Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry.

BACKGROUND: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. OBJECTIVE: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. METHODS: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. RESULTS: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). CONCLUSION: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe.

BACKGROUND: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. METHODS: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. RESULTS: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. CONCLUSION: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe.

Proton pump inhibitor therapy reverses endoscopic features of fibrosis in eosinophilic esophagitis.

BACKGROUND: Long-standing inflammation leads to esophageal remodeling with stricture formation in patients with eosinophilic esophagitis (EoE). The ability of proton pump inhibitors (PPI) to reverse endoscopic features of fibrosis is still unknown. OBJECTIVE: To investigate the effect of a short course of PPI treatment in reducing endoscopic findings indicative of esophageal fibrosis in EoE patients. METHODS: Cross-sectional analysis of the EoE CONNECT registry. Patients who received PPI to induce EoE remission were evaluated. Endoscopic features were graded using the EoE Endoscopic Reference Score (EREFS), with rings and strictures indicating fibrosis. Results were compared to those from patients treated with swallowed topic corticosteroids (STC). RESULTS: Clinico-histological remission was achieved in 83/166 adult patients treated with PPI (50%) and in 65/79 (82%) treated with STC; among responders, 60 (36%) and 57 (72%) patients respectively achieved deep histological remission (<5 eosinophils/hpf). At baseline, mean±SD EREFS was lower in patients treated with PPI compared to those who received STC (p < 0.001). Short term treatment significantly reduced EREFS scores in patients treated either with PPI or STC as well as rings and strictures. Among patients treated with PPI, deep histological remission (<5 eosinophils/hpf) provided further reduction in total EREFS score. CONCLUSION: Effective PPI therapy for EoE significantly reduced endoscopic esophageal fibrosis in the short term.

Pan-enteric capsule for bleeding high-risk patients. Can we limit endoscopies?

INTRODUCTION: obscure gastrointestinal bleeding is defined as bleeding from a source that cannot be identified on upper or lower gastrointestinal endoscopy and capsule endoscopy is the next step in these patients. Some patients may be unsuitable for conventional endoscopy and performing a capsule panendoscopic test as a first line procedure might potentially reduce the number of endoscopies and their subsequent risk. AIM: to analyze our experience with capsule endoscopy in the bleeding setting. METHODS: the first 100 panendoscopic capsule procedures performed in our center from August 2011 until December 2016 were retrospectively reviewed. RESULTS: positive findings were observed in 61.2 % of patients; 46.26 % had a previous negative gastroscopy and the capsule detected small bowel lesions in 67.7 % and colonic findings in 80.64 %. Taking into consideration that our population were high-risk patients (mainly because of comorbidities) and that we used up to 45 ml of sodium phosphate, sodium, potassium and creatinine changes were analyzed before and after procedure. The mean "before" values were 140.68, 4.04 and 1.36, respectively. The mean "after" values were 140.28, 3.9 and 1.35 (p = n.s.). According to our findings, no other endoscopic studies would be needed in 64.5 % of patients with negative gastroscopy. According to capsule results, conventional endoscopy could have been avoided in 68.6 % of cases. CONCLUSION: panendoscopy with a capsule may be useful and safe in bleeding high-risk patients, by selecting those who need therapeutic endoscopy, avoiding up to 68.6 % of diagnostic endoscopies in our series.

Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry.

