Scribble Deficiency Promotes Pancreatic Ductal Adenocarcinoma Development and Metastasis.

Perturbation of cell polarity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) progression. Scribble (SCRIB) is a well-characterized polarity regulator that has diverse roles in the pathogenesis of human neoplasms. To investigate the impact of SCRIB deficiency in PDAC development and progression, Scrib expression was genetically ablated in well-established mouse models of PDAC.

The four seasons of pancreatitis - Etiology of acute pancreatitis during the course of the year.

Background/objectives: Whether seasonality is a factor that influences the incidence of acute pancreatitis (AP) is an under-investigated area. If seasonal incidence peaks can be detected, specifically with regard to biliary pancreatitis, has so far been answered in contradictory ways in the literature.

Methods: All AP cases from two tertiary German referral centers were identified between 2016 and 2022 based on ICD-10 discharge codes.

Expression of gemcitabine metabolizing enzymes and stromal components reveal complexities of preclinical pancreatic cancer models for therapeutic testing.

Background: Pancreatic ductal adenocarcinoma (PDAC) poorly responds to antineoplastic agents. Discrepancies between preclinical success and clinical failure of compounds has been a continuous challenge and major obstacle in PDAC research.

Aim: To investigate the association of the tumor microenvironment (TME) composition and gemcitabine metabolizing enzyme (GME) expression in vitro and several in vivo models.

Time to Deliver on Promises: The Role of ERBB2 Alterations as Treatment Options for Colorectal Cancer Patients in the Era of Precision Oncology.

(), also known as (), represents an oncogenic driver and has been effectively targeted in breast and gastric cancer. Recently, next-generation sequencing (NGS) discovered as a promising therapeutic target in metastatic colorectal cancer (mCRC), where it is altered in 3-5% of patients, but no therapies are currently approved for this use. Herein, we present the experience of a single center in diagnosing actionable genetic alterations using NGS and utilizing the latest therapeutic options.

Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

Objective: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission.

Design: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres.

An NFATc1/SMAD3/cJUN Complex Restricted to SMAD4-Deficient Pancreatic Cancer Guides Rational Therapies.

Background & Aims: The highly heterogeneous cellular and molecular makeup of pancreatic ductal adenocarcinoma (PDAC) not only fosters exceptionally aggressive tumor biology, but contradicts the current concept of one-size-fits-all therapeutic strategies to combat PDAC. Therefore, we aimed to exploit the tumor biological implication and therapeutic vulnerabilities of a clinically relevant molecular PDAC subgroup characterized by SMAD4 deficiency and high expression of the nuclear factor of activated T cells (SMAD4/NFATc1).

Methods: Transcriptomic and clinical data were analyzed to determine the prognostic relevance of SMAD4/NFATc1 cancers.

Machine learning-based decision tool for selecting patients with idiopathic acute pancreatitis for endosonography to exclude a biliary aetiology.

Background: Biliary microlithiasis/sludge is detected in approximately 30% of patients with idiopathic acute pancreatitis (IAP). As recurrent biliary pancreatitis can be prevented, the underlying aetiology of IAP should be established.

Aim: To develop a machine learning (ML) based decision tool for the use of endosonography (EUS) in pancreatitis patients to detect sludge and microlithiasis.

Endoscopic mucosal resection and endoscopic submucosal dissection with an external additional working channel (EMR+ and ESD+) are equivalent to using a double-channel endoscope: a systematic evaluation in a porcine ex vivo model.

Background And Aims: With an external additional working channel (AWC) endoscopic mucosal resection (EMR) as well as endoscopic submucosal dissection (ESD) can be extended to techniques termed "EMR+" and "ESD+." These novel techniques are systematically compared to EMR and ESD under the use of a double-channel endoscope (DC).

Methods: Our trial was conducted prospectively in a pre-clinical porcine animal model (EASIE-R simulator) with standardized gastric lesions measuring 3 or 4 cm.

Dynamics of intestinal and intratumoral microbiome signatures in genetically engineered mice and human pancreatic ductal adenocarcinoma.

Background: Emerging evidence has recently revealed a prominent role of the microbiome in pancreatic ductal adenocarcinoma (PDAC). However, while most observations were made in patients, mouse models still require a precise characterization of their disease-related microbiome to employ them for mechanistic and interventional preclinical studies.

Methods: To investigate the fecal and tumoral microbiome of LSL-Kras;LSL-Trp53;Pdx-1-Cre (KPC) and control (CTRL) mice, Oxford Nanopore sequencing was applied.

