Albrecht Hoffmeister

Background: Patients after partial or total gastrectomy suffer from malnourishment and diminished quality of life (QOL). Due to altered physiological processes after gastric surgery, coordination between chyme and digestive enzymes produced by the pancreas is affected in many ways, finally leading to maldigestion and malabsorption. These in turn promote various symptoms such as discomfort or steatorrhea. Supplementation of digestive enzymes during food intake may improve digestion and decrease nutrition-related abdominal symptoms, finally leading to higher QOL. To date, trials examining the role of digestive enzyme supplementation in patients with gastrectomy are lacking. Methods: We designed a randomized, phase III, parallel-arm, placebo-controlled, double-blind, multi-center superiority trial comparing QOL after 6 months of oral digestive enzyme supplementation vs. placebo in a sample of 188 patients after partial or total gastrectomy. Digestive enzymes or placebo are taken orally with the meals. Cancer specific QOL (physical sub-score from EORTC-QLQ-C30) at six months is the primary outcome. Secondary outcomes include other measures of QOL, weight loss, use of supplemental nutrition, and laboratory measurements related to malnutrition and metabolism. Discussion: This trial will help assess using digestive enzymes in patients with partial or total gastrectomy. Trial Registration: EU Trial Number: 2022-501944-14-00. Clinical Trial Number: NCT06058442 (Registration date: 09/08/2023).

INTRODUCTION: Multiple randomized studies have demonstrated that computer-assisted detection (CADe) improves the colonoscopic adenoma detection rate (ADR); however, these improvements have not been consistently reproduced in some more recent studies. METHODS: Patients aged 50 years and older undergoing outpatient colonoscopy in 12 German institutions were randomized to either the CADe group or the control group. The primary outcome parameter was the ADR, while secondary outcomes included the adenomas per colonoscopy rate, detection rates of different histologic subgroups, and adverse events. The median examiner-specific observed rates and examiner-adjusted rates were compared between treatment groups. RESULTS: One thousand six hundred twenty-seven patients were included (mean age 63.1 years, 39.8% female; 71% screening indications). The observed median examiner ADR was 40.0% (interquartile range 20.0%–57.1%) in the study vs 37.5% (inter-quartile range 20.0%–50.0%) in the control group. Similarly, adjusted overall ADR was 40.6% (95% confidence interval [CI]: 35.8%, 45.5%) in the study and 38.3% (95% CI: 33.5%, 43.1%) in the control group. No differences were observed in adenomas per colonoscopy or any of the adenoma subgroups with regard to size, morphology, location, and histology as well as colonoscopy indication. The examiner had a large influence on ADR (adjusted median odds ratio [OR] 1.32), similar to patient age (OR per 10-year increase 1.40, 95% CI: 1.23–1.59) and sex (OR 1.62, 95% CI: 1.30–2.04). On the other hand, more hyperplastic polyps were found by CADe (OR for adjusted hyperplastic polyp detection rate = 1.29; 95% CI: 1.02–1.63; P = 0.033). DISCUSSION: In patients older than 50 years with mixed colonoscopy indications, CADe did not increase the ADR. Further studies should define the requirements for selective CADe use in routine clinical practice, particularly in relation to the examiner's baseline ADR.

Background. The pandemic situation of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) and its associated disease (coronavirus disease 2019 (COVID-19)) represents a challenging condition with a plethora of aspects. The course of COVID-19 in patients with immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD) and rheumatic diseases (RD) is not well known. Our study is one step toward closing this gap by collecting data on vaccination rates, infection-free survival, and individual symptom severity. Methods. We conducted a prospective questionnaire-based study between April 2022 and October 2022 at our university hospital. Outward patients over the age of 18 years were screened for participation and reported about their infection/infection-free survival since the start of the pandemic. Results. Finally, 156 patients were included in the study, 117 (75.0%) of which had inflammatory bowel disease and 39 (25.0%) patients with rheumatic disease. Altogether, 143 (91.7%) persons had received at least one vaccination against SARS-CoV-2. A total of 153 patients provided information regarding their COVID-19 history: 81 patients (52.0%) self-reported about their SARS-CoV-2 infection. In general, courses of infection were mild: only two patients (2.5% of patients with reported COVID-19) were hospitalized due to COVID-19 with one (1.2%) of the two needing intensive care. Asymptomatic COVID-19 had been described by 7 persons (8.6% of patients with reported COVID-19). Acute COVID-19 was accompanied by fatigue/tiredness in 58 persons (71.6% of patients with history of COVID-19) as the most frequent symptom. Other complaints were common cold (55 patients = 67.9%), cough (51 patients = 63.0%), headache (44 patients = 54.3%), and fever (35 patients = 43.2%). Stratified by vaccination status (unvaccinated vs. at least once vaccinated), the time to infection differed significantly (logrank test: p=0.04, Chi2 4.1). At least once vaccinated people had a median COVID-19-free survival of 28.5 months (confidence interval (CI): 23.6 months-not reached). Without any vaccination, the estimated time to infection was 25.1 months (CI: 23.6 months-not reached). Conclusion. Our IMID patients have a high rate of vaccination against SARS-CoV-2. Data show a significantly longer infection-free survival in vaccinated IMID patients as compared to unvaccinated patients. Discrimination between symptoms of COVID-19 and a concomitant inflammatory disease is difficult as complaints might be overlapping. This trial is registered with DRKS00028880.

