Accumulation of Non-Pathological Liver Fat Is Associated with the Loss of Glyoxalase I Activity in Humans.

The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced liver diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading to elevated methylglyoxal (MG) and dicarbonyl stress, has been implicated in various diseases, including obesity-related conditions. This study aimed to investigate changes in the glyoxalase system in individuals with non-pathological liver fat. Liver biopsies were obtained from 30 individuals with a narrow range of BMI (24.6-29.8 kg/m2). Whole-body insulin sensitivity was assessed using HOMA-IR. Liver biopsies were analyzed for total triglyceride content, Glo1 and Glo2 mRNA, protein expression, and activity. Liquid chromatography-tandem mass spectrometry determined liver dicarbonyl content and oxidation and glycation biomarkers. Liver Glo1 activity showed an inverse correlation with HOMA-IR and liver triglyceride content, but not BMI. Despite reduced Glo1 activity, no associations were found with elevated liver dicarbonyls or glycation markers. A sex dimorphism was observed in Glo1, with females exhibiting significantly lower liver Glo1 protein expression and activity, and higher liver MG-H1 content compared to males. This study demonstrates that increasing liver fat, even within a non-pathological range, is associated with reduced Glo1 activity.

Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer-A Pilot Study.

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin.

Quantitative Metabolomics and Lipoprotein Analysis of PDAC Patients Suggests Serum Marker Categories for Pancreatic Function, Pancreatectomy, Cancer Metabolism, and Systemic Disturbances.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in the early stages and lacks reliable biomarkers. The scope of this project was to establish quantitative nuclear magnetic resonance (NMR) spectroscopy to comprehensively study blood serum alterations in PDAC patients. Serum samples from 34 PDAC patients obtained before and after pancreatectomy as well as 83 age- and sex-matched control samples from healthy donors were analyzed with in vitro diagnostics research (IVDr) proton NMR spectroscopy at 600 MHz. Uni- and multivariate statistics were applied to identify significant biofluid alterations. We identified 29 significantly changed metabolites and 98 lipoproteins when comparing serum from healthy controls with those of PDAC patients. The most prominent features were assigned to (i) markers of pancreatic function (e.g., glucose and blood triglycerides), (ii) markers related to surgery (e.g., ketone bodies and blood cholesterols), (iii) PDAC-associated markers (e.g., amino acids and creatine), and (iv) markers for systemic disturbances in PDAC (e.g., gut metabolites DMG, TMAO, DMSO2, and liver lipoproteins). Quantitative serum NMR spectroscopy is suited as a diagnostic tool to investigate PDAC. Remarkably, 2-hydroxybutyrate (2-HB) as a previously suggested marker for insulin resistance was found in extraordinarily high levels only after pancreatectomy, suggesting this metabolite is the strongest marker for pancreatic loss of function.

High-dimensional in situ proteomics imaging to assess γδ T cells in spatial biology.

This study presents a high-dimensional immunohistochemistry approach to assess human γδ T cell subsets in their native tissue microenvironments at spatial resolution, a hitherto unmet scientific goal due to the lack of established antibodies and required technology. We report an integrated approach based on multiplexed imaging and bioinformatic analysis to identify γδ T cells, characterize their phenotypes, and analyze the composition of their microenvironment. Twenty-eight γδ T cell microenvironments were identified in tissue samples from fresh frozen human colon and colorectal cancer where interaction partners of the immune system, but also cancer cells were discovered in close proximity to γδ T cells, visualizing their potential contributions to cancer immunosurveillance. While this proof-of-principle study demonstrates the potential of this cutting-edge technology to assess γδ T cell heterogeneity and to investigate their microenvironment, future comprehensive studies are warranted to associate phenotypes and microenvironment profiles with features such as relevant clinical characteristics.

Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma.

Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy.

Development and evaluation of artificial organ models for ERCP training in patients with surgically altered anatomies.

