Learning curve of achieving competency in emergency endoscopy in upper gastrointestinal bleeding: how much experience is necessary?

OBJECTIVES: The management of upper gastrointestinal bleeding (UGIB) has seen rapid advancements with revolutionising innovations. However, insufficient data exist on the necessary number of emergency endoscopies needed to achieve competency in haemostatic interventions. DESIGN: We retrospectively analysed all oesophagogastroduodenoscopies with signs of recent haemorrhage performed between 2015 and 2022 at our university hospital. A learning curve was created by plotting the number of previously performed oesophagogastroduodenoscopies with signs of recent haemorrhage against the treatment failure rate, defined as failed haemostasis, rebleeding and necessary surgical or radiological intervention. RESULTS: The study population included 787 cases with a median age of 66 years. Active bleeding was detected in 576 cases (73.2%). Treatment failure occurred in 225 (28.6%) cases. The learning curve showed a marked decline in treatment failure rates after nine oesophagogastroduodenoscopies had been performed by the respective endoscopists followed by a first plateau between 20 and 50 procedures. A second decline was observed after 51 emergency procedures followed by a second plateau. Endoscopists with experience of <10 emergency procedures had higher treatment failure rates compared with endoscopists with >51 emergency oesophagogastroduodenoscopies performed (p=0.039) or consultants (p=0.041). CONCLUSIONS: Our data suggest that a minimum number of 20 oesophagogastroduodenoscopies with signs of recent haemorrhage is necessary before endoscopists should be considered proficient to perform emergency procedures independently. Endoscopists might be considered as advanced-qualified experts in managing UGIB after a minimum of 50 haemostatic procedure performed. Implementing recommendations on minimum numbers of emergency endoscopies in education programmes of endoscopy trainees could improve their confidence and competency in managing acute UGIB.

Timing of endoscopy in patients with elevated lactate levels and acute upper gastrointestinal bleeding; a retrospective comparative study.

BACKGROUND/AIMS: While current guidelines recommend performing endoscopy within 24 h in case of acute upper gastrointestinal bleeding (AUGIB), the precise timing remains an issue of debate. Lactate is an established parameter for risk stratification in a variety of medical emergencies. This study evaluated the predictive ability of elevated lactate levels in identifying patients with UGIB, who may benefit from emergent endoscopy. METHODS: We retrospectively analyzed all patients with elevated lactate levels, who presented to our emergency department between 01 January 2015 and 31 December 2019 due to suspected AUGIB. RESULTS: Of 134 included cases, 81.3% had an Charlson comorbidity index of ≥3 and 50.4% presented with shock. Fifteen (11.2%) patients died and mortality rates rose with increasing lactate levels. Emergent endoscopy within 6 h (EE) and non-EE were performed in 64 (47.8%) and 70 (52.2%) patients, respectively. Patients who underwent EE had lower systolic blood pressure (107.6 mmHg vs. 123.2 mmHg; p = 0.001) and received blood transfusions more frequently (79.7% vs 64.3%; p = 0.048), but interestingly need for endoscopic intervention (26.6% vs 20.0%; p = 0.37), rebleeding (17.2% vs. 15.7%; p = 0.82) and mortality (9.4% vs. 11.4%; p = 0.7) did not differ significantly. CONCLUSION: In conclusion, our findings support the recommendations of current guidelines to perform non-EE after sufficient resuscitation and management of comorbid illnesses.

Prognostic assessment of liver cirrhosis and its complications: current concepts and future perspectives.

Liver cirrhosis is an irreversible stage of chronic liver disease with varying clinical course. Acute decompensation of liver cirrhosis represents a watershed in prognosis and is characterized by the occurrence of clinical complications such as ascites, jaundice, hepatic encephalopathy, infections, or portal-hypertensive hemorrhages. Emergent data indicate that an acute decompensation can be subdivided into stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on chronic liver failure (pre-ACLF) and acute-on chronic liver failure (ACLF), while the mortality risk varies greatly between the respective subgroups. ACLF is the most severe form of acutely decompensated cirrhosis and characterized by the development of organ failure(s) and a high short-term mortality. Due to the dynamic disease course of acute decompensation, it is paramount to detect patients at particular risk for severe complications those at high risk for developing ACLF as early as possible in order to initiate optimal management. This review describes new concepts and perspectives in the definition and classification of decompensated cirrhosis and provides on overview on emerging predictive scoring systems, non-invasive measurement methods and new biomarkers, which allow an early identification of patients with acute decompensation at risk.

