Six-Food Elimination Diet Is Less Effective During Pollen Season in Adults With Eosinophilic Esophagitis Sensitized to Pollens.

INTRODUCTION: The role of inhaled and swallowed aeroallergens in treatment outcomes of adult patients with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of the 6-food elimination diet (SFED) in EoE. METHODS: We compared outcomes of patients with EoE who underwent SFED during vs outside of the pollen season. Consecutive adult patients with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Individual pollen sensitization and pollen count data were analyzed to define whether each patient had been assessed during or outside of the pollen season after SFED. All patients had active EoE (≥15 eosinophils/high-power field) before SFED and adhered to the diet under the supervision of a dietitian. RESULTS: Fifty-eight patients were included, 62.0% had positive SPT for birch and/or grass, whereas 37.9% had negative SPT. Overall, SFED response was 56.9% (95% confidence interval, 44.1%-68.8%). When stratifying response according to whether the assessment had been performed during or outside of the pollen season, patients sensitized to pollens showed significantly lower response to SFED during compared with outside of the pollen season (21.4% vs 77.3%; P = 0.003). In addition, during the pollen season, patients with pollen sensitization had significantly lower response to SFED compared with those without sensitization (21.4% vs 77.8%; P = 0.01). DISCUSSION: Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. The SPT for pollens may identify patients less likely to respond to the diet during the pollen season.

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.

BACKGROUND: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

Endoscopic eradication therapy for Barrett's esophagus-related neoplasia: a final 10-year report from the UK National HALO Radiofrequency Ablation Registry.

BACKGROUND AND AIMS: Long-term durability data for effectiveness of radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in patients with dysplastic Barrett's esophagus (BE) are lacking. METHODS: We prospectively collected data from 2535 patients with BE (mean length, 5.2 cm; range, 1-20) and neoplasia (20% low-grade dysplasia, 54% high-grade dysplasia, 26% intramucosal carcinoma) who underwent RFA therapy across 28 UK hospitals. We assessed rates of invasive cancer and performed detailed analyses of 1175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA therapy. We assessed relapses and rates of return to CR-D (CR-D2) and CR-IM (CR-IM2) after further therapy. CR-D and CR-IM were confirmed by an absence of dysplasia and intestinal metaplasia on biopsy samples taken at 2 consecutive endoscopies. RESULTS: Ten years after starting treatment, the Kaplan-Meier (KM) cancer rate was 4.1% with a crude incidence rate of .52 per 100 patient-years. CR-D and CR-IM after 2 years of therapy were 88% and 62.6%, respectively. KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM at 8 years, with most occurring in the first 2 years. Both were successfully retreated with rates of CR-D2 of 63.4% and CR-IM2 of 70.0% 2 years after retreatment. EMR before RFA increased the likelihood of rescue EMR from 17.2% to 41.7% but did not affect the rate of CR-D, whereas rescue EMR after RFA commenced reduced CR-D from 91.4% to 79.7% (χ2P < .001). CONCLUSIONS: RFA treatment is effective and durable to prevent esophageal adenocarcinoma. Most treatment relapses occur early and can be successfully retreated.

Patient perspectives on key symptoms and preferences for follow-up after upper gastro-intestinal cancer surgery.

