PurposeModern liver surgery has improved the percentage of potentially resectable malignant tumors. However, if the future liver remnant is small, patients remain at risk of developing postoperative liver failure. Thus, the future liver remnant must be increased, while at the same time, the primary tumor may have to be controlled by chemotherapy. To address this conflict, we retrospectively analyzed the changes in hypertrophy before and after Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) or Portal Vein Embolization (PVE), with or without parallel systemic chemotherapy.Materials and methodsWe retrospectively analysed 172 patients (54 female and 118 male), treated with ALPPS in 90 patients (median age 61 years [Q1, Q3: 52,71]) and with PVE in 82 patients (median age 66 years [Q1, Q3: 56,73]). The median control interval was 4.9 [Q1, Q3: 4.0, 6.0] weeks after the PVE, and 2.6 [Q1, Q3: 1.6, 5.8] weeks after ALPPS step 1.ResultsThe overall kinetic growth rate (median) for the entire group was 0.02 (2%) per week. When systemic chemotherapy was administered prior to intervention, the kinetic growth rate of these treated patients (vs. untreated) exhibited a median of 0.020 [Q1, Q3: 0.011, 0.067] compared to 0.024 [Q1, Q3: 0.013, 0.041] (p = 0.949). When chemotherapy was administered after the PVE/ ALPPS treatment, the kinetic growth rate declined from a median of 0.025 [Q1, Q3: 0.013, 0.053] to 0.011 [Q1, Q3: 0.007, 0.021] (p = 0.005). Subgroup analysis showed statistically significant effects only in the PVE group (median ALPPS -45% (p = 0.157), PVE -47% (p = 0.005)).ConclusionThis retrospective analysis indicated that systemic chemotherapy given after PVE/ the first step of the ALPPS procedure, i.e., the growth phase, has a negative effect on the kinetic growth rate.

BACKGROUND AND GOALS:The therapy of buried bumper syndrome (BBS) is difficult. The aim of this retrospective multicenter study was to analyze the treatment methods with focus on effectiveness and safety of endoscopic techniques. METHODS:The analysis of all therapies and a comparison of the papillotome technique (PT) and needle knife-based nonpapillotome technique (NPT) were performed. Primary endpoint was technical success in one session, secondary endpoints overall technical success, number and duration of treatment sessions, SAE, and mortality. RESULTS:The primary treatment of 160 BBS cases, diagnosed between 2003 and 2021, was NPT in 60 (37.5%), PT in 43 (26.9%), push/pull technique (PPT) in 40 (25.0%), no removal in 9 (5.6%), laparotomy in 7 (4.4%) cases, and external incision in 1 (0.6%) case. For PT and NPT rates of technical success in one session were 95.5% and 45.0% ( P <0.01), rates of overall technical success 100% and 88.3% ( P =0.02), and mean number and duration of treatment sessions 1.05 (±0.21) versus 1.70 (±0.91) ( P <0.01) and 32.17 (±21.73) versus 98,00 (±62.28) minutes ( P <0.01), respectively. No significant differences between PT and NPT were found for SAE (15.9% vs. 25.0%) and mortality (2.3% vs. 1.7%). For PPT, laparotomy and external incision rates of technical success in one session and overall technical success were 100%, rates of SAE 2.5%, 50.0%, and 0% and mortality 0%, 10.0%, and 0%. CONCLUSIONS:Endoscopic therapy of BBS is treatment of choice in most cases with removal of incomplete BB by PPT. In case of complete BB PT appears more effective than NPT.

