Primary endoluminal bariatric procedures

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Primary Endoluminal Bariatric Procedures Mujjahid Abbas MD , Leena Khaitan MDMPH PII: DOI: Reference:

S1096-2883(18)30056-1 https://doi.org/10.1016/j.tgie.2018.10.003 YTGIE 50586

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Techniques in Gastrointestinal Endoscopy

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6 August 2018 3 October 2018 6 October 2018

Please cite this article as: Mujjahid Abbas MD , Leena Khaitan MDMPH , Primary doluminal Bariatric Procedures, Techniques in Gastrointestinal Endoscopy (2018), https://doi.org/10.1016/j.tgie.2018.10.003

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Primary Endoluminal Bariatric Procedures Mujjahid Abbas, MD, Leena Khaitan, MD, MPH

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University Hospitals, Cleveland, Ohio

Leena Khaitan, MD, MPH [email protected]

Ph: (216)844-4918

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Fax: (216)844-5957

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Cleveland, Ohio 44106

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11100 Euclid Avenue, Mailstop 5047

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Mujjahid Abbas, MD

[email protected]

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11100 Euclid Avenue, Mailstop 5047 Cleveland, Ohio 44106 Ph: (216)8443355 Fax: (216)844-5957

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Correspondence to:

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Abstract Endoscopic treatment of obesity is an area of growing interest. These endoscopic treatment options are less invasive than traditional surgical operations and are considered more effective

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than available medical and life style modification options. Endoscopic interventions currently available work through several mechanisms including space filling devices that reduce volume of food intake, reduction in the stomach volume with endoscopic suturing, mucosal liners that

reduce absorption, and aspiration therapy to remove the ingested food before absorption. Other

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devices are on the horizon with other mechanisms. This article will review the mechanisms and data surrounding endoscopic devices and procedures currently approved by the FDA and those in development. Some of the devices have limited data available due to being early in their clinical

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application.

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Keywords: weight loss, endoscopic weight loss, endoluminal bariatric procedures, balloon,

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endoscopic sleeve, nonsurgical weight loss

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Highlights 1. There are several endoluminal options for weight loss that bridge the gap between surgery and diet/exercise for weight loss. 2. The current data surrounding the available devices is reviewed in the manuscript.

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Introduction Obesity has been acknowledged as a global health problem of epidemic proportions (1). Obesity causes physiologic and anatomical derangements resulting in the development of numerous physical and mental health related conditions, which then leads to a shorter life span and poor

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quality of life (2). Diet, exercise and life style modifications are the base of all weight loss programs, but on average result in only 5-15% total body weight loss when used alone (3).

Medications cause a modest weight loss which is slightly greater, however, this is often not sustainable once the medication is stopped (4). Surgery has been shown to be the most durable

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option for weight loss, however it is expensive and is associated with anatomical alterations, side

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effects and complications (5). It is estimated that only 1% individuals eligible for bariatric surgery actually undergo weight loss surgical procedures. Many individuals who qualify for

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surgery are not ready to make the leap to a procedure to lose weight and be healthier (6). To date there has been a wide gap between surgical interventions and non-surgical weight loss

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options available to treat obesity. Obesity has been identified as one of the most expensive

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conditions currently being treated in America (7). One area of growing interest is the endoscopic treatment of obesity. These endoscopic treatment options are less invasive than traditional surgical operations and are considered more effective than available medical and life style modification options.

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The endoscopic interventions currently available work through several mechanisms including space filling devices that reduce volume of food intake, reduction in the stomach volume with endoscopic suturing, mucosal liners that reduce absorption, and aspiration therapy to remove the ingested food before absorption. Other devices are on the horizon with other mechanisms (8).

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This article will review the mechanisms and data surrounding endoscopic devices and procedures currently approved by the FDA and those in development. Some of the devices have limited data available due to being early in their clinical application.

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Procedures Currently being used in the United States Intragastric Space Filling Devices:

Filling the stomach with a space occupying device to reduce food intake is not a new concept.

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The Garren-Edward Gastric Bubble (GEGB) was the earliest gastric balloon approved for obesity treatment in 1985. This was a cylindrical air-filled (200-220 ml) device made of

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polyurethane. This quickly ran out of favor due to limited success with weight loss, unfavorable side effects and devastating complications including spontaneous deflation, migration, and bowel

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obstruction. This ultimately resulted in withdrawal of the device from the market (9).