Objective Accurate distinction between benign and malignant biliary strictures (BS) is challenging. The use of bile duct biopsies and brush cytology via endoscopic retrograde cholangiopancreatography (ERCP) remains suboptimal. Single-operator cholangioscopy increases the diagnostic yield in BS but has limited availability and high costs. Convolutional neural network (CNN)-based systems have the potential to assist in the diagnostic process and improve reproducibility. Thus, we assessed the feasibility of using deep learning to differentiate BS out of fluoroscopy images during ERCP. Design We conducted a retrospective review of adult patients (n=251) from three university centers in Germany (Leipzig, Dresden, Halle) who underwent an ERCP. We developed and evaluated a deep learning-based model (DenseNet) by means of fluoroscopy images. We measured the area under the receiver operating characteristic curve (AUROC) to evaluate the performance of the classifier and used saliency maps analyses to understand the decision-making process of the model. Results In cross-validation (Leipzig cohort), malignant BS were detected with a mean AUROC of 0.88± 0.02. On two independent external validation cohorts (Dresden, Halle), the of the deep learned based classifier reached a mean AUROC of 0.71+±+0.04 and 0.74+±+0.07, respectively. The artificial intelligence model's predictions identify plausible characteristics within the fluoroscopy images. Conclusion By using a deep learning model, we were able to discriminate malignant BS from benign biliary conditions. Artificial intelligence improves the diagnostic yield of malignant BS and needs to be validated in prospective design. Article published online: 28 August 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

Zusammenfassung: Ösophagusmotilitätsstörungen sind Erkrankungen, bei denen es aufgrund einer Veränderung der neuromuskulären Strukturen zu Fehlfunktionen des Schluckakts kommt. Das Leitsymptom ist daher die Dysphagie für feste und/oder flüssige Speisen, häufig begleitet von Symptomen wie Thoraxschmerz, Regurgitation, Sodbrennen und Gewichtsverlust. Die Ösophagusmanometrie ist der Goldstandard in der Diagnostik. Endoskopie und Radiologie dienen dem Ausschluss entzündlicher oder maligner Veränderungen.Durch die Einführung der hochauflösenden Ösophagusmanometrie (HRM) hat sich die Diagnostik der Ösophagusmotilitätsstörungen verbessert und mit der Chicago-Klassifikation zu einer neuen Einteilung geführt, die im letzten Jahrzehnt mehrfach modifiziert wurde, zuletzt 2021 mit der Chicago-Klassifikation v4.0. Verglichen mit der Vorversion v3.0 finden sich einige wichtige Änderungen, die anhand der im klinischen Alltag wichtigsten Ösophagusmotilitätsstörungen vorgestellt werden.

(1) Background: Colorectal cancer risk and survival have previously been associated with telomere length in peripheral blood leukocytes and tumor tissue. A systematic review and meta-analysis of the literature was conducted. The PubMed, Embase, and Web of Science databases were searched through March 2022. (2) Methods: Relevant studies were identified through database searching following PRISMA guidelines. Risk estimates were extracted from identified studies; meta-analyses were conducted using random effects models. (3) Results: Fourteen studies were identified (eight on risk; six on survival) through systematic review. While no association was observed between circulating leukocyte telomere length and the risk of colorectal cancer [overall OR (95% CI) = 1.01 (0.82–1.24)], a worse survival for those with shorter telomeres in leukocytes and longer telomeres in tumor tissues was observed [Quartile₁/Quartile_2–4 overall HR (95% CI) = 1.41 (0.26–7.59) and 0.82 (0.69–0.98), respectively]. (4) Conclusions: Although there was no association with colorectal cancer risk, a poorer survival was observed among those with shorter leukocyte telomere length. Future larger studies evaluating a potentially non-linear relationship between telomeres and colorectal cancer are needed.

