Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

The endoscopic model for gastric carcinogenesis and Helicobacter pylori infection: A potential visual mind-map during gastroscopy examination.

Helicobacter pylori (Hp) is the main trigger of chronic gastric atrophy and the main leading cause of gastric cancer. Hp infects the normal gastric mucosa and can lead to chronic inflammation, glandular atrophy, intestinal metaplasia, dysplasia and finally adenocarcinoma. Chronic inflammation and gastric atrophy associated with Hp infection appear initially in the distal part of the stomach (the antrum) before progressing to the proximal part (the corpus-fundus). In recent years, endoscopic developments have allowed for the characterization of various gastric conditions including the normal mucosa (pyloric/fundic gland pattern and regular arrangement of collecting venules), Hp-related gastritis (Kyoto classification), glandular atrophy (Kimura-Takemoto classification), intestinal metaplasia (Endoscopic Grading of Gastric Intestinal Metaplasia), and dysplasia/adenocarcinoma (Vessel plus Surface classification). Despite being independent classifications, all these scales can be integrated into a single model: the endoscopic model for gastric carcinogenesis. This model would assist endoscopists in comprehending the process of gastric carcinogenesis and conducting a systematic examination during gastroscopy. Having this model in mind would enable endoscopists to promptly recognize the implications of Hp infection and the potential patient's risk of developing gastric cancer.

Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy.

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists.

BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

Diagnosis of Helicobacter pylori Infection by the Arrangement of Collecting Venules Using White Light Endoscopy: Evaluation of Interobserver Agreement.

BACKGROUND: Regular arrangement of collecting venules (RAC) in gastric mucosa accurately identifies patients without Helicobacter pylori (H pylori) infection. The aim of our study was to evaluate the reproducibility of RAC using white light endoscopy without magnification, in a European country, and to assess the impact of proton pump inhibitors (PPIs). METHODS: A multicenter prospective study with image capture of the distal lesser gastric curvature and gastric biopsies was performed. The presence of starfish-like minute points regularly distributed throughout lesser curvature was considered as RAC positive (RAC+). A set of 20 images was used for the training phase and inter and intra-observer agreements were calculated. RESULTS: 174 patients were included and 85 (48.9%) were taking PPIs. Kappa values for interobserver and intra-observer agreements were substantial (0.786) and excellent (0.906), respectively. H. pylori infection was diagnosed in 29 patients (16.7%): 10/85 with PPIs and 19/89 without PPIs (11.8% vs. 21.3%; p = 0.09). All RAC + patients were free of H. pylori infection, with a sensitivity and negative predictive value of 100%, regardless of PPI intake. CONCLUSION: The endoscopic diagnosis of H. pylori by RAC is an easy-to-learn and highly reproducible technique, even with PPI intake. Our results warrant RAC as a real-time diagnostic method for H. pylori-negative infection in Western practice.

Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain. / Frecuencia y aspectos clínicos del cáncer gástrico precoz en relación con el avanzado en un área sanitaria de España.

INTRODUCTION: Gastric cancer (GC) incidence is currently decreasing; however, survival is still low. Early GC (EGC) has better prognosis and it could be cured by endoscopic methods. PATIENTS AND METHODS: Observational study of a retrospective cohort of all patients with GC during a five-year period in a health area of Spain. EGC diagnosis was defined as mucosal or submucosal (T1) cancers regardless of lymph node involvement, whereas the advanced GC were T2-T4. RESULTS: 209 patients were included, and 26 (12%) of them were EGC. There was no difference between EGC and advanced GC in age, sex, HP infection, precancerous lesions or histological type. Other characteristics of EGC were different from advanced GC: location (antrum and incisura in 76% vs 38%, p=0.01), alarm symptoms (69% vs 90%, p<0.01), curative treatment (100% vs 30%, p<0.01), performance status (PS 0-1: 92% vs 75%, p=0.03) and survival (85% vs 20%, p<0.001). Among patients who received curative treatment, 98% (79/81) underwent surgery and 2% (2/81) were treated by mucosectomy. Seven (27%) patients with EGC could have benefited from treatment by endoscopic submucosal resection. DISCUSSION: EGC frequency was low (12% of GCs) in our health area. EGC had a high percentage of alarm symptoms, and was located in the distal third of the stomach (antrum and incisura) and had better prognosis compared to advanced GC. Strategies to increase detection and endoscopic treatment of EGC should be implemented.

Evaluation of long-term adherence to oesophagogastroduodenoscopy quality indicators. / Evaluación del cumplimiento a largo plazo de los indicadores de calidad en la esofagogastroduodenoscopia.

