Evangelisches Diakoniekrankenhaus

Background/Objectives: Endoscopic submucosal dissection (ESD) is a state-of-the-art en bloc resection for early gastro-intestinal cancers and precursors developed and validated in Japan. Western expertise with this complex technique remains limited. Tutored training might be optimal for patients and ESD learning. We established ESD tutoring courses led by experienced Japanese experts to provide (i) optimal long-term curative outcomes and low complication rates for patients and (ii) hands-on training on difficult lesions for European endoscopists under direct expert supervision. Methods: Prospective data from 2011 to 2015 (follow-up to 12/2024) were analyzed. A total of 118 neoplasms (50% HGIEN and cancer) in 101 patients (median age 68 [37-91] years; 38% with significant comorbidities) were treated with expert or tutored ESD. Japanese experts performed 28 ESDs, while 22 trained beginners conducted 90 supervised procedures on difficult lesions during 5 live and 20 tutoring events (1-4 days each). Results: Analysis of the complete data showed curative and en bloc resection rates of 88% and 95%, respectively, with no recurrence after R0 resections during a median follow-up of 9.8 [1.5-14.9] years. Long-term survival remained recurrence-free after endoscopic resection of 3 recurrent adenomas (at R1/Rx) and curative surgery/2nd ESD for 5 non-curative ESDs. Adverse events occurred in 9.3% without emergency surgery or 30-day mortality. Comparing expert-only vs. tutored ESD procedures, beginners correctly applied curative ESD indications in 94% of 118 neoplasms. Experts resected larger lesions (22 cm2) at a rate of 9.3 cm2/h in 121 min. Tutored beginners achieved a 75% [25-100] self-completion rate on 33% smaller lesions in 112 min. Conclusions: ESD tutoring courses led by Japanese experts ensure excellent patient outcomes and standardized procedural training. This model may foster professional ESD performance across European referral centers.

4187 Background: The PREDICT trial, a recent phase IIIb/IV study, aimed to address the critical need for improved personalized treatment strategies in advanced pancreatic cancer. This translational investigation examined the predictive value of 1 st line chemotherapy (CTX) response on the efficacy of subsequent 2 nd line treatment by using liquid biomarkers combined with machine learning (ML). Methods: Pts. were stratified into two cohorts based on short or long 2 nd line CTX time to treatment failure (S-/L-TTF2; n = 10 per group, 80/20% quantiles). Treatment-naïve PDAC tissue specimens underwent laser microdissection for tumor cell enrichment, followed by RNA profiling using NanoString™ PanCancer IO360. Selected differentially regulated genes from the omics results were utilized to screen peripheral blood mononuclear cells (PBMCs) from 2 nd line treatment-naïve patients at protein (flow cytometry, FC) or RNA (RT-qPCR) levels. FC data was analyzed using R-based single-cell clustering (x-Shift, FlowSOM, T-REX) to generate HyperGates (HGs), with subsequent ML-based back-gating (HyperFinder algorithm) of the most differential clusters. Additionally, classical ManualGates (MGs) were generated. Feature selection employed the Weka-based WrapperSubsetEval (WSE) algorithm with eight different classifiers (NB, KLR, LR, SMO, IBk, RT, RF, J48). The classifier/subset with optimal performance was utilized for binary classification (S-TTF2 vs. L-TTF2) of training (80%, n = 66) and validation (20%, n = 16) datasets. Results: Transcriptome analysis of L- vs. S-TTF2 tumor tissues revealed increased inflammation (upregulated 18-gene signature), immune cell activation/infiltration (e.g. CD4/CD8 T cells), and immune exhaustion (upregulation of e.g. PDCD1, LAG3, CTLA4, TIGIT) in L-TTF tumors. Further, the favorable Bailey immunogenic subtype was enriched in the L-TTF2 group. Analysis of eight FC panels (19 candidates) revealed 1198 differential clusters with HGs and 881 classical MGs. Feature selection, combining FC data with RT-qPCR results and clinical parameters, identified a best performing signature of 5 HGs and 2 MGs for 7 protein markers (CXCR4, CD8, CD4, CD62P, CD307b, CD45, CD121b). ML using a kernel logistic regression successfully predicted S- and L-TTF2 binary groups prior to 2 nd line CTX with nal-IRI/5-FU/LV (ROC-AUC > 0.90 for training and validation). Conclusions: We identified a favorable tumor immune microenvironment in L-TTF aPDAC patients, characterized by CD8 T cell-inflamed ("hot") tumor tissues prior to 2 nd line CTX. A 7-marker liquid biomarker panel, comprising 7 flow cytometry PBMC population gates, was developed for early prediction of 2 nd line nal-IRI/5-FU/LV CTX success. These findings aim to advance personalized treatment strategies. Clinical trial information: NCT03468335 .

