoiding early, futile transplantation. The authors report a case of adult to adult right lobe living donor liver transplantation performed for a recipient affected by primary biliary cirrhosis with MELD score of 15, in …
Case report: Trans-papillary free stenting of the cystic duct and of the common bile duct in a double biliary ducts anastomoses of a right lobe living donor transplantation.
Abstract Background One of the major issues related to the living donor liver transplantation recipient outcome is still the high rate of biliary complication, especially when multiple biliary ducts are present and multiple anastomoses have to be performed. Case presentation and conclusion We report a case of adult-to-adult right lobe living donor liver transplantation performed for a recipient affected by alcohol-related cirrhosis with MELD score of 17. End-stage liver disease was complicated by refractory ascites, portal hypertension, small esophageal varices and portal gastropathy, hypersplenism, and abundant right pleural effusion. Here in the attached video we described the adult-to-ad…
Impact of margin status on long-term results of liver resection for hepatocellular carcinoma: single-center time-to-recurrence analysis
Occult metastasis from the initial tumor and a de novo second primary hepatocellular carcinoma (HCC) were recognized as the main causes for the onset of early and late HCC recurrence, after liver resection (LR). This study aims to compare the time to recurrence after LR for HCC in which a margin ≤ 1 mm or > 1 mm was achieved. A single-center retrospective study involving 256 patients was conducted from June 2005 to June 2019. HCC patients resected with a radical surgical approach were investigated and stratified into groups A (resection margins ≤ 1 mm) and B (> 1 mm), as measured on final pathologic assessment. Kaplan–Meier estimators were used to estimate the probability of recurrenc…
Impact of Extended-Criteria Donor Liver Grafts on Benchmark Metrics of Clinical Outcome After Liver Transplantation: A Single Center Experience.
Abstract Background The adoption of extended criteria for donors remains the best strategy to widen the pool of available liver graft against the chronic shortage of donors. Benchmarking in liver transplantation (LT) offers the unprecedented opportunity to compare clinical outcome measures to a set of validated reference values. We aimed to evaluate the impact of marginal grafts usage in a cohort of low-risk benchmark cases from an area with a very low rate of deceased donation. Methods A cohort of low-risk benchmark cases was identified from all adult patients who underwent LT at our center. Among these patients, those transplanted with a graft from an extended-criteria donor (ECD) were id…
Enhanced Recovery after Implementation of Surgery Protocol in Living Kidney Donors: The ISMETT Experience
Abstract Introduction Laparoscopic living donor nephrectomy (LLDN) has become the standard procedure for living kidney transplantation. Enhanced recovery after surgery (ERAS) is a multimodal perioperative management aimed at facilitating rapid patient recovery after major surgery by modifying the response to stress induced by exposure to surgery. This association can further reduce hospital stay, surgical stress, and perioperative morbidity of living kidney donors. Material and methods In this retrospective analysis conducted at our institute, we compared the first 21 patients who underwent LLDN enrolled with the ERAS protocol with 55 patients who underwent LLDN with the fast-track protocol…
Liver Perfusate Natural Killer Cells from Deceased Brain Donors and Association with Acute Cellular Rejection after Liver Transplantation: A Time-to-Rejection Analysis
Background The ability to predict which recipients will successfully complete their posttransplant clinical course, which is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates could help identify risk factors portending adverse LT outcomes. Methods Liver perfusates were collected during the back-table surgical time after the procurement procedures for donors after brain death. Lymphocytic concentrations and phenotypes were matched with donors after brain death characteristics and indications, timing, surgical techniques, outcomes, and biopsy-proven acute cellular…
Use of Hepatitis C-Positive Deceased Liver Donors in Response to the Organ Shortage in an Endemic Area
The region of Sicily, Italy, is witnessing a chronic organ shortage. Thus, to face this critical issue, the use of marginal donors has increased over time. An example of marginal donor expansion is the use of liver donors who are positive for the hepatitis C antibody (HCV+) for HCV+ patients requiring liver transplantation (LT). In view of new advances in HCV therapy, including direct-acting agents (DAAs) to treat HCV in the post-transplant setting, our study focused on a monocentric experience in a series of consecutive LTs performed in adult patients receiving HCV+ liver donor allografts. From 2003 to 2016 at our institute we performed 10 LT using HCV+ deceased donors. In particular, the …
Crucial Role of Extended Criteria Donors in Deceased Donor Single Kidney Transplantation to Face Chronic Shortage in the Heart of the Mediterranean Basin: A Single-Center Experience.