INTRODUCTION: In a previous study we demonstrated that a simple training programme improved quality indicators of Oesophagogastroduodenoscopy (OGD) achieving the recommended benchmarks. However, the long-term effect of this intervention is unknown. The aim of this study was to assess the quality of OGDs performed 3 years after of having completed a training programme. MATERIAL AND METHODS: A comparative study of 2 cohorts was designed as follows: Group A included OGDs performed in 2016 promptly after a training programme and Group B with OGDs performed from January to March 2019, this group was also divided into 2 subgroups: subgroup B1 of Endoscopists who had participated in the previous training programme and subgroup B2 of Endoscopists who had not. The intra-procedure quality indicators proposed by ASGE-ACG were used. RESULTS: A total of 1236 OGDs were analysed, 600 from Group A and 636 from Group B (439 subgroup B1 and 197 subgroup B2). The number of complete examinations was lower in Group B (566 [94.3%] vs. 551 [86.6%]; p<0.001). A significant decrease was observed in nearly all quality indicators and they did not reach the recommended benchmarks: retroflexion in the stomach (96% vs. 81%; p<0.001); Seattle biopsy protocol (86% vs. 50%; p=0.03), description of the upper GI bleeding lesion (100% vs. 62%; p<0.01), sufficient intestinal biopsy specimens (at least 4) in suspected coeliac disease (92.5% vs. 18%; p<0.001), photo documentation of the lesion (94% vs. 90%; p<0.05). Regarding the overall assessment of the procedure (including correct performance and adequate photo documentation), a significant decrease was also observed (90.5% vs. 62%; p<0.001). There were no differences between subgroups B1 and B2. CONCLUSIONS: The improvement observed in 2016 after a training programme did not prevail after 3 years. In order to keep the quality of OGDs above the recommended benchmarks, it is necessary to implement continuous training programmes.

Quality indicators for esophagogastroduodenoscopy: A comparative study of outcomes after an improvement programme in a tertiary hospital. / Indicadores de calidad en la esofagogastroduodenoscopia: estudio comparativo de los resultados tras un programa de mejora en un hospital terciario.

INTRODUCTION: There is an opportunity for improvement in the recording and measuring of quality indicators. However, no previous experiences exist in our field in terms of their compliance in esophagogastroduodenoscopy (EGD). OBJECTIVE: To analyse compliance with EGD quality criteria and evaluate improvement after conducting a training programme. PATIENTS AND METHODS: Comparative study of 2 cohorts: one retrospective (control group) and one prospective (intervention group), before and after a training programme consisting of an information session and the report writing improvement programme. The quality indicators proposed by the American Society for Gastrointestinal Endoscopy and the American College of Gastroenterology were used. RESULTS: A total of 1,200 EGDs were included in a sequential manner (600 in each group). Following the training programme, a significant improvement was observed in the following indicators: documented indication (93 vs. 99.8%; P<0.01), documented full examinations (94.7 vs. 97.3%; P<0.01), correct performance (63.7 vs. 87.9%; P<0.01), appropriate biopsies according to protocols (57.9 vs. 83.8%; P<0.01), photo-documentation of described lesions (84.1 vs. 94.9%; P<0.01), photo-documentation per segment (52.9 vs. 70.5%; P<0.01) and correct overall assessment (56,9 vs. 90.5%; P<0.01). Biopsies for coeliac disease, documented indication, full examination and correct performance, if it went ahead, exceeded the recommended standard. CONCLUSION: A very simple training programme improves EGD quality indicators, with the majority reaching the standards recommended by the American Society for Gastrointestinal Endoscopy and the American College of Gastroenterology.

Curative criteria for endoscopic treatment of gastric cancer.

Endoscopic treatment, particularly endoscopic submucosal dissection, has become the primary treatment for early gastric cancer. A comprehensive optical assessment, including white light endoscopy, image-enhanced endoscopy, and magnification, are the cornerstones for clinical staging and determining the resectability of lesions. This paper discusses factors that influence the indication for endoscopic resection and the likelihood of achieving a curative resection. Our review stresses the critical need for interpreting the histopathological report in accordance with clinical guidelines and the imperative of tailoring decisions based on the patients' and lesions' characteristics and preferences. Moreover, we offer guidance on managing complex scenarios, such as those involving non-curative resection. Finally, we identify future research avenues, including the role of artificial intelligence in estimating the depth of invasion and the urgent need to refine predictive scores for lymph node metastasis and metachronous lesions.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Gastroenterologists' attitudes on the detection and management of gastric premalignant conditions: results of a nationwide survey in Spain.

