Endoscopic sphincterotomy to prevent post-ERCP pancreatitis after self-expandable metal stent placement for distal malignant biliary obstruction (SPHINX): a multicentre, randomised controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with fully covered self-expandable metal stent (FCSEMS) placement is the preferred approach for biliary drainage in patients with suspected distal malignant biliary obstruction (MBO). However, FCSEMS placement is associated with a high risk of post-ERCP pancreatitis (PEP). Endoscopic sphincterotomy prior to FCSEMS placement may reduce PEP risk. OBJECTIVE: To compare endoscopic sphincterotomy to no sphincterotomy prior to FCSEMS placement. DESIGN: This multicentre, randomised, superiority trial was conducted in 17 hospitals and included patients with suspected distal MBO. Patients were randomised during ERCP to receive either endoscopic sphincterotomy (sphincterotomy group) or no sphincterotomy (control group) prior to FCSEMS placement. The primary outcome was PEP within 30 days. Secondary outcomes included procedure-related complications and 30-day mortality. An interim analysis was performed after 50% of patients (n=259) had completed follow-up. RESULTS: Between May 2016 and June 2023, 297 patients were included in the intention-to-treat analysis, with 156 in the sphincterotomy group and 141 in the control group. After the interim analysis, the study was terminated prematurely due to futility. PEP did not differ between groups, occurring in 26 patients (17%) in the sphincterotomy group compared with 30 patients (21%) in the control group (relative risk 0.78, 95% CI 0.49 to 1.26, p=0.37). There were no significant differences in bleeding, perforation, cholangitis, cholecystitis or 30-day mortality. CONCLUSION: This trial found that endoscopic sphincterotomy was not superior to no sphincterotomy in reducing PEP in patients with distal MBO. Therefore, there was insufficient evidence to recommend routine endoscopic sphincterotomy prior to FCEMS placement. TRIAL REGISTRATION NUMBER: NL5130.

Pancreas units within gastroenterology departments. Organizational and operational standards for a patient-centered service. / Las unidades de páncreas en los servicios de aparato digestivo. Estándares de organización y funcionamiento para un servicio centrado en el paciente.

The Asociación Española de Pancreatología (AESPANC), Asociación Española de Gastroenterología (AEG), and Sociedad Española de Patología Digestiva (SEPD) have developed a consensus document on the standards and recommendations they consider essential for the organization of pancreas units (PUs) within gastroenterology services (GSs) in order to conduct their activities in an efficient, high-quality manner. The consensus document defines PUs and lays down standards relating to their organization, structure, service portfolio, processes, and teaching and research activities. Standards have been categorized as mandatory (requirements to be met to qualify for certification by the scientific societies responsible for the standards) or recommendations. Standards should be updated at most within five years based on the experience gained in Spanish PUs and the advance of knowledge regarding pancreas disease. Development of health outcome indicators, including patient-reported outcome measures (PROMs), is considered a relevant challenge, as is evidence on the association of PU structure and activity standards with health outcomes.

Is Occupation a Risk Factor for Developing Inflammatory Bowel Disease? A Case-Control Study.

Background and aims: The role of occupation is uncertain in the onset of inflammatory bowel diseases. The aim of this study is to identify if there is a role of occupation in these diseases. Materials and methods: A case-control study with incident cases with inflammatory bowel diseases was designed. Cases and controls were recruited simultaneously and controls followed a sex and age frequency matching with cases. A detailed questionnaire was completed by all the participants. To analyze the results, a logistic regression was used. A subgroup analysis was performed for each inflammatory bowel disease. Results: A total of 141 patients with incident inflammatory bowel disease (80 ulcerative colitis, 55 Crohn's disease, and 6 unclassified colitis) and 114 controls were included. There were no statistically significant differences in type of work, working hours, contact with animals, or physical activity at work between inflammatory bowel disease patients and controls. After stratifying results according to type of IBD, there were no statistically significant differences either. Conclusions: There seems to be no risk for inflammatory bowel disease onset regarding the type of work, working hours, contact with animals, or sedentariness.

Quality of Tissue Samples Obtained by Endoscopic Ultrasound-Guided Liver Biopsy: A Randomized, Controlled Clinical Trial.