BACKGROUND: Proton pump inhibitors (PPIs) are the most commonly used first-line therapy for patients with eosinophilic oesophagitis (EoE). However, many aspects related to PPIs in EoE are still unknown. AIMS: To assess the effectiveness of PPI therapy for EoE in real-world practice. METHODS: This cross-sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom score; histological remission was defined as a peak eosinophil count below 15 eosinophils per high-power field. Factors associated with effectiveness of PPI therapy were identified by binary logistic regression multivariate analyses. RESULTS: Overall, 630 patients (76 children) received PPI as initial therapy (n = 600) or after failure to respond to other therapies (n = 30). PPI therapy achieved eosinophil density below 15 eosinophils per high-power field in 48.8% and a decreased symptom score in 71.0% of patients. More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico-histological remission after PPI therapy (OR 3.7; 95% CI, 1.4-9.5); as well as those who prolonged treatment length from 8 to 12 weeks (OR 2.7; 95% CI, 1.3-5.3). After achieving clinico-histological remission of EoE, PPI dosage reduction was effectively maintained in 69.9% of patients, but tended to be less effective among those with a stricturing phenotype. CONCLUSIONS: Inflammatory EoE phenotype and treatment duration up to 12 weeks correlated with greater chance for inducing remission of EoE. A stricturing phenotype decreased response rates to PPI therapy both initially and in the long term.

Efficacy of Therapy for Eosinophilic Esophagitis in Real-World Practice.

BACKGROUND & AIMS: Topical steroids, proton pump inhibitors (PPIs), and dietary interventions are recommended first- and second-line therapies for eosinophilic esophagitis (EoE). We investigated differences in their effectiveness in a real-world, clinical practice cohort of patients with EoE. METHODS: We collected data on the efficacy of different therapies for EoE (ability to induce clinical and histologic remission) from the multicenter EoE CONNECT database-a database of patients with a confirmed diagnosis of EoE in Europe that began in 2016. We obtained data from 589 patients, treated at 11 centers, on sex, age, time of diagnosis, starting date of any therapy, response to therapy, treatment end dates, alternative treatments, and findings from endoscopy. The baseline endoscopy was used for diagnosis of EoE; second endoscopy was performed to evaluate response to first-line therapies. After changes in treatment, generally because lack of efficacy, a last endoscopy was performed. The time elapsed between endoscopies depended on the criteria of attending physicians. Clinical remission was defined by a decrease of more than 50% in Dysphagia Symptom Score; improvement in symptoms by less than 50% from baseline was considered as clinical response. Histologic remission was defined as a peak eosinophil count below 5 eosinophils/hpf. A peak eosinophil count between 5 and 14 eosinophils/hpf was considered histologic response. We identified factors associated with therapy selection and effectiveness using χ2 and multinomial logistic regression analyses RESULTS: PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%). Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%). Among the 344 patients who switched to a second-line therapy, dietary interventions were selected for 47.1% of patients, followed by PPIs (for 29.1%) and topical steroids (for 18.6%). Clinical and histologic remission or response was achieved by 80.7% of patients treated with topical steroids, 69.2% of patients given PPIs, and 41.7% of patients on empiric elimination diets. Multivariate analyses found the stricturing phenotype of EoE to be associated with selection of topical steroids over PPIs as the first-line therapy; lack of fibrotic features at initial endoscopy was associated with selection of elimination diets over topical steroids as a second-line therapy. The recruiting center was significantly associated with therapy choice; second-line treatment with topical steroids or PPIs were the only variables associated with clinical and histologic remission. CONCLUSIONS: In an analysis of data from a large cohort of patients with EoE in Europe, we found topical steroids to be the most effective at inducing clinical and histologic remission, but PPIs to be the most frequently prescribed. Treatment approaches vary with institution and presence of fibrosis or strictures.

Split-dose sodium picosulfate-magnesium citrate colonoscopy preparation achieves lower residual gastric volume with higher cleansing effectiveness than a previous-day regimen.

