Opinion Review Open Access
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2019; 25(32): 4567-4579
Published online Aug 28, 2019. doi: 10.3748/wjg.v25.i32.4567
New Era: Endoscopic treatment options in obesity–a paradigm shift
Jason Glass, Zeeshan Ramzan, Department of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Ahson Chaudhry, Muhammad S Zeeshan, Zeeshan Ramzan, Division of Gastroenterology and Hepatology, Department of Medicine, Dallas VA Medical Center, VA North Texas Health Care System, Dallas, TX 75216, United States
Ahson Chaudhry, School of Medicine, Temple University Hospital, Philadelphia, PA 19140, United States
ORCID number: Jason Glass (0000-0002-5185-0182); Ahson Chaudhry (0000-0001-9307-4823); Muhammad Shehroz Zeeshan (0000-0001-6552-0355); Zeeshan Ramzan (0000-0003-2989-8304).
Author contributions: Glass J was responsible for review of the literature, manuscript writing, and figure/table generation; Chaudhry A and Zeeshan MS were responsible for collecting reference articles, manuscript writing and figure/table generation; Ramzan Z provided expertise in the field of gastrointestinal endoscopy, manuscript writing and editing, and designing the aims of the manuscript.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest.
Open-Access: This article is an open-access article which was selected byan in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zeeshan Ramzan, MD, FACP, FACG, FASGE, Assistant Professor, Division of Gastroenterology and Hepatology, Department of Medicine, Dallas VA Medical Center, VA North Texas Health Care System, 4500 South Lancaster Road, Dallas, TX 75216, United States. zeeshanramzan@hotmail.com
Telephone: +1-214-8571603 Fax: +1-214-4624842
Received: March 29, 2019
Peer-review started: March 29, 2019
First decision: June 10, 2019
Revised: July 30, 2019
Accepted: August 7, 2019
Article in press: August 7, 2019
Published online: August 28, 2019

Abstract

The prevalence of obesity continues to rise, and along with it comes a multitude of health-related consequences. The healthcare community has consistently struggled with providing treatment options to obese patients, in part due to the reluctance of patients in pursuing the more effective (yet invasive) surgical approaches such as sleeve gastrectomy and Rou-en-Y gastric bypass. On the other hand, the less invasive approach such as lifestyle/behavioral interventions and pharmacotherapy (Orlistat, Phenteramine, Phentermine/Topiramate, Locaserin, Naltrexon/Buproprion, and Liraglutide) have very limited efficacy, especially in the morbidly obese patients. Despite our best efforts, the epidemic of obesity continues to rise and pose enormous costs on our healthcare system and society. Bariatric endoscopy is an evolving field generated to combat this epidemic through minimally invasive techniques. These procedures can be performed in an ambulatory setting, are potentially reversible, repeatable, and pose less complications than their invasive surgical counterparts. These modalities are designed to alter gut metabolism by means of space occupation, malabsorption, or restriction. In this review we will discuss different bariatric endoscopic options (such as intragastric balloons, endoscopic sleeve gastroplasty, endoscopic aspiration therapies and gastrointestinal bypass sleeves), their advantages and disadvantages, and suggest a new paradigm where providers may start incorporating this modality in their treatment approach for obese patients.

Key Words: Bariatric endoscopy, Bariatrics, Obesity, Intragastric balloon, Bariatric medicine, AspireAssist, Endoscopic sleeve gastroplasty

Core tip: The prevalence of obesity has risen to an alarming level. The associated morbidity and mortality of this epidemic affects the community and health related economics directly. Current options include lifestyle modifications, pharmacotherapy, and surgery; the latter being the most effective, however most invasive and prone to complications. Bariatric endoscopy, with methods including intragastric balloons, sleeve gastroplasty, and aspiration techniques, provides an effective and less invasive option for weight loss in obese patients.



