Andreas Anton Schnitzbauer

Portale Hypertonie ist mit erheblicher Morbidität und Mortalität verbunden. Die Leberzirrhose macht bis zu 90 % der Fälle von portaler Hypertonie aus, während etwa 10 % auf nicht-zirrhotische Faktoren, einschließlich vaskulärer Lebererkrankungen, zurückzuführen sind. Diese Erkrankung kann zu schweren Komplikationen führen, wie der Entwicklung von gastroösophagealen Varizen, die das Risiko von varikösen Blutungen erheblich erhöhen. Weitere häufige Komplikationen der portalen Hypertonie sind Aszites und hepatorenales Syndrom (HRS). Eine transjuguläre intrahepatische portosystemische Shunt (TIPS)-Implantation wird als die effektivste Behandlung zur Bewältigung der portalen Hypertonie angesehen. Studien zeigen, dass die TIPS-Implantation die Überlebensraten bei Patienten mit wiederkehrendem Aszites sowie bei ausgewählten Patienten mit refraktärem Aszites und varikösen Blutungen verbessern kann. Allerdings können periinterventionelle und postinterventionelle Komplikationen die Anwendung von TIPS einschränken. Neueste Entwicklungen bei Geräten, Techniken und prophylaktischen Medikamenten zielen darauf ab, das Risiko von Komplikationen nach dem Eingriff zu minimieren. Dieses interdisziplinäre Positionspapier fasst Empfehlungen und Anleitung zur Patientenwahl, zu Indikationen und Kontraindikationen, zu Techniken sowie zur Nachsorge von Patienten zusammen, die in Deutschland ein TIPS-Verfahren erhalten. Portal hypertension is associated with significant morbidity and mortality. Liver cirrhosis accounts for up to 90 % of portal hypertension cases, while approximately 10 % are due to non-cirrhotic factors, including vascular liver diseases. This condition can lead to various complications, such as the development of gastroesophageal varices, which greatly increase the risk of variceal bleeding. Other common complications of portal hypertension include ascites and hepatorenal syndrome (HRS). The transjugular intrahepatic portosystemic shunt (TIPS) procedure is regarded as the most effective treatment for managing portal hypertension. Research shows that TIPS insertion can improve survival rates for patients with recurrent ascites, as well as for select individuals with refractory ascites and variceal bleeding. However, peri-interventional and post-interventional complications may pose challenges to the use of TIPS. Recent advancements in devices, techniques, and prophylactic medications aim to minimize the risk of complications following this procedure. This interdisciplinary position paper summarizes recommendations and guidance regarding patient selection, indications and contraindications, techniques, and follow-up care for patients undergoing TIPS in Germany. ^* Teilen die erste oder die letzte Autorschaft. Received: 25 November 2024 Accepted after revision: 08 May 2025 Article published online: 10 November 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/). Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Data on the impact of autophagy in primary cholangiocarcinoma (CCA) remain scarce. Here, we therefore investigated the role of active autophagy and its impact on survival in CCA patients. All CCA patients who underwent surgical resection with curative intent between 08/2005 and 12/2021 at University Hospital Frankfurt were evaluated. Autophagic key proteins were studied by immunohistochemistry. iCCA processed for gene expression profiling of immune-exhaustion gene sets was used for an autophagy approach in silico. Active autophagy was present in 23.3% of the 172 CCA patients. Kaplan–Meier curves revealed median OS of 68.4 months (95% CI = 46.9–89.9 months) and 32.7 months (95% CI = 23.6–41.8 months) for active and non-active autophagy, respectively (p ≤ 0.001). In multivariate analysis, absence of active autophagy (HR = 2, 95% CI = 1.1–3.5, p = 0.015) was an independent risk factor for OS. Differential-expression profiling revealed significantly upregulated histone deacetylases (HDAC) mRNA in patients showing non-active autophagy. In line with this, pan-acetylated lysine was significantly more prominent in CCA patients with ongoing autophagy (p = 0.005). Our findings strengthen the role of active autophagy as a prognostically relevant marker and a potential therapeutic target.