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There has been a resurgence in space filling devices now that more robust materials such as silicone are available. The deflation and migration rates are much lower, they are simple to place,

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and initially had few side effects. These devices induce satiety by reducing the gastric capacity and slowing gastric emptying. Stretching of the gastric wall may also be responsible for a vagally controlled reflex for causing satiety (10). Additionally, the levels of different gut hormones and peptides are altered after placement of intragastric devices and could explain a neurohormonal mechanism of weight loss, early satiety and delayed gastric emptying (11).

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The indication for these devices is BMI 30-40, and although they have been placed internationally for years, they have only been FDA approved since 2015 in the United States. It is recommended that patients who have had prior gastric operations, active gastrointestinal pathology, bleeding diathesis, and/or severe medical conditions prohibiting endoscopy should

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not have these devices placed. It is recommended these devices be removed 6 months after

placement and that patients receive ongoing weight management counseling for an additional 6 months. This will help the patient to maintain healthy lifestyle changes.

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The FDA has been informed of over 12 deaths in patients who had a fluid-filled intragastric balloon (IGB) placed. Not all deaths were thought to be directly related to the device itself. For that reason, the FDA has cautioned providers to inform patients about potential risks of spontaneous hyperinflation, pancreatitis, balloon deflation, gastrointestinal obstruction,

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ulceration, gastric and esophageal perforation and the risk of death (12) (13).

Orbera™ (Figure 1)

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The space filling devices will be reviewed individually.

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Orbera™ Intragastric Balloon (Apollo Endosurgery, Austin, TX, USA), was approved by the

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FDA for use in the USA in August 2015, although it has been commercially available for use outside of the United States since 2004. It is a silicone balloon with a fill volume of 400-700 cc.

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The balloon is filled with saline endoscopically within the stomach. Many will add methylene blue to help to identify rupture of the balloon if the urine changes color. This device requires endoscopy for placement and removal 6 months later. No adjustment of volume is possible after the device has been placed. The usual side effects include nausea, vomiting, abdominal pain, reflux, and intolerance to device, all of which usually improve after the initial adjustment period.

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The weight loss outcomes are favorable with an average of 30-50 pounds lost over the treatment period (2-3 times more than diet and exercise alone). The Orbera US post-approval multi-center study reported outcomes in 321 subjects with an average BMI of 37.6. Average total body weight loss (TBWL) was 11.8% at six months, which is approximately 16% greater than

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reported in Orbera’s initial US Pivotal Study. In addition to weight loss, a significant improvement in type 2 DM, hypertension and hyperlipidemia were noted (14).

A consensus meeting by Brazilian endoscopists was held in São Paulo, Brazil, in June 2016.

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Their experience with over 41,000 IGB procedures showed a mean %TBWL of 18.4% ± 2.9% with an adverse event rate of 2.5% after the initial adaptation period was noted. Rates of hyperinflation (0.9%) and spontaneous deflation (0.8%) of the device were amongst the most common device related adverse events. They reported a 2.2% early removal rate due to device

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intolerance. Three of the 12 total deaths were reportedly related to the IGBs with a mortality rate of 0.03% (15). This is the largest single experience with IGB reported. Since that time, several

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publications have reported similar results. The general consensus is that this is the most widely

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used balloon worldwide and fills a need for patients who are not successful with diet and exercise alone but are not ready for surgery.

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ReShape Duo® (Figure 1)

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ReShape Duo® (ReShape Medical, San Clemente, CA, USA) was also approved by the FDA in 2015. The device is comprised of two interconnected intragastric balloons. Placement and removal require an endoscopic procedure. The balloons are inflated with 450 mL of methylene blue-mixed saline each. This dual balloon system claims to reduce deflation-associated complications as the balloons are independently sealed, thereby minimizing the risk of migration and intestinal obstruction. The REDUCE pivotal trial reported a 25.1% EWL at 24 weeks in

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Reshape patients compared to 11.3% in DIET patients (16). A recent study with 202 patients and mean BMI of 36.8 + 8.4 kg/m2 reported %TBWL at 1, 3, 6, 9 and 12 months of 4.8 ± 2.4%, 8.8 ± 4.3%, 11.4 ± 6.7%, 13.3 ± 7.8%, and 14.7 ± 11.8%, respectively. Seventeen patients (8.4%) had esophageal tears during balloon insertion, with no intervention required. Thirteen patients (6.4%)

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had the device removed prematurely. Nausea, vomiting, and abdominal pain were the most

common adverse effects. In one patient, the IGB migrated distally leading to small intestinal obstruction requiring surgical removal (17).