PURPOSE: Long-lasting symptoms and reductions in quality of life are common after oesophago-gastric surgery. Post-operative follow-up has traditionally focussed on tumour recurrence and survival, but there is a growing need to also identify and treat functional sequelae to improve patients' recovery. METHODS: An electronic survey was circulated via a British national charity for patients undergoing oesophago-gastric surgery and their families. Patients were asked about post-operative symptoms they deemed important to their quality of life, as well as satisfaction and preferences for post-operative follow-up. Differences between satisfied and dissatisfied patients with reference to follow-up were assessed. RESULTS: Among 362 respondents with a median follow-up of 58 months since surgery (range 3-412), 36 different symptoms were reported as being important to recovery and quality of life after surgery, with a median of 13 symptoms per patient. Most (84%) respondents indicated satisfaction with follow-up. Satisfied patients were more likely to have received longer follow-up (5-year or longer follow-up 60% among satisfied patients vs 27% among unsatisfied, p < 0.001). These were also less likely to have seen a dietitian as part of routine follow-up (37% vs 58%, p = 0.005). CONCLUSION: This patient survey highlights preferences regarding follow-up after oesophago-gastrectomy. Longer follow-up and dietician involvement improved patient satisfaction. Patients reported being concerned by a large number of gastrointestinal and non-gastrointestinal symptoms, highlighting the need for multidisciplinary input and a consensus on how to manage the poly-symptomatic patient.

Radiofrequency ablation for Barrett's oesophagus related neoplasia with the 360 Express catheter: initial experience from the United Kingdom and Ireland-preliminary results.

BACKGROUND: Radio-frequency ablation (RFA) for Barrett's oesophagus (BE)-related neoplasia is currently used after endoscopic resection of visible neoplasia. The HALO 360 balloon has been used to ablate long segment BE. The Barrx™ 360 Express RFA self-sizing catheter ('RFA Express') may potentially allow quicker ablation times and improved treatment outcomes. The aim of this paper is to present real world data on the use of the 360 Express Device. METHODS: Centres in the UK and Ireland submitted cases where the RFA Express was used. The primary outcome was regression of BE at 3 months. Secondary outcomes were the rate of symptomatic stricture formation and resolution of intestinal metaplasia (CR-IM) and dysplasia (CR-D) at End of Treatment (EoT). RESULTS: 11 centres submitted 123 consecutive patients. 112 had a follow up endoscopy. The median age was 67 years (IQR 62-75). 3 dosimetries were used. The mean reduction in Circumferential (C) length was 78% ± 36 and mean reduction in Maximal length (M) was 55% ± 36. 17 patients (15%) developed strictures requiring dilation. There was a higher rate of stricture formation when the 12 J energy was used (p < 0.05). 47 patients had EoT biopsies, 40 (85%) had CR-D and 34(76%) had CR-IM. CONCLUSIONS: The RFA 360 Express catheter shows reduction in length of baseline BE at 3 months after index treatment, and eradication of intestinal metaplasia and dysplasia at 12 months similar to other studies with earlier devices. It appears that the symptomatic stricture rate is slightly higher than previous series with the HALO 360 catheter. This study was performed as part of the HALO registry and has been approved by the Research Ethics Committee - MREC Number 08/H0714/27 Local project reference 08/0104 Project ID 15,033 IRAS Number 54678 EudraCT 2009-015980-1. Registered on ISRCTN as below: ISRCTN93069556. https://doi.org/10.1186/ISRCTN93069556.

Transition from esophagectomy to endoscopic therapy for early esophageal cancer.

BACKGROUND: To assess the outcomes of patients with early esophageal cancer and high-grade dysplasia comparing esophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET). METHODS: Retrospective cohort study of consecutive patients with early esophageal cancer/high-grade dysplasia, treated between 2000 and 2018 at a tertiary center. Primary outcomes were all-cause and disease-specific mortality assessed by multivariable Cox regression and a propensity score matching sub analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, tumor grade (G1/2 vs. G3), tumor stage, and lymphovascular invasion. Secondary outcomes included complications, hospital stay, and overall costs. RESULTS: Among 269 patients, 133 underwent esophagectomy and 136 received EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85, 95% CI 0.73, 4.72) and disease-specific mortality (HR 1.10, 95% CI 0.26, 4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien-Dindo ≥3 26.3% vs. endoscopic therapy 0.74%), longer in-patient stay (median 14 vs. 0 days endoscopic therapy) and higher hospital costs(£16 360 vs. £8786 per patient). CONCLUSION: This series of patients treated during a transition period from surgery to EET, demonstrates a primary endoscopic approach does not compromise oncological outcomes with the benefit of fewer complications, shorter hospital stays, and lower costs compared to surgery. It should be available as the gold standard treatment for patients with early esophageal cancer. Those with adverse prognostic features may still benefit from esophagectomy.