INTRODUCTION

The prevalence of obesity has seen a drastic increase over the last thirty years, now approaching 35% in men and 40% in women[1]. Obesity has been associated with a multitude of adverse health outcomes including all cause cardiovascular mortality, diabetes, hyperlipidemia, and all-cause mortality[2]. Lifestyle modifications, pharmacological agents, and surgical options are all amongst the myriad treatments in obesity.

Lifestyle modifications, despite being the least expensive and less invasive, have been shown to be the least successful of the options. Intensive behavioral in-terventions (such as identifying barriers, self-monitoring of weight, peer support, etc.) with a combination of dietary changes and increased physical activity over multiple sessions can result in > 5% weight loss in adults with obesity. Hence, US Preventive Services Task Force recommends that clinicians offer or refer adults with a body mass index (BMI) of 30 or higher to intensive, multicomponent behavioral interventions (grade B recommendation)[3].

Pharmacological agents currently Food and Drug Administration (FDA) approved for weight loss include Orlistat, Phenteramine, Phentermine/Topiramate, Locaserin, Naltrexon/Buproprion, and Liraglutide[4]. These agents have been approved for patients with a BMI of ≥ 27 kg/m2 with one obesity related complication or patients with a BMI of ≥ 30 kg/m2. They have shown modest benefits for weight loss with an estimate weight loss of 3%-7% efficacy compared with placebo. At 12 to 18 mo, participants in pharmacotherapy-based weight loss trials (32 trials) had more weight loss compared with placebo groups [mean or least squares mean difference in weight change, -1.0 kg (-2.2 lb) to -5.8 kg (−12.8 lb)][5]. Participants also experienced a greater decrease in waist circumference and a greater likelihood of losing 5% of their initial weight compared with placebo groups. Three pharmacotherapy-based weight loss maintenance trials showed that participants receiving the intervention had better weight loss maintenance compared with placebo groups over 12 to 36 mo (mean difference, -0.6 to -3.5 kg)[6]. Although these options have shown promise, along with some intolerable side effects, their longstanding efficacy has not been particularly encouraging[7].

For patients with BMI ≥ 40 or BMI ≥ 35 with comorbidity, referral to an experienced bariatric surgeon should be considered. To date, bariatric surgery has shown the most dramatic results in treatment of obesity. Current literature has shown this treatment to be lasting and effective, with improvement of obesity related co-morbidity. Despite these advantages, bariatric surgery poses several disadvantages. As with all procedures, bariatric surgery comes with possible complications, the most common including anastomotic ulceration, anastomotic stenosis, gastro-gastric fistulas, surgical leaks, intestinal obstruction, and choledocholithiasis[8]. In addition, the process of undergoing bariatric surgery is complex, requiring multiple physician visits over a prolonged period of time. As a result, only < 1% of all eligible patients actually undergo bariatric surgery[9]. A detailed discussion of various surgical options, advantages and disadvantages, adverse effect profile, etc. is beyond the scope of this article. A brief overview has been summarized in Figure 1.

Figure 1
Figure 1 Common bariatric surgical procedures. A: Rou-en-Y gastric bypass; B: Adjustable gastric band; C: Sleeve gastrectomy; D: Biliopancreatic diversion with duodenal switch. Reprinted from “Nguyen NT, Varela JE. Bariatric surgery for obesity and metabolic disorders: State of the art. Nat Rev Gastroenterol Hepatol 2017; 14: 160-169”. With permission from RightsLink.

Given the limited efficacy of lifestyle/behavioral interventions and pharmacotherapy, as well as the barriers associated with bariatric surgery, new therapies must be discovered to handle the growing population of obese patients. In this review, we introduce bariatric endoscopy as a methodology and tool that physicians may start incorporating in their treatment algorithms for management of obesity (Figure 2).