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Obalon® (Figure 1)

The Obalon Gastric Balloon® (Obalon Therapeutics Inc, Carlsbad, CA, United States) is an ingestible air-filled balloon and is the most recently FDA-approved space filling device. The balloon comes packaged inside a gelatin capsule and is connected to tubing with a one-way

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valve. The balloon is swallowed by the patient, the gelatin layer disintegrates in stomach, and

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after confirming its placement in the stomach using fluoroscopy, the balloon is filled with 250 mL of nitrogen gas. The tubing is disconnected from the balloon and it floats into the gastric

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fundus. Up to three balloons can be placed at 6-12-week intervals. This sequential placement reduces the nausea usually seen with space filling devices. The balloons are then removed at 6

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months using endoscopy. Weight loss of 5 kg has been reported after 12 weeks (18). A recent

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study identifies the gas filled balloons as having less weight loss than the fluid filled balloons, but fewer side effects (19). Since the placement of the balloon does not require a procedure, this opens the device up to being placed by medical practices when these devices have traditionally been placed by surgeons and gastroenterologists. To date, the concerns of pancreatitis, hyperinflation and death have not

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been seen with the air-filled balloons, however the weight loss has also been slightly less than the fluid filled balloons. There are other endoscopic procedures for weight loss currently being used in the United States.

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This includes suturing and aspiration therapy. Both have been shown to be more effective for weight loss than diet and exercise alone. Aspiration Therapy Aspire Assist™

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Aspire Assist™ device (Aspire Bariatrics, King of Prussia, PA, USA) is a modified percutaneous endoscopic gastrostomy (PEG) device used for weight loss. The device consists of an aspiration tube made of Silicone, placed similar to a standard PEG tube. This is connected to a skin port

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containing a valve that allows the escape of gastric contents through the Aspire Assist device using a siphon effect. Aspiration is performed 20 minutes after consuming a meal and roughly

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one third of the ingested food is aspirated and discarded. For food to drain the patient must practice mindful eating. In a recent study of 201 participants, with a mean BMI of 43.6 ± 7.2

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kg/m2, the mean percent total weight loss at 1, 2, 3, and 4 years, respectively, was 18.2% ± 9.4%,

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19.8% ± 11.3%, 21.3% ± 9.6% and 19.2% ± 13.1%. Clinically significant reductions in glycated hemoglobin (HbA1C), triglycerides, and blood pressure were observed. For participants with

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diabetes, HbA1C decreased by 1% (P < 0.0001) from 7.8% at baseline to 6.8% at 1 year (20). These outcomes are similar to the space filling devices. The difference is that this device can theoretically stay in indefinitely whereas the balloons have to be removed at 6 months. Adverse events included abdominal pain and discomfort, granulation tissue and peristomal irritation. Serious adverse events were reported in 3.6% of participants. This device has demonstrated

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effectiveness in multiple studies, however, the concept of aspiration has limited its widespread use. This remains a tool for weight loss but its longevity is yet to be determined. Endoscopic Sleeve Gastroplasty

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Endoscopic Sleeve Gastroplasty (ESG) creates an endoscopic equivalent of a sleeve gastrectomy by suturing the greater curvature of the stomach with a commercially available endoscopic

suturing device (Overstitch™; Apollo Endosurgery, Austin, TX). Numerous sutures are placed through the gastric wall, extending from the antrum to the gastric fundus thus reducing the

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gastric volume. No sutures are placed on the lesser curvature. The goal is to create an endoscopic equivalent of the sleeve gastrectomy while obtaining full-thickness sutures, aided by the use of the tissue helix grasping device. A multicenter study with 242 patients showed 16.8%±6.4%, 18.2%±11.6%, and 19.8%±11.6% TBWL at 6, 12, and 18 months, respectively (21). Another

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recent study comprising 112 patients across 3 centers showed a change in weight of 9.0 ± 4.6 kg

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(TBWL 8.4 ± 4.1%), 12.9 ± 6.4 kg (TBWL 11.9 ± 4.5%), and 16.4 ± 10.7 kg (TBWL 14.9 ± 6.1%) at 1, 3, and 6 months respectively. The proportion of patients who attained greater

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than 10% TBWL and 25% EWL was 81.0 and 86.5% at 6 months after ESG (22). A significant decrease in gastric emptying, increased satiation, and hormonal effects have been reported and

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thought to cause the metabolic advantages of the weight loss after ESG (23).

