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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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pagano, Khouzam, Magro, Barbara, Cintorino, di Francesco, Li Petri, Bonsignore, Calamia, Deiro, Cammà, Canzonieri and Gruttadauria.)

Background: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known., Methods: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly., Results: HAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%-7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122-755 days). Indications for biopsy were follow-up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss., Conclusion: HAGPN is an infrequent, unanticipated, and clinically significant complication of KT., (© 2022 Wiley Periodicals LLC.)

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 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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Induction immunosuppression has improved the long-term outcomes after lung transplant. This is the first report exploring the association of induction immunosuppression with the development of de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) in lung transplant recipients (LTR)., Methods: Sixty-seven consecutive primary LTR were followed for 3 years posttransplant. A total of 41/67 (61%) LTR-received induction immunosuppression using a single dose of rabbit Antithymocyte Globulin (rATG; 1.5 mg/kg) within 24 h of transplant. All recipients had a negative flow cytometry crossmatch on the day of transplant. Serum samples at 1, 3, 6, and 12 months posttransplant were assessed for the presence of de novo HLA DSA., Results: De novo HLA DSA were detected in 22/67 (32.8%) LTR within 1-year posttransplant. Of these, 9/41 (21.9%) occurred in the induction therapy group and 13/26 (50%) in the noninduction group. Class II DSA were detected in 3/41 (7.3%) LTR who received induction compared to 9/26 (34.6%) LTR without induction immunosuppression (p = .005). Differences in overall survival or freedom from chronic lung allograft dysfunction rates between the two groups were not statistically significant., Conclusion: Induction immunosuppression utilizing a modified regimen of single-dose rATG is associated with a significant reduction in de novo DSA production in LTR., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction. COVID-19 presents a special challenge to the kidney transplant population. Methods. A systematic review of articles that examined COVID-19 in kidney transplant recipients was performed. Patients' demographics, clinical, laboratory and radiological presentations, immunosuppression modification, and COVID-19 specific management were abstracted and analyzed. COVID-19 severity was classified into mild, moderate, and severe. Disease outcome was classified by whether the patient was discharged, still hospitalized, or died. Results. 44 articles reporting individual data and 13 articles reporting aggregated data on 149 and 561 kidney transplant recipients respectively with COVID-19 from Asia, Europe and America fulfilled all inclusion and exclusion criteria. Among studies reporting case specific data, 76% of cases had severe disease. Compared to patients with mild/moderate disease, patients with severe disease had higher CRP, LDH, Ferritin, D-dimer and were more likely to have bilateral lung involvement at presentation and longer time since transplantation (P < 0.05 for all). Recipients' age, gender and comorbidities did not impact disease severity. Patients with severe disease had a more aggressive CNI reduction and more antiviral medications utilization. Outcome was reported on 145 cases, of those 34 (23%) died all with severe disease. Longer duration from transplant to disease diagnosis, hypoxia and higher LDH were associated with mortality (P < 0.05). Different immunosuppression reduction strategies, high dose parenteral corticosteroids use and various antiviral combinations did not demonstrate survival advantage. Similar finding was observed for studies reporting aggregated data. Conclusion. COVID-19 in kidney transplant patients is associated with high rate of disease severity and fatality. Higher LDH and longer time since transplantation predicted both disease severity and mortality. None of the COVID-19 specific treatment correlated with, or improved disease outcome in kidney transplant recipients., (© 2021 Irtiza Hasan et al., published by Sciendo.)

Background: Improvement in short-term outcomes after kidney transplant has been achieved by using different induction and maintenance therapeutic approaches. Long-term outcomes have not matched the expectations of the transplant stakeholders. Our study aimed to address the early impact of induction agents on long-term outcome of kidney transplant when measured by iothalamate clearance., Methods: All adult kidney transplant recipients between January of 2012 and December of 2016 were reviewed. Six hundred forty-nine patients were divided into three groups based on the induction agent (basiliximab, alemtuzumab, and thymoglobulin). Protocoled 4 months and 48 months kidney allograft function evaluations with iothalamate clearance test were compared among the three groups., Results: Patients who received basiliximab were significantly older with no difference among African American and Caucasians. The 48 months assessment showed significant decline in median iothalamate clearance in basiliximab group at 49 mL/min vs. alemtuzumab group 64.8 mL/min and thymoglobulin 60 mL/min with P = 0.007. The basiliximab group developed a significant higher proteinuria measured by spot urine to creatinine ratio at 48 months., Conclusions: The use of basiliximab as an induction agent for kidney transplant is associated with significant decline in kidney function 4 years post transplantation when measured by iothalamate clearance., Competing Interests: None to declare., (Copyright 2020, Jarmi et al.)

Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre-LT predictors of potentially reversible renal injury using histological information obtained on pre-LT renal biopsy. Data on 128 LT candidates who underwent pre-LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End-Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision-making process to list patients with renal dysfunction for LT alone versus simultaneous liver-kidney transplantation., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 .

Over the past decade, four randomized, controlled trials have evaluated therapies for prevention of sudden cardiac death in patients with coronary disease. Three of the four trials have shown significant reductions in mortality with implanted defibrillators. Two studies failed to demonstrate any benefit from pharmacologic antiarrhythmic therapy. The results of these studies in similar patient populations have erased any doubt regarding the ability of implanted defibrillators to reduce the risk of sudden death in patients with coronary disease. Our major challenge at this time is understanding how best to utilize this therapy in order to bring the benefit to the maximum number of patients while minimizing expense.

From overall data on 54 diabetic patients, who, over a period of 7 years, underwent operations to save their feet from ischaemia (whether linked or not to infection), the authors study 31 cases of revascularization through arterial bridging in the diabetic's lower limbs. The lesions were identified by doppler examination followed by arteriography. Various types of bridging were undertaken: 24 femoro-popliteal bridges, including 16 super-articular and 8 sub-articular ones; and 7 femoro-distal bridges on the leg artery trunks. For the post operational period, only one amputation, resulting from precocious thrombosis in the graft, had been noted. All the patients had been followed up, and the authors remarked that, after an average lapse of 43 months, actuarial survival without amputation of the lower limb amounted to 94.97% after 7 years, and the level of actuarial permeability of the bridges amounted to 72.61% after the same period. The authors stress that revascularization indications should be the same for atheromatous diabetics as for non diabetics.

We have evaluated the cardiac risk for 212 patients who underwent internal carotid surgery (245 operations). The mean age at the time of operation was of 63 +/- 8 years. A complete pre-operative cardiac assessment was performed splitting the patients in two groups: one considered as having a coronary heart disease (CHD) and the other as "healthy heart" (HH). The peri-operative cardiac morbidity and mortality rate were low (CHD group: 16.88%; HH group: 2.22%). At a 2 years follow-up we notice 31% of cardiac problems in the CHD group (with a mortality rate of 5.7%) for 3.9% in the HH group (with a mortality rate of 3.9%). The 4 years follow-up gives similar results.