A convolutional neural network for bleeding detection in capsule endoscopy using real clinical data.

BACKGROUND: The goal of the present study was to develop a convolutional neural network for the detection of bleedings in capsule endoscopy videos using realistic clinical data from one single-centre. METHODS: Capsule endoscopy videos from all 133 patients (79 male, 54 female; meanage = 53.73 years, SDage = 26.13) who underwent capsule endoscopy at our institution between January 2014 and August 2018 were screened for pathology. All videos were screened for pathology by two independent capsule experts and confirmed findings were checked again by a third capsule expert. From these videos, 125 pathological findings (individual episodes of bleeding spanning a total of 5696 images) and 103 non-pathological findings (sections of normal mucosal tissue without pathologies spanning a total of 7420 images) were used to develop and validate a neural network (Inception V3) using transfer learning. RESULTS: The overall accuracy of the model for the detection of bleedings was 90.6% [95%CI: 89.4%-91.7%], with a sensitivity of 89.4% [95%CI: 87.6%-91.2%] and a specificity of 91.7% [95%CI: 90.1%-93.2%]. CONCLUSION: Our results show that neural networks can detect bleedings in capsule endoscopy videos under realistic, clinical conditions with an accuracy of 90.6%, potentially reducing reading time per capsule and helping to improve diagnostic accuracy.

[Gastrointestinal and hepatic emergencies in acute and emergency care]. / Gastrointestinale und hepatologische Notfälle in der klinischen Akut- und Notfallmedizin.

Acute gastrointestinal emergencies are one of the most common presentations to the emergency department. If the main symptom is acute abdominal pain, this is referred to as "acute abdomen". An acute abdomen demands urgent attention and treatment and can be caused by different pathologies (e.g., peptic ulcer disease, acute pancreatitis, diverticulitis). Hepatic emergencies include acute liver failure and acute-on-chronic liver failure. Due to the large number of possible differential diagnoses with variable clinical symptoms, rapid diagnosis of the underlying etiology of gastrointestinal and liver emergencies is a major challenge in daily clinical practice. A structured approach and prompt initiation of adequate diagnostic and treatment measures are essential in order to reduce mortality.

Efficacy of endoscopic therapy and long-term outcomes of upper gastrointestinal tumor bleeding in patients with esophageal cancer.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) from malignancies is associated with a poor outcome. Only a small number of studies on gastrointestinal tumor bleeding have been published so far, focusing mainly on bleeding from gastric cancer. Since the information on patients with UGIB from esophageal cancer appears insufficient, this study aimed to present clinical and endoscopic findings, treatment options as well as clinical outcomes such as rebleeding and survival of those patients. METHODS: This retrospective analysis included all patients admitted with UGIB from esophageal cancer at our university hospital during a 10-year period. RESULTS: 45 patients were analyzed of whom 26 (57.8%) already had cancer stage IV at index bleeding. 22 (48.9%) patients presented with hemodynamic instability and 30 (66.7%) patients received blood transfusions. Active bleeding was present in 24 (53.3%) patients, of whom 20 (83.3%) received endoscopic therapy. Successful hemostasis was achieved in 18 (90%) of 20 patients with Argon plasma coagulation used most frequently (52.4%). Early and delayed rebleeding occurred in 5 (12.5%) and 11 (27.5%) of all inoperable patients, respectively. Intake of anticoagulation or anti-platelet drugs were risk factors for delayed rebleeding and the median overall survival after index bleeding was 1.2 months. CONCLUSION: UGIB from esophageal cancer occurred most frequently in advanced tumor stages and was associated with significant blood loss. Even though initial endoscopic therapy was effective, rebleeding occurred in a significant number of patients. Those taking anticoagulants or anti-platelet drugs should be closely monitored for rebleeding. The overall survival after index bleeding was poor.

Comparison of Lactate Clearance with Established Risk Assessment Tools in Predicting Outcomes in Acute Upper Gastrointestinal Bleeding.

