Bariatric surgery post-liver transplantation: A Belgian nationwide study.

Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. We conducted a national retrospective analysis in 5 Belgian transplant centers and included 25 patients with an LT followed by a bariatric procedure. A total of 187 LT patients without BS were included for comparison. Clinical, biochemical, and outcome data were retrospectively retrieved. In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared with the non-BS population (54.5 vs. 60.6, p <0.001). Weight loss was significant and sustained, with a decrease in body mass index from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS ( p <0.001) and 31.1±5.8 3-5 years post-BS ( p <0.001). Three pre-BS (12.0%) patients presented with recurrent and one (4.0%) de novo metabolic dysfunction-associated steatotic liver disease after LT, with 100% resolution post-BS ( p =0.016). Notable reductions were observed in alanine transaminase levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p =0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p <0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a nonhepatic malignancy and one (4.0%) due to liver failure. SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent metabolic dysfunction-associated steatotic liver disease post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

Impact of enhanced recovery program implementation on postoperative outcomes after liver surgery: a monocentric retrospective study.

INTRODUCTION: It is still unclear whether enhanced recovery programs (ERPs) reduce postoperative morbidity after liver surgery. This study investigated the effect on liver surgery outcomes of labeling as a reference center for ERP. MATERIALS AND METHODS: Perioperative data from 75 consecutive patients who underwent hepatectomy in our institution after implementation and labeling of our ERP were retrospectively compared to 75 patients managed before ERP. Length of hospital stay, postoperative complications, and adherence to protocol were examined. RESULTS: Patient demographics, comorbidities, and intraoperative data were similar in the two groups. Our ERP resulted in shorter length of stay (3 days [1-6] vs. 4 days [2-7.5], p = 0.03) and fewer postoperative complications (24% vs. 45.3%, p = 0.0067). This reduction in postoperative morbidity can be attributed exclusively to a lower rate of minor complications (Clavien-dindo grade < IIIa), and in particular to a lower rate of postoperative ileus, after labeling. (5.3% vs. 25.3%, p = 0.0019). Other medical and surgical complications were not significantly reduced. Adherence to protocol improved after labeling (17 [16-18] vs. 14 [13-16] items, p < 0.001). CONCLUSIONS: The application of a labeled enhanced recovery program for liver surgery was associated with a significant shortening of hospital stay and a halving of postoperative morbidity, mainly ileus.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. METHODS: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. RESULTS: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DISCUSSION: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Utilization of livers donated after circulatory death for transplantation - An international comparison.

BACKGROUND & AIMS: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. METHODS: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. RESULTS: A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS: Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. IMPACT AND IMPLICATIONS: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.

ERS: A simple scoring system to predict early recurrence after surgical resection for hepatocellular carcinoma.

BACKGROUND: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking. OBJECTIVES: To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC. METHODS: 2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS. RESULTS: Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10-100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival. CONCLUSIONS: ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials.

Assessment of resource capacity and barriers to effective practice of laparoscopic surgery in training hospitals affiliated with the College of Surgeons of East, Central and Southern Africa (COSECSA).

BACKGROUND: The adoption and accessibility of laparoscopy have been serious issues in countries with limited resources, and for varied reasons. This study assessed resource capacity and barriers to the effective practice of laparoscopic surgery in training hospitals affiliated with the College of Surgeons of East, Central and Southern Africa (COSECSA). METHODS: A multi-country survey was conducted from January 2021 to October 2021 using a questionnaire distributed to surgeons in COSECSA hospitals located in 16 different countries. Available resources and surgical volume were assessed, and the barriers to routinely performing laparoscopy were determined. RESULTS: Ninety-four surgeons working in 44 different hospitals from 16 countries participated in the survey. The majority of respondents were general surgeons (n = 75, 79.7%). Other specialties included urology (n = 12, 12.8%) and pediatric surgery (n = 7, 7.4%). Senior surgeons accounted for 60.6% of participants, more than 40% had a managerial position and approximately 20% were surgical trainees. Most respondents practiced in public hospitals (n = 66, 70.2%). A median of three surgeons per hospital performed laparoscopic surgery with, on average, two laparoscopic towers and two sets of laparoscopic instruments available. A median of 10 procedures was carried out per month. The cost of laparoscopic procedures and laparoscopic consumables were reported as being covered by some health insurance payments in 76.9% and 48.4% of cases, respectively. Cholecystectomy was the most commonly reported laparoscopic procedure performed. The five top barriers to performing laparoscopic surgery were: a lack of consumables, a limited quantity of equipment, a lack of skilled surgeons, the high cost of laparoscopic procedures and complicated cases. In addition, having access to skilled anesthesiologists and anesthesia equipment, carbon dioxide, a consistent electric power supply and equipment maintenance were cited as significant challenges. CONCLUSION: The practice of laparoscopy is currently limited in COSECSA countries due to a scarcity of skilled staff and the lack of a funding plan to make laparoscopic services accessible. Therefore, policymakers and stakeholders should take strategic measures to respond to this need.