Oral Versus Intravenous Antibiotics for Residual Osteomyelitis After Amputation in the Diabetic Foot.

The standard management for residual osteomyelitis following amputation in a diabetic foot infection includes a prolonged course of intravenous antibiotic agents. The purpose of this analysis was to investigate whether oral antibiotic therapy led to treatment failure more than intravenous antibiotic therapy for this indication. The primary endpoint was treatment failure within one year of the initial amputation, defined by re-operation for residual osteomyelitic infection or a remaining nonhealing wound at the surgical site. All patients received at least 4 weeks of antibiotics and were chosen for oral or intravenous route of administration by infectious disease specialists. Characteristics including age, sex, hemoglobin A1c, BMI, tobacco use, PVD, homelessness and IDSA classification were also assessed for influence on antibiotic success and failure. Of the 65 patients meeting inclusion criteria, treatment failure occurred in 32 and treatment success occurred in 33. Of the treatment failures, 17 (53%) were in the intravenous group, and 15 (47%) were in the oral group. The differences between the modalities of antibiotic administration and their failure rates were not found to be statistically significant (p = .28 (proportional difference: -14%, 95% confidence interval [CI]:-36% to 10%)).

Validation of the Lyon classification for GORD diagnosis: acid exposure time assessed by prolonged wireless pH monitoring in healthy controls and patients with erosive oesophagitis.

OBJECTIVE: Acid exposure time (AET) from ambulatory pH studies and reflux oesophagitis are independent measurements used by the Lyon classification to diagnose GORD. This study aimed to validate AET reference ranges and diagnostic thresholds by analysis of 96-hour wireless pH studies from healthy, asymptomatic controls (HCs) and patients with and without oesophagitis. DESIGN: HC and consecutive patients referred for wireless pH studies (off acid suppressants for >7 days) underwent 96-hour pH studies at two tertiary referral centres. Erosive oesophagitis was categorised by the Los Angeles (LA) classification. Linear regression and receiver operating curve (ROC) analysis were performed to define optimal diagnostic cut-offs. RESULTS: Prolonged, 96-hour pH studies were completed in 39 HCs (age 28 (18-53) years, 72% female) and 944 patients (age 46 (16-85) years, 65% female), of whom 136 (14.5%) had reflux oesophagitis. Median AET in HC was 1.3% (upper 95th percentile 4.6%) for any study day and 2.6% (upper 95th percentile 6.9%) for the worst day (24-hour period) during the study. ROC analysis for average AET differentiated HC from patients with moderate-to-severe oesophagitis (LA BCD; sensitivity 87%, specificity 95%, positive predictive value (PPV) 59%, negative predictive value 99% for a cut-off AET of 4.3%; area under the receiver operating curve 0.95). Specificity was higher, but PPV was substantially lower for severe oesophagitis (LA CD). 'Worst-day' analysis provided similar results; however, day-to-day variability was high. CONCLUSION: Diagnostic thresholds for average AET were identified that accurately discriminate between HCs and patients with erosive oesophagitis. The findings provide conditional support for diagnostic criteria for GORD proposed by the Lyon Consensus.

Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a leading cause of morbidity and is associated with a 2 % - 17 % mortality rate in the UK and USA. Bleeding peptic ulcers account for 50 % of UGIB cases. Endoscopic intervention in a timely manner can improve outcomes. Hemostatic spray is an endoscopic hemostatic powder for GI bleeding. This multicenter registry was created to collect data prospectively on the immediate endoscopic hemostasis of GI bleeding in patients with peptic ulcer disease when hemostatic spray is applied as endoscopic monotherapy, dual therapy, or rescue therapy. METHODS: Data were collected prospectively (January 2016 - March 2019) from 14 centers in the UK, France, Germany, and the USA. The application of hemostatic spray was decided upon at the endoscopist's discretion. RESULTS: 202 patients with UGIB secondary to peptic ulcers were recruited. Immediate hemostasis was achieved in 178/202 patients (88 %), 26/154 (17 %) experienced rebleeding, 21/175 (12 %) died within 7 days, and 38/175 (22 %) died within 30 days (all-cause mortality). Combination therapy of hemostatic spray with other endoscopic modalities had an associated lower 30-day mortality (16 %, P < 0.05) compared with monotherapy or rescue therapy. There were high immediate hemostasis rates across all peptic ulcer disease Forrest classifications. CONCLUSIONS: This is the largest case series of outcomes of peptic ulcer bleeding treated with hemostatic spray, with high immediate hemostasis rates for bleeding peptic ulcers.

Hemostatic powder TC-325 treatment of malignancy-related upper gastrointestinal bleeds: International registry outcomes.

BACKGROUND AND AIM: Upper gastrointestinal tumors account for 5% of upper gastrointestinal bleeds. These patients are challenging to treat due to the diffuse nature of the neoplastic bleeding lesions, high rebleeding rates, and significant transfusion requirements. TC-325 (Cook Medical, North Carolina, USA) is a hemostatic powder for gastrointestinal bleeding. The aim of this study was to examine the outcomes of upper gastrointestinal bleeds secondary to tumors treated with Hemospray therapy. METHODS: Data were prospectively collected on the use of Hemospray from 17 centers. Hemospray was used during emergency endoscopy for upper gastrointestinal bleeds secondary to tumors at the discretion of the endoscopist as a monotherapy, dual therapy with standard hemostatic techniques, or rescue therapy. RESULTS: One hundred and five patients with upper gastrointestinal bleeds secondary to tumors were recruited. The median Blatchford score at baseline was 10 (interquartile range [IQR], 7-12). The median Rockall score was 8 (IQR, 7-9). Immediate hemostasis was achieved in 102/105 (97%) patients, 15% of patients had a 30-day rebleed, 20% of patients died within 30 days (all-cause mortality). There was a significant improvement in transfusion requirements following treatment (P < 0.001) when comparing the number of units transfused 3 weeks before and after treatment. The mean reduction was one unit per patient. CONCLUSIONS: Hemospray achieved high rates of immediate hemostasis, with comparable rebleed rates following treatment of tumor-related upper gastrointestinal bleeds. Hemospray helped in improving transfusion requirements in these patients. This allows for patient stabilization and bridges towards definitive surgery or radiotherapy to treat the underlying tumor.

Baboon biogeography, divergence, and evolution: Morphological and paleoecological perspectives.

Papio originated in the early Pleistocene and diverged into multiple species, six of which are extant. Among parapatric Papio species, there are obvious phenotypic differences that arose during the radiation of the genus. We use data from modern baboon ecology and morphology, as well as fossils and paleoecology, to examine baboon biogeography, divergence, and evolution, focusing on skull form and body mass. To provide context, techniques of historical biogeography, combining data from modern distributions in statistical models alongside qualitative assessments of the fossil record, were used to estimate ancestral ranges in papionins. The ancestral range of Papio was estimated to be in South Tropical Africa rather than in the far south of the continent, followed by multiple movements south and west. Progress to the north and east may have been slowed because of high-density blocking of niches by other monkeys. Geometric morphometric data were used in partial least squares analysis with dietary, environmental, and other variables to investigate skull differentiation. Environment was significantly correlated with skull form, but diet emerged as more significant. Exploitation of subterranean foods was found to be an important influence on skull morphology. Bayesian modeling of cercopithecid body mass data allowed reconstruction of ancestral body mass and showed a pattern of accelerating body mass evolution in a number of lineages. This appears to be related to exploitation of terrestrial niches in the Pliocene, with terrestriality also implicated in the large geographic distributions of many fossil and modern papionins, including Papio. Given the greater heterogeneity of body masses in males, size differentiation within Papio seems most likely to be linked to sexual selection rather than environmental factors, although further work is required to examine the relative importance of plasticity versus local adaptation in shaping baboon phenotypic variation.