BACKGROUND AND AIMS: It is known that sodium picosulfate-magnesium citrate (SPMC) bowel preparations are effective, well tolerated and safe, and that split-dosing is more effective for colon cleansing than previous-day regimens. Anesthetic guidelines consider that residual gastric fluid is independent of clear liquid fasting times. However, reluctance to use split-dosing persists. This may be due to limited data on residual gastric fluid volumes (RGFVs) and split-dosing bowel preparations, and that these may not be perceived as standard clear liquids. Furthermore, no studies are available on RGFV/residual gastric fluid pH (RGFpH) and SPMC. We aimed to evaluate the cleansing effectiveness and the RGFV/RGFpH achieved after an SPMC split-dosing regimen compared with a SPMC previous-day regimen. METHODS: This was a single-center observational study. A total of 328 outpatients scheduled for simultaneous EGD and colonoscopy and following a split-dosing or previous-day regimen of SPMC were included. We prospectively measured colon cleanliness by using the Ottawa Bowel Preparation Scale, RGFV, and RGFpH. RESULTS: Ottawa Bowel Preparation Scale scores for overall, right, mid-colon, and colon fluid were significantly better in the split-dosing group. In the split-dosing group, the 3- to 4-hour fasting time consistently achieved the best cleansing quality. RGFV was significantly lower in the split-dosing group (11.09 vs 18.62, P < .001). No significant differences in RGFpH were detected. CONCLUSIONS: Split-dosing SPMC provides higher colon cleansing quality with lower RGFVs than previous-day SPMC regimens. SPMC in split-dosing acts exactly as a standard clear liquid acts, and thus anesthetic guidelines on this issue may be applied with no concerns.

Comparative study of a responsive insertion technology (RIT) colonoscope versus a variable-stiffness colonoscope.

BACKGROUND AND OBJECTIVES: recently, Olympus developed a new prototype (XCF-Q180AY2L) with responsive insertion technology (RIT), which besides the still known variable stiffness technology, included a passive bending section and a new high force insertion tube. Our objective was to investigate whether the use of this prototype could ease colonoscope insertion, increasing the cecal intubation rate, and/or shortening the cecal intubation time. MATERIAL AND METHODS: the study was designed as a prospective observational study in 305 consecutive patients from a colo-rectal cancer screening program. We compared colonoscopies performed with conventional colonoscopes (CFH180AL/CFQ160L) with those performed with the prototype XCF-Q180AY2L. End points were mean cecal and terminal ileal intubation times, cecum intubation rate, and need for specific maneuvers. All colonoscopies were performedunder sedation with intravenous propofol. Finally, 288 patients were included. RESULTS: no complications were observed. Complete cecal intubation rate was 100 % in both groups. The ileum could be reached in 98.95 % of cases. Mean time required to reach the cecum was shorter in the prototype endoscope group (4.31 min, SD 2.63 min) than in the conventional endoscope group (4.66 min, SD 2.52 min) (p < 0.05). Compared with the standard colonoscope group, we observed in the prototype group less subjective sensation of difficultyin the passage of the sigma (p < 0.01), fewer maneuvers when it proved necessary to straighten the scope (p < 0.01), and less frequent need to modify the stiffness of the endoscope (p < 0.05). CONCLUSION: we concluded that the prototype endoscope (XCFQ180AY2L) facilitated colonoscope insertion, requiring slightly less time to reach the cecum than a standard colonoscope.

Diagnostic and therapeutic management of eosinophilic oesophagitis in children and adults: results from a Spanish registry of clinical practice.

BACKGROUND: Eosinophilic oesophagitis has emerged as a common cause of oesophageal symptoms. AIMS: To document practice variation in care provided to eosinophilic oesophagitis patients in Spain and to assess adherence to available guidelines. METHODS: A prospective survey-based registry including data from all patients receiving care from gastroenterologists and allergists throughout Spain was developed. RESULTS: Data from 705 patients (82% adults, male:female ratio 4.1:1) were collected from 26 Spanish hospitals. 42.7% received care in teaching hospitals. Adults presented dysphagia and food impaction more frequently; vomiting and weight loss predominated in children (p < 0.01). A mean diagnostic delay of 54.7 and 28.04 months was documented for adults and children, respectively. Normal endoscopic exams were reported in 27.6% and directly related to the experience in managing the disease (p < 0.05). Paediatric patients, non-teaching hospitals and greater experience in managing eosinophilic oesophagitis were associated with increased frequency in eosinophil count reports and with taking gastric and duodenal biopsies (p < 0.001). Initial therapy consisted of topical steroids (61.7% of patients), proton pump inhibitors (52.4%), dietary modifications (51.26%) and endoscopic dilation (7.2%). Referrals to allergy units occurred more frequently in teaching hospitals (p = 0.003) where food restrictions generally followed allergy test results (p < 0.001). CONCLUSIONS: Availability of facilities and the physician's experience constituted the most important factors in explaining differences in patient management.