Figure 2
Figure 2 A step wise approach to obesity management. A shift in the paradigm of current trends of obesity. The authors of this manuscript suggest that bariatric endoscopy should be incorporated in the armamentarium of obesity treatment, with the potential of using each modality in combination (when clinically feasible).
BARIATRIC ENDOSCOPY

Bariatric endoscopy is an innovative technology designed to mimic weight loss surgery without the associated co-morbidities. There are several modalities used in endoscopic bariatrics, each with its own physiologic method behind weight loss. These include malabsorption techniques, use of space occupying devices, restrictive methods, and aspiration therapies. In this section we will discuss three forms of bariatric endoscopy including intragastric balloon (IGB) therapy, endoscopic sleeve gastroplasty (ESG), and aspiration techniques (AspireAssist). Further we will discuss other small bowel therapies currently in clinical trial. Figure 3 illustrates a summary of all FDA approved and non-FDA approved bariatric endoscopic modalities, whereas Table 1 summarizes an overview of the commonly used modalities in the world of bariatrics.

Table 1 A summary of currently available non-lifestyle modalities in bariatric medicine.
Treatment optionsIndicationDurationEfficacyAdvantagesDisadvantages
Pharmacological methodsBMI of ≥ 27 kg/m2 with one obesity related complication or patients with a BMI of ≥ 30 kg/m2Varies depending on the agent2%-10% weight loss depending on the agent[33]Mild to moderately effectiveAdverse side effect profile dependent on the medication
Non-invasive
ReusableNo evidence for long term effectiveness
Intragastric BalloonsBMI between 30 and 40 kg/m26 mo%TBWL 7%-15%ReversibleHigh rates of nausea and vomiting
%EWL 30%-47%Repeatable
At 6 mo duration[34]Can be used in combination of other modalitiesSome reports of gastric perforation in rare cases
Aspiration therapyBMI of 35-55 kg/m2Long term duration%TBWL 14%-18%EffectiveMust see doctors at scheduled intervals
%EWL 37-54%Minimal side effects
From 6-24 mo[35]Long duration of useAbdominal pain, peristomal complications
Endoscopic GastroplastyBMI between 30 and 40 kg/m2Long term follow-up studies in progress%TBWL 12%-19%Adaptive new technology with a lot of promiseRequires expertise and technical skills
At 6-24 mo duration[35]Minimally invasivePerigastric fluid collections, extragastric bleeding
Lap BandBMI of 35 kg/m2 with obesity related complications or BMI of 40 kg/m2ReversibleMean percentage weight loss at 5 yr was 15.9 ± 12.4%[35]Sustained weight loss at 5 yrNeed for explant up to 12% Vomiting, nausea, dysphagia, GERD
Improvements in hgb a1c, cholesterol
Sleeve gastrectomyBMI of 35 kg/m2 with obesity related complications or BMI of 40 kg/m2Permanent, but can be bridged to RYGB49%EWL at 5 yr[36]Long term sustained weight lossSignificant adverse events
Cardiometabolic risk factor modifying; hyperlipidemia, diabetesOverall morbidity rate of 19% at 5 yr
RYGBBMI of 35 kg/m2 with obesity related complications or BMI of 40 kg/m2Permanent57%EWL at 5 yr[36]Long term sustained weight lossSignificant adverse events related to surgery
Cardiometabolic risk factor modifying; hyperlipidemia, diabetesOverall morbidity rate of 26% at 5 yr
Figure 3
Figure 3 A summary of bariatric endoscopic techniques. EBTs: Endoscopic bariatric treatments; GI: Gastrointestinal; ESG: Endoscopic sleeve gastroplasty; IGB: Intragastric balloon. Reprinted from “ASGE Bariatric Endoscopy Task Force; ASGE Technology Committee, Abu Dayyeh BK, Edmundowicz SA, Jonnalagadda S, Kumar N, Larsen M, Sullivan S, Thompson CC, Banerjee S. Endoscopic bariatric therapies. Gastrointest Endosc 2015; 81: 1073-1086”. With permission from Elsevier.
SPACE OCCUPYING TECHNIQUES
Intragastric balloon

