Identification of prognostic phenotypes of esophageal adenocarcinoma in two independent cohorts.

BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) present de novo. Although this may be due to inadequate screening strategies, the precise reason for this observation is not clear.. We compared survival of patients with prevalent EAC with and without synchronous BE/intestinal metaplasia of the esophagus (IM) at the time of EAC diagnosis. METHODS: Clinical data were studied using Cox Proportional Hazards regression to evaluate the effect of synchronous BE/IM on EAC survival independent of age, sex, TNM stage and tumor location. Two cohorts from the Mayo Clinic and a U.K. multicenter prospective cohort were included. RESULTS: The Mayo cohort had 411 EAC patients with 49.3% with BE/IM demonstrating a survival benefit as compared to those without (hazard ratio (HR), 0.44; 95% CI: 0.34 - 0.57, P<0.001). In a multivariable analysis BE/IM was associated with better survival independent of age, sex, stage and tumor location and length (adjusted HR: 0.66, 95% CI: 0.5-0.88, P=0.005). The UK cohort contained 1417 patients, 45% with BE/IM demonstrating a survival benefit as compared with non-BE/IM patients (HR 0.59, 95% CI: 0.5-0.69, P<0.001) with continued significance in multivariable analysis that included age, sex, stage, and tumor location (adjusted HR 0.77, 95% CI: 0.64-0.93, P=0.006). CONCLUSION: Two types of esophageal adenocarcinoma can be characterized based on the presence or absence of Barrett's epithelium. These findings have implications for understanding the etiology of EAC and determining prognosis as well as for development of optimal clinical strategies to identify patients at risk

Safety and Acceptability of Esophageal Cytosponge Cell Collection Device in a Pooled Analysis of Data From Individual Patients.

BACKGROUND & AIMS: Diagnosis and surveillance of Barrett's esophagus (BE) and eosinophilic esophagitis (EoE) have become emerging public health issues. Cytosponge is a novel, minimally invasive esophageal cell collection device. We aimed to assess the data on safety and acceptability of this device. METHODS: We performed a patient-level review of 5 prospective trials assessing Cytosponge performance in patients with reflux disease, BE and EoE in primary and secondary care. Acceptability of Cytosponge and subsequent endoscopy were recorded with visual analogue scale (VAS), wherein 0 and 10 denoted lowest and highest acceptability. Median VAS scores were compared using a Mann-Whitney test. The number of attempts, failures in swallowing the device and occurrence of adverse events were analyzed. Risk factors for failure in swallowing were analyzed using a multivariate regression model. RESULTS: In total, 2672 Cytosponge procedures were performed, in 2418 individuals from 2008 through 2017. There were 2 adverse events related to the device: a minor pharyngeal bleed and a case of detachment (<1:2000). The median acceptability score for the Cytosponge was 6.0 (interquartile range [IQR], 5.0-8.0), which was higher than the score for endoscopy without sedation (median 5.0; IQR, 3.0-7.0; P < .001) and lower than the score for endoscopy with sedation (median 8.0; IQR, 5.0-9.0; P < .001). Nearly all patients (91.1%) successfully swallowed the Cytosponge, most on the first attempt (90.1%). Failure to swallow the device was more likely to occur in secondary care (odds ratio, 5.13; 95% CI, 1.48-17.79; P < .01). CONCLUSIONS: The Cytosponge test is a safe procedure with good acceptability ratings in a variety of health care settings

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS)

BACKGROUND End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients’ assessments of disease severity. We also evaluated relationships between patients’ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings

Current management of the gastrointestinal complications of systemic sclerosis.

Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation

"Sane in the membrane" - Wie gelangen lipidierte Ras-Proteine in die Plasmamembran?

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