Endoscopy training models (ETM) using artificial organs are practical, hygienic and comfortable for trainees. However, few models exist for training endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy. This training is necessary as the number of bariatric surgeries performed worldwide increases. ETM with human-like anatomy were developed to represent the postoperative anatomy after Billroth II (BII) reconstruction for a standard duodenoscope and the situs of a long-limbed Roux-en-Y (RY) for device-assisted enteroscopy (DAE). In three independent workshops, the models were evaluated by international ERCP experts. In RY model, a simulation for small bowel behavior in endoscopy was created. Thirty-three experts rated the ETM in ERCP expert courses. The BII model was evaluated as suitable for training (school grades 1.36), with a haptic and visual impression rating of 1.73. The RY model was rated 1.50 for training suitability and 2.06 for overall impression. Animal tissue-free ETMs for ERCP in surgically altered anatomy were successfully created. Evaluation by experienced endoscopists indicated that the models are suitable for hands-on ERCP training, including device-assisted endoscopy. It is expected that patient care will improve with appropriate training in advanced procedures.

Second annual report from the ISSPP PIPAC database.

Objectives: To monitor the results of PIPAC directed therapy based on data from the International Society for the Study of the Pleura and Peritoneum (ISSPP) PIPAC database. Methods: Analysis of data from patients entered between June 15th, 2020, and February 28th, 2023. Results: Twelve centers reported 2,456 PIPAC procedures in 809 patients (median 2, range 1-18) with peritoneal metastasis (PM) from different primary tumors. Approximately 90 % had systemic chemotherapy prior to PIPAC. Twenty-eight percent were treated in prospective protocols. Overall non-access rate was 3.5 %. Concomitant surgical procedures were performed during PIPAC in 1.6 % of the patients. Median length of stay was 2 days. A total of 95 surgical complications were recorded, but only 22 % of these were graded ≥3b. Seventeen-hundred-and-three adverse events were noted, and 8 % were classified ≥3. The rate of complete or major histological response (peritoneal regression grade score, PRGS≤2) increased between the first and the third PIPAC in the group of patients who were evaluated by PRGS, and a PRGS ≤2 or a reduction of the mean PRGS of at least 1 between first and third PIPAC were observed in 80 %. Disease progression (50 %) or technical issues (19 %) were the most important reasons for stopping PIPAC treatment. Median overall survival from first PIPAC directed treatment varied from 10.7 months (CI 8.7-12.5) in gastric cancer to 27.1 months (16.4-50.5) in mesothelioma. Conclusions: The ISSPP PIPAC database provides substantial real-world data supporting the use of PIPAC directed therapy in patients with PM from different primary tumors.

Evaluation of the feasibility of a video-transmitted surgical ward round: a proof of concept study.

BACKGROUND: Surgical ward rounds are key element to point-of-care interprofessional postoperative treatment and technical and communicational aspects are relevant for the patient's safety and satisfaction. Due to COVID-19 restrictions, the training opportunity of experiencing a face-to-face surgical ward round was massively hampered and thus, we developed a digital concept. This study aims to investigate the feasibility of video-transmitted ward rounds integrating surgical and communicational aspects with live streaming from wards. Further, medical students were asked for their satisfaction and their subjective learning success. METHODS: The proof-of-concept study consisted of self-reported subjective evaluation of competences in ward round skills. Qualitative feedback was collected to gain deeper insight and students' empathy was rated by using the student version of the Jefferson Empathy Scale (JES). RESULTS: One hundred three medical students participated. The students were satisfied with the video-transmitted ward round (M = 3.54; SD = 1.22). In the subjective evaluation students' ward round competencies rose significantly (p < .001, Mpre = 3.00, SD = 0.77; Mpost = 3.76, SD = 0.75). The surgeon was rated as empathic (M = 119.05; SD = 10.09). In the qualitative feedback they named helpful aspects like including an expert for communication. However, they preferred the face-to-face setting in comparison to the digital concept. CONCLUSIONS: It was feasible to implement a video-transmitted ward round within a pandemic. The format worked technically, was well-accepted and also led to a subjective rise in the students' competencies. Video-transmitted ward rounds may be integrated to support the medical education, though, they cannot replace the face-to-face setting.

Development of an interactive elective "altered anatomy" for students as part of the Z-curriculum according to the NKLM 2.0.

