Background & Aims Abdominal surgery often precipitates postoperative ileus (POI), a frequent and severe gastrointestinal (GI) motility disorder, through mechanisms that involve intestinal inflammation. Emerging data show that enteric glia acquire a reactive phenotype that aggravates POI, but how glia exert this effect remains unclear. Enteric glia express connexin-43 hemichannels (gCx43), which are implicated in neurological and inflammatory disorders. Thus, we aimed to decipher contributions of glial connexin-43 (Cx43) in the pathophysiology of POI. Methods We induced POI in mice using in vivo intestinal manipulation and used glial Cx43cKO (Sox10CreERT2;Cx43fl/fl) or RiboTag (Sox10CreERT2/Rpl22HA/+) mice to evaluate Cx43-dependent signaling. Human enteric glial cultures (hEGC) and muscularis externa obtained during intestinal surgery translated findings to patients. Transcriptome analysis, immunofluorescence co-labeling, Western blots, and Cx43 hemichannel activation were used for quantitative analysis. Results Cx43 is the highest expressed connexin in enteric glia in mice and humans. Up-regulation of Cx43 occurs in various disease models linked to POI, GI surgical trauma, inflammation, immune cell activation, and enteric gliosis. In the mouse POI model, glial Cx43-deletion reduces glial reactivity, pro-inflammatory signals, upregulates host protection genes, regulates immune cell activation, and prevents enteric neuropathy. In hEGCs, interleukin (IL)-1β induction opens Cx43 and stimulates release of IL-6 and C-C motif ligand 2 (CCL2). The Cx43 peptide inhibitor, 43Gap26, inhibits glial Cx43 activation, reduces IL-6 release, and blocks upregulation of macrophage activation factors and immune cell regulation factors. Surgical intestinal trauma in patients upregulates Cx43 during inflammation and enteric gliosis in mouse POI. Conclusions Glial Cx43 signaling promotes enteric gliosis, immune cell activation, inflammation, and enteric neuropathy in mice with potential translatability to humans after intestinal surgical trauma and mechanical stress in POI. Interventions that block glial Cx43 activation may be protective against POI development.

Background: Kidney disease is frequent among recipients of liver allografts. However, data on non-renal risk factors for change of kidney function after transplant are limited. We aimed to identify clinical non-renal parameters at transplant predicting deterioration or improvement of kidney function stage after transplant.Methods: All adult patients undergoing liver transplant at our centre over a ten-year period were retrospectively analysed for non-renal risk factors for change of kidney function after transplant. Kidney function was categorized by estimated glomerular filtration rate. Improvement or deterioration of kidney function was defined as change of at least one category compared to time of transplant. Statistical analysis was done by chi-squared test, Mann-Whitney U test and conditional forward binary regression analysis.Results: Six months after transplant, kidney function had stabilised in most patients, which was therefore chosen as timepoint for comparison. 33/165 (20%) of patients showed decreased kidney function, while 31/165 patients (19%) displayed improved kidney function by at least one stage. Presence of hepatocellular carcinoma (HCC) was the only risk factor associated significantly with deterioration of kidney function in multivariate analysis (OR 4.1; p=0.004). Conversely, hepatorenal syndrome was the only predictive parameter for improvement of kidney disease in multivariate analysis (OR 4.4; p=0.03). Patients with HCC were characterized by an accumulation of risk factors for kidney disease such as older age and diabetes.Conclusion: If confirmed in larger multicentric studies, HCC patients, whose frequency among liver transplant recipients is rising, should receive more awareness concerning preserving kidney function after transplant.