INTRODUCTION: Gastric premalignant conditions (GPC) surveillance has been proposed to improve the prognosis of gastric cancer (GC), but the early GC detection rate remaining low, and missing GC during an esophago-gastro-duodenoscopy is still a problem. We aimed to explore the gastroenterologists' attitudes on the detection and management of GPC. METHODS: A cross-sectional study was designed based on a survey among gastroenterologists from Asociación Española de Gastroenterología. RESULTS: The participation rate was 12% (146/1243). Eighty-one percent worked at secondary or tertiary-care hospitals with the capability to perform mucosectomy (80%), but with a lesser availability of endoscopic submucosal dissection (35%). Most respondents had high-definition endoscopes (88%), and virtual chromoendoscopy (86%), but during performing an upper endoscopy, 34% never or rarely use chromoendoscopy, and 73% apply a biopsy protocol often/very often when atrophy or intestinal metaplasia (IM) is suspected. Half of the respondents self-reported their ability to recognize atrophy or IM ≤7 (on a scale from 0 to 10), whereas ≤6 for dysplasia or early GC. Helicobacter pylori infection is eradicated and verified by ≥90%. Endoscopic surveillance of atrophy/IM is performed by 62%. An immediate endoscopy for dysplasia is not always performed. For low-grade dysplasia, 97.6% consider endoscopic management, but for high-grade dysplasia, 23% regard gastric surgery. CONCLUSION: There is a wide variability in the detection and management of GPC among Spanish gastroenterologists, and compliance with guidelines and biopsy protocols could be improved. Performance of high-quality gastroscopies including use of virtual chromoendoscopy, that might allow an improvement in the GPC detection, needs also to be generalized.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease.

BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

Gastric cancer missed at esophagogastroduodenoscopy in a well-defined Spanish population.

BACKGROUND: Although esophagogastroduodenoscopy (EGD) is the standard procedure for the diagnosis of gastric cancer (GC), some GCs are missed. There are no published data on the missed rate of GC in Spain. AIMS: To determine the frequency and characteristics of missed GCs and assess the quality of the EGD in a specific population with GC. METHODS: Records of all patients diagnosed with gastric adenocarcinoma between 2012 and 2016 in a defined geographic area were reviewed. Missed GC was defined as a case with a prior negative EGD for cancer. Quality indicators from the prior EGDs were measured. RESULTS: From 212 cases of GC, 25 cases were excluded. Seventeen out of 187 patients had a prior EGD (9.1%). Twelve of those 17 missed GC had a prior EGD with some abnormal findings. In 6 of them, biopsies were taken. Survival was no different between patients with missed and non-missed GC. Quality indicators that failed to meet standards were recording time, image documentation, and a protocol of biopsies. CONCLUSIONS: Missed GC in an EGD in a defined population in Spain is not uncommon (9.1%). The endoscopist is an important factor in missed GC due to lack of adequate detection and sampling error. Compliance with performance of quality indicators could reduce missed GC.

Hernia umbilical en pacientes cirróticos con ascitis: ¿tratamiento conservador o quirúrgico? / Umbilical hernia in liver cirrhosis with ascites: conservative or surgical treatment?

Resumen La ascitis es la complicación más común en los pacientes con cirrosis hepática. Las hernias umbilicales (HU) ocurren en 20% de estos pacientes y 40% en aquellos con ascitis severa. La HU ocurre debido al aumento de presión intraabdominal, al debilitamiento de la fascia abdominal y la pérdida de masa muscular. Además, tienen tendencia a aumentar rápidamente y presentar alto riesgo de complicaciones que amenazan la vida del paciente. El tratamiento de la HU no complicada es controversial, tanto el manejo quirúrgico (herniorrafia) como el manejo conservador (control de ascitis) presentan alta tasa de complicaciones, en consecuencia incrementa la morbimortalidad. Actualmente, se recomienda herniorrafia umbilical con previo control de la ascitis en el manejo de HU no complicada, reduce el riesgo de infección de herida operatoria, evisceración, drenaje de ascitis, peritonitis y reduce hasta 41% la recidiva de HU. El éxito de este enfoque también depende del grado de disfunción hepática. El tratamiento de la HU complicada es quirúrgico (herniorrafia sin malla), con menor tasa de mortalidad respecto al manejo conservador. Estudios revelan ventajas de la herniorrafia umbilical laparoscópica (mínimamente invasiva y sin tensión) en comparación a la cirugía abierta, sin embargo, aún no hay evidencia al respecto.

Ascites is the most common complication in patients with liver cirrhosis. Umbilical hernias (HU) occur in 20% of these patients and 40% in those with severe ascites. HU occurs due to increased intra-abdominal pressure, weakening of the abdominal fascia and loss of muscle mass. In addition, they have a tendency to enlarge rapidly and present high risk of complications that threaten the patient's life. The treatment of the uncomplicated HU is controversial, both the surgical management (herniorrhaphy) and the conservative management (control of ascites) present high rate of complications, consequently high morbidity and mortality. Currently, umbilical herniorrhaphy is recommended with prior control of ascites in uncomplicated HU management, it reduces the risk of surgical wound infection, evisceration, ascites drainage, peritonitis, and it reduces up to 41% of HU recurrence. The success of this approach also depends on the degree of liver dysfunction. The treatment of complicated HU is surgical (herniorrhaphy without mesh), with lower mortality rate compared to conservative management. Studies reveal advantages of umbilical herniorrhaphy laparoscopy (minimally invasive and stress-free) compared to open surgery; however there is still no evidence about it.