Objective: Many patients have undergone visceral surgery. The effects on anatomy and physiology, which can result in further surgical or gastroenterological clinical pictures, are equally significant and require special knowledge. This content should be taught in an interdisciplinary elective course. The draft of the new 2025 approval regulation and the current approval regulation specify that preclinical and clinical content should specifically be combined within the framework of a Z-curriculum and that the new elective course should meet these requirements. Methodology: Practical and theoretical aspects of recognising and treating patients with postoperative modified anatomy are to be taught and the findings are to be demonstrated using anatomical and artificial preparations. The curriculum of the preclinical course covers anatomy and physiology. The target group of the curriculum is all participating students with a special interest in topics such as anatomy, visceral surgery and gastroenterology. However, the goal is to involve student tutors of the anatomical dissection courses, who, in turn, will pass on knowledge of modified anatomy to the supervised preclinical students. Results: According to Thomas and Kern, the curriculum development process entails the following six stages: general needs assessment, targeted needs assessment, the formulation of goals and content, the description of strategies, planned implementation and evaluation. Conclusion: A "modified anatomy" curriculum for an interdisciplinary elective course in surgery, gastroenterology, and anatomy was developed. Through the training of anatomy table tutors, a "dovetailing" with the preclinical stage is to be achieved. In addition, new concepts related to the transfer of knowledge and competencies were introduced and should be evaluated for suitability.

Predicting complicated appendicitis is possible without the use of sectional imaging-presenting the NoCtApp score.

PURPOSE: Appendicitis is among the most common acute conditions treated by general surgery. While uncomplicated appendicitis (UA) can be treated delayed or even non-operatively, complicated appendicitis (CA) is a serious condition with possible long-term morbidity that should be managed with urgent appendectomy. Distinguishing both conditions is usually done with computed tomography. The goal of this study was to develop a model to reliably predict CA with widespread available clinical and laboratory parameters and without the use of sectional imaging. METHODS: Data from 1132 consecutive patients treated for appendicitis between 2014 and 2021 at a tertiary care hospital were used for analyses. Based on year of treatment, the data was divided into training (n = 696) and validation (n = 436) samples. Using the development sample, candidate predictors for CA-patient age, gender, body mass index (BMI), American Society of Anesthesiologist (ASA) score, duration of symptoms, white blood count (WBC), total bilirubin and C-reactive protein (CRP) on admission and free fluid on ultrasound-were first investigated using univariate logistic regression models and then included in a multivariate model. The final development model was tested on the validation sample. RESULTS: In the univariate analysis age, BMI, ASA score, symptom duration, WBC, bilirubin, CRP, and free fluid each were statistically significant predictors of CA (each p < 0.001) while gender was not (p = 0.199). In the multivariate analysis BMI and bilirubin were not predictive and therefore not included in the final development model which was built from 696 patients. The final development model was significant (x2 = 304.075, p < 0.001) with a sensitivity of 61.7% and a specificity of 92.1%. The positive predictive value (PPV) was 80.4% with a negative predictive value (NPV) of 82.0%. The receiver operator characteristic of the final model had an area under the curve of 0.861 (95% confidence interval 0.830-0.891, p < 0.001. We simplified this model to create the NoCtApp score. Patients with a point value of ≤ 2 had a NPV 95.8% for correctly ruling out CA. CONCLUSIONS: Correctly identifying CA is helpful for optimizing patient treatment when they are diagnosed with appendicitis. Our logistic regression model can aid in correctly distinguishing UA and CA even without utilizing computed tomography.

Possible Advantages of Minimal-Invasive Approaches in Rectal Cancer Surgery: A Nationwide Analysis.

(1) Background: Laparoscopic resection for colon and rectal cancer was introduced in the early 1990s; the aim of this analysis was to show possible advantages of minimal-invasive approaches in rectal cancer surgery. (2) Methods: From 2016 to 2020, all patients undergoing open, laparoscopic or robotic-assisted rectal cancer surgery in Germany were retrospectively analyzed regarding sex distribution, conversion rates and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRGs). (3) Results: In total, 68,112 patients were analyzed, and most commonly, low anterior rectal resections with primary anastomosis (n = 25,824) were performed with an increase of minimal-invasive procedures over the years (open: 51% to 27%; laparoscopic: 47% to 63% and robotic: 2% to 10%). In-hospital mortality rate was 2.95% (n = 2012). In total, 4.61%, 1.77%, 1.14% and 3.95% of patients with open, laparoscopic, robotic and converted-to-open surgery died during hospital stay, respectively (open vs. laparoscopic p < 0.0001; open vs. robotic p < 0.00001; laparoscopic vs. robotic p = 0.001). Conversion rates were significantly more favorable in the robotic compared to the laparoscopic group. (11.94% vs. 2.53%; p < 0.0001). (4) Conclusion: Minimal-invasive rectal cancer surgery might have some advantages in terms of a reduced in-hospital mortality, and an improved conversion rate for the robotic approach.