Carbon dioxide vs. air insufflation in ileo-colonoscopy and in gastroscopy plus ileo-colonoscopy: a comparative study.

INTRODUCTION: insufflation with carbon dioxide (CO2) during endoscopies compared to air is associated with a decrease in abdominal discomfort after the examination, because CO2 is readily absorbed through the small intestine and eliminated by the lungs. AIM: the objective of this randomized clinical trial was to assess the effect of CO2 insufflation on pain and abdominal distension after an ileo-colonoscopy (I) and after an ileo-colonoscopy plus gastroscopy (I+G). MATERIAL AND METHODS: we included a total of 309 patients in the study and all endoscopies were performed under sedation with propofol. Two hundred fourteen patients underwent an I (132 with CO2 / 82 with air) and 95 underwent an I+G (53 with CO2 / 42 with air). Abdominal pain was studied at 10, 30 and 120 minutes of exploration and abdominal perimeter difference before and after the procedure. RESULTS: both in group I and in group I+G, the use of CO2 translated into an average of abdominal pain significantly lower (p < 0.05). Similarly, a smaller increase in waist circumference was found among group I and group I+G, in patients where CO2 was used (p < 0.05). CONCLUSION: the insufflation of CO2 instead of air during the performance of endoscopy significantly reduces the discomfort and abdominal pain after an ileo-colonoscopy and after a gastroscopy + ileo-colonoscopy.

Herpetic esophagitis: a case report on an immunocompetent adolescent.

Herpetic esophagitis in immunocompetent individuals is a rare entity that should be suspected clinically by an acute onset of symptoms, and without apparent cause of a symptomatic triad consisting on odynophagia, heartburn and fever. Its occurrence may be due to reactivation of a previous infection or less often a primary infection. Herpes simplex type 1 is the most common cause. Upper endoscopy establishes the diagnosis of suspicion of herpetic esophagitis. It also allows to take multiple biopsy samples and viral culture, leading to a definitive diagnosis. The severity of symptoms is related to the degree of oesophageal involvement. In immunocompromised patients treatment is indicated with acyclovir, but the indication in immunocompetent patients is controversial because the process is time, limited with a low probability of complications. We present a case of acute herpetic esophagitis in an immunocompetent host that debuted acutely with severe upper gastrointestinal tract symptoms, associated with an insidious and nonspecific onset of flu-like symptoms. Endoscopic findings showed a severe involvement in the lower third of the oesophageal mucosa.

[Giant Brunner's gland hamartoma: diagnosis and endoscopic treatment]. / Hamartoma gigante de glándulas de Brunner: diagnóstico y tratamiento endoscópico.

Brunner's gland hamartoma is a polypoid lesion typically composed of an increased quantity of normal-appearing Brunner's glands, accompanied by a variable proportion of smooth muscle. Most of these masses are asymptomatic and behave as benign tumors. Occasionally tumoral growth can provoke gastrointestinal problems which, together with the possibility of malignant transformation, will require resection after a broad differential diagnosis has been made with solitary duodenal mass. Both clinical and radiographic studies are nonspecific and often do not allow diagnosis of these tumors. Basic endoscopic studies (upper endoscopy) with adequate characterization of the lesion by endoscopic ultrasound (EUS) can establish a high diagnostic suspicion and determine the best therapeutic option (endoscopy or surgery). We present a case of giant Brunner's gland hamartoma. The initial manifestation was iron-deficiency anemia with no evidence of bleeding. After adequate characterization of the lesion, EUS allowed complete and safe endoscopic resection, avoiding more invasive surgical treatment.

Gastroduodenal injury after radioembolization of hepatic tumors.