Outcomes from an international multicenter registry of patients with acute gastrointestinal bleeding undergoing endoscopic treatment with Hemospray.

BACKGROUND AND AIM: Acute gastrointestinal bleeding carries poor outcomes unless prompt endoscopic hemostasis is achieved. Mortality in these patients remains significant. Hemospray is a novel intervention that creates a mechanical barrier over bleeding sites. We report the largest dataset of patient outcomes after treatment with Hemospray from an international multicenter registry. PATIENTS AND METHODS: Prospective data (Jan 2016-May 2018) from 12 centers across Europe were collected. Immediate hemostasis was defined as endoscopic cessation of bleeding within 5 min after application of Hemospray. Rebleeding was defined as subsequent drop in hemoglobin, hematemesis, persistent melena with hemodynamic compromise post-therapy. RESULTS: Three hundred and fourteen cases were recruited worldwide (231 males, 83 females). Median pretreatment Blatchford score was 11 (IQR: 8-14) and median complete Rockall score (RS) was 7 (IQR: 6-8) for all patients. Peptic ulcer disease (PUD) was the most common pathology (167/314 = 53%) and Forrest Ib the most common bleed type in PUD (100/167 = 60%). 281 patients (89.5%) achieved immediate hemostasis after successful endoscopic therapy with Hemospray. Rebleeding occurred in 29 (10.3%) of the 281 patients who achieved immediate hemostasis. Seven-day and 30-day all-cause mortality were 11.5% (36/314) and 20.1% (63/314), respectively (lower than the predicted rates as per the RS). Similar hemostasis rates were noted in the Hemospray monotherapy (92.4%), combination therapy (88.7%) and rescue therapy (85.5%) groups. CONCLUSIONS: These data show high rates of immediate hemostasis overall and in all subgroups. Rebleeding and mortality rates were in keeping/lower than predicted rates.

Long-term outcomes of the randomized controlled trial comparing 5-aminolaevulinic acid and Photofrin photodynamic therapy for Barrett's oesophagus related neoplasia.

OBJECTIVE: Photodynamic therapy (PDT) was used as therapy for early neoplasia associated with Barrett's oesophagus (BE). This is 5-year follow-up of patients enrolled into randomised controlled trial of 5-aminolaevulinic acid (ALA) vs. Photofrin PDT. METHODS: Biopsies were taken from original Barrett's segment during endoscopic follow up using Seattle protocol. Endoscopic mucosal resection (EMR) ± radiofrequency ablation (RFA) was preferred therapy in patients who failed PDT and/or had recurrent neoplasia. RESULTS: Fifty eight of 64 patients enrolled in the original trial were followed up including 31 patients treated with ALA PDT (17 patients with ≤6 cm, 14 patients with >6 cm segment of BE) and 27 treated with Photofrin PDT (14 patients with ≤6 cm, 13 patients with >6 cm BE). Initial success was achieved in 65% (20/31) ALA and 48% (13/27) Photofrin patients (p = .289). Thirty five percent patients (7/20) relapsed in ALA group and 54% (7/13) relapsed in Photofrin group (p = .472). At a median follow-up of 67 months, no significant difference was found in long-term complete reversal of intestinal metaplasia (CR-IM) and complete reversal of dysplasia (CR-D) between ALA and Photofrin groups (78% vs. 63%; p = .18; 90% vs. 76%; p = .26). Original length of BE did not alter long-term outcome. Four patients from each group progressed to invasive oesophageal adenocarcinoma. Initial success of ALA PDT was associated with significantly better likelihood of long-term remission (p = .03). CONCLUSIONS: Initial response to PDT plays key role in long term outcome. RFA ± EMR have, however, become preferred minimally invasive ablative therapy for BE-related neoplasia due to poor efficacy of PDT.