STE20-type kinases MST3 and MST4 promote the progression of hepatocellular carcinoma: Evidence from human cell culture and expression profiling of liver biopsies.

Hepatocellular carcinoma (HCC) is one of the most fatal and fastest growing malignancies. Recently, nonalcoholic steatohepatitis (NASH), characterized by liver steatosis, inflammation, cell injury (hepatocyte ballooning), and different stages of fibrosis, has emerged as a major catalyst for HCC. Because the STE20-type kinases, MST3 and MST4, have been described as critical molecular regulators of NASH pathophysiology, we here focused on determining the relevance of these proteins in human HCC. By analyzing public datasets and in-house cohorts, we found that hepatic MST3 and MST4 expression was positively correlated with the incidence and severity of HCC. We also found that the silencing of both MST3 and MST4, but also either of them individually, markedly suppressed the tumorigenesis of human HCC cells including attenuated proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistic investigations revealed lower activation of STAT3 signaling in MST3/MST4-deficient hepatocytes and identified GOLGA2 and STRIPAK complex as the binding partners of both MST3 and MST4. These findings reveal that MST3 and MST4 play a critical role in promoting the progression of HCC and suggest that targeting these kinases may provide a novel strategy for the treatment of liver cancer.

Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes.

Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-ß1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover.

Primary admission to a surgical service facilitates early cholecystectomy in acute cholecystitis but does not influence patient outcome.

PURPOSE: Early cholecystectomy is recommended for acute calculous cholecystitis to reduce complications and lower health care costs. However, not all patients admitted to emergency services due to acute calculous cholecystitis are considered for surgery immediately. Our intention was therefore to evaluate patient management and outcome parameters following cholecystectomy depending on the type of emergency service patients are primarily admitted to. METHODS: We performed a retrospective analysis of all patients that were treated for acute cholecystitis at our hospital between 2014 and 2021. Only patients that underwent surgical treatment for acute calculous cholecystitis were included. Patients with cholecystectomies that were performed due to other medical conditions were not incorporated. Primary outcomes were the perioperative length of stay and postoperative complications. Perioperative antimicrobial management and disease deterioration according to Tokyo Guidelines from 2018 due to inhouse organization were assessed as secondary outcome parameters. RESULTS: Of 512 patients included in our final analysis, 334 patients were primarily admitted to a surgical emergency service (SAG) whereas 178 were initially treated in a medical service (MAG). The latency between admission and cholecystectomy was significantly prolonged in the MAG with a median time to surgery of 2 days (Q25 1, Q75 3.25, IQR 2.25) compared to the SAG with a median time to surgery of 1 day (Q25 1, Q75 2, IQR 1) (p < 0.001). The duration of surgery was comparable between both groups. Necrotizing cholecystitis (27.2% vs. 38.8%, p = 0.007) and pericholecystic abscess or gallbladder perforation (7.5% vs. 14.6% p = 0.010) were less frequently described in the SAG. In the SAG, 85.7% of CCEs were performed laparoscopically, 6.0% were converted to open, and 10.4% were performed as open surgery upfront. In the MAG, 80.9% were completed laparoscopically, while 7.2% were converted and 11.2% were performed via primary laparotomy (p = 0.743). Histologically gangrenous cholecystitis was confirmed in 38.0% of the specimen in the SAG compared to 47.8% in the MAG (p = 0.033). While the prolonged preoperative stay led to prolonged overall length of stay, the postoperative length of stay was similar at a median of 3 days in both groups. CONCLUSIONS: To our knowledge, we present the largest single center cohort of acute calculous cholecystitis evaluating the perioperative management and outcome of patients admitted to either medical or surgical service prior to undergoing cholecystectomy. In patients that were primarily admitted to medical emergency services, we found disproportionately more gallbladder necrosis, perforation, and gangrene. Despite prolonged time intervals between admission and cholecystectomy in the MAG and advanced cases of cholecystitis, we did not record a prolonged procedure duration, conversion to open surgery, or complication rate. However, patients with acute calculous cholecystitis should either be primarily admitted to a surgical emergency service or at least a surgeon should be consulted at the time of diagnosis in order to avoid disease progression and unnecessary health care costs.