BACKGROUND:Prophylactic application of a haemostatic gel to the resection field may be an easy way to prevent delayed bleeding, a frequent complication after endoscopic mucosal resection (EMR). OBJECTIVE:We aimed to evaluate if the prophylactic application of a haemostatic gel to the resection field directly after EMR can reduce the rate of clinically significant delayed bleeding events. DESIGN:We conducted a prospective randomised trial of patients undergoing hot-snare EMR of flat lesions in the duodenum (≥10 mm) and colorectum (≥20 mm) at 15 German centres. Prophylactic clip closure was not allowed, but selective clipping or coagulation could be used prior to randomisation to treat intraprocedural bleeding or for prophylactic closure of visible vessels. Patients were randomised to haemostatic gel application or no prophylaxis. The primary endpoint was delayed bleeding within 30 days. RESULTS:The trial was stopped early due to futility after an interim analysis. The primary endpoint was analysed in 232 patients (208 colorectal, 26 duodenal). Both groups were comparable in age, sex, comorbidities and lesion characteristics. Preventive measures, such as selective clipping or coagulation, were applied prior to randomisation in 51.9% of cases, with no difference between groups. Delayed bleeding occurred in 14 cases (11.7%; 95% CI 7.1% to 18.6%) after Purastat and in 7 cases (6.3%; 95% CI 3.1% to 12.3%) in the control group (p=0.227), with no difference between colorectal and duodenal subgroups. CONCLUSION:The application of a haemostatic gel following EMR of large flat lesions in the duodenum and colorectum does not reduce the rate of delayed bleeding.

BACKGROUND AND AIMS:Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy - including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented. PATIENTS AND METHODS:We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients. RESULTS:56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia. CONCLUSIONS:Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

BACKGROUND & AIMS:Endoscopic mucosal resection (EMR) is standard therapy for nonpedunculated colorectal polyps ≥20 mm. It has been suggested recently that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AEs), but evidence from a randomized trial is missing. METHODS:In this randomized controlled multicentric trial involving 19 centers, nonpedunculated colorectal polyps ≥20 mm were randomly assigned to cold or hot EMR. The primary outcome was major AE (eg, perforation or postendoscopic bleeding). Among secondary outcomes, major AE subcategories, postpolypectomy syndrome, and residual adenoma were most relevant. RESULTS:Between 2021 and 2023, there were 396 polyps in 363 patients (48.2% were female) enrolled for the intention-to-treat analysis. Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001; odds ratio [OR], 0.12; 95% CI, 0.03-0.54). Rates for perforation and postendoscopic bleeding were significantly lower in the cold group, with 0% vs 3.9% (P = .007) and 1.0% vs 4.4% (P = .040). Postpolypectomy syndrome occurred with similar frequency (3.1% vs 4.4%; P = .490). After cold resection, residual adenoma was found more frequently, with 23.7% vs 13.8% (P = .020; OR, 1.94; 95% CI, 1.12-3.38). In multivariable analysis, lesion diameter of ≥4 cm was an independent predictor both for major AEs (OR, 3.37) and residual adenoma (OR, 2.47) and high-grade dysplasia/cancer for residual adenoma (OR, 2.92). CONCLUSIONS:Cold resection of large, nonpedunculated colorectal polyps appears to be considerably safer than hot EMR; however, at the cost of a higher residual adenoma rate. Further studies have to confirm to what extent polyp size and histology can determine an individualized approach. German Clinical Trials Registry (Deutsches Register Klinischer Studien), Number DRKS00025170.

The therapy of buried bumper syndrome (BBS) is difficult. The aim of this retrospective multicenter study was to analyze the treatment methods with focus on effectiveness and safety of endoscopic techniques. The analysis of all therapies and a comparison of the papillotome technique (PT) and needle knife–based nonpapillotome technique (NPT) were performed. Primary endpoint was technical success in one session, secondary endpoints overall technical success, number and duration of treatment sessions, SAE, and mortality. The primary treatment of 160 BBS cases, diagnosed between 2003 and 2021, was NPT in 60 (37.5%), PT in 43 (26.9%), push/pull technique (PPT) in 40 (25.0%), no removal in 9 (5.6%), laparotomy in 7 (4.4%) cases, and external incision in 1 (0.6%) case. For PT and NPT rates of technical success in one session were 95.5% and 45.0% (P<0.01), rates of overall technical success 100% and 88.3% (P=0.02), and mean number and duration of treatment sessions 1.05 (±0.21) versus 1.70 (±0.91) (P<0.01) and 32.17 (±21.73) versus 98,00 (±62.28) minutes (P<0.01), respectively. No significant differences between PT and NPT were found for SAE (15.9% vs. 25.0%) and mortality (2.3% vs. 1.7%). For PPT, laparotomy and external incision rates of technical success in one session and overall technical success were 100%, rates of SAE 2.5%, 50.0%, and 0% and mortality 0%, 10.0%, and 0%. Endoscopic therapy of BBS is treatment of choice in most cases with removal of incomplete BB by PPT. In case of complete BB PT appears more effective than NPT.

