Underwater Endoscopic Mucosal Resection Vs Conventional Endoscopic Mucosal Resection for Superficial Nonampullary Duodenal Epithelial Tumors in the Western Setting.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial nonampullary duodenal epithelial tumors (SNADETs), but recently underwater endoscopic mucosal resection (U-EMR) has emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR vs C-EMR for SNADETs in a Western setting. METHODS: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of endoscopic mucosal resection and the occurrence of AEs or RRAs using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤20 mm or >20 mm. RESULTS: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR: n = 201, 69.3%; U-EMR: n = 89, 30.7%). The overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (odds ratio [OR], 4.95; 95% CI, 2.87-8.53), postprocedural bleeding (OR, 7.92; 95% CI, 3.95-15.89), and RRAs (OR, 3.66; 95% CI, 2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions. CONCLUSIONS: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRAs, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs.

Management of malignant Gastric Outlet Obstruction (mGOO) due to pancreatic cancer in the era of EUS-Gastrojejunostomy: an international practice survey and case vignette study by Pancreas 2000 from the European Pancreatic Club.

BACKGROUND: Malignant Gastric Outlet Obstruction (mGOO) has been standardly treated by surgical Gastrojejunostomy (S-GJ) or Endoscopic Stenting (ES). Recently, EUS-Gastrojejunostomy (EUS-GJ) has emerged as an alternative, despite its worldwide diffusion is heterogeneous. The aim of this survey was to assess clinical decision-making around mGOO and to explore current opinions regarding EUS-GJ. METHODS: An online survey, spread through social networks and EPC newsletter, was created exploring opinions regarding indications, contraindications, benefits/risks, availability of mGOO treatments; 2 case vignettes explored clinical decision-making in different scenarios. RESULTS: Overall, 290 pancreatologists from 44 countries responded, of whom 35% surgeons and 65% gastroenterologists. The most common treatment for mGOO was ES (86%), followed by laparoscopic GJ (76%). EUS-GJ was accessible to 59% of respondents, with 10% proficient in this technique. Gold-standard treatment for mGOO varied by specialty; 45% of gastroenterologists preferred ES, 20% EUS-GJ, and 10% surgical GJ, while among surgeons, these were 24%, 8%, and 25%, respectively. A higher annual volume of mGOO treated correlated with increased EUS-GJ adoption and reduced surgical advice. For 51%, EUS-GJ will become the primary treatment for mGOO, notably higher among gastroenterologists and high-volume centers. For 14%, EUS-GJ spread will be limited in the future, or used only when ES fails (19%). Life expectancy, disease stage and patient's frailty are the main decision driver in therapeutic choice, whereas future surgical resectability does not contraindicate any treatment for 75%. EUS-GJ's main advantages were its minimally invasive nature and clinical efficacy, offset by its steep learning curve. CONCLUSIONS: This survey revealed significant differences in the management of mGOO, depending on specialties, local expertise and treatment volume, suggesting the lack of standardized algorithms. Life expectancy and patients' frailty are the main decision drivers. Regarding EUS-GJ, its availability remains suboptimal, with learning curve as the main perceived barrier.

Endoscopic Ultrasound Through-The-Needle Biopsy of Pancreatic Cysts: Toward Procedure Standardization.

BACKGROUND AND AIMS: EUS-guided through-the-needle microforceps biopsy (EUS-TTNB) was introduced as a new diagnostic tool to establish pancreatic cyst histotype and help to better risk stratify the patients. The aim of this study was to describe the technical success, diagnostic yield, and adverse events of through-the-needle biopsy and discuss the technique variations, focusing on future procedure standardization. METHODS: We performed a prospective single-center study including patients with presumed mucinous cysts harboring worrisome features or indeterminate cyst type on imaging, submitted to EUS-TTNB using Moray® microforceps between March 2018 and September 2021. Specimens were processed as a cell-block. RESULTS: We included 40 patients. Technical success was 97.5%. The diagnostic yield was 72.5% for TTNB whereas for cyst fluid cytology/analysis it was 27.5%. Moreover, without TTNB 5 mucinous lesions would not have been diagnosed. TTNB had a sensitivity of 76% and a specificity of 91%, while FNA cytology had a sensitivity and specificity of 35% and 91%, respectively. Moreover for IPMN lesions, subtyping was possible in 63% of cases. TTNB resulted in change in clinical management in 20% of patients. We registered three adverse events: 2 self-limited intracystic bleeding and 1 patient with abdominal pain not associated with pancreatitis. CONCLUSION: TTNB proved superior to cyst fluid analysis and cytology for the definition of cyst histotype and mucinous cyst diagnosis with acceptable risk profile. Further studies should explore the best steps for procedure standardization.

