Evaluation of a novel cryoballoon swipe ablation system in bench, porcine, and human esophagus models.

Current ablation devices for dysplastic Barrett's esophagus are effective but have significant limitations. This pilot study aims to evaluate the safety, feasibility, and dose response of a novel cryoballoon swipe ablation system (CbSAS) in three experimental in vitro and in vivo models. CbSAS is a through-the-scope compliant balloon that is simultaneously inflated and cooled by liquid nitrous oxide delivered from a disposable handheld unit. When the cryogen is applied through a special diffuser it covers a 90° section of the circumference of the esophagus for 3 cm length. Doses range from 0.9 to 0.5 mm/second. (1) Bench model: The fixture consisted of an 'esophagus-like' tube lined with agar at 37°C to create an inner diameter of 20 or 30 mm, within which thermocouples were embedded. (2) In vivo porcine esophagus: CbSAS ablations were performed in animals that were euthanized and histological assessments of depth and percentage of esophageal mucosa successfully ablated were done. (3) In vivo, pre-esophagectomy human esophagus. After CbSAS ablations, histological assessments were performed (at 0, 4, and 28 days) to assess the depth and percentage of ablated mucosa. As outcomes, we assessed the safety and tolerability (pain and serious, device-related adverse events); efficacy (depth and uniformity) of ablation; and device performance (ease of deployment and device malfunction). In the bench model, during CbSAS, thermocouples measured minimal temperatures of -40 to -48 °C at all doses. In the porcine model, maximal effect on the mucosa was reached with a dose of 0.8 mm/second that extended to superficial submucosa, while 0.5 mm/second extended through the submucosa. All animals tolerated the treatments and, regardless of ablation dose, continued oral intake and gained weight. In the human model, six patients (5 male, 1 female, mean age 68) tolerated the procedure without adverse events. CbSAS was simple to operate, and balloon contact with tissue was easily and uniformly maintained. The maximal effect on the mucosa is achieved with a 0.8 mm/second dose. We concluded that the CbSAS device enables uniform 3 cm long, quarter-circumferential mucosal ablation in a one-step process by using a novel, through-the-scope balloon. The CbSAS delivers predictable ablation with mucosal and limited submucosal necrosis in bench, animal, and human esophagus. Because of its ease of use, this new device merits further clinical study in the treatment of patients with dysplastic Barrett's esophagus.

The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Ineffective esophageal motility: clinical, manometric, and outcome characteristics in patients with and without abnormal esophageal acid exposure.

The etiology and clinical impact of ineffective esophageal motility (IEM) remain poorly understood. Unless gastroesophageal acid reflux (GERD) is identified, symptomatic patients with IEM are challenging to treat. We sought to determine whether any clinical or functional characteristics could distinguish those patients with IEM and either normal or abnormal esophageal acid exposure.In this retrospective cohort study, we identified 46 consecutive patients presenting with heartburn, and other GER symptoms who underwent clinical, endoscopic, and functional evaluation that included high-resolution manometry (HRM) and ambulatory pH monitoring. IEM was defined using the Chicago Classification criteria (v.3) as ≥50% ineffective swallows (DCI ≤ 450 mmHg.s.cm). Esophageal acid exposure by ambulatory pH monitoring was considered abnormal when total time with esophageal pH < 4 exceeded 4.2%.Of the 46 IEM patients identified, 19 (mean age: 42 years, 37% female), had normal esophageal acid exposure and 27 patients, mean age 54 years, 33% female, evidence of pathologic acid reflux. There was a 12 years age difference between the groups, with those with normal acid exposure being significantly younger (P < 0.01); the mean body mass index (BMI) was 22.6 ± 0.6 in the normal group and 25.4 ± 0.7 in the abnormal group (P < 0.001); otherwise the groups were endoscopically and histologically similar. Symptoms were not discriminatory and heartburn and regurgitation were the most prevalent in both groups. HRM did not discriminate symptomatic patients with IEM and either normal or abnormal esophageal acid exposure. Proton pump inhibition (PPI) therapy was significantly more effective (74% vs. 10%) in patients with pathologic acid reflux (P < 0.001). As pH exposure becomes abnormal in the context of IEM, there is dominance for supine reflux.IEM appears to be an early, primary event, eventually associated with pathologic acid exposure, particularly supine. Higher BMI is also associated with abnormal esophageal acid exposure in such patients. GER symptoms are not discriminatory in patients with IEM with and without underlying pathologic acid reflux. Clinical response to PPI in such patients depends on the presence of esophageal pathologic acid exposure. Those with IEM and normal acid exposure remain symptomatic and mostly resistant to therapy.

Precision GERD management for the 21st century.

The highly heterogeneous nature of gastroesophageal reflux disease (GERD), together with the multiplicity of available diagnostic and therapeutic options (lifestyle, pharmacologic, endoscopic and surgical) available today call for a new approach that funnels the multidimensionality of the disease into precise and effective algorithms - reviewed herein- aimed at improving clinical outcomes.

Whole greater than the parts: integrated esophageal centers (IEC) and advanced training in esophageal diseases.

An integrated esophageal center (IEC) is a multidisciplinary team with expertise, skill, range, and facilities necessary to achieve optimal outcomes in patients with esophageal diseases efficiently and expeditiously. Within IEC, patients presenting with esophageal symptoms undergo a detailed clinical, functional and structural evaluation of their esophagus prior to implementation of tailored medical, endoscopic or surgical therapy. Serving as a core, the IEC clinical practice also supports research and innovation in esophageal diseases as well as public and physician education. Referrals to the unit may be primary, either from primary care or self-initiated, or secondary from other specialty practices, to reassess patients who have previously failed therapies and to manage complex or complicated cases. The fundamental goals of the IEC are to provide value for patients with esophageal diseases, streamlining complex diagnostic investigations and expediting therapies aiming at reducing costs while improving clinical outcomes, and to accelerate knowledge generation through robust interaction and cross-training across disciplines. The organization of the IEC goes beyond traditional academic and clinical silos and involves a director and administrative team coordinating faculty and fellows from both medical and surgical disciplines and supported by other clinical lines, such as radiology, pathology, etc., while it interfaces with physicians, the public, basic, translational and clinical research groups, and related industry partners.

Clinical and manometric characteristics of patients with Parkinson's disease and esophageal symptoms.

Dysphagia is a common problem in patients with Parkinson's disease (PD); its etiology is multifactorial and its management is challenging. In this retrospective cohort analysis using prospectively collected data, we aimed to objectively characterize dysphagia and/or other esophageal symptoms in patients with PD, assess the prevalence of outflow obstruction as well as major or minor disorders of esophageal peristalsis leading to impaired esophageal clearance and highlight objective parameters that can help in the current management algorithm. Thirty-three consecutive patients with PD presenting with dysphagia, odynophagia, heartburn, regurgitation, chest pain, and weight loss underwent clinical and functional evaluation by high-resolution manometry (HRM). Esophagogastric junction (EGJ) outflow obstruction and major as well as minor disorders of peristalsis were then assessed using the Chicago classification (v3). Thirty-three PD patients with esophageal symptoms were enrolled in the study; 12 of them reported weight loss that was considered as potentially reflecting underlying esophageal dysfunction. The median age of the patients was 70 years (range: 53-89 years), 24 (75%) were men. The majority (62%) experienced dysphagia, likely contributing to weight loss in 41% of patients. Odynophagia was rare (6%) while GER symptoms, such as heartburn, regurgitation, and chest pain were noted in 37%, 31%, and 28% of patients, respectively. Using the hierarchy of the Chicago classification, 12 patients (39%) exhibited EGJ outflow obstruction, 16 (48%) diffuse esophageal spasm (DES), 18 (55%), ineffective esophageal peristalsis (IEM), 16 (48%) fragmented peristalsis, and only 2 patients (6%) had normal HRM tracings. There were no patients with HRM features of achalasia. Dysphagia is common in patients with PD and is associated with a high prevalence of underlying motility disturbances as identified by HRM. The exact impact of these motility abnormalities on symptom induction and their role in influencing clinical management are unclear and will require further study.

Balloon-based esophageal cryoablation with a novel focal ablation device: dose-finding and safety in porcine and human models.

The new Cryoballoon Focal Ablation System (CbFAS), a through-the-scope catheter with battery-powered handle that delivers cryogenic fluid into an inflated balloon, differs from current cryotherapy methods used for treatment of Barrett's epithelium. In this dose-finding study, short- and long-term histopathological effects and safety of the CbFAS were evaluated. Cryoablations with (supra)therapeutic durations (4-24 seconds) were performed in pigs that survived for 12 or 48 hours or 4 or 28 days. Next, cryoablations (durations based on animal data) were performed in normal mucosa of esophageal cancer patients scheduled to undergo esophagectomy. The outcome parameters, the occurrence of any bleeding or perforation, the histological presence of edema, inflammation, and necrosis throughout the esophageal wall layers, were evaluated. A total of 60 cryoablations were performed in 11 pigs. 48 hour cryoablations with therapeutic durations (4-10 seconds) resulted in edema/inflammation as deep as the serosa and necrosis ranging from submucosa to serosa with a median depth of 3.2 mm. In 4 day cryoablations this was in the serosa, and muscularis tunica to serosa at a median depth of 4.5 mm, respectively. No necrosis or inflammation remained after 28 days, not even after supratherapeutic cryoablation (12-24 seconds). No acute or delayed bleeding or perforation was observed. Next, eight 6-second cryoablations were performed in four patients. Direct postablation mucosal necrosis was observed; after 4 days necrosis and inflammation was limited to the submucosa. CbFAS cryoablation penetrates deeply into the esophageal wall layers resulting in severe early ablation. After 4 weeks, little injury and no fibrosis remain, even after supratherapeutic durations of administration, suggesting that CbFAS combines deep ablation with a potentially favorable safety profile.