IGBs were first introduced in the United States in 1985 as the Garren-Edwards gastric bubble which was made of polyurethane and filled with 200-220cc of air[10]. This balloon gave way for the three IGBs which are currently FDA approved for use. These include the Orbera IGB (Apollo Endosurgery, Austin, TX, United States), the ReShape Duo (ReShape Medical, San Clemente, CA, United States), and the most recent Obalon IGB (Obalon Therapeutics, Inc, Carlsbad, CA, United States). The balloons act as space-occupying device thereby inducing early satiety leading to weight reduction and altering gut neuroendocrinology[11]. Each balloon has been approved for a 6 mo duration for those with a BMI between 30 to 40 mg/kg2 who have failed lifestyle modifications[12]. The most common complication of the IGBs include nausea (29%) and pain (33.7%), which are usually self-limited. Other rare side effects include small bowel obstruction, perforation, and death at rates of 0.3%, 0.1%, and 0.08%, respectively[13].

Orbera balloon

The Orbera balloon is an elastic spherical balloon made of silicone. It is inserted in the stomach blindly via transoral advancement on a preloaded catheter. An endoscope is advanced to confirm correct placement, after which the balloon is injected with 450-700 mL of normal saline mixed with methylene blue. The methylene blue provides a marker for balloon malfunction. If the balloon ruptures, the methylene blue will be systemically absorbed and change the color of urine to blue, prompting the patient to seek medical attention. Pain and nausea are frequent side effects of Orbera IGB implantation, occurring in about 33.7% of subjects, with serious side effects being balloon migration and gastric perforation of 1.4% and 0.1%, respectively.

Orbera has shown efficacy in several trials. It has been used in other countries for many years before being approved by FDA for use in the United States in 2015. Based on a large meta-analysis of 17 studies, the percentage of excess weight loss (%EWL) with the Orbera IGB at 12 mo was 25.44% and total body weight loss (%TBWL) was 12.3% 13.16%, and 11.27% at 3, 6, and 12 mo after implantation, respectively[13,14]. In a recent multicenter, randomized, open-label clinical trial, 255 adults with a BMI of 30-40 kg/m2 were treated and outcomes were assessed up to 12 mo. Patients were randomized to IGB (Obera) plus lifestyle modifications (n = 125) vs lifestyle modification alone (control; n = 130). Balloons were removed at 6 mo and lifestyle intervention continued for both groups through 12 mo. At 6 mo, weight loss was -3.3% (-3.2 kg) in the lifestyle modification arm vs -10.2 % (-9.9 kg) in the balloon plus lifestyle intervention arm (P < 0.001); at 9 mo (3 mo post balloon removal), weight loss was -3.4% (-3.2 kg) vs -9.1% (-8.8 kg, P < 0.001); and at 12 mo, -3.1% (-2.9 kg) vs -7.6% (-7.4 kg, P < 0.001). The authors concluded that IGB was more successful than life style modifications alone in achieving short term weight loss at 9 mo (3 mo post balloon removal) and 12 mo (6 mo post balloon removal.) The study lacked the long term follow up needed to determine effectiveness on diabetes, hyperlipidemia, and cardiovascular outcomes[15]. IGBs have now been studied in conjunction with bariatric surgery, with a more recent study showing the Orbera balloon plus bariatric surgery [Roux-en-Y gastric bypass (RYGB)/Sleeve gastrectomy] to be more effective in the super obese (BMI > 50 kg/m2) than either alone[16].