Successful multimodal management of a large hepatocellular carcinoma in a non-cirrhotic liver: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) found in a non cirrhotic liver represents a minority of HCC cases and remains poorly studied. Due to its specific characteristics and evolution, this tumour requires a different management compared to HCC in a cirrhotic liver. CASE REPORT: The authors describe the case of a 68-year-old man diagnosed with a large giant and only mildly symptomatic HCC in a non-cirrhotic liver. The 23 cm HCC was discovered when a thoracoabdominal computed tomography was performed following mild abdominal pain. After a multidisciplinary discussion the tumour was judged to be borderline, but potentially resectable after neoadjuvant therapy and preparation for surgery. The patient underwent selective internal radiation therapy radioembolization of the right hepatic artery lobe with 5,5 GBq of 90Y-labeled glass microspheres. It was followed by extended right hepatectomy after preparation by embolization of the right portal and the right hepatic veins. Thirty months after surgical resection the patient showed neither clinical, radiological nor biological signs of HCC recurrence. DISCUSSION: HCC in non-cirrhotic liver is less common than in cirrhotic liver but has a better prognosis, thanks to a greater opportunity for surgical resection. The symptoms often emerge late and are unspecific, thus delaying the HCC diagnosis. Advances in surgical resection by laparotomy or laparoscopy, and neoadjuvant therapy in preparation for surgery, have proven to be effective. However, high mortality persists due to late diagnosis linked to the inability of identifying groups at risk of HCC in the non-cirrhotic population and inadequate screening.

[Evaluation of the knowledge on alveolar echinococcosis among general practitioners in the province of Liege : impact of a formative intervention]. / Évaluation des connaissances de l'échinococcose alvéolaire réalisée auprès des médecins généralistes de la Province de Liège : impact d'une intervention formative.

Alveolar echinococcosis is an indigenouszoonosis caused by the growth of the larval stage of a small tapeworm, Echinococcus multilocularis. Despite a low incidence in Belgium, with about 10 cases on average recorded per year, this parasitosis poses a real public health problem because it often remains difficult to diagnose and is potentially fatal in the absence of treatment. General practitioners are on the frontline, but they do not always know enough about the disease, which causes a delay in the diagnosis and impacts the prognosis. The present study aims to assess the level of knowledge of alveolar echinococcosis among general practitioners in the province of Liège via a questionnaire, on the one hand, and to increase their level of knowledge via a formative intervention using a video capsule, on the other hand. We have performed a randomized controlled experimental study, which showed that general practitioners in the province of Liège have limited knowledge on alveolar echinococcosis. This mainly concerns symptomatology, diagnostic tools and treatment. The formative intervention carried out allowed increasing their level of knowledge about this disease.

L'échinococcose alvéolaire est une zoonose autochtone provoquée par le développement tissulaire de la larve d'un petit ténia, Echinoccocus multilocularis. Malgré une faible incidence en Belgique, avec une moyenne de 10 cas recensés par an, cette parasitose pose un réel problème de santé publique car elle reste souvent difficile à diagnostiquer et potentiellement mortelle en l'absence de traitement. Les médecins généralistes sont en première ligne, mais ils ne connaissent pas toujours suffisamment la maladie, ce qui retarde le diagnostic et compromet le pronostic. La présente étude visait à évaluer les connaissances à propos de l'échinococcose alvéolaire des médecins généralistes de la province de Liège via un questionnaire approprié et à accroître leur niveau de connaissance via une intervention formative sous forme de capsule vidéo. Nous avons réalisé une étude à visée expérimentale randomisée contrôlée qui a montré que les médecins généralistes de la province de Liège ont des connaissances partielles sur la symptomatologie, les outils de diagnostic et le traitement. L'intervention formative réalisée a permis d'augmenter leur niveau de connaissances à propos de cette maladie.

[Delayed graft function : an ongoing clinical challenge]. / Reprise retardée de fonction du greffon après transplantation rénale : un challenge clinique toujours d'actualité.