BACKGROUND: Radioembolization is a new tool for the treatment of hepatic tumors that consists in the injection of biocompatible microspheres carrying radioisotopes into the hepatic artery or its branches. METHODS: We have performed radioembolization in 78 patients with hepatic tumors using resin-based microspheres loaded with yttrium-90. All patients were previously evaluated to minimize the risk of hazardous irradiation to nontarget organs and to obtain the data needed for dose calculation. RESULTS: We report a complication found in three cases (3.8%) that consists of abdominal pain resulting from gastroduodenal lesions and that had a chronic, insidious course. Microscopically, microspheres were detected in the specimens obtained from all affected gastric areas. Since these gastroduodenal lesions do not appear when nonradiating microspheres are injected in animals, lesions are likely to be due to radiation and not to an ischemic effect of vascular occlusion by spheres. CONCLUSIONS: We believe that a pretreatment evaluation that includes a more thorough scrutiny of the hepatic vascularization in search of small collaterals connecting to the gastroduodenal tract can help prevent this awkward complication.

Diagnostic value of distal colonic polyps for prediction of advanced proximal neoplasia in an average-risk population undergoing screening colonoscopy.

BACKGROUND: For colorectal cancer screening, the predictive value of distal findings in the ascertainment of proximal lesions is not fully established. The aims of this study were to assess distal findings as predictors of advanced proximal neoplasia and to compare the predictive value of endoscopy alone vs. combined endoscopic and histopathologic data. METHODS: Primary colonoscopy screening was performed in 2210 consecutive, average-risk adults. Age, gender, endoscopic (size, number of polyps), and histopathologic distal findings were used as potential predictors of advanced proximal neoplasms (i.e., any adenoma > or =1 cm in size, and/or with villous histology, and/or with severe dysplasia or invasive cancer). Polyps were defined as distal if located in the descending colon, the sigmoid colon, or the rectum. Those in other locations were designated proximal. RESULTS: Neoplastic lesions, including 11 invasive cancers, were found in 617 (27.9%) patients. Advanced proximal neoplasms without any distal adenoma were present in 1.3% of patients. Of the advanced proximal lesions, 39% were not associated with any distal polyp. Older age, male gender, and distal adenoma were independent predictors of advanced proximal neoplasms. The predictive ability of a model with endoscopic data alone did not improve after inclusion of histopathologic data. In multivariate logistic regression analysis, the predictive ability of models that use age, gender, and any combination of distal findings was relatively low. The proportion of advanced proximal neoplasms identified if any distal polyp was an indication for colonoscopy was only 62%. CONCLUSIONS: A strategy in which colonoscopy is performed solely in patients with distal colonic findings is not effective screening for the detection of advanced proximal neoplasms in an average-risk population.

Use of colonoscopy as a primary screening test for colorectal cancer in average risk people.

OBJECTIVE: The use of colonoscopy as a primary screening test for colorectal cancer (CRC) in average risk adults is a subject of controversy. Our primary objective was to build a predictive model based on a few simple variables that could be used as a guide for identifying average risk adults more suitable for examination with colonoscopy as a primary screening test. METHODS: The prevalence of advanced adenomas was assessed by primary screening colonoscopy in 2210 consecutive adults at least 40 yr old, without known risk factors for CRC. Age, gender, and clinical and biochemical data were compared among people without adenomas, those with non-advanced adenomas, and those with any advanced neoplasm. A combined score to assess the risk of advanced adenomas was built with the variables selected by multiple logistic regression analysis. RESULTS: Neoplastic lesions were found in 617 subjects (27.9%), including 259 with at least one neoplasm that was 10 mm or larger, villous, or with moderate-to-severe dysplasia, and 11 with invasive cancers. Advanced lesions were more frequent among men, older people, and those with a higher body mass index (BMI). These three variables were independent predictors of advanced adenomas in multivariate analysis. A score combining age, sex, and BMI was developed as a guide for identifying individuals more suitable for screening colonoscopy. CONCLUSIONS: Age, gender, and BMI can be used to build a simple score to select those average risk adults who might be candidates for primary screening colonoscopy.