PurposeOur aim was to develop new evidence-based and consensus-based recommendations for imaging strategies in patients with multiple and/or severe injuries in the resuscitation room. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries.MethodsMEDLINE and Embase were systematically searched to August 2021. Inclusion criteria: patients with multiple and/or severe injuries in the resuscitation room, randomised controlled trials, prospective cohort studies, cross-sectional studies, and comparative registry studies; comparison of interventions for imaging strategies; patient-relevant clinical outcomes such as diagnostic test accuracy and mortality. Further literature reports were obtained from clinical experts. We considered patient-relevant clinical outcomes such as diagnostic test accuracy and mortality. Risk of bias was assessed using NICE 2012 checklists. The evidence was synthesised narratively, and expert consensus was used to develop recommendations and determine their strength.ResultsTwenty-one studies with a total of 55,227 patients were identified. There were studies with low risk (n = 2), high risk (n = 5) and unclear risk of bias (n = 14). Relevant topics were sonographic imaging of the chest and abdomen (n = 8 studies), X-ray of the chest (n = 1), indications for whole-body computed tomography (n = 6), CT scanner location (n = 1), whole-body computed tomography in haemodynamically unstable patients (n = 3), and prehospital sonography (n = 2). There were studies with low risk (n = 2), high risk (n = 5) and unclear risk of bias (n = 14). One new recommendation was developed, six were modified. All achieved strong consensus.ConclusionWhile extended focused assessment with sonography for trauma should be performed for diagnostic purposes after blunt and/or penetrating thoracic and/or abdominal trauma as part of the primary survey in the resuscitation room, whole-body computed tomography (WBCT) gains highest importance as part of the diagnostic procedures for severely injured patients. WBCT with a trauma-specific protocol must be performed in a timely manner if the patient does not require an immediate intervention. Magnetic resonance imaging can be indicated as a further primary diagnostic tool for specific conditions. Two studies were judged to be of low risk of bias in all domains. The risk of selection bias was high in two studies and unclear in seven studies.

BackgroundProphylactic 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).ObjectiveWe 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.DesignWe 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.ResultsThe 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.ConclusionThe application of a haemostatic gel following EMR of large flat lesions in the duodenum and colorectum does not reduce the rate of delayed bleeding.

Aims Artificial Intelligence (AI) systems in gastrointestinal endoscopy are narrow because they are trained to solve only one specific task. Unlike Narrow-AI, general AI systems may be able to solve multiple and unrelated tasks. We aimed to understand whether an AI system trained to detect, characterize, and segment early Barrett's neoplasia (Barrett's AI) is only capable of detecting this pathology or can also detect and segment other diseases like early squamous cell cancer (SCC).

Abstract In newly diagnosed acute myeloid leukemia, immediate initiation of treatment is standard of care. However, deferral of antileukemic therapy may be indicated to assess comorbidities or pre-therapeutic risk factors. We explored the impact of time from diagnosis to treatment on outcomes in newly diagnosed acute myeloid leukemia undergoing venetoclax-based therapy in two distinct cohorts. By querying the Study Alliance Leukemia database and the health network TriNetX, we identified 138 and 717 patients respectively with an average age of 76 and 72 years who received venetoclax-based first-line therapy. When comparing patients who started treatment earlier or later than 10 days after initial diagnosis, no significant difference in median overall survival was observed - neither in the SAL cohort (7.7 vs. 9.6 months, p=.42) nor in the TriNetX cohort (7.5 vs. 7.2 months, p=.41). Similarly, severe infections, bleeding, and thromboembolic events were equally observed between early and later treatments, both in the overall patient groups and specific subgroups (age ≥75 years or leukocytes ≥20/nl). This retrospective analysis indicates that delaying the start of venetoclax-based therapy in newly diagnosed acute myeloid leukemia might be a safe option for selected patients, provided that close clinical monitoring is performed.

Einleitung Die Endoskopische Submukosadissektion (ESD) erlaubt die en bloc Resektion größerer flächiger Adenome mit geringem Rezidivrisiko. Im Falle eines Frühkarzinoms ermöglicht sie eine optimale histopathologische Auswertung und im günstigen Falle einer low risk Situation kann eine chirurgisch onkologische Resektion unterbleiben. Der wesentliche Nachteil der ESD (im Vergleich zur fraktionierten EMR) ist die höhere technische Komplexität, vor allem im proximalen Kolon.