Predictors of adverse events after endoscopic ultrasound-guided through-the-needle biopsy of pancreatic cysts: a recursive partitioning analysis.

BACKGROUND AND STUDY AIMS : Endoscopic ultrasound-guided through-the-needle biopsy (TTNB) of pancreatic cystic lesions (PCLs) is associated with a non-negligible risk for adverse events (AEs). We aimed to identify the hierarchic interaction among independent predictors for TTNB-related AEs and to generate a prognostic model using recursive partitioning analysis (RPA). PATIENTS AND METHODS : Multicenter retrospective analysis of 506 patients with PCLs who underwent TTNB. RPA of predictors for AEs was performed and the model was validated by means of bootstrap resampling. RESULTS : Mean cysts size was 36.7 mm. Most common diagnoses were intraductal papillary mucinous neoplasm (IPMN, 45 %), serous cystadenoma (18.8 %), and mucinous cystadenoma (12.8 %). Fifty-eight (11.5 %) AEs were observed. At multivariate analysis, age (odds ratio [OR] 1.32, 1.09-2.14; p = 0.05), number of TTNB passes (OR from 2.17, 1.32-4.34 to OR 3.16, 2.03-6.34 with the increase of the number of passes), complete aspiration of the cyst (OR 0.56, 0.31-0.95; p = 0.02), and diagnosis of IPMN (OR 4.16, 2.27-7.69; p < 0.001) were found to be independent predictors of AEs, as confirmed by logistic regression and random forest analyses. RPA identified three risk classes: high-risk (IPMN sampled with multiple microforceps passes, 28 % AEs rate), low-risk (1.4 % AE rate, including patients < 64 years with other-than-IPMN diagnosis sampled with ≤ 2 microforceps passes and with complete aspiration of the cyst) and middle-risk class (6.1 % AEs rate, including the remaining patients). CONCLUSION : TTNB should be selectively used in the evaluation of patients with IPMN. The present model could be applied during patient selection as to optimize the benefit/risk of TTNB.

Development of an Online App to Predict Post-Endoscopic Retrograde Cholangiopancreatography Adverse Events Using a Single-Center Retrospective Cohort.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure with a high risk for adverse events (AEs). AIM: evaluate patient- and procedure-related risk factors for ERCP-related AEs and develop an online app to estimate risk of AEs. METHODS: retrospective study of 1,491 consecutive patients who underwent 1,991 ERCPs between 2012 and 2017 was conducted. AEs definition and severity were classified according to most recent ESGE guidelines. Each variable was tested for association with occurrence of overall AEs, post-ERCP pancreatitis (PEP) and cholangitis. For each outcome, 2 regression models were built, from which an online Shiny-based app was created. RESULTS: Overall AE rate was 15.3%; in 19 procedures, >1 AE occurred. Main post-ERCP AE was PEP (7.5%), followed by cholangitis (4.9%), bleeding (1.3%), perforation (1%), cardiopulmonary events (0.9%), and cholecystitis (0.3%). Seventy-eight percent of AEs were mild/moderate; of severe (n = 55) and fatal (n = 20) AEs, more than half were related to infection, cardiac/pulmonary AEs, and perforation. AE-related mortality rate was 1%. When testing precannulation, procedural covariates, and ERCP findings, AE occurrence was associated with age (odds ratio [OR] 0.991), previous PEP (OR 2.198), ERCP complexity grade III/IV (OR 1.924), standard bile duct cannulation (OR 0.501), sphincterotomy (OR 1.441), metal biliary stent placement (OR 2.014), periprocedural bleeding (OR 3.024), and biliary duct lithiasis (OR 0.673). CONCLUSION: Our app may allow an optimization of the patients' care, by helping in the process of decision-making, not only regarding patient or endoscopist's selection but also definition of an adequate and tailored surveillance plan after the procedure.

Gastric caustic injury after organophosphate poisoning.

An 83-year-old male was brought to the Emergency Room after ingesting an unknown dose of dimethoate, an organophosphate pesticide. He had been previously diagnosed with depression but there were no previous suicide attempts. The admission Glasgow Coma Scale score was 3 and he had miotic pupils and copious oropharyngeal secretions. The patient was hemodynamically stable, mildly tachypneic (respiratory rate 22/minute) and nonfebrile. Laboratory workup revealed a normal complete blood count (Hb 15 g/dl, platelets 178,000/µl), normal liver tests and no coagulopathy. Low acetylcholinesterase levels confirmed organophosphate poisoning. He was admitted to the Intensive Care Unit (ICU) under treatment with obidoxime.

