Primary pure squamous cell carcinoma of the gallbladder.

SummarySquamous cell carcinoma (SCC) is an uncommon and frequently aggressive subtype of gallbladder cancer known for its poor outcomes compared with other gallbladder tumours. Gallbladder SCC typically presents as higher grade and more advanced than adenocarcinoma, resulting in lower estimated survival. Early recognition of these tumours is ideal, but infrequently achieved. Herein is a case of a male patient in his 80s with new onset abdominal pain who was initially diagnosed with cholecystitis, but diagnostic imaging revealed a gallbladder mass. Surgical resection and pathology revealed pure SCC of the gallbladder without local organ invasion or metastatic disease. Pure SCC histology of the gallbladder is rare, with limited studies on clinical presentation, natural history, and optimal treatment.

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.

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.

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.

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 logistic regression models were used to estimate and compare the probability of death and to find potential risk factors for waiting-list death. RESULTS: There were 286 patients on the waiting list for LT during the study period, 122 of whom entered the waiting list prior to the implementation of ISO (Group A) and 164 afterward (Group B). Group A had 62 transplants, and Group B had 116 transplants. Group B showed a lesser probability of death (P = .005) and a greater probability of transplant (P < .001) compared to Group A. In the 2 groups, post-transplant survival was similar. CONCLUSION: Based on preliminary clinical experience from a single transplant center, the ISO allocation system demonstrated an overall reduced probability of patient death while on the waiting list without impairing post-LT survival, suggesting that the ISO system might represent an improved method of organ allocation, with a more beneficial distribution of livers.

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 .