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…

Single center report on complications in steroid-free immunosuppressive therapy of liver transplant recipients

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 …

Left Spigelian Hernia in Super-Obese Patient: A Case-Report.

Abstract: We report a case in which a giant Spigelian hernia presented with severe, persistent abdominal pain in a 62- year-old super-obese woman with a history of total abdominal hysterectomy-bilateral salpingo-oopherectomy at the age of 40 years for benign neoplasia, who later underwent open hernia repair (maximal diameter of the hernia sac: 21 cm) because of the development of compartment syndrome. Afterward, although a large incarcerated hernia disease was found, the sac removal was technically difficult and an open procedure was carried out, with double-mesh placement. No complications were recorded during the post-operative course. We report a difficult issue related to the diagnosis …

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…

Merits and differences between single-site robotic and laparoscopic cholecystectomy: What is unfair? Commentary on "Propensity score-matching analysis for single-site robotic cholecystectomy versus single-incision laparoscopic cholecystectomy: A retrospective cohort study"

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…

Importance of sarcopenia parameter changes after living donor liver transplantation

The systemic role of muscle tissue is strengthened by the large system of hormones, chemokines and other mediators that constitute a dense network of communication between the skeletal muscle and the liver (1,2). This, associated with the evidence of a progressive malnutrition and depletion of muscle mass in end-stage liver disease (ESLD) patients, has led many to study the role of sarcopenia and its systemic effects in this setting, and to identify it as critical risk factor for post- liver transplantation (LT) mortality (3-5). Englesbe and colleagues found a direct correlation between central sarcopenia, measured by computerized tomography (CT), the total area of the psoas muscle (psoas a…

Risk factors for bile leakage after liver resection for neoplastic disease.

Biliary leakage (BL) remains the most frequent and feared complication after hepatoresective surgery. Placement of the abdominal drainage at the end of liver surgery remains controversial due to the delicate balance between risks and potential benefits in case of BL. The study was aimed to detect possible risk factors for BL occurrence after liver surgery. We enrolled all oncologic patients who underwent liver resection from June 2016 to March 2021. BL was diagnosed according to the ISGLS definition. We have examined demographic characteristics of the patients, type of neoplasia, presence of cirrhosis, neoadjuvant chemotherapy and type of intervention. Uni- and multivariable analyses were p…

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…

The STROCSS statement: Strengthening the Reporting of Cohort Studies in Surgery

Abstract Introduction The development of reporting guidelines over the past 20 years represents a major advance in scholarly publishing with recent evidence showing positive impacts. Whilst over 350 reporting guidelines exist, there are few that are specific to surgery. Here we describe the development of the STROCSS guideline ( St rengthening the R eporting o f C ohort S tudies in S urgery). Methods and analysis We published our protocol apriori . Current guidelines for case series (PROCESS), cohort studies (STROBE) and randomised controlled trials (CONSORT) were analysed to compile a list of items which were used as baseline material for developing a suitable checklist for surgical cohort…

Early 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 between November 2004 and January 2010. Liver regeneration was evaluated with multidetector computed tomography (MDCT) at a mean of 61.07 days after surgery. Presurgical variables [eg, age, weight, height, body mass index (BMI), liver function tests, creatinine levels, platelet counts, international normalized ratio, and glucose levels] and variables detected with preoperative MDCT imaging [eg, main portal vein diameter, steatosis, original liver volume, and spleen volume (SV)] were investigated as potential predictors of liver regeneration. The future remnant liver volume (FR…

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 …

Machine Perfusions in Liver Transplantation: The Evidence‐Based Position Paper of the Italian Society of Organ and Tissue Transplantation

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d’Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of th…

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…

Benign liver lesions 2022: Guideline for clinical practice of Associazione Italiana Studio del Fegato (AISF), Società Italiana di Radiologia Medica e Interventistica (SIRM), Società Italiana di Chirurgia (SIC), Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB), Associazione Italiana di Chirurgia Epatobilio-Pancreatica (AICEP), Società Italiana Trapianti d'Organo (SITO), Società Italiana di Anatomia Patologica e Citologia Diagnostica (SIAPEC-IAP) – Part I – Cystic lesions

Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicat…

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…

Sicily Network for Liver Cancer: A Multidisciplinary Network Model for the Management of Primary Liver Tumors

Background: The management of primary liver tumors requires the involvement of multiple specialist skills and the best possible treatment in terms of cost, risk, and benefit that could be provided by hepatobiliary or transplant surgeon, interventional radiologist, hepatologist, radiotherapist, or oncologist is needed to be chosen for each patient. This is particularly relevant for hepatocellular carcinoma (HCC), that is the most common primary liver tumor, and it occurs in more than 90% of cases in the setting of cirrhosis. Methods: To address the increasing complexity of cancer care, multidisciplinary tumor boards (MDTBs) have evolved to offer patients appropriate and tailored cancer treat…

Mini-Invasive Approach Contributes to Expand the Indication for Liver Resection for Hepatocellular Carcinoma Without Increasing the Incidence of Posthepatectomy Liver Failure and Other Perioperative Complications: A Single-Center Analysis.

Liver resection (LR) for hepatocellular carcinoma (HCC) is the best alternative option for increasing the survival of many patients with intermediate or advanced stages of the Barcelona Clinic Liver Cancer staging classification. Mini-invasive approach may play a positive role in treating a tumor rising almost exclusively in a diseased liver.A prospectively collected database was retrospectively reviewed for 167 consecutive patients who underwent LR between 1999 and 2015.A total of 38 LRs were performed from 1999 to 2009 (Period I), and 129 between 2010 and 2015 (Period II). Laparoscopic procedures increased from 5.3% to 38.1%. Not undergoing laparoscopic LR increased length of stay, and Cl…

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.