There are several limitations to the widespread use of any of these procedures. First these procedures cannot achieve the weight loss seen with weight loss surgery. Because of the limited efficacy, some physicians have not recommended these endoscopic procedures to their patients. However, again, only 1% of those qualifying for weight loss surgery actually get it. These

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endoscopic procedures help to fill the large gap that remains between diet and exercise, and surgery. Additionally, insurers remain hesitant to pay for these procedures. This is unfortunate as there are several patients who can benefit from weight loss. Despite these barriers, many see the benefit of these endoscopic weight loss procedures and there are several in development.

be reviewed. Non-FDA approved devices/procedures

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The Primary Obesity Surgery, Endoluminal (POSE)

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These will now be reviewed. There is limited data on these devices and the nuances of each will

POSE is performed endoscopically through a large overtube using a device (USGI Medical, San Clemente, CA, USA) and places transmural tissue anchor plications that reduce accommodation

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of the gastric fundus. Additional anchors are placed in gastric body. The platform has four working channels with a slim endoscope and three specialized instruments for tissue grasping

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and suturing. In a pivotal multi-center randomized blinded trial with 221 patients who underwent POSE and a low intensity lifestyle intervention for 12 months, patients achieved a 4.94%±7%

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TBWL compared to 1.38%±5.6% TBWL achieved by the 111 patients in the control group with

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lifestyle interventions alone (24). Lastly, POSE was associated with improved satiation and gut neuroendocrine reaction. This is currently under investigation for FDA approval in the United

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States. The device may actually provide more benefit for revision of other procedures rather than primary weight loss. Spatz 3

The Spatz Adjustable Balloon System (Spatz Medical, NY, USA) is a silicone-based balloon that is filled with 400-800 mL of normal saline. The unique aspect of this balloon is that the volume

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can be tailored according to tolerance and needs of the patient. The Spatz is approved outside of the USA for intragastric implantation for up to 12 months, making it the longest implanted space-filling device. The previous generation of Spatz adjustable balloon reported total body weight loss of 19% over 12 months in 49 of the 73 patients. There were some issues noted with

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the design of the device. It was difficult to grasp and adjust. Three patients failed insertion. There were 21 early removals (4 intolerant refusing adjustment; 3 deflations; 14 satisfied

patients). Three catheter impactions required surgical extraction, and three deflated balloons didn't migrate beyond stomach (25). The Spatz 3 is the updated version of the device and claims

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to overcome the previous shortcomings. Patients can have the volume of the balloon reduced after a few months to allow it to stay implanted longer. This is currently being tested in a multicenter randomized trial in the United States and is not yet FDA approved.

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The Elipse™ (Figure 1)

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The Elipse™ (Allurion Technologies, Wellesley, MA, United States) is a new balloon that is not yet FDA approved. It is swallowed by the patient and comes with a delayed absorbable valve

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inside. After it is swallowed by the patient, the balloon is filled with 550 ml of a fluid mixture. The balloon has a valve made of a resorbable substance that breaks down after 4 months, causing

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the balloon to deflate and pass through the gastrointestinal tract. The major advantage is that there is no need for endoscopy for placement or removal of the device. A recent trial reported

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results of 34 patients with mean BMI 34.8 kg/m2 with 100% successful device swallow rate. They noted minimal side effects that could be medically treated, and all balloons were safely excreted. A mean 10 % Total Body Weight Lost was reported after 4 months with an 8.4 cm mean waist circumference reduction. Improvements were also noted in hemoglobin A1c, triglycerides, low density lipoprotein, and blood pressure (26).

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Another study of 135 patients reported a 13.0 kg mean weight loss and 4.9 unit drop in BMI with mean percent total weight loss of 15.1%. Nausea was the most common complaint and usually resolved by the third day. Two patients (1.5%) vomited the balloon, 3 patients (2.2%) had the balloon removed due to intolerance, and 3 patients (2.2%) had early deflation. Diarrhea and

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colicky abdominal pain were also reported side effects during the week of balloon deflation and may reflect a partial bowel obstruction. One patient experienced a complete small bowel obstruction requiring the balloon to be removed via a laparoscopic enterotomy (27).

TransPyloric Shuttle TPS™ (Figure 1)

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The TransPyloric Shuttle (TPS [BAROnova, Goleta, CA, USA]) is comprised of a large spherical silicone orb attached to a smaller cylindrical silicone bulb with a flexible cord. The

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device is inserted into the stomach endoscopically using an overtube. Due to peristalsis, the

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smaller part of the device passes across the pylorus and larger piece works as an anchor to hold the device proximal to the pyloric sphincter. This causes an intermittent obstruction, thus

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delaying gastric emptying and producing early and prolonged satiety. An initial study of 20 patients with a mean BMI of 36 kg/m2 were divided in two groups and randomized to TPS

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placement for either 3 or 6 months. Patients who had the device for 3 months noticed 25.1%

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EBWL, while patients in the 6 months group lost an average of 41% EWL (28). A pivotal multicenter randomized trial (ENDObesity II) is reported to have been completed in the US. The ENDObesity II study was a randomized, double-blinded, sham-controlled study which enrolled 302 patients from 9 sites across the United States. Primary outcomes were percent total body weight loss (%TBL) at twelve months and the proportion of subjects in the treatment group who achieved 5% TBL or more after 12 months. The trial successfully met its endpoints according to

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the company press release. Results from the study are expected to be published soon. The company has applied for premarket approval (PMA) (29). The Full Sense Device™ (Figure 2)

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The Full Sense Bariatric Device (Baker, Foote, Kemmeter, Walburn [BFKW] LLC, Grand Rapids, MI, USA) is another endoscopically placed weight loss device. The device has two

portions, an esophageal stent and a gastric disk. The device produces the sense of fullness by filling the gastric cardia. Great weight loss results were reported by the inventors of the

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technology with no peer-reviewed data published to date (30). The device is currently not commercially available anywhere. Gastrointestinal liners:

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EndoBarrier (Figure 2)

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The EndoBarrier™ (GI Dynamics, Lexington, MA, USA) is a 65-cm long Teflon-coated sleeve which is deployed in the proximal duodenum and bypasses the proximal jejunum and works as a

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Duodeno-Jejunal Bypass Sleeve (DJBS). The device is placed and removed endoscopically. The device was being used in a phase 2 US clinical trial but the trial was discontinued because of a

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3.5% rate of hepatic abscess formation. Redesign is reportedly being worked on and future trials may resume after design modifications. Initial studies reported a 12% EWL after one year of

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therapy and a reduction in the severity of diabetes (31). This is currently being offered in Europe as a potential way to manage diabetes. ValenTx (Figure 2)

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Gastroduodenojejunal bypass sleeve (ValenTx, Inc., Hopkins, MN, USA) is another endoluminal liner device that is designed to mimic the therapeutic effects of the gastric bypass. The sleeve is 120 cm long and is deployed at the distal esophagus at the gastroesophageal junction. A 53% excess weight loss at the 1-year explant date has been shown in a study using combined

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endoscopic and laparoscopic approaches for placement of the device (32). Current development is focused on a purely endoscopic deployment. This is not yet FDA approved, but is in trial. The device is promising but is not yet commercially available.

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Magnetic Anastomoses (Figure 2)

Magnamosis and GI Window are investigating endoscopic anastomoses. The magnets are deployed endoscopically and arrange themselves into a ring configuration due to the attraction between each magnet. The tissue in between the magnets undergoes ischemic necrosis thus

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creating an entero-enterostomy. The GI Window magnets are deployed with simultaneously

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performed upper and lower endoscopy, with creation of an anastomosis within the midgut and results in at least a partial intestinal bypass. A press release of their first in-human pilot for

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partial jejunal diversion consisted of 10 patients and the patients were not enrolled in an intensive lifestyle/diet management program. Total body weight loss was 14.6% at 12 months,

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with a 1.9% reduction in Hemoglobin A1C in diabetic patients and 1% HgbA1c reduction in

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prediabetic patients (33). Because of the need for upper and lower endoscopy, these procedures are technically challenging and require multimodal approaches to make them work. This technology is promising for many uses including weight loss. Duodenal Mucosal Resurfacing

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In the duodenal mucosal resurfacing procedure, superficial duodenal mucosa is ablated using thermal energy with the help of a special catheter that delivers hot water after a sub-mucosal lift is performed. The resulting mucosal remodeling theoretically will reset the diseased duodenal enteroendocrine cells and restore signaling, which then can improve diabetes control through an

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incretin effect, along with a minimal transient decrease in body weight (34). The primary

intention of this procedure is diabetes control and not weight loss. But the side effect of weight loss provides some more insight into obesity management.