Background/Aims Hypoxemia is a common side effect of propofol sedation during endoscopy. Applying mild positive airway pressure (PAP) using a nasal mask may offer a simple way to reduce such events and optimize the conditions for diagnostic and therapeutic upper gastrointestinal endoscopies. Methods We compared overweight patients (body mass index >25 kg/m2) with a nasal PAP mask or standard nasal cannula undergoing upper gastrointestinal endoscopies by non-anesthesiologists who provided propofol sedation. Outcome parameters included the frequency and severity of hypoxemic episodes. Results We analyzed 102 procedures in 51 patients with nasal PAP masks and 51 controls. Episodes of hypoxemia (oxygen saturation [SpO2] <90% at any time during sedation) occurred in 25 (49.0%) controls compared to 8 (15.7%) patients with nasal PAP masks (p<0.001). Severe hypoxemia (SpO2 <80%) occurred in three individuals (5.9%) in both groups. The mean delta between baseline SpO2 and the lowest SpO2 recorded was significantly decreased among patients with nasal PAP mask compared to controls (3.7 and 8.2 percentage points difference, respectively). There were significantly fewer airway interventions performed in the nasal PAP mask group (15.7% vs. 41.2%, p=0.008). Conclusions Using a nasal PAP mask may be a simple means of increasing patient safety and ease of examination.

The European Society of Gastroenterology and Endoscopy recommends a primarily flexible endoscopic approach for the treatment of Zenker’s diverticulum. Due to the rarity of the disorder, evidence for its effectiveness and safety comes mainly from small, retrospective, single-center studies. In this retrospective, observational, multicenter cohort study, data from six German tertiary referral centers were analyzed. The primary outcome parameters were technical and clinical success; among the secondary outcomes, the rates of adverse events (AE) and re-admission with symptomatic recurrence and mortality were the most relevant. Between 2003 and 2024, 384 treatments were performed in 327 patients (61.8

Expression of the double homeobox 4 (DUX4) transcription factor is highly regulated in early embryogenesis and is subsequently epigenetically silenced. Ectopic expression of DUX4 due to hypomethylation of the D4Z4 repeat array on permissive chromosome 4q35 alleles is associated with facioscapulohumeral muscular dystrophy (FSHD). In peripheral blood samples from 188 healthy individuals, D4Z4 methylation was highly variable, ranging from 19% to 76%, and was not affected by age. In 48 FSHD2 patients, D4Z4 methylation varied from 3% to 30%. Given that DUX4 is one of the earliest transcribed genes after fertilization, the D4Z4 array is expected to be unmethylated in mature germ cells. Deep bisulfite sequencing of 188 mainly normozoospermic sperm samples revealed an average methylation of 2.5% (range 0.3–22%). Overall, the vast majority (78%) of individual sperm cells displayed no methylation at all. In contrast, only 19 (17.5%) of 109 individual germinal vesicle (GV) oocytes displayed D4Z4 methylation <2.5%. However, it is not unexpected that immature GV oocytes which are not usable for assisted reproduction are endowed with D4Z4 (up to 74%) hypermethylation and/or abnormal (PEG3 and GTL2) imprints. Although not significant, it is interesting to note that the pregnancy rate after assisted reproduction was higher for donors of sperm samples and oocytes with <2.5% methylation.

Introduction: Surgery for perihilar cholangiocarcinoma (pCCA) is associated with high rates of postoperative morbidity and mortality. Extended liver resection (EXT) increases R0 resection rate and survival; however, patients with high perioperative risk are not suitable for extended resection. This study aimed to compare overall survival and surgical morbidity in patients with extended liver resection and parenchyma-preserving hepatectomy (PPH). Methods: Between January 2010 and November 2020, 113 consecutive patients with pCCA underwent surgery at our institution. Eighty-two patients were resected in curative intent. Sixty-four patients received extended liver resection, and 18 patients PPH. Outcomes of resections were evaluated. Results: There was no significant difference in overall survival in patients with PPH compared to extended liver resection (log-rank p = 0.286). Patients with PPH experienced lower rates of postoperative morbidity and mortality. There was no case of in-house mortality in PPH-resected patients compared to 10 cases (16%) in patients that received EXT (p = 0.073). Conclusion: PPH shows similar overall survival with lower rates of postoperative morbidity and mortality. Our findings support the role of a PPH, in selected patients with pCCA, that are not suitable for extended resection due to increased perioperative risk.