Early risk stratification is mandatory in acute upper gastrointestinal bleeding (AUGIB) to guide optimal treatment. Numerous risk scores were introduced, but lack of practicability led to limited use in daily clinical practice. Lactate clearance is an established risk assessment tool in a variety of diseases, such as trauma and sepsis. Therefore, this study compares the predictive ability of pre-endoscopic lactate clearance and established risk scores in patients with AUGIB at the University Hospital of Cologne. Active bleeding was detected in 27 (25.2%) patients, and hemostatic intervention was performed in 35 (32.7%). In total, 16 patients (15%) experienced rebleeding and 12 (11.2%) died. Initially, lactate levels were elevated in 64 cases (59.8%), and the median lactate clearance was 18.7% (2.7-48.2%). Regarding the need for endoscopic intervention, the predictive ability of Glasgow Blatchford Score, pre-endoscopic Rockall score, initial lactate and lactate clearance did not differ significantly, and their area under the receiver operating characteristic curves were 0.658 (0.560-0.747), 0.572 (0.473-0.667), 0.572 (0.473-0.667) and 0.583 (0.483-0.677), respectively. Similar results were observed in relation to rebleeding and mortality. In conclusion, lactate clearance had comparable predictive ability compared to established risk scores. Further prospective research is necessary to clarify the potential role of lactate clearance as a reliable risk assessment tool in AUGIB.

Assessment of pyloric sphincter physiology after Ivor-Lewis esophagectomy using an endoluminal functional lumen imaging probe.

OBJECTIVE OF THE STUDY: The most common functional complication after Ivor-Lewis esophagectomy is the delayed emptying of the gastric conduit (DGCE) for which several diagnostic tools are available, e.g. chest X-ray, upper esophagogastroduodenoscopy (EGD) and water-soluble contrast radiogram. However, none of these diagnostic tools evaluate the pylorus itself. Our study demonstrates the successful measurement of pyloric distensibility in patients with DGCE after esophagectomy and in those without it. METHODS AND PROCEDURES: Between May 2021 and October 2021, we performed a retrospective single-centre study of all patients who had an oncological Ivor-Lewis esophagectomy and underwent our post-surgery follow-up programme with surveillance endoscopies and computed tomography scans. EndoFlip™ was used to perform measurements of the pylorus under endoscopic control, and distensibility was measured at 40 ml, 45 ml and 50 ml balloon filling. RESULTS: We included 70 patients, and EndoFlip™ measurement was feasible in all patients. Successful application of EndoFlip™ was achieved in all interventions (n = 70, 100%). 51 patients showed a normal postoperative course, whereas 19 patients suffered from DGCE. Distensibility proved to be smaller in patients with symptoms of DGCE compared to asymptomatic patients. For 40 ml, 45 ml and 50 ml, the mean distensibility was 6.4 vs 10.1, 5.7 vs 7.9 and 4.5 vs 6.3 mm2/mmHg. The differences were significant for all three balloon fillings. No severe EndoFlip™ treatment-related adverse events occurred. CONCLUSION: Measurement with EndoFlip™ is a safe and technically feasible endoscopic option for measuring the distensibility of the pylorus. Our study shows that the distensibility in asymptomatic patients after esophagectomy is significantly higher than that in patients suffering from DGCE. However, more studies need to be conducted to demonstrate the general use of EndoFlip™ measurement of the pylorus after esophagectomy.

Using an Endoluminal Functional Lumen Imaging Probe (EndoFLIP™) to Compare Pyloric Function in Patients with Gastroparesis to Patients After Esophagectomy.

BACKGROUND: Gastroparesis (GP) occurs in patients after upper gastrointestinal surgery, in patients with diabetes or systemic sclerosis and in idiopathic GP patients. As pyloric dysfunction is considered one of the underlying mechanisms, measuring this mechanism with EndoFLIP™ can lead to a better understanding of the disease. METHODS: Between November 2021 and March 2022, we performed a retrospective single-centre study of all patients who had non-surgical GP, post-surgical GP and no sign of GP after esophagectomy and who underwent our post-surgery follow-up program with surveillance endoscopies and further exams. EndoFLIP™ was used to perform measurements of the pylorus, and distensibility was measured at 40 ml, 45 ml and 50 ml balloon filling. RESULTS: We included 66 patients, and successful application of the EndoFLIP™ was achieved in all interventions (n = 66, 100%). We identified 18 patients suffering from non-surgical GP, 23 patients suffering from GP after surgery and 25 patients without GP after esophagectomy. At 40, 45 and 50 ml balloon filling, the mean distensibility in gastroparetic patients was 8.2, 6.2 and 4.5 mm2/mmHg; 5.4, 5.1 and 4.7 mm2/mmHg in post-surgical patients suffering of GP; and 8.5, 7.6 and 6.3 mm2/mmHg in asymptomatic post-surgical patients. Differences between symptomatic and asymptomatic patients were significant. CONCLUSION: Measurement with EndoFLIP™ showed that asymptomatic post-surgery patients seem to have a higher pyloric distensibility. Pyloric distensibility and symptoms of GP seem to correspond.