Particular aspects of gastroenterological disorders in chronic kidney disease and end-stage renal disease patients: a clinically focused review.

Besides renal disease, gastrointestinal (GI) disorders are frequently reported in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Related gastrointestinal symptoms tend to increase as the renal disease progresses. Also, in patients with ESRD, the modality of dialysis is related to particular forms of GI disorders.The kidney can interact with the digestive organs through functional endogenous systems such as the 'kidney-colon axis' and the 'kidney-liver axis'. Digestive diseases are one of the visible manifestations of the disturbance between hemostatic, hemodynamic and immunological balance in such patients.No clear management guidelines currently exist for many of the gastrointestinal problems that accompany renal failure. This review aims to describe the particular aspects of GI diseases present in CKD/ESRD. We focus our discussion in the specificities of epidemiology, diagnosis, and prognosis of such disorders between the different segments of the digestive system.

Role of Peroral Cholangioscopy for Diagnosis and Staging of Biliary Tumors.

OBJECTIVES: Peroral cholangioscopy (POC) has shown to be a useful diagnostic procedure in the evaluation of biliary strictures; however, data regarding its role on preoperative staging are scarce. The aim of this study was to evaluate POC role in the diagnosis and preoperative intraductal staging of perihilar cholangiocarcinoma (CCA). METHODS: Retrospective study that included all patients who underwent POC with SpyGlassTM Direct Visualization System for the diagnosis of biliary strictures or for preoperative evaluation of extrahepatic biliary tumors, between 2015 and 2019, in a single tertiary center. RESULTS: Forty-three patients were included, 63% male with a median age of 62 years. Thirty-eight (88.3%) underwent POC due to indeterminate biliary strictures, 3 (7%) due to bile duct filling defect, and 2 (4.7%) for intraductal staging of perihilar CCA. In the follow-up, a final diagnosis of malignancy was established in 56% of the patients. Visual impression accuracy with SpyGlass was 95.1% (with 100% sensitivity and 89.5% specificity). SpyBite biopsies accuracy was 80.5% (63.6% sensitivity and 100% specificity). In the 19 patients with a final perihilar CCA diagnosis, intraductal evaluation with SpyGlass altered anatomic classification (Bismuth-Corlette) defined by previous imagiologic findings in 8 (42.1%) patients. Alteration in anatomic classification changed therapeutic approach in 4 (21%). CONCLUSIONS: POC use for evaluating intraductal spread in potentially resectable perihilar CCA can detect more extensive and change surgical management. In the future, preoperative staging of perihilar CCA with POC combined with imagiologic evaluation of vascular extension of the lesions may optimize surgical results.

Pancreatic Cystic Lesions: New Endoscopic Trends in Diagnosis.

The diagnosis of incidental pancreatic cystic lesions is increasing in the general population because of the routine use of cross-sectional imaging modalities. Not all cysts are neoplastic, and the majority of cystic neoplasms have a low overall likelihood of progression to malignancy. Current management is based on imaging and cyst fluid analysis, but we are not able to diagnose the specific type of cyst and its malignant potential in a significant number of patients. Better diagnostic tools are required to avoid unnecessary surgical resections that carry an important risk of morbidity and mortality. Herein we review current evidence concerning the use of new endoscopic modalities for the evaluation of pancreatic cystic lesions. We focus our discussion on the new cyst fluid markers, and the advancements on modalities such as confocal endomicroscopy, contrast-enhanced endoscopic ultrasound, and the use of Spyglass. We also discuss the use of new devices to improve the cellular yield from cyst fluid and to obtain cyst-wall tissue, namely the cytology brush, the fine needle biopsy, and forceps for cyst-wall biopsy.

Hydrogen peroxide regulates angiogenesis-related factors in tumor cells.

Tumor angiogenesis is required for tumor development and growth, and is regulated by several factors including ROS. H2O2 is a ROS with an important role in cell signaling, but how H2O2 regulates tumor angiogenesis is still poorly understood. We have xenografted tumor cells with altered levels of H2O2 by catalase overexpression into zebrafish embryos to study redox-induced tumor neovascularization. We found that vascular recruitment and invasion were impaired if catalase was overexpressed. In addition, the overexpression of catalase altered the transcriptional levels of several angiogenesis-related factors in tumor cells, including TIMP-3 and THBS1. These two anti-angiogenic factors were found to be H2O2-regulated by two different mechanisms: TIMP-3 expression in a cell-autonomous manner; and, THBS1 expression that was non-cell-autonomous. Our work shows that intracellular H2O2 regulates the expression of angiogenic factors and the formation of a vessel network. Understanding the molecular mechanisms that govern this multifunctional effect of H2O2 on tumor angiogenesis could be important for the development of more efficient anti-angiogenic therapies.