The ReShape Duo

The ReShape Duo (ReShape Medical, San Clemente, CA, United States) is another type of IGB with two balloons attached to each other by flexible tube. Each balloon requires about 450 mL of saline solution (mixed with methylene blue). This unique shape enables one balloon to continue working as a space occupying device even if the other balloon gets deflated spontaneously. Initial data on the efficacy of ReShape Duo balloon has shown promise. The REDUCE trial was the first large multicenter prospective study looking at efficacy and safety of the ReShape dual balloon. In this study, 326 participants with a BMI between 30-40 kg/m2 were randomized to endoscopic ReShape Duo balloon placement plus diet and exercise vs. sham endoscopy plus diet and exercise alone. Duo patients had significantly greater %EWL at 24 wk (25.1% intent-to-treat (ITT), 27.9% completed cases (CC, n = 167) compared with DIET patients (11.3%ITT, P = 0.004, 12.3% CC, n = 126). This significant weight loss noted with ReShape Duo balloon (i.e., %EWL noted with Duo balloon was double that of lifestyle modification) was coupled with very low adverse event (AE) profile (such as accommodative symptoms, balloon deflation, gastric ulceration)[17]. High incidence of gastric ulcers and erosions (39%) was initially observed at or near the gastric incisura during the study period but the frequency reduced to 10.3% with design modification.

The most recent data was published in 2018 through John’s Hopkins where they analyzed 202 adult patients who underwent ReShape Duo IGB insertion and they determined %TBWL and %EWL over a 12 mo period. Mean %TBWL at 1, 3, 6, 9 and 12 mo was 4.8%, 8.8%, 11.4%, 13.3% and 14.7%, respectively. Of the data available, 60.4% of patients achieved more than 10% TBWL and 55.4% had more than 25% EWL. Common AE included nausea, vomiting, and abdominal pain, with more severe AE being one small bowel obstruction. Secondary endpoints such as systolic and diastolic blood pressure, hemoglobin a1c, fasting blood sugar, and total cholesterol were found to be statistically significantly lower at balloon removal than at baseline[18].

Obalon

Obalon (Obalon Therapeutics Inc, Carlsbad, CA, United States) is the first and only swallowable, FDA approved balloon system for weight loss. This is approved to facilitate weight loss in patients with a BMI between 30 and 40 kg/m2 in conjunction with diet and exercise. The Obalon balloon is packaged with a gelatin capsule. The patient swallows the capsule which is attached to a small catheter. Fluoroscopy is used to confirm intragastric location. The gelatin capsule dissolves allowing the balloon to enter the stomach. The catheter is used to inflate the balloon by using a gas filled canister, after which the catheter is detached and removed. The balloons should be removed after 6 mo.

The advantage of this mechanism is that the placement of the IGB endoscopically (with all procedural and anesthesia related risks) is not required; however, it still must be retrieved after a 6-mo time period. Up to three balloons may be placed at one time equivalent to 750 mL of gastric space which allows modifiability[19]. The most recent data showing efficacy of this system was published in 2018 where the authors conducted a double-blind, randomized sham controlled trial of Obalon balloon plus lifestyle therapy compared to lifestyle therapy alone for weight loss at 6 mo. The authors found that compared with lifestyle alone, the Obalon IGB resulted in twice the weight loss compared to controls with minimal AEs[20].

IGB advantages

The IGB offers several advantages. One, it is a relatively simple procedure that could be adopted within the realm of general gastroenterology with minimal additional training needed. The procedure can be performed on an outpatient basis, thereby saving costs. It is minimally invasive with little risk as compared to the most common surgical bariatric procedures (RYGB and Sleeve gastrectomy). Further, studies are now revealing superior weight loss effect with combination of IGB and bariatric surgical procedures than either alone, suggesting that it can be used in combination with standard surgical approaches. Lastly, it can be easily reversed and repeated multiple times over. Although there is promise for IGB’s, there still remains a need for further evidence of safety, efficacy, and established guidelines that can be followed by the medical community.

Other intragastric balloons and space occupying devices

Other IGBs are available worldwide but not approved in United States at the current time. Spatz adjustable balloon system (Spatz Medical, Great Neck, NY, United States) is an endoscopically placed saline filled IGB with a unique design that allows for volume adjustment. Hence, increasing or decreasing balloon volume may result in better patient tolerance, making it adjustable per patient’s preference. Another IGB, Elipse Balloon (Allurion Technologies, Wellesley, MA, United States) remains in the stomach for approximately 4 mo, at which time a valve opens spontaneously, deflating the balloon and allowing it to be spontaneously excreted through the GI tract.