Zusammenfassung Die akute Pankreatitis ist eine primär sterile Entzündung der Bauchspeicheldrüse, die durch eine unphysiologische Enzymaktivierung gekennzeichnet ist. Diese führt zu einer Entzündungsreaktion mit Ödem, Gefäßschädigung und Zelluntergang. Im Jahr 2012 wurde die erste deutsche interdisziplinäre S3-Leitlinie zur chronischen Pankreatitis publiziert. Unter Federführung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und unter Beteiligung verschiedener Gesellschaften sowie von Patientenvertretungen wurde die Leitlinie aktuell überarbeitet und erweitert. Es wurde eine umfassende S3-Leitlinie zur akuten und chronischen Pankreatitis erstellt und konsentiert. In diesem Beitrag werden wichtige klinische Aspekte zur akuten Pankreatitis aus dieser Leitlinie in kompakter Form dargestellt und Empfehlungen begründet.

Molekulare Subtypen Die molekularen Alterationen beim Magenkarzinom wurden umfassend charakterisiert. Darauf basiert eine Einteilung in 4 Subtypen, die sich hinsichtlich ihrer Frequenz in unterschiedlichen Lokalisationen des Magens sowie im biologischen Verhalten und der Prognose unterscheiden. Vorsorge und erbliche Formen Chronische Entzündungen der Schleimhaut (unter dem Einfluss von Helicobacter pylori) spielen bei den Nicht-Kardia-Karzinomen eine zentrale pathogenetische Rolle. Patienten mit ausgedehnter Atrophie oder intestinaler Metaplasie sollten endoskopisch überwacht werden. Bei Risikopersonen sollte Helicobacter pylori eradiziert werden. Ein frühes Erkrankungsalter kann auf eine erbliche Disposition hinweisen (Keimbahnmutationen im E-Cadherin-Gen). Patienten mit hereditärem nicht polypösem kolorektalem Karzinom haben ebenfalls ein erhöhtes Risiko, an Magenkarzinomen zu erkranken. Eine humangenetische Beratung ist in beiden Fällen obligat. Therapie des Magenkarzinoms und des Adenokarzinoms des gastroösophagealen Übergangs Frühkarzinome können unter klar definierten Voraussetzungen mittels endoskopischer Resektion behandelt werden. Lokal fortgeschrittene Magenkarzinome werden mit einer perioperativen Systemtherapie behandelt. Das FLOT-Regime, bestehend aus Folinsäure/5-Fluorouracil, Oxaliplatin und Docetaxel, wurde kürzlich als neuer Standard etabliert. Patienten mit metastasierter Erkrankung profitieren von einer Systemtherapie. Diese führt sowohl zu einer Verlängerung des Überlebens als auch über die Kontrolle der Tumorerkrankung zu einer Verbesserung der Symptomkontrolle und Lebensqualität. Platin-Fluoropyrimidin-Doubletten sind in der ersten Behandlungslinie Standard, im Falle von HER2-Positivität in Kombination mit Trastuzumab. Aktuell wurde Pembrolizumab, ein gegen PD-1 gerichteter Antikörper in Kombination mit einer Platin- und Fluoropyrimidin-basierten Chemotherapie bei Her-2 negativen, metastasierten Adenokarzinomen des gastroösophagealen Übergangs mit einer PD-L1 Expression (Combined Positive Score, CPS ≥ 10) zugelassen. Paclitaxel und der antiangiogene Antikörper Ramucirumab sind zugelassen für die zweite Therapielinie. Die orale Wirkstoffkombination Trifluridin/Tipiracil (TAS-102) steht basierend auf einer Phase-III-Studie seit Kurzem für die Drittlinientherapie zur Verfügung. Epstein-Barr-Virus-positive und Mikrosatelliten-instabile Magenkarzinome sind in besonderem Maße immunogen. Immuncheckpoint-Inhibitoren sind hier hoch wirksam, aber in Europa nicht zugelassen. Gastric and esophago-gastric junction (EGJ) adenocarcinoma are leading causes of cancer mortality and morbidity worldwide. In this short update article, we outline novel key developments in this field. Molecular defined subtypes can guide treatment decisions and create a roadmap for development of future agents in distinct subgroups of gastric cancer. In locally advanced EGJ cancer chemo-radiotherapy or perioperative chemotherapy are recommended treatment strategies. The FLOT regimen has evolved as a new standard for perioperative chemotherapy due to improved survival outcomes. For gastric cancer with limited metastasis, multimodality treatment approaches are under investigation. Systemic treatment over several lines along with best supportive care represents a standard in the management of metastatic disease. First line treatment should include trastuzmab in case of Her2 positivity. Immune checkpoint inhibitors are very effective in microsatellite instable tumors even in late treatment lines. In perspective, checkpoint inhibitors hold promise to become part of the standard treatment in the near future and novel Her2 targeted treatment approaches currently under development show promising results. Publication Date: 26 November 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany