Endoluminal weight loss and metabolic therapies: current and future techniques

Background The majority of obese patients remain untreated, creating the need for an effective, well-tolerated, safe and appealing therapeutic approach. Endoluminal therapies have the potential to fulfil this unmet clinical need, though traditionally, these approaches mimic the restrictive elements of bariatric surgery but ignore the complex physiologic and neurohormonal mechanisms responsible for bariatric surgeries’ weight-independent reduction in metabolic comorbidities. Hypothesis The overarching hypothesis of this thesis was that although endoluminal gastric space occupying and restrictive interventions result in weight loss, weight-independent improvements in obesity related comorbidities require eradication of the gastric mucosa. Aims The aims of this thesis were to assess the efficacy and safety of the intragastric balloon (IGB) and endoscopic sleeve gastroplasty (ESG), and to evaluate whether gastric mucosal devitalization (GMD) is a potential therapeutic approach to treat patients with obesity. Methods Gastric space occupation and gastric volume reduction were modelled using IGB and ESG, respectively. To evaluate the effects of GMD (without alteration in gastric volume), high fat diet rats were compared to GMD, laparoscopic sleeve gastrectomy (LSG), and sham rats. To determine the translatability of GMD, the feasibility, efficacy and safety of GMD was compared to LSG and sham in a porcine model. Results The clinical research demonstrated that IGBs and ESG result in clinically meaningful weight loss with an acceptable safety profile. However, neither produced improvements in metabolic parameters that were disproportionate to the weight loss observed. GMD resulted in a reduction in body weight and visceral adiposity, improved serum lipid and glucose profiles, and reduced liver lipid content. GMD also resulted in a significant reduction in blood pressure, plasma renin activity and cardiac as well as aortic lipid droplet deposition. In a porcine model, GMD reduced visceral adiposity, with outcomes greater than what would be expected from weight loss alone. Conclusions Weight-independent metabolic improvements can be achieved by selecting the gastric mucosa as a therapeutic target; therefore, endoscopic GMD is a new potential approach for the management of obesity

International multicenter expert survey on endoscopic treatment of upper gastrointestinal anastomotic leaks

Background and study aims: A variety of endoscopic techniques are currently available for treatment of upper gastrointestinal (UGI) anastomotic leaks; however, no definite consensus exists on the most appropriate therapeutic approach. Our aim was to explore current management of UGI anastomotic leaks. Methods: A survey questionnaire was distributed among international expert therapeutic endoscopists regarding management of UGI anastomotic leaks. Results: A total of 44 % of 163 surveys were returned; 69 % were from gastroenterologists and 56 % had > 10 years of experience. A third of respondents treat between 10 and 19 patients annually. Fifty-six percent use fully-covered self-expandable metal stents as their usual first option; 80% use techniques to minimize migration; 4 weeks was the most common reported stent dwell time. Sixty percent perform epithelial ablation prior to over-the-scope-clip placement or suturing. Regarding endoscopic vacuum therapy (EVT), 56 % perform balloon dilation and intracavitary EVT in patients with large cavities but small leak defects. Regarding endoscopic septotomy, 56 % consider a minimal interval of 4 weeks from surgery and 90 % consider the need to perform further sessions. Regarding endoscopic internal drainage (EID), placement of two stents and shorter stents is preferred. Persistent inflammation with clinical sepsis was the definition most commonly reported for endoscopic failure. EVT/stent placement and EVT/EID were the therapeutic options most often chosen in patients with previous oncologic surgery and previous bariatric surgery, respectively. Conclusions: There is a wide variation in the management of patients with UGI anastomotic leaks. Future prospective studies are needed to move from an expert- to evidence- and personalization-based care

New insights into valve-related intramural and intracellular bacterial diversity in infective endocarditis

Aims: In infective endocarditis (IE), a severe inflammatory disease of the endocardium with an unchanged incidence and mortality rate over the past decades, only 1% of the cases have been described as polymicrobial infections based on microbiological approaches. The aim of this study was to identify potential biodiversity of bacterial species from infected native and prosthetic valves. Furthermore, we compared the ultrastructural micro-environments to detect the localization and distribution patterns of pathogens in IE. Material and methods: Using next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the entire bacterial community within a single sample, we investigated the biodiversity of infectious bacterial species from resected native and prosthetic valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the ultrastructural infected valve micro-environment by focused ion beam scanning electron microscopy (FIB-SEM). Results: Biodiversity was detected in 7 of 8 resected heart valves. This comprised 13 bacterial genera and 16 species. In addition to 11 pathogens already described as being IE related, 5 bacterial species were identified as having a novel association. In contrast, valve and blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and did not show any relevant antibiotic resistance. The antibiotics chosen on this basis for treatment, however, did not cover the bacterial spectra identified by our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural distribution patterns of infective bacteria, intracellular localization with evidence of bacterial immune escape mechanisms was identified. Conclusion: The high frequency of polymicrobial infections, pathogen diversity, and intracellular persistence of common IE-causing bacteria may provide clues to help explain the persistent and devastating mortality rate observed for IE. Improved bacterial diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy may result in improved outcomes

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America

Background & Aims Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. Methods We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. Results Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. Conclusions ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions

Advances in the Endoscopic Management of Obesity

Obesity has become a worldwide epidemic with significant impact on quality of life, morbidity, and mortality rates. Over the past two decades, bariatric surgery has established itself as the most effective and durable treatment for patients with obesity and its associated comorbidities. However, despite the use of minimally invasive techniques, bariatric surgery is associated with complications in approximately 15% of patients, has a substantial cost, and is used by only 1% of patients who are eligible. Therefore, there is a need for effective minimally invasive therapies, which will be utilized by the large proportion of obese patients who are in desperate need of treatment but are not receiving any. Endoscopic approaches to the management of obesity have been developed, with the aim of delivering more effective, durable, and safer methods of weight reduction. In this paper, we review currently available and future endoscopic therapies that will likely join the armamentarium used in the management of obesity