Management of Aortoesophageal Fistula in a Palliative Patient with Non-Small-Cell Lung Cancer: A Case Report.

Introduction: Aortoesophageal fistulas are a rare but life-threatening complication in patients with thoracic malignancies.

Case Presentation: We describe a case of a 55-year-old female patient with metastatic non-small-cell lung cancer. Due to esophageal tumor compression, a fully covered self-expanding metal stent (fcSEMS) had been deployed in the esophagus several months before.

Urokinase-Type Plasminogen Activator Receptor (uPAR) Cooperates with Mutated in Regulating Cellular Plasticity and Gemcitabine Response in Pancreatic Adenocarcinomas.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers. Given the currently limited therapeutic options, the definition of molecular subgroups with the development of tailored therapies remains the most promising strategy. Patients with high-level gene amplification of urokinase plasminogen activator receptor () have an inferior prognosis.

NFATc1 Is a Central Mediator of EGFR-Induced ARID1A Chromatin Dissociation During Acinar Cell Reprogramming.

Background & Aims: Loss of AT-rich interactive domain-containing protein 1A (ARID1A) fosters acinar-to-ductal metaplasia (ADM) and pancreatic carcinogenesis by down-regulating transcription programs controlling acinar cell identity. However, how ARID1A reacts to metaplasia-triggering environmental cues remains elusive. Here, we aimed to elucidate the role of ARID1A in controlling ductal pancreatic gene signatures and deciphering hierarchical signaling cues determining ARID1A-dependent chromatin regulation during acinar cell reprogramming.

[Acute necrotizing pancreatitis with hemorrhagic shock in secondary splenic rupture: a case report and literature review].

Atraumatic splenic rupture is a rare complication of acute and chronic pancreatitis. It arises due to its anatomical proximity to the pancreas, for instance, due to erosion of large pseudocysts or walled-of-necrosis (WON).Following we describe the case of a 62-year-old woman who presented for further diagnostics and treatment of acute pancreatitis with the development of large walled-of necrosis (WON) in the pancreatic corpus and tail.

The Microbiome in PDAC-Vantage Point for Future Therapies?

Microorganisms have been increasingly implicated in the pathogenesis of malignant diseases, potentially affecting different hallmarks of cancer. Despite the fact that we have recently gained tremendous insight into the existence and interaction of the microbiome with neoplastic cells, we are only beginning to understand and exploit this knowledge for the treatment of human malignancies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor with limited therapeutic options and a poor long-term survival.

Axon guidance receptor ROBO3 modulates subtype identity and prognosis via AXL-associated inflammatory network in pancreatic cancer.

Metastatic pancreatic cancer (PDAC) has a poor clinical outcome with a 5-year survival rate below 3%. Recent transcriptome profiling of PDAC biopsies has identified 2 clinically distinct subtypes - the "basal-like" (BL) subtype with poor prognosis and therapy resistance compared with the less aggressive and drug-susceptible "classical" (CLA) subtype. However, the mechanistic events and environmental factors that promote the BL subtype identity are not very clear.

Clinical Post-SARS-CoV-2 Infection Scenarios in Vaccinated and Non-Vaccinated Cancer Patients in Three German Cancer Centers: A Retrospective Analysis.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers.

-Status-Dependent Oncogenic EZH2 Activity in Pancreatic Cancer.

Pancreatic Ductal Adenocarcinoma (PDAC) represents a lethal malignancy with a consistently poor outcome. Besides mutations in PDAC driver genes, the aggressive tumor biology of the disease and its remarkable therapy resistance are predominantly installed by potentially reversible epigenetic dysregulation. However, epigenetic regulators act in a context-dependent manner with opposing implication on tumor progression, thus critically determining the therapeutic efficacy of epigenetic targeting.

Activity of acute pancreatitis is modified by secreted protein acidic and rich in cysteine ablation.

Background: Acute pancreatitis (AP) is a frequent cause for hospitalization. However, molecular determinants that modulate severity of experimental pancreatitis are only partially understood.

Objective: To investigate the role of secreted protein acidic and rich in cysteine (SPARC) during cerulein-induced AP in mice.

Systematic Retesting for : The Potential Overestimation of Suppressive Conditions.

Background And Aims: In contrast to guideline recommendations, endoscopic testing for is frequently performed under suppressive conditions, e.g., intake of proton-pump inhibitors (PPI), preceded antibiotic treatment, or recent gastrointestinal bleeding.