Learning curves and the influence of procedural volume for the treatment of dysplastic Barrett's esophagus

BACKGROUND AND AIMS: Endoscopic resections (ER) and radiofrequency ablation (RFA) are the established treatments for Barrett's-associated dysplasia and early esophageal neoplasia. The UK RFA Registry collects patient outcomes from 24 centers in the United Kingdom and Ireland treating patients. Learning curves for treatment of Barrett's dysplasia and the impact of center caseload on patient outcomes is still unknown. METHODS: We examined outcomes of 678 patients treated with RFA in the UK Registry using risk-adjusted CUSUM plots to identify change points in complete resolution of intestinal metaplasia (CR-IM) and complete resolution of dysplasia (CR-D) outcomes. We compared outcomes between those treated at high- (>100 enrolled patients), medium- (51-100) and low- (<50) volume centers. RESULTS: There was no association between center volume and CR-IM and CR-D rates, but there were lower recurrence rates in high-volume versus low-volume centers (Log Rank p=0.001).There was a significant change-point for outcomes at 12 cases for CR-D (reduction from 24.5% to 10.4%; P<0.001) and at 18 cases for CR-IM (30.7% to 18.6%; P<0.001) from RA-CUSUM curve analysis. CONCLUSION: Our data suggest that 18 supervised cases of endoscopic ablation may be required before competency in endoscopic treatment of Barrett's dysplasia can be achieved. The difference in outcomes between a high-volume and low-volume center does not support further centralization of services to only high-volume centers

Bariatric and Metabolic Endoscopy: A New Paradigm.

The prevalence of obesity, type 2 diabetes mellitus, and metabolic syndromes is increasing globally. Minimally invasive metabobariatric (MB) endoscopic therapies are adjunct treatments that can potentially bridge the gap between surgical interventions and medical therapy. A growing number of MB techniques are becoming available, allowing for more personalized and patient-targeted treatment options for specific disease states. MB techniques are less invasive than surgery and can precisely target different parts of the gastrointestinal tract that may be responsible for the pathophysiology of obesity and metabolic syndromes such as type 2 diabetes mellitus. These alternatives should be selected on an individualized patient basis to balance the expected clinical outcomes and desired anatomical targets with the level of invasiveness and degree of acceptable risk. Each MB intervention presents great flexibility allowing for a tailored intervention and different levels of patient engagement. Patient awareness and motivation are essential to avoid therapy withdrawal and failure. Differences between MB procedures in terms of weight loss and metabolic benefit will be discussed in this review, along with the insights on clinical decision-making processes to evaluate the potential of further evolution and growth of bariatric and metabolic endoscopy

Abnormal Chest X-Ray Leading to Diagnosis of Partial Anomalous Pulmonary Venous Connection

With the growing use of imaging to aid in both diagnosis and treatment of patients presenting with a myriad of clinical presentations, incidental findings on imaging have become commonplace. Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital cardiovascular condition that often goes undiagnosed due to lack of symptoms early in life. In adulthood, it can manifest clinically as right-sided heart failure or pulmonary hypertension. We present a case of PAPVC, which, like most cases, was discovered incidentally on chest X-ray

A roadmap to develop dementia research capacity and capability in Pakistan: a model for low- and middle-income countries

Objective To produce a strategic roadmap for supporting the development of dementia research in Pakistan. Background While global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan. Methods We undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan. This included Expert Reference Groups (ERGs), strategic planning techniques, a “research question” priority survey, and consultations with Key Opinion Leaders. Results We agreed on ten principles to guide dementia research in Pakistan, emphasizing pragmatic, resource sparing, real-world approaches to support people with dementia, both locally and internationally. Goals included capacity/capability building. Priority research topics included raising awareness and understanding of dementia, and improving quality of life. Conclusion This roadmap may be a model for other LMIC health ecosystems with emerging dementia research cultures

A Nevus of OTA with Intraoral Involvement: A Rare Case Report

Nevus of Ota, which originally was described by Ota and Tanino in 1939. It is characterized as congenital or acquired hamartoma of dermal melanocytes, presents clinically as a blue or gray patch on the face within the distribution of the ophthalmic and maxillary branches of the fifth cranial (trigeminal) nerve. Involvement of the palatal mucosa occurs rarely in nevus of Ota, when it occurs, it usually blends with the oral mucosa and is typically irregular, ill defined and often present as a mottled patch. Nevus of Ota is rare in the Indian subcontinent. So far very less cases of nevus of ota with intraoral involvement have been documented in the English literature. We report a rare case of intraoral nevus of Ota in a 20 year-old female patient

The cost-effectiveness of radiofrequency ablation for treating patients with gastric antral vascular ectasia refractory to first line endoscopic therapy