Quantification of intratumoural heterogeneity in mice and patients via machine-learning models trained on PET-MRI data.

In oncology, intratumoural heterogeneity is closely linked with the efficacy of therapy, and can be partially characterized via tumour biopsies. Here we show that intratumoural heterogeneity can be characterized spatially via phenotype-specific, multi-view learning classifiers trained with data from dynamic positron emission tomography (PET) and multiparametric magnetic resonance imaging (MRI). Classifiers trained with PET-MRI data from mice with subcutaneous colon cancer quantified phenotypic changes resulting from an apoptosis-inducing targeted therapeutic and provided biologically relevant probability maps of tumour-tissue subtypes. When applied to retrospective PET-MRI data of patients with liver metastases from colorectal cancer, the trained classifiers characterized intratumoural tissue subregions in agreement with tumour histology. The spatial characterization of intratumoural heterogeneity in mice and patients via multimodal, multiparametric imaging aided by machine-learning may facilitate applications in precision oncology.

Peritoneal regression grading score (PRGS): first evidence for independent predictive and prognostic significance.

Objectives: The peritoneal regression grading score (PRGS) is a four-tied pathologic score measuring tumor regression in biopsies from patients with peritoneal metastasis (PM) receiving chemotherapy. Methods: This retrospective analysis of a prospective registry (NCT03210298) analyses 97 patients with isolated PM under palliative chemotherapy. We examined the predictive value of the initial PRGS for overall survival (OS) and the prognostic value of PRGS in repeated peritoneal biopsies. Results: The 36 (37.1 %) patients with an initial mean PRGS≤2 had a longer median OS (12.1 months, CI 95 % 7.8-16.4) vs. 8.0 months (CI 95 % 5.1-10.8 months) in 61 (62.9 %) patients with PRGS≥3 (p=0.02) After stratification, the initial PRGS was an independent predictor of OS (Cox-regression, p<0.05). Out of 62 patients receiving≥two chemotherapy cycles, 42 (67.7 %) had a histological response (defined as a lower or stable mean PRGS in successive therapy cycles), and 20 (32.3 %) progressed (defined as an increasing mean PRGS). PRGS response was associated with a longer median OS (14.6 months, CI 5-95 % 6.0-23.2) vs. 6.9 (CI 5-95 % 0.0-15.9) months. PRGS response was prognostic in the univariate analysis (p=0.017). Thus, PRGS had both a predictive and prognostic significance in patients with isolated PM receiving palliative chemotherapy in this patient cohort. Conclusions: This is the first evidence for the independent predictive and prognostic significance of PRGS in PM. These encouraging results need validation in an adequately powered, prospective study.

Endoscopic negative pressure therapy for duodenal leaks.

Background and study aim: Endoscopic negative pressure therapy (ENPT) is well established in the treatment of perforations of various etiologies in the upper and lower gastrointestinal tract. For duodenal perforations exist only case reports and series. Different indications are possible for ENPT in duodenal position: primary therapy for leaks, preemptive therapy after surgery for example, after ulcer suturing or resection with anastomoses, or as second line therapy in cases of recurrent anastomotic insufficiencies with leakage of duodenal secretion. Methods: A retrospective 4-year case series of negative pressure therapy in duodenal position indicated by different etiologies and a comprehensive review of current literature on endoscopic negative pressure duodenal therapy are presented. Results: Patients with primary duodenal leaks n= 6 and with duodenal stump insufficiencies n = 4 were included. In seven patients ENPT was the first line and sole therapy. Primary surgery for duodenal leak was performed in n = 3 patients. Mean duration of ENPT was 11.0 days, mean hospital stay was 30.0 days. Re-operation after start of ENPT was necessary in two patients with duodenal stump insufficiencies. Surgery after termination of the ENPT was not necessary in any patient. Discussion: In our case series and in the literature, ENPT has been shown to be very successful in the therapy of duodenal leaks. A challenge in ENPT for duodenal leaks is the appropriate length of the probe to safely reach the leak and keep the open pore element at the end of the probe in place despite intestinal motility.