Outcome of endoscopic vacuum therapy for duodenal perforation.

BACKGROUND: Duodenal defects are complex clinical situations, and their management is challenging and associated with high mortality. Besides surgery, endoscopic treatment options exist, but the size and location of the perforation can limit their application. We present a retrospective study, demonstrating a successful application of endoscopic vacuum therapy (EVT) for duodenal leaks. METHODS: We performed a retrospective study of all patients who underwent EVT for duodenal perforations between 2016 and 2021 at two tertiary centers. We analyzed demographic and clinical patient characteristics, surgical outcomes, leak characteristics, sponge-related complications, and success rate. RESULTS: Indications for treatment with EVT in the duodenum consisted of leak after duodenal suture of a perforated ulcer (n = 4), iatrogenic perforation after endoscopic resection (n = 2), iatrogenic perforation during surgery (n = 2), and anastomotic leak after upper gastrointestinal surgery (n = 2). EVT was used as a first-line treatment in seven patients and as a second-line treatment in three patients. EVT was successfully applied in all interventions (n = 10, 100%). Overall, EVT lead to definitive closure of the defects in eight out of ten patients (80%). No severe EVT-related adverse events occurred. CONCLUSION: EVT is safe and technically feasible, so it emerges as a promising endoscopic treatment option for duodenal leaks. However, multidisciplinary collaboration and management are important to reduce the occurrence of postoperative complications, and to improve recovery rates.

Dietary omega-6/omega-3 ratio is not associated with gut microbiota composition and disease severity in patients with nonalcoholic fatty liver disease.

In this cross-sectional study, we hypothesized that a high dietary ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids could be associated with an altered gut bacterial composition and with the disease severity in patients with nonalcoholic fatty liver disease (NAFLD). A total of 101 NAFLD patients were included in the study, of which 63 underwent a liver biopsy. All 101 patients completed a 14-day food and activity record. Ebispro 2016 professional software was used to calculate individual macronutrients and micronutrients consumed. Patients were grouped into 3 quantiles (Q) according to a low (Q1: <6.1, n = 34), moderate (Q2: 6.1-7.8, n = 33), or high (Q3: >7.8, n = 34) dietary n-6/n-3 ratio. Stool samples were analyzed using 16S rRNA gene sequencing. Spearman correlation coefficients and principal coordinate analysis were used to detect differences in the bacterial composition of the gut microbiota. The median dietary n-6/n-3 ratio of all patients was 6.7 (range, 3.1-14.9). No significant associations between the dietary n-6/n-3 ratio and the gut microbiota composition or disease severity were observed. However, the abundance of specific bacteria such as Catenibacterium or Lactobacillus ruminis were found to be positively correlated and the abundance of Clostridium were negatively correlated with dietary n-6 fatty acid intake. The results indicate that a high dietary n-6/n-3 ratio is probably not a highly relevant factor in the pathogenesis of human NAFLD. Further studies are needed to clarify the importance of interactions between gut bacterial taxa and n-6 fatty acids in the pathophysiology of NAFLD.

Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response, Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice.

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.

Management of Dyslipidemia in Patients with Non-Alcoholic Fatty Liver Disease.

PURPOSE OF REVIEW: Patients with non-alcoholic fatty liver disease (NAFLD), often considered as the hepatic manifestation of the metabolic syndrome, represent a population at high cardiovascular risk and frequently suffer from atherogenic dyslipidemia. This article reviews the pathogenic interrelationship between NAFLD and dyslipidemia, elucidates underlying pathophysiological mechanisms and focuses on management approaches for dyslipidemic patients with NAFLD. RECENT FINDINGS: Atherogenic dyslipidemia in patients with NAFLD results from hepatic and peripheral insulin resistance along with associated alterations of hepatic glucose and lipoprotein metabolism, gut dysbiosis, and genetic factors. Since atherogenic dyslipidemia and NAFLD share a bi-directional relationship and are both major driving forces of atherosclerotic cardiovascular disease (ASCVD) development, early detection and adequate treatment are warranted. Thus, integrative screening and management programs are urgently needed. A stepwise approach for dyslipidemic patients with NAFLD includes (i) characterization of dyslipidemia phenotype, (ii) individual risk stratification, (iii) definition of treatment targets, (iv) lifestyle modification, and (v) pharmacotherapy if indicated.