OBJECTIVE: This economic evaluation aims to provide a preliminary assessment of the cost-effectiveness of radiofrequency ablation (RFA) compared with argon plasma coagulation (APC), when used to treat APC-refractory gastric antral vascular ectasia (GAVE) in symptomatic patients.METHODS: A Markov model was constructed to undertake a cost-utility analysis for adults with persistent symptoms secondary to GAVE refractory to first line endoscopic therapy. The economic evaluation was conducted from a UK NHS and personal social services (PSS) perspective, with a 20-year time horizon, comparing RFA with APC. Patients transfer between health states defined by haemoglobin level. The clinical effectiveness data were sourced from expert opinion, resource use and costs were reflective of the UK NHS and benefits were quantified using Quality Adjusted Life Years (QALYs) with utility weights taken from the literature. The primary output was the Incremental Cost-Effectiveness Ratio (ICER), expressed as cost per QALY gained.RESULTS: Over a lifetime time horizon, the base case ICER was £4,840 per QALY gained with an 82.2% chance that RFA was cost-effective at a threshold of £20,000 per QALY gained. The model estimated that implementing RFA would result in reductions in the need for intravenous iron, endoscopic intervention and requirement for blood transfusions by 27.1%, 32.3% and 36.5% respectively. Compared to APC, RFA was associated with an estimated 36.7% fewer procedures.CONCLUSIONS: RFA treatment is likely to be cost-effective for patients with ongoing symptoms following failure of first line therapy with APC and could lead to substantive reductions in health care resource

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

Utility and Cost-Effectiveness of a Nonendoscopic Approach to Barrett's Esophagus Surveillance After Endoscopic Therapy

BACKGROUND & AIMS: A non-endoscopic approach to Barrett's esophagus (BE) surveillance after radiofrequency ablation (RFA) would offer a less invasive method for monitoring. We assessed the test characteristics and cost-effectiveness of the Cytosponge® in post-RFA patients. METHODS: We performed a multicenter study of dysplastic BE patients after at least one round of RFA. A positive Cytosponge® before endoscopy was defined as intestinal metaplasia (IM) on cytological assessment and/or TFF3 immunohistochemistry. Sensitivity, specificity, and receiver operator characteristic (ROC) curves were calculated. Multivariable regression was used to estimate the odds of a positive Cytosponge® in BE. A microsimulation cost-effectiveness model was performed to assess outcomes of various surveillance strategies: endoscopy-only, Cytosponge®-only, and alternating endoscopy/Cytosponge®. RESULTS: Of 234 patients, Cytosponge® adequately sampled the distal esophagus in 175 (75%). Of the 142 with both endoscopic and histologic data, 19 (13%) had residual/recurrent BE. For detecting any residual Barrett's, Cytosponge® had a sensitivity of 74%, specificity of 85%, accuracy of 84%, and ROC curve showed an area under the curve of 0.74. The adjusted odds of a positive Cytosponge® in BE were 17.1 (95% CI: 5.2-55.9). Cytosponge®-only surveillance dominated all the surveillance strategies, being both less costly and more effective. Cytosponge®-only surveillance required <1/4th the endoscopies, resulting in only 0.69 additional EAC cases/1,000 patients, and no increase in EAC deaths when compared to currently-practiced endoscopy-only surveillance. CONCLUSIONS: A positive Cytosponge® test was strongly associated with residual BE after ablation. While the assay needs further refinement in this context, it could serve as a cost-effective surveillance examination

The natural history of low-grade dysplasia in Barrett's esophagus and risk factors for progression

Background and Aim: Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma. The optimal management of low-grade dysplasia arising in Barrett's esophagus remains controversial. We performed a retrospective study from a tertiary referral center for Barrett's esophagus neoplasia, to estimate time to progression to high-grade dysplasia/esophageal adenocarcinoma in patients with confirmed low-grade dysplasia compared with those with downstaged low-grade dysplasia from index presentation and referral. We analyzed risk factors for progression. Methods: We analyzed consecutive patients with low-grade dysplasia in Barrett's esophagus referred to a single tertiary center (July 2006–October 2018). Biopsies were reviewed by at least two expert pathologists. Results: One hundred and forty-seven patients referred with suspected low-grade dysplasia were included. Forty-two of 133 (32%) of all external referrals had confirmed low-grade dysplasia after expert histopathology review. Multivariable analysis showed nodularity at index endoscopy (P < 0.05), location of dysplasia (P = 0.05), and endoscopic therapy after referral (P = 0.09) were associated with progression risk. At 5 years, 59% of patients with confirmed low-grade dysplasia had not progressed versus 74% of patients in the cohort downstaged to non-dysplastic Barrett's esophagus. Conclusion: Our data show variability in the diagnosis of low-grade dysplasia. The cumulative incidence of progression and time to progression varied across subgroups. Confirmed low-grade dysplasia had a shorter progression time compared with the downstaged group. Nodularity at index endoscopy and multifocal low-grade dysplasia were significant risk factors for progression. It is important to differentiate these high-risk subgroups so that decisions on surveillance/endotherapy can be personalized

The Clinical Relevance of Manometric Esophagogastric Junction Outflow Obstruction Can Be Determined Using Rapid Drink Challenge and Solid Swallows

INTRODUCTION: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO. METHODS: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated. RESULTS: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02). DISCUSSION: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol