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.

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 graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test. DISCUSSION: This trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes. TRIAL REGISTRATION: ISRCTN27083228

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?

Introduction: Hepatocellular 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). Methods: We 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-stage liver disease severity, oncologic staging, tumor characteristics, and surgical treatments. The Cox model was used to evaluate variables that could predict relapse risks. Relapse risk curves were calculated according to the Kaplan-Meier method, and the log-rank test was used to compare them. Results: There were 557 HCC patients treated with a first-line approach of LR and/or LRTs (n = 335) or LT (n = 222). The median age at initial transplantation was 59 versus 68 for those whose first surgical approach was LR and/or LRT. In univariate analysis with the Cox model, nodule size was the single predictor of recurrence of HCC in the posttreatment setting (HR: 1.61, 95% CI: 1.05-2.47, p = 0.030). For the LRT group, we have enlightened the following clinical characteristics as significantly associated with RHCC: hepatitis B virus infection (which has a protective role with HR: 0.34, 95% CI: 0.13-0.94, p = 0.038), number of HCC nodules (HR: 1.54, 95% CI: 1.22-1.94, p < 0.001), size of the largest nodule (HR: 1.06, 95% CI: 1.01-1.12, p = 0.023), serum bilirubin (HR: 1.57, 95% CI: 1.03-2.40, p = 0.038), and international normalized ratio (HR: 16.40, 95% CI: 2.30-118.0, p = 0.006). Among the overall 111 patients with RHCC in the LRT group, 33 were iteratively treated with further curative treatment (12 were treated with LR, two with MWTA, three with a combined LR-MWTA treatment, and 16 underwent LT). Only one of 18 recurrent patients previously treated with LT underwent LR. For these RHCC patients, multivariable analysis showed the protective roles of LT for primary RHCC after IDLS (HR: 0.06, 95% CI: 0.01-0.36, p = 0.002), of the time relapsed between the first and second IDLS treatments (HR: 0.97, 95% CI: 0.94-0.99, p = 0.044), and the impact of previous minimally invasive treatment (HR: 0.28, 95% CI: 0.08-1.00, p = 0.051). Conclusion: The coexistence of RHCC with underlying cirrhosis increases the complexity of assessing the net health benefit of ILDS before LT. Minimally invasive surgical therapies and time to HCC relapse should be considered an outcome in randomized clinical trials because they have a relevant impact on tumor-free survival

Protective benefit of minimally invasive liver surgery for hepatocellular carcinoma prior to transplant

Aim: The purpose of this study is to assess the benefit of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) given recurrence and future need for liver transplantation (LT). Methods: Data on liver resections were gathered from the Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (IRCCS-ISMETT) from 2003-2021. A retrospective analysis of 1408 consecutive adult patients who had a liver resection was performed with categorization based on the underlying disease process. A sub-analysis studied the 291 patients who had an LLR with an intention to transplant approach after LLR. Results: From 2012 to 2020, ISMETT’s mean annual LLR rate was 45%. Data suggests that a laparoscopic approach to iterative surgical treatment for HCC has demonstrated protective benefits. Compared to open surgery or LT, LLR is protective against the risk of de-listing, post-transplant patient death, tumor recurrence, adhesions, and bleeding in a cirrhotic patient. Kaplan Meier’s analysis showed no difference between post-LT survival curves for those with prior open abdominal surgery or LLR (P = 0.658). Conclusion: Laparoscopic surgery has important protective advantages over laparotomy surgery for the surgical treatment of HCC, particularly since treatment is not always curative. LLR can be considered a bridge therapy for transplantation, ensuring less crowding of waiting lists, a desirable condition in areas of donor storage

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-stage liver disease severity, oncologic staging, tumor characteristics, and surgical treatments. The Cox model was used to evaluate variables that could predict relapse risks. Relapse risk curves were calculated according to the Kaplan–Meier method, and the log-rank test was used to compare them.ResultsThere were 557 HCC patients treated with a first-line approach of LR and/or LRTs (n = 335) or LT (n = 222). The median age at initial transplantation was 59 versus 68 for those whose first surgical approach was LR and/or LRT. In univariate analysis with the Cox model, nodule size was the single predictor of recurrence of HCC in the posttreatment setting (HR: 1.61, 95% CI: 1.05–2.47, p = 0.030). For the LRT group, we have enlightened the following clinical characteristics as significantly associated with RHCC: hepatitis B virus infection (which has a protective role with HR: 0.34, 95% CI: 0.13–0.94, p = 0.038), number of HCC nodules (HR: 1.54, 95% CI: 1.22–1.94, p < 0.001), size of the largest nodule (HR: 1.06, 95% CI: 1.01–1.12, p = 0.023), serum bilirubin (HR: 1.57, 95% CI: 1.03–2.40, p = 0.038), and international normalized ratio (HR: 16.40, 95% CI: 2.30–118.0, p = 0.006). Among the overall 111 patients with RHCC in the LRT group, 33 were iteratively treated with further curative treatment (12 were treated with LR, two with MWTA, three with a combined LR-MWTA treatment, and 16 underwent LT). Only one of 18 recurrent patients previously treated with LT underwent LR. For these RHCC patients, multivariable analysis showed the protective roles of LT for primary RHCC after IDLS (HR: 0.06, 95% CI: 0.01–0.36, p = 0.002), of the time relapsed between the first and second IDLS treatments (HR: 0.97, 95% CI: 0.94–0.99, p = 0.044), and the impact of previous minimally invasive treatment (HR: 0.28, 95% CI: 0.08–1.00, p = 0.051).ConclusionThe coexistence of RHCC with underlying cirrhosis increases the complexity of assessing the net health benefit of ILDS before LT. Minimally invasive surgical therapies and time to HCC relapse should be considered an outcome in randomized clinical trials because they have a relevant impact on tumor-free survival