Opi1p translocation to the nucleus is regulated by hydrogen peroxide in Saccharomyces cerevisiae.

During exposure of yeast cells to low levels of hydrogen peroxide (H2 O2 ), the expression of several genes is regulated for cells to adapt to the surrounding oxidative environment. Such adaptation involves modification of plasma membrane lipid composition, reorganization of ergosterol-rich microdomains and altered gene expression of proteins involved in lipid and vesicle traffic, to decrease permeability to exogenous H2 O2 . Opi1p is a transcriptional repressor that is inactive when present at the nuclear membrane/endoplasmic reticulum, but represseses transcription of inositol upstream activating sequence (UASINO )-containing genes, many of which are involved in the synthesis of phospholipids and fatty acids, when it is translocated to the nucleus. We investigated whether H2 O2 in concentrations inducing adaptation regulates Opi1p function. We found that, in the presence of H2 O2 , GFP-Opi1p fusion protein translocates to the nucleus and, concomitantly, the expression of UASINO -containing genes is affected. We also investigated whether cysteine residues of Opi1p were implicated in the H2 O2 -mediated translocation of this protein to the nucleus and identified cysteine residue 159 as essential for this process. Our work shows that Opi1p is redox-regulated and establishes a new mechanism of gene regulation involving Opi1p, which is important for adaptation to H2 O2 in yeast cells. Copyright © 2017 John Wiley & Sons, Ltd.

All that glitters is not gold. A different cause for an "ulcerative colitis".

The authors present the case of a 32-year-old Caucasian male, engineer, who was submitted to a colonoscopy after a presumptive diagnosis of ulcerative colitis. The patient referred an acute bloody and mucous diarrhea, lasting for three weeks, with no fever or rectal tenesmus. Stool studies were negative. During the procedure, colonic segments with continuous hyperemic and exudative mucosa, with small papules with apical ulcers and erosions, were observed.

Over-the-scope clip closure of gastrocutaneous fistula.

A 35-year-old female patient, with Batten's disease, submitted to a surgical gastrostomy in 2005, and had it replaced in 2007, 2011 and 2014 with one with a filled balloon as its internal retention mechanism. In 2015, she presented to the emergency room due to stomal enlargement, leakage and chemical dermatitis and cellulitis. A 12 mm over-the-scope clip was placed, after anchoring the fistula edges with the twin grasper and suction of the defect into the applicator cap. Endoscopic resolution of the fistula was achieved.

Predictive factors of small bowel patency in Crohn's disease patients.

BACKGROUND: Patency capsule was developed to avoid small bowel video capsule endoscopy retention, namely in patients with Crohn's disease. AIMS: To evaluate the predictive factors of small bowel patency in Crohn's disease patients. PATIENTS AND METHODS: Retrospective analysis including 151 Crohn's disease patients submitted to patency capsule (Agile® Patency Capsule) from 2011 to 2012. Patients that excreted the intact patency capsule were classified as having a patent small bowel (without patency capsule retention), other patients were considered to have negative patency of the small bowel (patency capsule retention). RESULTS: Patients had a mean age of 41±14 years, 54% were female and 25% had been previously submitted to surgery. Stricturing disease was seen in 20% of cases and penetrating disease in 16% of cases. Left-sided colonic lesions and ileal strictures were observed at colonoscopy in 13% and 9% of patients, respectively. In our sample, 28% of patients had negative patency of the small bowel (patency capsule retention). In multivariate analysis, independent factors that were associated with negative patency of the small bowel in Crohn's disease patients were stricturing (OR 10.16, p < 0.001) and penetrating phenotypes (OR 11.73, p = 0.001), left-sided colonic lesions (OR 3.77, p = 0.038), ileal stricture (OR 9.76, p = 0.003); previous intestinal surgery was found to be protective (OR 0.16, p = 0.006). CONCLUSIONS: Stricturing or penetrating disease, ileal strictures, no previous surgery and left-sided colonic lesions were the factors associated with negative small bowel patency in Crohn's disease patients.