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Conclusion

Obesity has reached epidemic proportions worldwide. There is a growing interest and need to treat obesity. There will be a greater role for a wide variety of treatment modalities including primary endoscopic bariatric treatment options. We strongly encourage using these options in a

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multidisciplinary setting where a team of bariatric surgeons, endoscopists, bariatricians,

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dietitians, psychologists and other like providers are involved in taking care of the individuals suffering from obesity, using a multimodality approach. Each of the procedures has its own risks

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and benefits. As physicians introduce these procedures into their practices, they should be well versed in all of them to have a discussion with the patient, and help tailor the approach to the

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patient’s needs and comfort. (Table 1)

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These procedures should be performed by properly trained and preferably certified endoscopists well adept in bariatric endoscopy. It is clear based on the data available that these endoscopic procedures are effective. The weight loss is greater than diet and exercise, however, is not the same as surgery. Endoscopic procedures should not necessarily be held to a bar of being equivalent to surgery, but fill the gap between surgical and non-interventional approaches to

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weight loss. It is unlikely that these procedures will have the same efficacy as surgical interventions for weight loss. These endoscopic procedures are also safe when the appropriate guidelines are followed. The

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FDA cautions regarding the fluid filled devices should be taken seriously and those performing these procedures should be mindful of these issues. The outcomes of these procedures should be part of data collection/monitoring programs like MBSAQIP, so that the true outcomes of these interventions can be recorded. This will also allow procedures to continue to be performed

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safely. Close monitoring of these emerging endoscopic technologies will hold these interventions and providers to the same standards of bariatric surgery. (34) A certification process has been endorsed by The American Society for Metabolic and Bariatric Surgery (ASMBS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). Both organizations

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have worked together to develop a verification process (Bariatric Endoscopy -Skill Acquisition Fundamentals Exam; BE-SAFE) for surgeons and endoscopists with experience in performing

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bariatric endoscopy to verify that they have acquired the necessary skills to perform these

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procedures. (35)

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Conflict of Interest Statement: The authors have no financial conflicts of interest to report.

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22. Sartoretto A, Sui Z, Hill C, Dunlap M, Rivera AR, Khashab MA, et al. Endoscopic Sleeve Gastroplasty (ESG) Is a Reproducible and Effective Endoscopic Bariatric Therapy Suitable for Widespread Clinical Adoption: a Large, International Multicenter Study. Obes Surg 2018;28:1812–21.

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23. Abu Dayyeh BK, Acosta A, Camilleri M, Mundi MS, Rajan E, Topazian MD, et al. Endoscopic Sleeve Gastroplasty Alters Gastric Physiology and Induces Loss of Body Weight in Obese Individuals. Clin Gastroenterol Hepatol 2017;15:37–43.e1. 24. Sullivan S, et al. Abstract #100. Presented at: Digestive Disease Week; May 21-24, 2016; San Diego.

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25. Brooks J, Srivastava ED, Mathus-Vliegen EM. One-year adjustable intragastric balloons: results in 73 consecutive patients in the U.K. Obes Surg 2014;24:813–9.

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26. Machytka E, Gaur S, Chuttani R, Bojkova M, Kupka T, Buzga M, et al. Elipse, the first procedureless gastric balloon for weight loss: a prospective, observational, open-label, multicenter study. Endoscopy 2017;49:154–60.

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27. Alsabah S, Al Haddad E, Ekrouf S, Almulla A, Al-Subaie S, Al Kendari M. The safety and efficacy of the procedureless intragastric balloon. Surg Obes Relat Dis 2018;14:311–7. 28. Marinos G, Eliades C, Raman Muthusamy V, Greenway F. Weight loss and improved quality of life with a nonsurgical endoscopic treatment for obesity: clinical results from a 3- and 6-month study. Surg Obes Relat Dis 2014;10:929–34. 29. BAROnova I. BAROnova Announces Submission of Premarket Approval (PMA) Application to the U.S. FDA for the TransPyloric Shuttle® (TPS®) Device Intended for the Treatment of Obesity [Internet]. Prnewswire.com. 2018 [cited 3 October 2018]. Available from: https://www.prnewswire.com/newsreleases/baronova-announces-submission-of-premarket-approval-pma-application-to-the-us-fda-for-thetranspyloric-shuttle-tps-device-intended-for-the-treatment-of-obesity-300681840.html