Dedicated Barrett's surveillance sessions managed by trained endoscopists improve dysplasia detection rate.

Background and study aim Barrett's esophagus (BE)-associated dysplasia is an important marker for risk of progression to esophageal adenocarcinoma (EAC) and an indication for endoscopic therapy. However, BE surveillance technique is variable. The aim of this study was to assess the effect of dedicated BE surveillance lists on dysplasia detection rate (DDR). Patients and methods This was a prospective study of patients undergoing BE surveillance at two hospitals - community (UHL) and upper gastrointestinal center (GSTT). Four endoscopists (Group A) were trained in Prague classification, Seattle protocol biopsy technique, and lesion detection prior to performing BE surveillance endoscopies at both sites, with dedicated time slots or lists. The DDR was then compared with historical data from 47 different endoscopists at GSTT and 24 at UHL (Group B) who had undertaken Barrett's surveillance over the preceding 5-year period. Results A total of 729 patients with BE underwent surveillance endoscopy between 2007 and 2012. There was no significant difference in patient age, sex, or length of BE between the two groups. There was a significant difference in detection rate of confirmed indefinite or low grade dysplasia and high grade dysplasia (HGD)/EAC between the two groups: 18 % (26 /142) Group A vs. 8 % (45/587) in Group B (P  < 0.001). Documentation of Prague criteria and adherence to the Seattle protocol was significantly higher in Group A. Conclusion This study demonstrated that a group of trained endoscopists undertaking Barrett's surveillance on dedicated lists had significantly higher DDR than a nonspecialist cohort. These findings support the introduction of dedicated Barrett's surveillance lists.

Radiofrequency ablation of symptomatic cervical inlet patch using a through-the-scope device: a pilot study.

BACKGROUND AND AIMS: The cervical inlet patch (CIP) is an area of heterotopic gastric mucosa at the proximal esophagus, which can secrete both acid and mucus. Attributable symptoms include chronic globus sensation and sore throat. Previous studies have demonstrated improvement in symptoms after ablation using argon plasma coagulation. Our aim was to assess a through-the-scope radiofrequency ablation (RFA) catheter for ablation of symptomatic CIP. METHODS: Ten patients with endoscopically and histologically proven CIP and symptoms of globus or sore throat were included in the study. An ablation protocol of 3 ablations at 12 J/cm2, without removal of coagulated tissue between ablations, was used. A maximum of 2 RFA sessions, 3 months apart, was allowed. A visual analog score was completed at baseline, 6 weeks (on proton pump inhibitor), 3 months (off proton pump inhibitor), and 12 months after treatment. RESULTS: Mean patient age was 56 years (±3 years, standard error of the mean), 60% were men, and 80% were white. Barrett's esophagus was present in 50%. The mean number of CIPs was 2 (range, 1-4) with a median surface area of 2 cm2 (range, .5-14). After a median of 2 treatments, 80% achieved complete endoscopic and histologic resolution, with a mean follow-up of 14 months (range, 12-17). Globus, sore throat, and cough significantly improved from baseline (P < .05). No strictures or buried glands were identified. CONCLUSIONS: This prospective pilot study demonstrates that RFA using a through-the-scope device is safe and effective for treating patients with symptomatic CIP. One-year follow-up data suggest the effect is durable.

Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry.

BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

Predictors of professional behaviour and academic outcomes in a UK medical school: A longitudinal cohort study.