Background and Aims: In patients with Rat sarcoma proto-oncogene (RAS) wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) antibodies have been established in first- and further therapy lines. Due to limited treatment options upon disease progression, anti-EGFR re-exposure is increasingly employed in real-world oncology. The aim of this study was to assess clinical implementation and utility of anti-EGFR retreatment strategies in real-world mCRC patients. Methods: In this monocentric retrospective study, we included 524 patients with CRC and identified patients who received an anti-EGFR-based treatment as well as anti-EGFR rechallenge (progression on first-line anti-EGFR therapy) or reintroduction (discontinuation due to intolerance/toxicity/other). Results: In total, 143 patients received an anti-EGFR-based first- or second-line treatment, showing a similar overall survival (OS) compared to the non-anti-EGFR treatment group (38.3 vs. 39.6 months, p = 0.88). Thirty-three patients met the inclusion criteria for anti-EGFR re-exposure and were either assigned to rechallenge (n = 21) or reintroduction (n = 12) subgroups. The median FU after re-exposure was 45.8 months. Cetuximab and Panitumumab were used in 21 and 12 patients, respectively, and the main chemotherapy at re-exposure was FOLFIRI in 39.4%. Anti-EGFR re-exposure was associated with a distinct trend towards a better outcome (median OS 56.0 vs. 35.4 months, p = 0.06). In a subgroup comparison, reintroduction was associated with a higher OS and PFS in trend compared to the rechallenge (mOS 66 vs. 52.4, n.s., mPFS 7.33 vs. 3.68 months, n.s.). Conclusions: This retrospective study provides real-world evidence underscoring that anti-EGFR re-exposure strategies might benefit patients independently of the reason for prior discontinuation.

The prognostic role of platelet count in hepatocellular carcinoma (HCC) remains unclear, and in fact both thrombocytopenia and thrombocytosis are reported as predictors of unfavourable outcomes. This study aimed to clarify the prognostic value of preoperative platelet count in potentially resectable HCC. We retrospectively reviewed 128 patients who underwent hepatic resection for HCC at a tertiary academic centre (2007–2019). Patient data were modelled by regression analysis, and platelet count was treated as a continuous variable. 89 patients had BCLC 0/A tumours and 39 had BCLC B tumours. Platelet count was higher in patients with larger tumours and lower in patients with higher MELD scores, advanced fibrosis, and portal hypertension (p < 0.001 for all listed variables). After adjusting for BCLC stage and tumour diameter, low platelet count associated with reduced overall survival (hazard ratio 1.25 per 50/nL decrease in platelet count, 95% confidence interval (CI) 1.02–1.53, p = 0.034) and increased perioperative mortality (odds ratio 1.96 per 50/nL decrease in platelet count, 95% CI 1.19–3.53, p = 0.014). Overall, low platelet count correlates with increased liver disease severity, inferior survival, and excess perioperative mortality in resectable HCC. These insights might be applied in clinical practice to better select patients for resection.

Immune-modulating therapy is a promising therapy for patients with cholangiocarcinoma (CCA). Microsatellite instability (MSI) might be a favorable predictor for treatment response, but comprehensive data on the prevalence of MSI in CCA are missing. The aim of the current study was to determine the prevalence of MSI in a German tertiary care hospital. Formalin-fixed paraffin-embedded tissue samples, obtained in the study period from 2007 to 2015 from patients with CCA undergoing surgical resection with curative intention at Johann Wolfgang Goethe University hospital, were examined. All samples were investigated immunohistochemically for the presence of MSI (expression of MLH1, PMS2, MSH2, and MSH6) as well as by pentaplex polymerase chain reaction for five quasimonomorphic mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-22, and NR-24). In total, 102 patients were included, presenting intrahepatic (n = 35, 34.3%), perihilar (n = 42, 41.2%), and distal CCA (n = 25, 24.5%). In the immunohistochemical analysis, no loss of expression of DNA repair enzymes was observed. In the PCR-based analysis, one out of 102 patients was found to be MSI-high and one out of 102 was found to be MSI-low. Thus, MSI seems to appear rarely in CCA in Germany. This should be considered when planning immune-modulating therapy trials for patients with CCA.