Delayed Graft Function (DGF) is defined as the need for dialysis during the first week after transplantation. DGF is frequent and mostly derived from the ischemia/reperfusion cascade to which the graft is subjected throughout the transplantation process. A graft biopsy is recommended after 7 days of DGF to exclude an episode of acute rejection. Note that DGF per se is associated with an increased risk of acute graft rejection, as well as with a shorter long-term graft survival. Several strategies are being studied to mitigate the ischaemic damage, thereby improving graft quality. Among these, cellular therapy using mesenchymal stromal cells (MSC) is promising, in particular via the administration of MSC in the machine perfusion during the preservation of the graft. We will discuss here the different definitions of DGF and the main predictive factors of DGF, as well as the impact on the graft outcomes. The current strategies to prevent DGF will be briefly reviewed.

La reprise retardée de fonction du greffon rénal (DGF en anglais pour Delayed Graft Function), définie notamment par la nécessité de dialyse durant la 1ère semaine après transplantation, reste un événement fréquent. La DGF résulte principalement des phénomènes d'ischémie/reperfusion auxquels le greffon est soumis tout au long du processus de transplantation. Néanmoins, une biopsie du greffon est préconisée après 7 jours de DGF afin d'exclure une cause non ischémique telle qu'un rejet aigu. La DGF est per se associée à un risque accru de rejet du greffon, ainsi qu'à une moins bonne survie du greffon rénal au long cours. Plusieurs stratégies sont étudiées afin d'atténuer les dommages ischémiques et améliorer la qualité du greffon. Parmi celles-ci, la thérapie cellulaire par cellules stromales mésenchymateuses est prometteuse, notamment via l'administration de celles-ci dans la machine de perfusion lors de la préservation du greffon. Nous aborderons les différentes définitions de la DGF ainsi que ses principaux facteurs prédictifs, l'impact sur le devenir du greffon et, brièvement, les stratégies actuelles dans le cadre de la prévention de la DGF.

Successful heart transplantation from donation after euthanasia with distant procurement using normothermic regional perfusion and cold storage.

While euthanasia has been legalized in a growing number of countries, organ donation after euthanasia is only performed in Belgium, the Netherlands, Spain, and Canada. Moreover, the clinical practice of heart donation after euthanasia has never been reported before. We describe the first case of a heart donated after euthanasia, reconditioned with thoraco-abdominal normothermic regional perfusion, preserved using cold storage while being transported to a neighboring transplant center, and then successfully transplanted following a procurement warm ischemic time of 17 min. Heart donation after euthanasia using thoraco-abdominal normothermic regional perfusion is feasible, it could expand the heart donor pool and reduce waiting lists in countries where organ donation after euthanasia can be performed.

A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation.

BACKGROUND & AIMS: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.

Prevention of Incisional Hernias by Prophylactic Mesh-augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: Five-year Follow-up of a Randomized Controlled Trial.

INTRODUCTION: The incidence of incisional hernias (IHs) after open repair of an abdominal aortic aneurysm (AAA) is high. Several randomized controlled trials have reported favorable results with the use of prophylactic mesh to prevent IHs, without increasing complications. In this analysis, we report on the results of the 60-month follow-up of the PRIMAAT trial. METHODS: In a prospective, multicenter, open-label, randomized design, patients were randomized between prophylactic retrorectus mesh reinforcement (mesh group), and primary closure of their midline laparotomy after open AAA repair (no-mesh group). This article reports on the results of clinical follow-up after 60 months. If performed, ultrasonography or computed tomography were used for the diagnosis of IHs. RESULTS: Of the 120 randomized patients, 114 were included in the intention-to-treat analysis. Thirty-three patients in the no-mesh group (33/58-56.9%) and 34 patients in the mesh group (34/56-60.7%) were evaluated after 5 years. In each treatment arm, 10 patients died between the 24-month and 60-month follow-up. The cumulative incidence of IHs in the no-mesh group was 32.9% after 24 months and 49.2% after 60 months. No IHs were diagnosed in the mesh group. In the no-mesh group, 21.7% (5/23) underwent reoperation within 5 years due to an IH. CONCLUSIONS: Prophylactic retrorectus mesh reinforcement after midline laparotomy for the treatment of AAAs safely and effectively decreases the rate of IHs. The cumulative incidence of IHs after open AAA repair, when no mesh is used, continues to increase during the first 5 years after surgery, which leads to a substantial rate of hernia repairs.

Infusion of Allogeneic Mesenchymal Stromal Cells After Liver Transplantation: A 5-Year Follow-Up.