Exerting Forces and Wall Load during Duodenoscopy for ERCP: An Experimental Measurement in an Artificial Model.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is crucial to the treatment of biliopancreatic diseases with iatrogenic perforation as a potential complication. As of yet, the wall load during ERCP is unknown, as it is not directly measurable during an ERCP in patients. METHODS: In a life-like, animal-free model, a sensor system consisting of five load cells was attached to the artificial intestines (sensors 1 + 2: pyloric canal-pyloric antrum, sensor 3: duodenal bulb, sensor 4: descending part of the duodenum, sensor 5: distal to the papilla). Measurements were made with five duodenoscopes (n = 4 reusable and n = 1 single use). RESULTS: Fifteen standardized duodenoscopies were performed. Peak stresses were found at the antrum during the gastrointestinal transit (sensor 1 max. 8.95 N, sensor 2 max. 2.79 N). The load reduced from the proximal to the distal duodenum and the greatest load in the duodenum was discovered at the level of the papilla in 80.0% (sensor 3 max. 2.06 N). CONCLUSIONS: For the first time, intraprocedural load measurements and exerting forces obtained during a duodenoscopy for ERCP in an artificial model were recorded. None of the tested duodenoscopes were classified as dangerous for patient safety.

Evaluation of a New Animal Tissue-Free Bleeding Model for Training of Endoscopic Hemostasis.

BACKGROUND: For endoscopists, knowledge of the available hemotherapeutic devices and materials as well as competence in using them is a life-saving expertise in the treatment of patients with acute gastrointestinal bleeding. These competences can be acquired in training on live animals, animal organs, or simulators. We present an animal tissue-free training model of the upper gastrointestinal tract for bleeding therapy. METHODS: An artificial, animal tissue-free mucosa and submucosa with the opportunity of injection and clipping therapy were created first. Patches with this artificial mucosa and submucosa were placed into silicone and latex organs with human-like anatomy. Esophageal bleeding situations were imitated as variceal bleeding and bleeding of a reflux esophagitis in latex organs. Finally, a modular training model with human anatomy and replaceable bleeding sources was created. Evaluation of the novel model for gastroscopic training was performed in a multicentric setting with endoscopic beginners and experts. RESULTS: Evaluation was carried out by 38 physicians with different levels of education in endoscopy. Evaluation of the model was made with grades from one (excellent) to six (bad): suitability for endoscopic training was 1.4, relevance of the endoscopic training was 1.6, and grading for haptic and optic impression of the model was 1.7. CONCLUSIONS: The creation of a gastroscopic model for the training of hemostatic techniques without animal tissues was possible and multiple endoscopic bleeding skills could be trained in it. Evaluation showed good results for this new training option, which could be used in every endoscopic unit or other places without hygienic doubts.

Is There a High Risk for GI Bleeding Complications in Patients Undergoing Abdominal Surgery?

INTRODUCTION: Gastrointestinal bleeding (GIB) can cause life-threatening situations. Here, endoscopy is the first-line diagnostic and therapeutic mode in patients with GIB among further therapeutic approaches such as embolization or medical treatment. Although GIB is considered the most common indication for emergency endoscopy in clinical practice, data on GIB in abdominal surgical patients are still scarce. PATIENTS AND METHODS: For the present study, all emergency endoscopies performed on hospitalized abdominal surgical patients over a 2-year period (1 July 2017-30 June2019) were retrospectively analyzed. Primary endpoint was 30-day mortality. Secondary endpoints were length of hospital stay, cause of bleeding, and therapeutic success of endoscopic intervention. RESULTS: During the study period, bleeding events with an indication for emergency endoscopy occurred in 2.0% (129/6455) of all surgical inhouse patients, of whom 83.7% (n = 108) underwent a surgical procedure. In relation to the total number of respective surgical procedures during the study period, the bleeding incidence was 8.9% after hepatobiliary surgery, 7.7% after resections in the upper gastrointestinal tract, and 1.1% after colonic resections. Signs of active or past bleeding in the anastomosis area were detected in ten patients (6.9%). The overall 30-day mortality was 7.75%. CONCLUSIONS: The incidence of relevant gastrointestinal bleeding events in visceral surgical inpatients was overall rare. However, our data call for critical peri-operative vigilance for bleeding events and underscore the importance of interdisciplinary emergency algorithms.