BACKGROUND: Over the past 70 years, there has been a recurring debate in the literature and in the popular press about how best to select medical students. This implies that we are still not getting it right: either some students are unsuited to medicine or the graduating doctors are considered unsatisfactory, or both. AIM: To determine whether particular variables at the point of selection might distinguish those more likely to become satisfactory professional doctors, by following a complete intake cohort of students throughout medical school and analysing all the data used for the students' selection, their performance on a range of other potential selection tests, academic and clinical assessments throughout their studies, and records of professional behaviour covering the entire five years of the course. METHODS: A longitudinal database captured the following anonymised information for every student (n = 146) admitted in 2007 to the Hull York Medical School (HYMS) in the UK: demographic data (age, sex, citizenship); performance in each component of the selection procedure; performance in some other possible selection instruments (cognitive and non-cognitive psychometric tests); professional behaviour in tutorials and in other clinical settings; academic performance, clinical and communication skills at summative assessments throughout; professional behaviour lapses monitored routinely as part of the fitness-to-practise procedures. Correlations were sought between predictor variables and criterion variables chosen to demonstrate the full range of course outcomes from failure to complete the course to graduation with honours, and to reveal clinical and professional strengths and weaknesses. RESULTS: Student demography was found to be an important predictor of outcomes, with females, younger students and British citizens performing better overall. The selection variable "HYMS academic score", based on prior academic performance, was a significant predictor of components of Year 4 written and Year 5 clinical examinations. Some cognitive subtest scores from the UK Clinical Aptitude Test (UKCAT) and the UKCAT total score were also significant predictors of the same components, and a unique predictor of the Year 5 written examination. A number of the non-cognitive tests were significant independent predictors of Years 4 and 5 clinical performance, and of lapses in professional behaviour. First- and second-year tutor ratings were significant predictors of all outcomes, both desirable and undesirable. Performance in Years 1 and 2 written exams did not predict performance in Year 4 but did generally predict Year 5 written and clinical performance. CONCLUSIONS: Measures of a range of relevant selection attributes and personal qualities can predict intermediate and end of course achievements in academic, clinical and professional behaviour domains. In this study HYMS academic score, some UKCAT subtest scores and the total UKCAT score, and some non-cognitive tests completed at the outset of studies, together predicted outcomes most comprehensively. Tutor evaluation of students early in the course also identified the more and less successful students in the three domains of academic, clinical and professional performance. These results may be helpful in informing the future development of selection tools.

Radiofrequency ablation and endoscopic mucosal resection for dysplastic barrett's esophagus and early esophageal adenocarcinoma: outcomes of the UK National Halo RFA Registry.

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or early neoplasia increasingly receive endoscopic mucosal resection and radiofrequency ablation (RFA) therapy. We analyzed data from a UK registry that follows the outcomes of patients with BE who have undergone RFA for neoplasia. METHODS: We collected data on 335 patients with BE and neoplasia (72% with HGD, 24% with intramucosal cancer, 4% with low-grade dysplasia [mean age, 69 years; 81% male]), treated at 19 centers in the United Kingdom from July 2008 through August 2012. Mean length of BE segments was 5.8 cm (range, 1-20 cm). Patients' nodules were removed by endoscopic mucosal resection, and the patients then underwent RFA every 3 months until all areas of BE were ablated or cancer developed. Biopsies were collected 12 months after the first RFA; clearance of HGD, dysplasia, and BE were assessed. RESULTS: HGD was cleared from 86% of patients, all dysplasia from 81%, and BE from 62% at the 12-month time point, after a mean of 2.5 (range, 2-6) RFA procedures. Complete reversal dysplasia was 15% less likely for every 1-cm increment in BE length (odds ratio = 1.156; SE = 0.048; 95% confidence interval: 1.07-1.26; P < .001). Endoscopic mucosal resection before RFA did not provide any benefit. Invasive cancer developed in 10 patients (3%) by the 12-month time point and disease had progressed in 17 patients (5.1%) after a median follow-up time of 19 months. Symptomatic strictures developed in 9% of patients and were treated by endoscopic dilatation. Nineteen months after therapy began, 94% of patients remained clear of dysplasia. CONCLUSIONS: We analyzed data from a large series of patients in the United Kingdom who underwent RFA for BE-related neoplasia and found that by 12 months after treatment, dysplasia was cleared from 81%. Shorter segments of BE respond better to RFA; http://www.controlled-trials.com, number ISRCTN93069556.