Other gastric non-balloon space-occupying devices have been introduced. TransPyloric Shuttle (BAROnova, Inc, Goleta, CA, United States) is composed of a large spherical silicone bulb connected to a smaller cylindrical silicone bulb by a flexible catheter. This unique design allows the device to assume transpyloric positioning creating an intermittent seal resulting in delayed gastric emptying and early satiety. The Full Sense Device (Barker, Foote, Kemmeter, Walburn, LLC, Grand Rapids, MI, United States) is a modified, fully covered, gastroesophageal stent. After deployment, the exclusive design allows the gastric disk component to apply pressure on the gastric cardia resulting in satiety.

Endoscopic sleeve gastroplasty

ESG is an incisionless method whereby full thickness sutures (OverStitch; Apollo Endosurgery) are placed within the greater curvature of the stomach during endoscopy. This, in essence, creates a gastric restriction by decreasing gastric volumes by approximately 70%, thereby leading to early satiety and weight loss. Additionally, this method has been shown to alter insulin sensitivity, gastric emptying, satiation, and appetite regulatory hormones; which becomes important in the altered neurohormonal physiology in obese individuals[21].

This method for endoscopic weight loss has shown promise in clinical trials and retrospective reviews. In a recent study published in 2017, Lopez-Nava et al[22] evaluated 248 patients to examine the short term and long-term outcomes after ESG. There they were able to show that %TBWL was 15.2 and 18.6 at 6 and 24 mo respectively. At 24 mo the proportion of patients achieving > 10% TBWL was 84.2% and 53% with per protocol and intention-to-treat analysis, respectively[22]. In a more recent multi-centered trial, 112 patients (baseline BMI 37.9 kg/m2) who underwent ESG were followed prospectively. TBWL at 1, 3, and 6 mo was 8.4%, 11.9%, and 14.9% respectively. The proportion of patients who attained greater than 10% TBWL and 25% EWL was 62.2 and 78.0% at 3 mo post-ESG and 81.0 and 86.5% at 6 mo post-ESG. Multivariable analysis revealed that male gender, greater baseline body weight, and no prior endoscopic bariatric treatment were predictors of weight loss at 6 mo follow up. The safety of this procedure was also evaluated. Mild AEs such as self-limited nausea and vomiting occurring in a large proportion of patients were noted. Three major AEs were noted (two patients had gastrointestinal (GI) bleeding and one patient had perigastric fluid collection; no patient required conversion to surgery for management of these complications)[23]. In summary, the current evidence suggests that ESG results in greater weight loss compared to gastric balloon but not as much as with bariatric surgery (although high quality head to head studies to answer this question are in progress).

In another study performed by Sharaiha et al[24], ESG has been able to reduce obesity associated medical co-morbidities. In this study, 91 consecutive patients who underwent ESG between August 2013 and March 2016 were analyzed. At 24 mo follow up, statistically significant reductions in levels of hemoglobin A1c, systolic blood pressure, waist circumference, low density lipoprotein cholesterol, alanine aminotransferase, and serum triglycerides were noted[24]. A multi-center ESG Randomized Interventional Trial (MERIT-Trial) with estimated 200 participants is underway and is expected to complete at the end of 2020.

ESG provides a unique intermediary between gastric bariatric surgery and the gastric balloon. Gastric balloons have only been studied and approved for a short-term period, with long lasting weight loss a limitation of this modality thus far. On the other hand, ESG may provide a feasible means of weight loss with a more durable effect than the IGB. Moreover, compared to bariatric surgery, ESG is less invasive, efficient, safe and less costly making it an attractive possibility for patients who want to lose weight without undergoing surgery.