INTRODUCTION: Liver biopsy (LB) remains essential for the diagnosis and staging of parenchymal liver diseases. Endoscopic ultrasound-guided LB (EUS-LB) has emerged as an attractive alternative to percutaneous and transjugular routes. We aimed at comparing the adequacy of samples obtained by EUS-LB with percutaneous LB. METHODS: A single-center, randomized, controlled clinical trial was designed. Patients undergoing LB were randomly assigned to EUS-LB or percutaneous LB groups. EUS-LB was performed with a 19-gauge Franseen core needle through a transduodenal and transgastric route. Percutaneous LB was performed with a 16-gauge Tru-Cut needle. The main outcome was the percentage of adequate samples obtained. Secondary outcomes were the percentage of accurate histologic diagnosis, number of complete portal tracts (CPT), total and longest specimen length (TSL and LSL), sample fragmentation, adverse events, and patients' satisfaction. An adequate specimen was defined as TSL ≥20 mm and including ≥11 CPT. RESULTS: Ninety patients were randomized (44 to EUS-LB and 46 to percutaneous LB) and included in the analysis. The percentage of adequate tissue samples was 32.6% and 70.4% for percutaneous LB and EUS-LB, respectively ( P < 0.001). A final histologic diagnosis was provided in all cases but one. TSL was longer after EUS-LB (23.5 vs 17.5 mm, P = 0.01), whereas the number of CPT was similar in both groups. Sample fragmentation occurred more often after EUS-LB ( P < 0.001). No differences in adverse events were found. Satisfaction reported with both procedures was high. DISCUSSION: EUS-LB is safe and accurate and may be considered an alternative to percutaneous LB for the evaluation of parenchymal liver diseases.

Differential Diagnosis of Chronic Diarrhea: An Algorithm to Distinguish Irritable Bowel Syndrome With Diarrhea From Other Organic Gastrointestinal Diseases, With Special Focus on Exocrine Pancreatic Insufficiency.

Chronic diarrhea, defined as diarrhea persisting for more than 4 weeks, affects up to 5% of the population regardless of patient age, sex, race, or socioeconomic status. The impact on patient health and quality of life is substantial, and diagnosis and management of these patients have significant economic consequences for health care services. The differential diagnosis of chronic diarrhea is broad, with etiologies including infections, endocrinopathies, maldigestive/malabsorptive conditions, and disorders of gut-brain interaction. The considerable overlap of symptoms across this spectrum makes accurate diagnosis problematic and may lead to delays in diagnosis or misdiagnosis. In this narrative review, we consider the differential diagnosis of chronic diarrhea, focusing on irritable bowel syndrome with diarrhea and exocrine pancreatic insufficiency, two conditions that may present similarly but have very different underlying causes and require significantly different management strategies. We outline a 4-step diagnostic strategy and propose a straightforward algorithm to assist in efficiently differentiating irritable bowel syndrome from exocrine pancreatic insufficiency and other causes of chronic diarrhea. We anticipate that these aids will improve diagnostic accuracy, which ultimately should lead to improvements in patients' health-related quality of life and reduce the societal burden on health care services.

Design and biopharmaceutical preclinical characterisation of a new thermosensitive hydrogel for the removal of gastric polyps.

BACKGROUND AND AIMS: Submucosal injection agents are widely used solutions in gastric polyp resection techniques. Currently, many different solutions are used in clinical practice, but most are not authorised for this use or are not biopharmaceutical characterised. The objective of this multidisciplinary work is to test the efficacy of a novel thermosensitive hydrogel designed specifically for this indication. METHODS: A mixture design of various components (Pluronic®, hyaluronic acid and sodium alginate) was carried out to select the combination with optimal properties for this use. Three final thermosensitive hydrogels were selected on which biopharmaceutical characterisation was performed and stability and biocompatibility were analysed. Efficacy in maintaining elevation was tested ex vivo on pig mucosa and in vivo in pigs RESULTS: The mixture design allowed selection of the ideal combinations of agents for the characteristics sought. The thermosensitive hydrogels studied showed high values of hardness and viscosity at 37 °C, maintaining good syringeability. One of them demonstrated superiority in maintaining polyp elevation in the ex vivo assay and non-inferiority in the in vivo assay. CONCLUSION: The thermosensitive hydrogel specifically designed for this use is promising both for its biopharmaceutical characteristics and for its demonstrated efficacy. This study lays the foundation for evaluating the hydrogel in humans.