Artificial Intelligence Tools for the Diagnosis of Eosinophilic Esophagitis in Adults Reporting Dysphagia: Development, External Validation, and Software Creation for Point-of-Care Use.

BACKGROUND: Despite increased awareness of eosinophilic esophagitis (EoE), the diagnostic delay has remained stable over the past 3 decades. There is a need to improve the diagnostic performance and optimize resources allocation in the setting of EoE. OBJECTIVE: We developed and validated 2 point-of-care machine learning (ML) tools to predict a diagnosis of EoE before histology results during office visits. METHODS: We conducted a multicenter study in 3 European tertiary referral centers for EoE. We built predictive ML models using retrospectively extracted clinical and esophagogastroduodenoscopy (EGDS) data collected from 273 EoE and 55 non-EoE dysphagia patients. We validated the models on an independent cohort of 93 consecutive patients with dysphagia undergoing EGDS with biopsies at 2 different centers. Models' performance was assessed by area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV). The models were integrated into a point-of-care software package. RESULTS: The model trained on clinical data alone showed an AUC of 0.90 and a sensitivity, specificity, PPV, and NPV of 0.90, 0.75, 0.80, and 0.87, respectively, for the diagnosis of EoE in the external validation cohort. The model trained on a combination of clinical and endoscopic data showed an AUC of 0.94, and a sensitivity, specificity, PPV, and NPV of 0.94, 0.68, 0.77, and 0.91, respectively, in the external validation cohort. CONCLUSION: Our software-integrated models (https://webapplicationing.shinyapps.io/PointOfCare-EoE/) can be used at point-of-care to improve the diagnostic workup of EoE and optimize resources allocation.

Population-based study reveals new risk-stratification biomarker panel for Barrett's esophagus.

BACKGROUND & AIMS: The risk of progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is low and difficult to calculate. Accurate tools to determine risk are needed to optimize surveillance and intervention. We assessed the ability of candidate biomarkers to predict which cases of BE will progress to EAC or high-grade dysplasia and identified those that can be measured in formalin-fixed tissues. METHODS: We analyzed data from a nested case-control study performed using the population-based Northern Ireland BE Register (1993-2005). Cases who progressed to EAC (n = 89) or high-grade dysplasia ≥ 6 months after diagnosis with BE were matched to controls (nonprogressors, n = 291), for age, sex, and year of BE diagnosis. Established biomarkers (abnormal DNA content, p53, and cyclin A expression) and new biomarkers (levels of sialyl Lewis(a), Lewis(x), and Aspergillus oryzae lectin [AOL] and binding of wheat germ agglutinin) were assessed in paraffin-embedded tissue samples from patients with a first diagnosis of BE. Conditional logistic regression analysis was applied to assess odds of progression for patients with dysplastic and nondysplastic BE, based on biomarker status. RESULTS: Low-grade dysplasia and all biomarkers tested, other than Lewis(x), were associated with risk of EAC or high-grade dysplasia. In backward selection, a panel comprising low-grade dysplasia, abnormal DNA ploidy, and AOL most accurately identified progressors and nonprogressors. The adjusted odds ratio for progression of patients with BE with low-grade dysplasia was 3.74 (95% confidence interval, 2.43-5.79) for each additional biomarker and the risk increased by 2.99 for each additional factor (95% confidence interval, 1.72-5.20) in patients without dysplasia. CONCLUSIONS: Low-grade dysplasia, abnormal DNA ploidy, and AOL can be used to identify patients with BE most likely to develop EAC or high-grade dysplasia.