Background: The gap between organ availability and patients on the waiting list for deceased donor kidney transplants has resulted in the wide use of extended criteria donors (ECDs).We aimed to compare the surgical outcomes of single kidney transplantation (KT) performed at our institute with standard criteria donor (SCD) or ECD grafts, according to the Organ Procurement and Transplantation Network definition. Patients and methods. Our retrospective analysis studied 115 adult recipients of KT from January 2016 to July 2018, with kidney grafts procured from adult donors after brain or circulatory death, performed at our institute. Among the 2 recipients’ groups, we compared the incidence of …
ERAS Protocol for Perioperative Care of Patients Treated with Laparoscopic Nonanatomic Liver Resection for Hepatocellular Carcinoma: The ISMETT Experience
Background: Liver resection (LR) remains the best therapeutic option for patients with early-stage hepatocellular carcinoma (HCC) with preserved hepatic function and who are not eligible for liver transplantation. After its inception, the enhanced recovery after surgery (ERAS) protocol was widely used for treating patients with liver cancer, although there are still no clear indications for improving upon it in both open and laparoscopic surgery. Objective: This study aims to describe our institute's experience in the application of the ERAS protocol in a cohort of HCC patients, and to explore possible factors that could have an impact on postoperative outcomes. Materials and Methods: We re…
LAPAROSCOPIC LEFT LIVER SECTIONECTOMY (LLLS) FOR PEDIATRIC LIVING RELATED LIVER TRANSPLANTATION (LRLT)
PURPOSE: LRLT in children is a method to provide organs for transplantation. We report 2 cases of LLLS for pediatric LRLT. METHOD: Donor position: lithotomy with surgeon in French position. Trocars: three 12 mm, placed 2 cm upper the supra-umbilical mid-line and sub-costal bi-lateral on the nipple lines; one 5 mm in epigastrium. Special instrumentation: harmonic scissor, ligasure®, Hem-O-Lock clips, and Endo Catch-II® bag. Main steps: division of round, falciform, left triangular ligaments and of lesser omentum; inspection of anatomy; hepatic hilum dissection with exposure of the left hepatic artery; dissection of the right side of the falciform ligament with exposure of the left branch of …
The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study.
Abstract Background Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure. Patient and methods We propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month g…
Role of Allelic Imbalance in Predicting Hepatocellular Carcinoma (HCC) Recurrence Risk After Liver Transplant.
BACKGROUND One of the most controversial problems for liver transplantation in patients affected by hepatocellular carcinoma (HCC) remains the lack of an oncologic staging system to predict cancer recurrence after liver transplantation (LT). We analyzed allelic imbalance (AI) in 19 microsatellites, and assessed the post-LT HCC recurrence risk. MATERIAL AND METHODS Seventy-one patients were included; 18 had tumor recurrence within 5 years post-transplant. Molecular analysis was done in the primary HCC and peripheral blood samples: a total of 19 microsatellites was used to assess AI. Specific AI was evaluated when outside of range value between 0.66 and 1.5. Based on data in the literature, w…
The use of normothermic machine perfusion to rescue liver allografts from expanded criteria donors
The use of expanded criteria donors is one of the strategies used to overcome the gap between the demand for organs and the number of donors. Physicians debate the extent to which marginal grafts can be used. In recent years, normothermic machine perfusion (NMP) has been used to test liver viability before transplantation. Grafts underwent NMP whenever histological steatosis was > 40% or there were at least three Eurotransplant criteria for expanded criteria donor (ECD). We used NMP to test 19 grafts, 3 from donation after type 3 controlled cardiac death (DCD), and 16 from donation after brain death (DBD). Only two grafts from DBD were not transplanted, because perfusion proved they were…
Additional file 1 of Case report: Trans-papillary free stenting of the cystic duct and of the common bile duct in a double biliary ducts anastomoses of a right lobe living donor transplantation
Additional file 1: Video. Imaging evaluation and surgical maneuvers.