Evaluation and management of patients with symptoms after anti-reflux surgery.

Over the past two decades, there has been an increase in the number of anti-reflux operations being performed. This is mostly due to the use of laparoscopic techniques, the increasing prevalence of gastroesophageal reflux disease (GERD) in the population, and the increasing unwillingness of patients to take acid suppressive medications for life. Laparoscopic fundoplication is now widely available in both academic and community hospitals, has a limited length of stay and postoperative recovery time, and is associated with excellent outcomes in carefully selected patients. Although the operation has low mortality and postoperative morbidity, it is associated with late postoperative complications, such as gas bloat syndrome, dysphagia, diarrhea, and recurrent GERD symptoms. This review summarizes the diagnostic evaluation and appropriate management of such postoperative complications. If a reoperation is needed, it should be performed by experienced foregut surgeons.

Multimodality evaluation of patients with gastroesophageal reflux disease symptoms who have failed empiric proton pump inhibitor therapy.

Patients with symptoms suggestive of gastroesophageal reflux disease (GERD), such as chest pain, heartburn, regurgitation, and dysphagia, are typically treated initially with a course of proton pump inhibitors (PPIs). The evaluation of patients who have either not responded at all or partially and inadequately responded to such therapy requires a more detailed history and may involve an endoscopy and esophageal biopsies, followed by esophageal manometry, ambulatory esophageal pH monitoring, and gastric emptying scanning. To assess the merits of a multimodality 'structural' and 'functional' assessment of the esophagus in patients who have inadequately controlled GERD symptoms despite using empiric PPI, a retrospective cohort study of patients without any response or with poor symptomatic control to empiric PPI (>2 months duration) who were referred to an Esophageal Studies Unit was conducted. Patients were studied using symptom questionnaires, endoscopy (+ or - for erosive disease, or Barrett's metaplasia) and multilevel esophageal biopsies (eosinophilia, metaplasia), esophageal motility (aperistalsis, dysmotility), 24-hour ambulatory esophageal pH monitoring (+ if % total time pH < 4 > 5%), and gastric emptying scanning (+ if >10% retention at 4 hours and >70% at 2 hours). Over 3 years, 275 patients (147 men and 128 women) aged 16-89 years underwent complete multimodality testing. Forty percent (n= 109) had nonerosive reflux disease (esophagogastroduodenoscopy [EGD]-, biopsy-, pH+); 19.3% (n= 53) had erosive esophagitis (EGD+); 5.5% (n= 15) Barrett's esophagus (EGD+, metaplasia+); 5.5% (n= 15) eosinophilic esophagitis (biopsy+); 2.5% (n= 7) had achalasia and 5.8% (n= 16) other dysmotility (motility+, pH-); 16% (n= 44) had functional heartburn (EGD-, pH-), and 5.8% (n= 16) had gastroparesis (gastric scan+). Cumulative symptom scores for chest pain, heartburn, regurgitation, and dysphagia were similar among the groups (mean range 1.1-1.35 on a 0-3 scale). Multimodality evaluation changed the diagnosis of GERD in 34.5% of cases and led to or guided alternative therapies in 42%. Overlap diagnoses were frequent: 10/15 (67%) of patients with eosinophilic esophagitis, 12/16 (75%) of patients with gastroparesis, and 11/23 (48%) of patients with achalasia or dysmotility had concomitant pathologic acid reflux by pH studies. Patients with persistent GERD symptoms despite empiric PPI therapy benefit from multimodality evaluation that may change the diagnosis and guide therapy in more than one third of such cases. Because symptoms are not specific and overlap diagnoses are frequent and multifaceted, objective evidence-driven therapies should be considered in such patients.

The Kagoshima consensus on esophageal achalasia.

Esophageal achalasia is a primary esophageal motility disorder characterized by lack of peristalsis and a lower esophageal sphincter that fails to relax appropriately in response to swallowing. This article summarizes the most salient issues in the diagnosis and management of achalasia as discussed in a symposium that took place in Kagoshima, Japan, in September 2010 under the auspices of the International Society for Diseases of the Esophagus.