Impact of gastrointestinal symptoms and psychological disturbances on patients' quality of life after restrictive or malabsorptive bariatric surgery.

AIM: The aim of this study was to evaluate and compare the presence and impact of Gastrointestinal (GI) symptoms, physical and psychological disturbances on patients' QoL after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion with duodenal switch (BPD/DS). METHODS: A prospective, observational, cross-sectional, comparative study was carried-out. GI symptoms and patients' QoL were evaluated by the SF-36 questionnaire and the GI quality of life index (GIQLI). Correlation between GI symptoms, psychological disturbances and QoL scores was analysed. RESULTS: 95 patients were included (mean age 50.5 years, range 22-70; 76 females). Presence of GI symptoms was a consistent finding in all patients, and postprandial fullness, abdominal distention and flatulence had a negative impact on patients' QoL. Patients after SG showed a worsening of their initial psychological condition and the lowest QoL scores. Patients after RYGB showed the best GI symptoms-related QoL. CONCLUSIONS: Both restrictive and malabsorptive bariatric surgical procedures are associated with GI symptoms negatively affecting patients' QoL. Compared to SG and BPD/DS, patients after RYGB showed the best GI symptoms-related QoL, which can be used as additional information to help in the clinical decision making of the bariatric procedure to be performed.

Kreon® (Creon®) vs. Lipancrea®: In Vitro Comparison of Two Encapsulated Pancreatin Preparations.

Kreon® (Creon®) and Lipancrea® are pancreatic enzyme supplements indicated in the treatment of exocrine pancreatic insufficiency. In order to determine their interchangeability, an in vitro comparison of their physical properties and enzymatic activity was carried out. Capsule fill weight and particle size were also determined in order to establish their physical properties. Amylase, lipase and protease activities, lipase release at different pHs and the dissolution time of pellets were assessed for enzymatic analysis. The length range of Kreon® and Lipancrea® pellets was 1.1-2.2 mm and 1.5-2.8 mm, respectively. Protease activity was below the label claim for Lipancrea® and above for Kreon® presentations. Lipase and amylase activity were equal to or higher than the label claim in both preparations. In dissolution experiments simulating the stomach passage, significant release of lipase activity was observed for Lipancrea® (% actual activity: 41% for Lipancrea® 8000; 21% for Lipancrea® 16000) after 60 min at pH 5.0. No release of lipase activity was observed for Kreon® at that particular pH. Enzyme release for Lipancrea® at pH 6.0 was generally slower than for Kreon® and seemed to be influenced by the preceding incubation at lower pH. More than 85% of Kreon® and Lipancrea® dissolved in a pH 6.0 phosphate buffer within 20 min. Despite the similarities of the enzyme content on the respective labels, Kreon® and Lipancrea® differ in pellet size, enzymatic activity and release. This may impact their therapeutic efficacy and, therefore, may limit their interchangeability.

Endoscopic ultrasonography: Enhancing diagnostic accuracy.

Endoscopic ultrasound (EUS) is an essential technique for the management of several diseases. Over the years, new technologies have been developed because to improve and overcome certain limitations related to EUS guided tissue acquisition. Among these new methods, EUS guided elastography and contrast enhanced EUS has arisen as the most widely recognized and available. We will review in this manuscript the different techniques of elastography and contrast enhancement. Nowadays, there are well establish indications for advance imaging, mainly for supporting the management of pancreatic diseases (diagnosis of chronic pancreatitis and differential diagnosis of solid and cystic pancreatic tumors) and characterization of lymph nodes. However, there are more data on new potential indications for the near future.

Pancreatic Elastography Predicts Endoscopic Secretin-Pancreatic Function Test Result in Patients With Early Changes of Chronic Pancreatitis: A Prospective, Cross-Sectional, Observational Study.

INTRODUCTION: The endoscopic pancreatic function test (ePFT) has been proposed for the evaluation of patients with suspected early chronic pancreatitis (CP) in the appropriate clinical context, but the cost and duration of the test limit its clinical applicability. Pancreatic secretion decreases as pancreatic fibrosis develops in CP. Pancreatic fibrosis can be quantified by endoscopic ultrasound-elastography (EUS-E). We aim at evaluating whether EUS-E correlates with and could replace ePFT for the evaluation of patients with suspected CP. METHODS: A prospective, cross-sectional, and observational study of patients with clinical suspicion of CP and inconclusive EUS findings was conducted. EUS-E and ePFT were performed. Diagnosis of CP was supported if the ePFT result (bicarbonate peak) was abnormally low (<80 mEq/L). Correlation between EUS-E (strain ratio [SR]) and ePFT results was analyzed by linear regression. Diagnostic accuracy of EUS-E for CP was calculated using ePFT as a reference method. RESULTS: Sixty-one patients were included and analyzed. The mean peak bicarbonate concentration at the ePFT was 63.8 ± 23.6 mEq/L, and it was abnormally low in 50 patients (82.0%). The mean SR was 3.85 ± 1.24. Correlation between SR and bicarbonate secretion was highly significant ( r = 0.715, P < 0.0001). Diagnostic accuracy of EUS-E for CP was 93.4%. DISCUSSION: The degree of pancreatic fibrosis as evaluated by EUS-E correlates significantly with the secretin-stimulated pancreatic secretion of bicarbonate in patients with clinical suspicion of CP and inconclusive EUS findings of the disease. EUS-E could replace ePFT for the evaluation of these patients in clinical practice.

Identification of patients with branch-duct intraductal papillary mucinous neoplasm and very low risk of cancer: multicentre study.

BACKGROUND: Different surveillance strategies for patients with low-risk branch-duct (BD) intraductal papillary neoplasm (IPMN) have been described. The aim of this study was to describe the natural history of low-risk BD-IPMN, and to identify risk factors for the development of worrisome features (WF)/high-risk stigmata (HRS) and of pancreatic malignancies. METHODS: This was a multicentre retrospective study of patients with BD-IPMN who were under active surveillance between January 2006 and December 2015. Patients were eligible if they had a low-risk lesion and had a minimum follow-up of 24 months. Outcomes were development of WF/HRS or cytologically/histologically confirmed malignant IPMN. RESULTS: Of 837 patients included, 168 (20 per cent) developed WF/HRS. At the end of the observation time, 132 patients (79 per cent) with WF/HRS were still under surveillance without progression to pancreatic cancer. Factors associated with the development of WF or HRS in multivariable analysis included localized nodules (versus diffuse: hazard ratio (HR) 0.43, 95 per cent c.i. 0.26 to 0.68), cyst size 15-19 mm (versus less than 15 mm: HR 1.88, 1.23 to 2.87) or at least 20 mm (versus less than 15 mm: HR 3.25, 2.30 to 4.60), main pancreatic duct size over 3 mm (versus 3 mm or less: HR 2.17, 1.41 to 3.34), and symptoms at diagnosis (versus no symptoms: HR 2.29, 1.52 to 3.45). Surveillance in an endoscopy-oriented centre was also associated with increased detection of WF or HRS (versus radiology-oriented: HR 2.46, 1.74 to 3.47). CONCLUSION: Conservative management of patients with low-risk BD-IPMN is safe and feasible.

Radon exposure and inflammatory bowel disease in a radon prone area.

INTRODUCTION: inflammatory bowel disease (IBD) is a multifactorial pathology with an increasing incidence. There is no study that has assessed a possible relationship with very high residential radon exposure in the study area. The aim of the study was to analyze if residential radon concentration is associated with a higher incidence of IBD. MATERIAL AND METHODS: an ecological study was performed. All incident cases of inflammatory bowel disease in the area of Santiago de Compostela were included between January and December 2017. Radon levels at a municipal level were correlated with demographic factors and type of IBD. RESULTS: ninety-six patients were included, 63 (65.6 %) with ulcerative colitis, 29 (30.25) with Crohn's disease and four (4.2 %) with indeterminate colitis. The incidence rate per 100,000 inhabitants-year was 21.6 cases. There were no statistically significant differences in the type of disease developed regarding radon levels (p > 0.05). No correlation between radon levels and the cumulative incidence of inflammatory bowel disease at the municipal level was observed (Spearman's rho = 0.13, p-value 0.5). CONCLUSION: in the area of Santiago de Compostela, there is a higher incidence of IBD in comparison with previous studies using western countries as reference. However, there was no correlation with the municipal average radon concentration and incidence of IBD or any of its types in this study.