Biliary strictures are among the most common complications following liver transplantation (LT). If endoscopic retrograde cholangiography fails, percutaneous transhepatic biliary drainage (PTBD) may serve as an alternative approach. Description of clinical important short- and long-term outcomes as well as outcome prediction following PTBD after LT are scarce. We analyzed outcomes of 56 liver-transplanted adults with biliary complications receiving a PTBD. We described the safety and longitudinal laboratory changes. We analyzed as endpoints, incidence of biliary complications, need for surgical biliary revision/re-LT and overall-survival at 12- and 60-months. We used simple comparison tests accordingly and performed competing risk analysis and multivariate competing risk regression as well as log-rank test and cox proportional hazard regression for further analysis. PTBD procedures had a high technical success rate (98

BackgroundCachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit.MethodsSerum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis.ResultsComparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways.ConclusionWe found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care.

Segmented self-expanding metal stents (SEMS) are an alternative to conventional unsegmented SEMS in the treatment of esophageal strictures. Due to their segmented design, they may adapt better to the surrounding structures making them less likely to migrate or cause trauma. We examined if there are clinically relevant differences between segmented and conventional esophageal SEMS in benign and malignant stenosis in terms of their functionality and safety. We performed a multicenter, retrospective case–control study of segmented and conventional SEMS implantations in esophageal stenosis. Outcome parameters were adverse events such as migration, occlusion, and severe complications (i.e., bleeding and perforation). 79 segmented SEMS were identified and compared to 79 conventional SEMS implantations. Groups were similar in terms of age, gender, and etiology. We observed 13.9

Advanced paternal age is associated with increased risks for reproductive and offspring medical problems.Accumulating evidence suggests age-related changes in the sperm epigenome as one underlying mechanism.Using reduced representation bisulfite sequencing on 73 sperm samples of males attending a fertility center, we identified 1,162 (74%) regions which were significantly (FDR-adjusted) hypomethylated and 403 regions (26%) being hypermethylated with age.There were no significant correlations with paternal BMI, semen quality, or ART outcome.The majority (1,152 of 1,565; 74%) of age-related differentially methylated regions (ageDMRs) were located within genic regions, including 1,002 genes with symbols.Hypomethylated ageDMRs were closer to transcription start sites than hypermethylated DMRs, half of which reside in gene-distal regions.In this and conceptually related genome-wide studies, so far 2,355 genes have been reported with significant sperm ageDMRs, however most (90%) of them in only one study.The 241 genes which have been replicated at least once showed significant functional enrichments in 41 biological processes associated with development and the nervous system and in 10 cellular components associated with synapses and neurons.This supports the hypothesis that paternal age effects on the sperm methylome affect offspring behaviour and neurodevelopment.It is interesting to note that sperm ageDMRs were not randomly distributed throughout the human genome; chromosome 19 showed a highly significant twofold enrichment with sperm ageDMRs.Although the high gene density and CpG content have been conserved, the orthologous marmoset chromosome 22 did not appear to exhibit an increased regulatory potential by age-related DNA methylation changes.

Hepatitis-C virus (HCV) chronically infects 58 million individuals worldwide with variable disease outcome. While a subfraction of individuals exposed to the virus clear the infection, the majority develop chronic infection if untreated. Another subfraction of chronically ill proceeds to severe liver disease. The underlying causes of this interindividual variability include genetic polymorphisms in interferon genes. Here, we review available data on the influence of genetic or pharmacological perturbation of HCV host dependency factors on the clinically observed interindividual differences in disease outcome. We focus on host factors mediating virus entry into human liver cells. We assess available data on genetic variants of the major entry factors scavenger receptor class-B type I, CD81, claudin-1, and occludin as well as pharmacological perturbation of these entry factors. We review cell culture experimental and clinical cohort study data and conclude that entry factor perturbation may contribute to disease outcome of hepatitis C.