Another similarly designed treatment modality, primary obesity surgery endoluminal (POSE), uses a peroral incisionless operating platform (USGI Medical, San Clemente, CA, United States) to place transmural tissue anchor plications that reduce accommodation of the gastric fundus. Additional plications are placed in the distal gastric body to delay gastric emptying. In a pivotal United States multicenter randomized blinded clinical trial, the %TBWL at 12 mo for the POSE group was 4.94% ± 7% compared to 1.38% ± 5.6% in the control group. The rate of serious AEs was 4.7%[25].

ASPIRATION THERAPIES

The AspireAssist (Aspire Bariatrics, King of Prussia, PA, United States) is an FDA approved device for patients with BMI of 35-55 kg/m2. It is a large caliber tube that is inserted percutaneously through the stomach (like a polyethylene glycol tube)[26]. Two weeks after insertion, the external portion of the tube is shortened and a skin port with a valve is attached to the skin. An Aspire Assist device is connected to the skin port to provide aspiration. A water reservoir is used to flush water into the stomach to help with aspiration. Usually, aspiration is performed over a 5-10 min period about 20 to 30 min following each meal, effectively removing up to one third of the ingested meal. Regular visits to a physician very one to two months is required in the first year (and less frequently thereafter) to help monitor the progress.

The PATHWAY trial was the largest multicentered randomized controlled trial looking at 207 patients, randomized in a 2:1 fashion, where 137 patients underwent AspireAssist and 70 patients received Lifestyle Counseling. 111 patients underwent final analysis (26 withdrew). At 52 wk, participants in AspireAssist group had lost a mean (± SD) of 31.5 ± 26.7% of their excess body weight (12.1 ± 9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8 ± 15.5% of their excess body weight (3.5 ± 6.0% total body weight, P < 0.001). A total of 58.6% of participants in the AspirteAssist group and 15.3% in the Lifestyle Counseling group lost at least 25% of their excess body weight (P < 0.001). Each of these outcomes achieved statistical significance. The AspireAssist group was also able to show statistically significant changes in glycated hemoglobin levels as well[27]. The advantages of aspiration therapies include reversibility, outpatient procedure, no alteration to the internal anatomy, limited risks, and long-term duration of use.

SMALL BOWEL ENDOSCOPIC BARIATRIC THERAPIES

The proximal small bowel plays an important role in glucose homeostasis and pathogenesis of diet-induced diabetes. Enteroendocrine cells within the small intestinal mucosa release gut peptides that mediate satiety and increase insulin secretion. Secretion of biliary and pancreatic enzymes within the proximal small bowel helps in digestion of food. To mitigate these beneficial physiological effects of the proximal small bowel mucosa, several barrier devices have been developed, which will be explained in the next section.

Gastrointestinal bypass sleeves

The small intestine is primarily used for nutrient absorption of carbohydrates, fats, and proteins. GI bypass sleeves are intended to bypass a part of small intestine to cause malabsorption of nutrients. This has shown promise in both weight reduction as well as control of diabetes.

Endobarrier (GI dynamics, Lexington, MA, United States) is a long duodenojejunal bypass (DJBS) sleeve made up of an impermeable polymer liner and a nitinol crown anchoring system which attaches to the duodenal bulb. The sleeve is designed to cause malabsorption by allowing food passage from the stomach into the small bowel while bypassing the first 65 cm of the small bowel. Due to the barrier function of the sleeve, contact of the food with pancreatic enzymes and biliary secretions in the duodenum is eliminated and hence, results in malabsorption of nutrients and resultant weight loss. This has shown excitement as it is designed to mimic the RYGB without the associated morbidity (1 year 14.9%) and 30 d mortality (0.5%)[28]. The sleeve is removed endoscopically in 12 mo.