Performance of Intracystic Glucose Measurement for the Characterization of Pancreatic Cystic Lesions.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is essential for the classification of pancreatic cystic lesions (PCLs). Recently, intracystic glucose has been suggested as an alternative to carcinoembryonic antigen (CEA) level as a predictor of mucinous cystic lesions (M-PCLs). This study aims to evaluate the diagnostic performance of intra-cystic glucose in distinguishing between M-PCLs and non M-PCLs (NM-PCLs) and to analyze the possibility of on-site glucose measurement with a standard glucometer. METHODS: Patients with PCLs submitted to EUS-FNA with simultaneous intracystic glucose measurement between 2017 and 2022 were included. The diagnostic performance of glucose versus CEA for the differentiation between M-PCLs and NM-PCLs was compared to a final diagnosis based on the analysis of surgical specimen, intracystic biopsy or, if this data was unavailable, multidisciplinary evaluation. A cut-off of <50 mg/dL was used for the diagnosis of MCLs. Additionally, the agreement between on-site glucose determination with a standard glucometer and laboratory glucose measurement was assessed. RESULTS: Mucinous lesions accounted for 56% of all PCLs. The median values of glucose and CEA for M-PCLs were 18 mg/dL and 286 ng/mL, respectively. Intracystic glucose had a sensitivity and specificity of 93.2% and 76.5%, respectively, for the diagnosis of MCLs (versus 55.6% and 87.5%, respectively, for CEA). The area under the curve was 0.870 for on-site glucose (versus 0.806 for CEA). An excellent correlation was observed between on-site and laboratory glucose measurement (ρ=0.919). CONCLUSIONS: The measurement of intracystic glucose showed superior performance compared with CEA in distinguishing between M-PCLs and NM-PCLs, with excellent correlation between on-site and conventional lab glucose measurement. Thus, on-site intracystic glucose appears to be an excellent biomarker for the characterization of PCLs due to its low cost, high availability, and the need for a minimal cyst fluid volume for its determination.

Portuguese Pancreatic Club Perspective on the Surveillance Strategy for Pancreatic Neuroendocrine Tumours: When and How to Do It?

Background: Pancreatic neuroendocrine tumours (pNETs) are a highly heterogeneous group of tumours with widely variable biological behaviour. The incidence of pNETs has risen exponentially over the last three decades, particularly for asymptomatic small pNETs (≤2 cm), due to the widespread use of cross-sectional imaging in clinical practice. Summary: Current consensus guidelines suggest that incidentally discovered pNETs ≤2 cm can be selectively followed due to the overall low risk of malignancy. Nevertheless, the "watch-and-wait" management strategy for small asymptomatic pNETs is still not widely accepted due to the lack of long-term data on the natural history of these small lesions. Additionally, it is clear that a subset of small pNETs may show malignant behaviour. Key Message: Given the non-negligible risk of malignancy even in small pNETs, it is of the utmost importance to identify other preoperative factors, other than size, that may help to stratify the risk of malignant behaviour and guide clinical management. In this article, the Portuguese Pancreatic Club reviews the importance of risk stratification of pNETs and presents an updated perspective on the surveillance strategy for sporadic well-differentiated pNETs.

Contexto: Os tumores neuroendócrinos do pâncreas (pNETs) correspondem a um grupo heterogéneo de tumores com comportamento biológico variável. A sua incidência aumentou exponencialmente nas últimas três décadas, particularmente à custa do diagnóstico incidental de pNETs de reduzidas dimensões (≤2 cm) devido à utilização crescente de exames de imagem seccional na prática clínica. Sumário: As normas de consenso internacionais sugerem que os pNETs ≤2 cm poderão ser seletivamente vigiados, dado o seu baixo risco global de comportamento maligno. No entanto, a estratégia proposta de "watch and wait" na abordagem dos pNETs assintomáticos ≤2cm não tem sido amplamente aceite devido à ausência de dados a longo-prazo relativos à sua história natural. Adicionalmente, é hoje evidente que um subgrupo destes pequenos tumores poderá apresentar comportamento maligno. Mensagens Chave: Dado o risco não desprezível de agressividade biológica mesmo nos pNETs incidentais de reduzidas dimensões, torna-se essencial identificar fatores pré-operatórios, para além da dimensão do tumor, que permitam estratificar o seu risco de malignidade e guiar a abordagem clínica. No presente artigo o Clube Português de Pâncreas apresenta uma perspectiva atual sobre a estratificação do risco e a estratégia a adoptar na vigilância dos pNETs esporádicos bem-diferenciados.