Malignome als insgesamt zweithäufigste Todesursache spielen auch bei Transplantationskandidaten und nach Transplantation eine große Rolle. Ein ausreichender Malignomausschluss vor der Transplantation verbessert die Sicherheit der Immunsuppression. In einzelnen Fällen kann die Transplantation der Leber allerdings auch Mittel der Tumortherapie sein. Nach einer Transplantation ist eine intensivierte Tumorvorsorge notwendig. Dabei sind nach der Transplantation nichtmelanomatöse Hauttumoren extrem häufig. Typischerweise und relativ zur Allgemeinbevölkerung steigt vor allem das Risiko virusbedingter Tumoren. Hier ist wegen der signifikanten Mortalität die lymphoproliferative Erkrankung nach Transplantation hervorzuheben, die mit dem Epstein-Barr-Virus assoziiert ist. Nach Nierentransplantation sind Nierenzellkarzinome, insbesondere der Eigennieren, überzufällig häufig. Chemotherapeutikadosierungen müssen an die Leber- und Nierenfunktion angepasst werden, gerade bei neueren Substanzen sind mögliche Arzneimittelinteraktionen mit hoher Aufmerksamkeit zu recherchieren. Die bei vielen Tumorentitäten erfolgreichen Immuntherapien sind nach Organtransplantation eine große Herausforderung, da sie regelhaft auch eine Immunreaktion gegen das Transplantat hervorrufen. Hier muss individuell entschieden werden, auch danach, ob das Transplantat lebenserhaltend ist oder gegebenenfalls durch Dialyse ersetzt werden kann.

Recipient warm ischemia time (rWIT) in liver transplantation (LT) – which is defined as the time from removal of the graft from cold storage until reperfusion with portal and/or arterial blood flow – has been linked to negative outcomes. Biliary complications, particularly biliary strictures, are a major cause of morbidity after LT. However, the relationship between rWIT in donation after brain death (DBD) LT and biliary strictures has not been well explored. This single-center study retrospectively analyzed data from 162 DBD-LT recipients (2013-2022). Patients were divided into two groups: rWIT ≤30 minutes (n=33) and rWIT >30 minutes (n=129). Livers did not undergo any in situ or ex situ machine perfusion techniques. Biliary complications occurred at similar rates in both groups (p=0.5). Biliary strictures tended to be more common in the rWIT >30 minutes group, although without statistical significance (40% vs. 24%; p=0.1). The median serum bilirubin levels on day 5 were significantly higher in the rWIT >30-minute group (5.2 (IQR 2.6, 8.9) mg/dl vs. 3.7 (IQR 1.9, 5.9) mg/dl; p=0.013). Patients with rWIT >30 minutes required significantly more blood transfusions intraoperatively (p=0.021). There was a high tendency for higher severe complication rates in the rWIT >30-minute group, which was not significant (58% vs. 39%; p=0.054). Prolonged rWIT in LT was associated with a trend toward a higher incidence of bile duct strictures and elevated liver enzymes. However, due to the retrospective design and risk of selection bias, rWIT should be interpreted as one of several contributing factors. Our findings suggest that minimizing rWIT may support better outcomes, but causality cannot be definitively established.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.

Liver transplantation (LT) is the preferred treatment for patients with cirrhosis who suffer from hepatopulmonary syndrome (HPS). However, the effects of HPS on LT are controversial. The present study investigated the correlation between the severity of HPS and survival after LT and compared the incidence of postoperative complications between patients with and without HPS who underwent LT.

4008 Background: Radical surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) and (incidental) Gallbladder Carcinoma ((I)GBC). Nevertheless, 5-year OS is only 20–40% after curatively intended resection and data regarding pure adjuvant chemotherapy in BTCs are currently conflicting. Encouraging results of neoadjuvant/perioperative concepts in other malignancies provide a rationale to use this treatment in the early phase management of GBC and intrahepatic as well extrahepatic cholangiocarcinoma (ICC/ECC). Methods: GAIN is a multicenter, randomized, controlled, open-label phase III trial, including patients (pts) with localized or locally advanced resectable non metastatic biliary tract cancer (intra-/extrahepatic cholangiocarcinoma ICC/ECC; GBC in front of radical liver resection). Pts were randomized to either neoadjuvant (perioperative) systemic chemotherapy (Gemcitabine + Cisplatin 3 cycles pre- and post-surgery) followed by radical surgery (Arm A) or to direct surgery followed by adjuvant treatment (Arm B) according to investigators choice. Primary endpoint was OS; secondary endpoints were PFS/EFS, R0-resection rate, toxicity, perioperative morbidity, mortality and QoL. Recruitment was stopped after enrollment of 68 pts due to a slow enrollment rate. Results: Between Dec 2019 and Feb 2024, 68 pts were randomized and the ITT comprised 32 pts in Arm A and 30 pts in Arm B. Baseline characteristics were similar between arms (overall, male 55%; median age 66.0; cT3/T4 29.0%; cN+ 30.6%; 37.1% ICC, 30.6% ECC and 32.3% GBC). 90.6% of pts in Arm A completed all 3 pre-operative cycles. 43.8% in Arm A completed adjuvant treatment and 23.3% in Arm B received adjuvant treatment. Median follow-up was 11.8 months. Neoadjuvant treatment improved OS (mOS, Arm A 27.8 vs. 14.6 months Arm B; HR 0.46 [0.22 - 0.96]; p = 0.04) and R0 resection rate (62.5% vs 33.3%). This effect was also seen in event-free survival. Postoperative morbidity rates were similar in both arms (33.3% (A) vs. 32% (B)) and the 30- and 90-days mortality rates were lower for Arm A (30-days: 4.2% vs. 24%; 90-days: 4.2% vs. 28%). No new safety/toxicity signals were observed. In Arm A, 12 pts (38.7%) had at least one treatment related adverse event (TRAE) with grade 3 and 1 pt (3.2%) with grade 4. No fatal TRAEs were observed. Conclusions: Neoadjuvant / perioperative gem/cis clearly improved OS and R0 resection rate in pts with biliary tract cancer compared to direct surgery and was able to nearly double mOS while not increasing the morbidity rate and even decreasing mortality rates. Clinical trial information: NCT03673072 .