In vitro Comparison of Pancreatic Enzyme Preparations Available in the Indian Market.

PURPOSE: Pancreatic enzyme replacement therapy (PERT) involves exogenous enzyme supplementation and is used in the treatment of pancreatic exocrine insufficiency. Clinical efficacy of PERT preparations is a function of physical properties and release kinetics that vary between commercially available products. In this study, we evaluated the physical properties, in vitro dissolution, and release kinetics of commercially available pancreatic enzyme preparations available in the Indian market. METHODS: Physical properties such as particle size distribution and water content of the capsules were measured by dynamic light scattering and Karl-Fischer titration method, respectively. An analytical procedure based on the European pharmacopoeia (EP) method was used to determine lipase activity, and a modified United States pharmacopoeia (USP)-based method was used for dissolution studies. Enzyme release was ascertained under gastroduodenal conditions in buffered media. RESULTS: Considerable variations in physical properties such as particle size and water content were observed between pancreatic enzyme preparations. Some preparations failed to meet the labeled lipase content as per USP standards (>90% label claim) and showed inconsistent release behavior (>5% relative standard deviation). CONCLUSION: Differences exist between pancreatic enzyme preparations in terms of physical properties, dissolution, and release behavior that can affect their clinical efficacy. The present study suggests, therefore, that these preparations should not be used interchangeably.

Exocrine pancreatic function and dynamic of digestion after restrictive and malabsorptive bariatric surgery: a prospective, cross-sectional, and comparative study.

BACKGROUND: Gastrointestinal anatomical changes after restrictive and malabsorptive bariatric surgery lead to important disturbances in the process of digestion and absorption of nutrients and could lead to exocrine pancreatic insufficiency (EPI). OBJECTIVE: The aim of the present study was to evaluate and to compare pancreatic function and the dynamic of digestion and absorption of nutrients after restrictive and malabsorptive bariatric surgical procedures. SETTING: University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. METHODS: A prospective, observational, cross-sectional, comparative study of patients after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion with duodenal switch (BPD/DS) was carried out. Patients with obesity who did not undergo surgery were included as control group. Pancreatic function and the dynamic of digestion and absorption of nutrients were evaluated by the 13C-mixed triglyceride (13C-MTG) breath test. Six-hour 13C-cumulative recovery rate (13C-CRR), 13C exhalation peak, and 1-hour maximal 13C-CRR were calculated. RESULTS: One-hundred five patients were included (mean age, 49.8 yr; 84 women). Six-hour 13C-CRR was significantly reduced after BPD/DS (P < .001) but not after SG and RYGB. EPI was present in 75% of patients after BPD/DS, 8.3% of patients after RYGB, and 4.3% of patients after SG. Compared with the control group who did not undergo surgery, digestion and absorption of nutrients tended to occur earlier after SG, whereas it was delayed after RYGB and mainly after BPD/DS (P < .001). CONCLUSION: Bariatric surgery significantly alters the dynamic of the digestive process. EPI is very common after BPD/DS, frequent after RYGB, and less frequent after SG. This information is clinically relevant since EPI is a treatable condition associated with symptoms, nutritional deficiencies, and complications.

Endoscopic Pancreatic Drainage Improves Exocrine Pancreatic Function in Patients With Unresectable Pancreatic Cancer: A Double-Blind, Prospective, Randomized, Single-Center, Interventional Study.