Motorcycle Crashes and Fatalities from 2007-2018 in Philadelphia, PA: A GIS Mapping and Statistical Analysis to Inform Helmet Law

Worldwide, road traffic injuries are a public health emergency, leading to 1.3 million deaths annually. Among major US cities, Philadelphia has the second-highest per capita rate of traffic deaths; it adopted a Vision Zero (VZ) Initiative in 2016 with the goal of reducing preventable traffic deaths to zero by 2030. Motorcyclists are particularly vulnerable road users: although motorcycles are only 3% of registered vehicles in the US, their operators account for 14% of traffic fatalities. Utilizing a retrospective analysis and Geographic Information System mapping of crash data cross-shared between the Pennsylvania (PA) Department of Transportation (DOT) and Jefferson Center for Injury Research and Prevention, this project analyzes motorcycle crashes between 2007 and 2018 in Philadelphia County. It focuses on the relationship between helmet usage and fatalities for motorcycle operations, as PA repealed its Universal Helmet Law (UHL) in 2003. The study identified the West Park and Lower Northeast Planning Districts as the areas in the city with the highest-burden of crashes and fatalities, including areas outside of current VZ planning, and found a helmet compliance rate among motorcyclists treated at Thomas Jefferson University Hospital of 60.9%. Despite the clear benefits of requiring helmet usage for motorcyclists, a UHL is not in Philadelphia’s VZ Action Plan 2030. The advent of micro-mobility in urban environments (e.g., rentable scooters) and the US DOT’s 2022 adoption of VZ goals suggest an urgent need in Philadelphia to reimplement a UHL and improve targeting resources in areas of danger to motorcyclists

Immunosuppression, compliance, and tolerance after orthotopic liver transplantation: state of the art

Orthotopic liver transplantation is the treatment of choice for several otherwise irreversible forms of acute and chronic liver diseases. Early implemented immunosuppressant regimens have had disappointing results with high rejection rates. However, new drugs have reduced the daily immunosuppression requirements, thereby improving graft and patient survival as well as kidney function. Liver rejection is a T-cell-driven immune response and is the active target of immunosuppressive agents. Immunosuppressants can be divided into pharmacological or biological drugs: the gold standard is the calcineurin inhibitors, steroids, mycophenolate mofetil, and mechanistic target of rapamycin inhibitors. Compliance with these agents is essential, although they can increase the risk of infections and neoplastic diseases. In some patients, graft tolerance can be achieved. Graft tolerance is defined as the absence of acute and chronic rejection in a graft, with normal function and histology in an immunosuppression-free, fully immunocompetent host, usually as the final result of a successful attempt at immunosuppression withdrawal. The occurrence of immunosuppressive-related complications has led to new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. The backbone of immunosuppression remains calcineurin inhibitors in association with other drugs, mainly over the short-term period. To avoid rejection and the side effects on renal dysfunction, de novo cancer, and cardiovascular syndrome, optimal long-term immunosuppressive therapy should be tailored in liver transplant recipients

Protective benefit of minimally invasive liver surgery for hepatocellular carcinoma prior to transplant

Aim: The purpose of this study is to assess the benefit of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) given recurrence and future need for liver transplantation (LT).Methods: Data on liver resections were gathered from the Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (IRCCS-ISMETT) from 2003-2021. A retrospective analysis of 1408 consecutive adult patients who had a liver resection was performed with categorization based on the underlying disease process. A sub-analysis studied the 291 patients who had an LLR with an intention to transplant approach after LLR.Results: From 2012 to 2020, ISMETT’s mean annual LLR rate was 45%. Data suggests that a laparoscopic approach to iterative surgical treatment for HCC has demonstrated protective benefits. Compared to open surgery or LT, LLR is protective against the risk of de-listing, post-transplant patient death, tumor recurrence, adhesions, and bleeding in a cirrhotic patient. Kaplan Meier’s analysis showed no difference between post-LT survival curves for those with prior open abdominal surgery or LLR (P = 0.658).Conclusion: Laparoscopic surgery has important protective advantages over laparotomy surgery for the surgical treatment of HCC, particularly since treatment is not always curative. LLR can be considered a bridge therapy for transplantation, ensuring less crowding of waiting lists, a desirable condition in areas of donor storage

Mesenteric cyst with GI symptoms: a fluid approach to treatment-case report and literature review

Mesenteric cysts are defined as a heterogeneous group of intra-abdominal cystic lesions of the mesentery or omentum that may be found in any portion of the gastrointestinal tract from the duodenum to the rectum. The clinical condition is entirely asymptomatic in many patients, particularly with small cysts. The diagnosis is typically incidental and secondary to imaging performed for other purposes. In symptomatic patients, the clinical picture is characterized by nonspecific gastrointestinal signs and symptoms. Treatment may be surgical or via interventional radiology. We report the case of a 55-year-old female patient complaining of left-sided abdominal discomfort and constipation lasting three months. An abdominal ultrasound showed the presence of a 10 × 14 × 16 cm anechoic cystic mass filling the whole anterior and left abdominal cavity, confirmed by CT and MRI. The cyst, removed laparoscopically, was histologically a simple mesothelial cyst. We reviewed the international literature over the last 10 years of all cases with mesenteric cysts > 10 cm in evaluating gastrointestinal symptoms at diagnosis, histology, performed treatment, and outcome