Outcome of prophylactic endoscopic vacuum therapy for high-risk anastomosis after esophagectomy.

Background: Endoscopic vacuum therapy (EVT) has become an established procedure for the treatment of anastomotic leaks (AL) in upper gastrointestinal surgery. A novel approach is the use of EVT for preventing leaks in high-risk anastomosis. The aim of this study was to analyze the outcome of prophylactic EVT (pEVT) in patients receiving surgical revision of the anastomosis after oncological Ivor-Lewis esophagectomy (ILE) due to AL.Material and methods: Between June 2016 and February 2019, all patients who underwent anastomotic revision after ILE due to a confirmed AL were included. The primary outcome was the success rate of pEVT, which was defined as absence of an AL after revision. Secondary outcome parameters were duration of treatment, inflammatory levels, and ICU/hospital stay.Results: Twenty-one patients underwent anastomotic revision due to an AL. The cause of the AL was ischemia in nine patients (42.9%) and non-ischemia (other) in 12 patients (57.1%). PEVT was performed in 14 patients (66.6%). The overall success rate of pEVT was five out of 14 patients (35.7%).Conclusions: Prophylactic EVT cannot prevent a re-leak in patients with high-risk anastomosis due to surgical revision of an AL after oncological ILE. However, pEVT might help to control the clinical condition of these patients.

Expression of Neighbor of Punc E11 (NOPE) in early stage esophageal adenocarcinoma is associated with reduced survival.

Current recommendations suggest neoadjuvant treatment in node-positive esophageal cancer or tumors staged T3 and upwards but some T2 N0 patients might benefit from neoadjuvant therapy. It is of clinical relevance to identify this subgroup. Loss of epithelial apicobasal polarity is a key factor in the development of invasive capabilities of carcinoma. The oncofetal stem/progenitor cell marker NOPE is expressed in adult depolarized murine hepatocytes and in murine/human hepatocellular carcinoma. We analyzed NOPE expression in 363 patients with esophageal adenocarcinoma using an RNA Scope Assay on a tissue microarray and correlated results with clinical data. Median follow-up was 57.7 months with a 5-year survival rate of 26.6%. NOPE was detectable in 32 patients (8.8%). In pT1/2 stages, NOPE expression was associated with a significantly reduced median OS of 6.3 months (95% CI 1.2-19.4 months), the median OS is not reached in the NOPE-negative group (calculated mean OS 117.1 months) (P = 0.012). In advanced tumor stages, a NOPE dependent survival difference was not detected. This is the first report of NOPE expression demonstrating a prognostic value in esophageal cancer. Early stage, NOPE positive patients are at a high risk of tumor progression and may benefit from neoadjuvant treatment analogous to advanced stage cancer.

Repolarization Precedes Oval Cell-mediated Hepatocytic Regeneration in the CDE Diet Mouse Model.

The liver has a unique ability to recover from injury unlike any other organ. A poorly understood aspect of liver regeneration is the role of hepatocellular polarization. Neighbor of Punc E11 (Nope) is an oncofetal stem/progenitor cell marker, which is expressed by depolarized adult hepatocytes after cholestatic liver injury and in hepatocellular carcinoma. Liver injury induced by a choline-deficient and ethionine-supplemented diet is reversible if followed by an additional dietary stop interval and enabled us to study the expression of Nope during the induction of chronic liver injury and during subsequent liver regeneration. We could show by quantitative RT-PCR, Western blotting, and immunohistochemistry that the expression of Nope is induced in depolarized adult hepatocytes during injury. However, after another 2 weeks of a normal diet, the polarization of hepatocytes was almost completely restored and the expression of Nope remained limited to bile ducts and oval cells. Using an inducible CK19-lineage tracing model, we could demonstrate that oval cell-mediated hepatocyte regeneration is rare and was preceded by repolarization of hepatocytes. In conclusion, polarization of hepatocytes is an important part of liver regeneration and precedes oval cell-mediated regeneration of the liver. This process can be visualized by a characteristic expression pattern of Nope.