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30. Waterfront B. New endoscopic stent can lead to 100% EWL [Internet]. Bariatric News. 2018 [cited 3 October 2018]. Available from: http://www.bariatricnews.net/?q=node/102 31. Bazerbachi F, Vargas Valls EJ, Abu Dayyeh BK. Recent Clinical Results of Endoscopic Bariatric Therapies as an Obesity Intervention. Clin Endosc 2017;50:42–50. 32. Jirapinyo P, Thompson CC. Endoscopic Bariatric and Metabolic Therapies: Surgical Analogues and Mechanisms of Action. Clin Gastroenterol Hepatol 2017;15:619–30.

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33. 6. GI Windows: News Articles [Internet]. Giwindows.com. 2018 [cited 3 October 2018]. Available from: https://giwindows.com/news/view/gi_windows_announces_data_from_first_ever_clinical_study. 34. Hadefi A, Huberty V, Lemmers A, Arvanitakis M, Maggs D, Costamagna G, et al. Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes. Dig Dis 2018;36:322–4.

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35. Besafe.asmbs.org. (2018). ASMBS / SAGES Bariatric Endoscopy Verification Certificate. [online] Available at: https://besafe.asmbs.org/ [Accessed 3 Oct. 2018].

ReShape Duo®

Yes

Advantages No Permanent Anatomical changes Better tolerance compared to single balloon

Disadvantages Has to be removed after 6 months Higher mucosal injury rate during insertion

No: for Insertion Yes: For Removal

Multiple Balloons can be placed

Yes

Yes: For insertion No: for Removal

Can maintain normal oral intake

Yes

Yes, for the procedure

No need for resection of stomach

Inferior weight loss compared to fluid filled balloons External component of device, psychosocial challenges Needs General anesthesia, special scope, endoscopic skill

Yes

CE

Obalon®

AC

Aspire Assist™

Endoscopic Sleeve

Gastroplasty

Needs Endoscopy Yes: for Insertion Yes: for Removal

ED

Orbera™

FDA Approved Yes

PT

Device/Procedure

M

Table 1. Endoscopic Procedures and summary of their advantages and disadvantages

Yes: for Insertion Yes: for Removal

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No

Yes

No need for resection of stomach

Spatz 3

No

Yes: for Insertion Yes: for Removal

The Elipse™

No

No need for endoscopy

No permanent anatomical change Can stay longer or even permanent Patient can swallow the balloon without endoscopy needed

TransPyloric

No

Yes: for Insertion Yes: for Removal

The Primary Obesity Surgery,

Needs General anesthesia, special scope, inferior weight loss reported

AN US

(POSE)

Magnetic

Unknown clinical data

Yes: for Insertion Yes: for Removal

Smaller device Normal eating pattern can be maintained

Hepatic abscess formation

No

Endoscopy and laparoscopy needed for insertion

Device successfully mimics RNY gastric bypass

High risk of Complications in previous model

No

Yes, for placement of device

A true enteric bypass can be created

Limited data available

No

Yes

Resolution of Diabetes

Suboptimal weight loss

PT No

Anastomoses Duodenal

Balloon dissolves after 4 months Minor side effects associated with deflation Limited data available

Smaller device No permanent anatomical change

CE

AC

ValenTx

Smaller device with less volume related issues encountered with larger balloons

Needs endoscopy for adjustment of volume

Yes: for Insertion Yes: for Removal

ED

No

Device™

EndoBarrier

M

Shuttle TPS™

The Full Sense

CR IP T

Endoluminal

ACCEPTED MANUSCRIPT

Mucosal Resurfacing

Figure 1. Space Filling devices for weight loss Orbera

M

Figure 1Obalon

Elipse

CE

PT

ED

ReShape Duo

AC

Spatz 3

AN US

Obalon

CR IP T

Pictures:

Trans Pyloric Shuttle TPS

ACCEPTED MANUSCRIPT

Figure 2. Other Endoscopic Procedures for weight Loss ValenTx

EndoBarrier

Duodenal Mucosal Resurfacing

Magnamosis

Overstitch Device

Endoscopic Sleeve Gastroplasty

AC

CE

PT

ED

M

AN US

CR IP T

Aspire Assist

The Primary Obesity Surgery, Endoluminal (POSE)