OBJECTIVES: Exocrine pancreatic insufficiency is a frequent and clinically relevant complication of pancreatic cancer probably secondary to pancreatic duct obstruction. We aimed at evaluating the impact of endoscopic pancreatic drainage on pancreatic function in patients with unresectable pancreatic cancer. METHODS: A double-blind, prospective, randomized, single-center, interventional study was designed. Patients undergoing endoscopic retrograde cholangiopancreatography for jaundice secondary to unresectable pancreatic cancer were randomized to biliary drainage (group A) or biliopancreatic drainage (group B). Pancreatic function was evaluated by 13C-mixed triglyceride breath test before and 2 weeks after endoscopic retrograde cholangiopancreatography. Breath test result is expressed as 13C-cumulative recovery rate. Abdominal symptoms and nutritional markers were evaluated as secondary outcomes. RESULTS: Twenty patients were included. Sixteen patients had exocrine pancreatic insufficiency, and 13 completed the study (7 in group A and 6 in group B). The median absolute improvement of 13C-cumulative recovery rate was of 23.75% (interquartile range, 9.62-31.74) after biliopancreatic drainage compared with -1.92% (interquartile range, -4.17 to 13.92) after biliary drainage (P = 0.015). Nutritional markers improved after biliopancreatic drainage, but not after biliary drainage. CONCLUSIONS: Biliopancreatic and not biliary endoscopic drainage is associated with a significant improvement of exocrine pancreatic function in patients with unresectable pancreatic cancer.

Targeted 1H NMR metabolomics and immunological phenotyping of human fresh blood and serum samples discriminate between healthy individuals and inflammatory bowel disease patients treated with anti-TNF.

Inflammatory bowel disease is a multifactorial etiology, associated with environmental factors that can trigger both debut and relapses. A high level of tumor necrosis factor-α in the gut is the main consequence of immune system imbalance. The aim of treatment is to restore gut homeostasis. In this study, fresh blood and serum samples were used to identify biomarkers and to discriminate between Crohn's disease and ulcerative colitis patients under remission treated with anti-TNF. Metabolomics based on Nuclear Magnetic Resonance spectroscopy (NMR) was used to detect unique biomarkers for each class of patients. Blood T lymphocyte repertories were characterized, as well as cytokine and transcription factor profiling, to complement the metabolomics data. Higher levels of homoserine-methionine and isobutyrate were identified as biomarkers of Crohn's disease with ileocolic localization. For ulcerative colitis, lower levels of creatine-creatinine, proline, and tryptophan were found that reflect a deficit in the absorption of essential amino acids in the gut. T lymphocyte phenotyping and its functional profiling revealed that the overall inflammation was lower in Crohn's disease patients than in those with ulcerative colitis. These results demonstrated that NMR metabolomics could be introduced as a high-throughput evaluation method in routine clinical practice to stratify both types of patients related to their pathology. KEY MESSAGES: NMR metabolomics is a non-invasive tool that could be implemented in the normal clinical practice for IBD to assess beneficial effect of the treatment. NMR metabolomics is a useful tool for precision medicine, in order to sew a specific treatment to a specific group of patients. Finding predictors of response to IFX would be desirable to select patients affected by IBD. Immunological status of inflammations correlates with NMR metabolomics biomarkers.

Endoscopic drainage with local infusion of antibiotics to avoid necrosectomy of infected walled-off necrosis.

BACKGROUND: Current treatment of infected pancreatic necrosis (IPN) follows a step-up approach. Our group designed a step-up protocol that associates endoscopic drainage with local infusion of antibiotics through transmural nasocystic catheter. Aim of our study was to evaluate our step-up protocol for IPN in terms of proportion of patients avoiding necrosectomy. METHODS: Retrospective analysis of patients admitted with acute pancreatitis (AP) between January 2015 and December 2018. The number of patients who responded to each therapeutic step were analysed: step 1, systemic antibiotics; step 2, endoscopic transmural drainage and local infusion of antibiotics; step 3, endoscopic necrosectomy. RESULTS: 1158 patients with AP were included. 110 patients (8.4%) suffered from necrotising pancreatitis; 48 of them had IPN (42.6% of necrotising pancreatitis) and were treated with systemic antibiotics. Nineteen patients (39.6% of IPN) responded and did not required any invasive therapy. Six patients with IPN on systemic antibiotics died within the first 4 weeks of disease before step 2 could be applied. Urgent surgical necrosectomy in the first 4 weeks was performed in three additional patients. Endoscopic drainage and local antibiotic therapy was performed in the remaining 20 patients; 9 (45% of them) did well and 9 patients underwent necrosectomy (18.7% of IPN). Two patients died on drainage. Overall mortality of the total cohort of AP was 2.53% CONCLUSIONS: Addition of local infusion of antibiotics to endoscopic drainage avoids the need of necrosectomy in half of patients with IPN not responding to systemic antibiotics.