Various properties of mesenchymal stromal cells (MSCs) might be particularly of interest after liver transplantation (LT). In this article, we report the long-term results of a prospective, controlled, and first-in-human phase 1 study evaluating the safety of a single MSC infusion after LT. A total of 10 LT recipients treated with standard immunosuppression received 1.5 to 3 × 106 /kg third-party unrelated MSCs on postoperative day 3 and were prospectively compared with a control group of 10 LT recipients. Primary endpoints were set to prospectively detect potentially delayed adverse effects of MSC infusion, particularly the occurrence of infections and cancers. Secondary endpoints of liver graft and patient survival, graft rejection and function, occurrence of bile duct complications, and development of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) against liver or MSC donors were studied. The median follow-up was 85 months. There was no difference in overall rates of infection or cancer at 5 years of follow-up between the 2 groups. There was also no difference in secondary endpoints. The prevalence of de novo liver DSAs related to HLA mismatches was twice as high in the MSC group compared with the control group. All of the de novo class II HLA antibodies against MSCs were linked to a shared HLA mismatch between the liver and MSCs. This study confirms the safety of a single MSC infusion after LT. The potential benefits of MSC injections in the context of organ transplantation have yet to be demonstrated by larger prospective studies. The development of anti-HLA antibodies against an MSC donor should be further evaluated, especially in cases of shared HLA mismatches between graft and MSC donors, despite the fact that no deleterious effect has been detected.

COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.

OBJECTIVE: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course. DESIGN: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed. RESULTS: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170). CONCLUSIONS: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

Clinical course and challenging management of early COVID-19 infection after heart transplantation: case report of two patients.

BACKGROUND: There are limited data on Coronavirus disease 2019 (COVID-19) in solid organ transplant patients, especially in heart transplant recipients, with only a few case reports and case series described so far. Heart transplant recipients may be at particular high risk due to their comorbidities and immunosuppressed state. CASE PRESENTATION: This report describes the clinical course and the challenging management of early COVID-19 infection in two heart transplant recipients who tested positive for the SARS-CoV-2 virus in the perioperative period of the transplant procedure. The two patients developed a severe form of the disease and ultimately died despite the initiation of an antiviral monotherapy with hydroxychloroquine coupled with the interruption of mycophenolate mofetil. CONCLUSIONS: These two cases illustrate the severity and poor prognosis of COVID-19 in the perioperative period of a heart transplant. Thorough screening of donors and recipients is mandatory, and the issue of asymptomatic carriers needs to be addressed.

Parastomal hernia after radical cystectomy with ileal conduit diversion: a narrative review.

Radical cystectomy (RC) with ileal conduit urinary diversion has become a common surgical procedure. Stomal complications and particularly parastomal hernia (PH) are the most frequent complications and causes of reintervention after RC with ileal conduit urinary diversion. PH is usually asymptomatic. When PH increases in size and becomes symptomatic, it clearly impairs patients' quality of life in terms of physical limitation, mental distress and social interaction. The aim of this article was to review the current knowledge on PH after RC with ileal conduit urinary diversion, regarding its natural history, risk factors, prevention and surgical management. There is no strong recommendation on the ideal surgical technique for repair of PH after RC, but laparoscopic Sugarbaker or Sandwich techniques with non-absorbable meshes are emerging as the preferred modern means of PH repair. Techniques for prevention and repair of PH after RC need to be specifically evaluated in future prospective studies.

COVID-19 in an international European liver transplant recipient cohort.

OBJECTIVE: Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. DESIGN: We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. RESULTS: 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. CONCLUSION: In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome.

Appendiceal neuroendrocrine neoplasms: incidentaloma or something we should worry about?

PURPOSE OF REVIEW: To synthesize the current knowledge and guidelines on the management of appendiceal neuroendocrine neoplasms (ANENs). RECENT FINDINGS: Most recent guidelines are essentially based on heterogeneous retrospective series. With the advent of a more precise classification of neuroendocrine neoplasms, this heterogeneity is rightly criticized and many 'grey areas' are now debated in expert literature. The only way to solve these issues is through the conduct of large prospective multicentre studies, but this seems somewhat utopian, given the rarity of this disease. SUMMARY: ANENs are rare tumours with a favourable prognosis, and mainly diagnosed in young patients. They are predominantly localized, and diagnosed incidentally on appendectomy. This procedure is curative for the vast majority of patients but ANENs can relapse even a significant time after the first diagnosis. Identifying the risks for recurrence is challenging, with some factors thought to be predictive of nodal involvement. The presence of one or more of these factors justifies an oncological radicalization of the surgical procedure (right hemicolectomy with lymphadenectomy). However, the beneficial impact of this surgical procedure on survival is still unproven.