Although this technology has yet to be approved by FDA within the United States, there have been multiple clinical trials which have shown promise with this device. In a large metanalysis by Force et al[29], published in 2015, EndoBarrier was associated with 35.3% EWL at 12 mo (95% confidence interval, 24.6-46.1). An interesting finding associated with this bypass sleeves was that hemoglobin a1c levels were markedly improved with the use of this device, even in as little as 24 wk[30]. This finding has been seen in RYGB, and is thought to be secondary to increased glucagon synthesis after exclusion of the proximal small bowel, as well as enhanced secretion of incretins, like GLP-1, in response to nutrients being delivered to the distal small bowel[31].

However, a pivotal multicenter double-blinded sham control United States trial was terminated early because of a 3.5% incidence of hepatic abscess formation. Interestingly, subjects who received the DJBS had more weight loss compared to the sham group at 12 mo (%TBWL, 7.7% ± 9.6% vs 2.1% ± 5.4%, P < 0.0001) and had more significant improvement in HgA1c level (-1.1% ± 1.5% vs -0.3% ± 1.6%). AEs occurred in 10.9% of patients requiring early device retrieval]. Unfortunately, long term follow up study revealed that the weight reduction of initial DJBL treatment seems to be diminished after 4 years of follow up[32]. Due to the results discussed above, the current system fell out of favor but paved the way for second generation DJBSs with atraumatic anchoring and retrieval systems, which are being currently studied in clinical human trials.

Other small bowel endoscopic bariatric therapies

Other small bowel endoscopic bariatric therapies are in the initial phase of development and are being studied in clinical trials. Gastroduodenojejunal bypass sleeve (ValenTx) is technology similar to EndoBarrier; however, it is a much longer sleeve and is anchored to the GE junction. The ValenTx endoluminal bypass therapy mimics the permanent anatomical changes made by the RYGB procedure, but does this with an adjustable, removable, and replaceable device. This technology is still undergoing early clinical trials.

A duodenal mucosal resurfacing procedure (Fractyl Laboratories, Cambridge, MA, United States) has been developed. In this procedure, a special catheter is used to deliver heat energy resulting in thermal ablation of the superficial duodenal mucosa. This results in mucosal remodeling and subsequent resetting of the signaling pathway of the duodenal neuroendocrine cells, translating into better control of hyperglycemia and diabetes. Self-assembling magnets for endoscopy (GI windows, Boston, MA, United States) have been developed with the idea of creating a communication between proximal jejunum and ileum. This would allow the nutrients to bypass the absorptive surface of a major part of small bowel leading to malabsorption and weight loss.

CONCLUSION

The medical community is exploring options to feed the unmet need of the United States obesity epidemic. These options include lifestyle/behavioral modifications, pharmacotherapy, bariatric surgery, or combination therapy. Studies have shown that lifestyle modifications and pharmacotherapy have only been able to achieve modest weight loss effects. Bariatric surgery has been shown to be a landmark intervention in obesity, but many patients find this invasive approach unacceptable due to the side effect profile and potential late complications. Endoscopic bariatric treatment options, although relatively novel, has shown efficacy in the treatment of obesity. It has potential to become more popular in near future considering being less invasive and having a more favorable side effect profile compared to surgery. Long term efficacy is not well known at this time but should be available in a few years as more studies are being reported. Additional studies must also include comparison of different modalities and outcomes on obesity related illnesses (cardiovascular disease, diabetes, hyperlipidemia, etc.). The future of this developing arena will also depend upon training future gastroenterologists in the technical and medical aspects of this field. To date, there is no formalized bariatric endoscopic training amongst gastroenterology fellowship programs. Primary care, bariatric medicine physicians, and bariatric surgeons must incorporate and determine appropriateness of bariatric endoscopy when evaluating patients. Given the promise of this new modality, the authors of this review believe the future of bariatric medicine will include endoscopic intervention as a major tool in its armamentarium.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: United States

Peer-review report classification

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P-Reviewer: Wang YP S-Editor: Yan JP L-Editor: A E-Editor: Zhang YL

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