Zusammenfassung Die vorliegende multizentrische, prospektive Beobachtungsstudie untersuchte die Wirksamkeit und Sicherheit einer neoadjuvanten Chemotherapie bei Patienten mit grenzwertig resektablem Pankreaskarzinom und bei Patienten mit resektablem Pankreaskarzinom, das Kontakt mit großen Gefäßen hat, im Vergleich mit einer historischen Kontrolle.

Malignant neoplasms constitute a major burden of morbidity and mortality in the general population. This necessitates intense screening of transplant candidates and even closer surveillance of immunosuppressed solid organ recipients. Active malignancy is an exclusion criterion to solid organ transplantation, with few exceptions, namely localized hepatic neoplasms. Accelerated tumor progression characterizes post-transplantation malignancies. Intensified surveillance is justified in elevated rates, e.g., of skin cancer and virus-associated neoplasms, especially Epstein-Barr virus-associated post-transplantation lymphoproliferative disease (PTLD). Renal cell cancer rates rise after kidney transplantation, predominantly affecting the native kidneys. Chemotherapeutic dose adjustments for renal and hepatic function pharmacokinetic interactions are frequent and require active monitoring. Immunotherapies pose new challenges by induction of allograft rejection. Data on management of immunosuppression are emerging. Individualized concepts need to take into account therapeutic options of both anti-cancer therapy and organ replacement.

The aim was to predict poor overall survival in patients with pancreatic cancer treated with FOLFIRINOX based on clinical and computed tomography findings.

Dexamethasone has been shown to be effective in improving postoperative outcomes in surgical patients, but its effect on postoperative complications after pancreaticoduodenectomy is unclear.

Organspende nach Kreislauftod (DCD) erweitert weiterhin den Zugang zu Transplantationen und verbessert die Wartelistenergebnisse fur Leber- und Herztransplantationskandidaten. Trotz eines erhohten Mortalitatsrisikos bei DCD-Nieren-, -Leber- und -Lungentransplantation bleibt das uberleben bei DCD-Transplantation akzeptabel.

Mehrere Studien deuten darauf hin, dass Patienten mit Nierenversagen im Vergleich zur Standard-Hämodialyse von einer hochdosierten Hämodiafiltration profitieren könnten. Angesichts der Einschränkungen der verschiedenen veröffentlichten Studien sind jedoch zusätzliche Daten erforderlich.

Ziel dieser Studie ist es, den Einfluss von Spenderdiabetes auf die klinischen Ergebnisse nach einer Lebertransplantation zu bewerten. Spenderdiabetes war mit schlechteren Ergebnissen nach LT verbunden, insbesondere bei Patienten, die LT wegen nicht alkoholischer Steatohepatitis-Zirrhose erhielten.

Es sollte untersucht werden, ob eine zielgerichtete Albuminsubstitution wahrend der Operation und nach der Anasthesie durch die Aufrechterhaltung einer Serumalbuminkonzentration von > 30 g/l postoperative Komplikationen reduzieren kann.