The Orbera™ (formerly Bioenterics) intragastric balloon (Apollo Endosurgery, Austin, Texas) is an elastic spherical balloon made of silicone (Fig. 10.1). It is placed blindly into the stomach and then under endoscopic visualization is filled with approximately 500–700 mL of saline solution and often 10 mL of methylene blue which acts as an indicator of inadvertent balloon deflation via urine discoloration. It is indicated for intragastric residence up to 6 months at which time it is punctured and retrieved endoscopically. The Orbera™ balloon has been used worldwide for several decades with extensive experience and data supporting its efficacy and safety. While a Cochrane Systematic Review in 2007 lacked sufficient evidence to clearly recommend benefit on weight loss via the Orbera™ balloon, a subsequent meta-analysis from 2008 showed clear safety and efficacy data for short-term weight loss [53, 56]. This 2008 meta-analysis evaluated 3608 patients and 15 studies with estimates for weight lost at time of balloon removal after 6 months of implantation was 14.7 kg in total weight, 12.2% TWL, 5.7 kg/m² BMI, and 32.1% EWL.

However, it is important to note that there were limited data following patients post balloon removal. Regarding safety, the majority of complications were mild, and the early removal rate was 4.2%. The largest study from the meta-analysis evaluating 2515 patients from Italy included dietary counseling recommending approximately 1000 kcal/day. The reported overall complication rate was 2.8% [49]. They reported gastric perforation occurring in 5 patients (0.19%), 4 of whom had undergone previous gastric surgery. Two died and 2 were successfully treated by laparoscopic repair after balloon removal. Thus, the authors of this study concluded that the previous gastric surgery is a contraindication to BIB placement.

Of note, 19 gastric obstructions (0.76%) presented in the first week after positioning and were successfully treated by balloon removal. Balloon rupture occurred in 9 patients (0.36%) and was treated by removal. Finally, esophagitis (n = 32; 1.27%) and gastric ulcer (n = 5; 0.2%) presented in patients without a history of peptic disease and were treated conservatively with medical therapy. After 6 months, %EWL was 33.9 and BMI loss was 4.9 kg/m². Of note, there was statistically significant improvement in fasting glucose, blood pressure, and lipid markers, while hemoglobin A1c decrease or normalization was reported in 87.2% of the 488 patients with diabetes in the study.

A recent ASGE Technology Review aggregated much of the available evidence on Orbera™ in over 18 studies and cited a median %TWL of 12% at 6 months when the device was removed [57]. With respect to longer-term weight loss, they reported %EWL ranging from 11 to 51% at 12 months (6 months after balloon removal) based on 10 prospective trials with 1161 patients. Two trials reported long-term data with approximately 6% TWL maintained 36 months after implantation, and mean %EWL was 55.6% at 6 months and 29.1% at 3 years [58, 59]. One study followed patients out to 5 years after balloon placement and found that about 40% of patients presented weight loss of 7 kg, BMI reduction of 2.5 kg/m², and %EWL of 13 [60]. In another meta-analysis of 17 studies including 1638 patients, Abu Dayyeh et al. [46] reported that %EWL with the Orbera™ IGB at 12 months was 25.44 (95% CI, 21.47–29.4). Three RCTs compared %EWL in patients who received the Orbera™ IGB with a control group, with the mean difference in %EWL in patients who received the Orbera™ IGB over controls being 26.9% (95% CI, 15.6–38.2; P < 0.001) [47–49]. Finally, a recent systematic review evaluating weight loss in 547 patients and 9 trials after Orbera™ removal showed that at removal patients lost on average 16.7 kg, 6 months post-removal, had a net loss of 15.9 kg (sustaining 95% weight loss), and 12 months post-removal had a net loss of 8.7 kg (sustaining 52% of the initial weight lost) [50].

Importantly, sequential placement of IGBs after an IGB-free time interval has been suggested as a mechanism for resetting the stomach’s normal motility prior to repeating therapy to provide additional weight loss. Lopez-Nava et al. [61] and Genco et al. [62] reported that a second Orbera™ IGB after a 1-month balloon-free period led to an additional average decrease in BMI of 2.6 and 4.2 kg/m², respectively, and to an increase in the percentage of EWL from 25.1 to 51.9% compared to patients who underwent a single 6-month Orbera™ balloon placement followed by 7 months of dietary counseling [62]. Finally, Dumonceau et al. [63] found that obese patients who repeat Orbera™ IGB therapy after a balloon-free period lost approximately 9.0 kg during their second Orbera™ balloon placement in addition to the 14.6 kg lost from the first balloon.

In a meta-analysis evaluating Orbera™ safety in 68 studies [46], the most frequent side effects were pain and nausea occurring in over one-third of subjects. The pooled early removal rate was approximately 7%, and serious adverse events from Orbera™ were uncommon with an incidence of migration and gastric perforation of 1.4 and 0.1%, respectively. Notably 4 of 8 gastric perforations occurred in patients with previous gastric surgeries, and the four reported deaths were related to gastric perforation or aspiration events. While delayed gastric emptying is felt to be induced by the IGB, once removed, it is felt the there is no long-term risk of gastroparesis based on current available evidence.

The ReShape Duo^® (ReShape Medical, San Clemente, California) is an endoscopically inserted and retrieved, saline-filled, dual intragastric balloon system with 2 balloons attached to each other by a flexible tube which helps prevents migration if one balloon inadvertently deflates (Fig. 10.2). Filling volume is recommended at 900 mL of saline solution with methylene blue via a power pump delivering 450 mL to each balloon. The device is recommended for removal after 6 months similar to Orbera™. Again similar to Orbera™, ReShape Duo^® was officially FDA-approved in 2015 for adult obese patients who have a BMI of 30–40 kg/m² and who have been unable to lose weight through diet and exercise. Furthermore, patients must also have one or more obesity-related conditions such as diabetes, high blood pressure, or high cholesterol, and they must also participate in a supervised diet and exercise plan. FDA approval was based on of the REDUCE Pivotal Trial which was a prospective, sham-controlled, double-blinded, randomized, Multicenter, clinical study that enrolled 326 subjects [55]. The results showed that ReShape Duo^® patients lost over twice the amount of weight of those patients who underwent sham endoscopy with diet and exercise alone. Duo patients had significantly greater %EWL at 24 weeks (25.1% intent to treat (ITT), 27.9% completed cases (CC, n = 167) compared with control group patients (11.3% ITT, P = 0.004, 12.3% CC, n = 126). Notably, the secondary endpoint evaluating weight maintenance was not met as more than 50% of treatment subjects who lost weight with the device did not maintain greater than 40% of their %EWL for the 24 weeks after the device was removed. Regarding total weight loss, the average number of pounds in the ReShape^® group was 14.4 (6.8% TWL) versus 7.2 (3.3% TWL) in the control group at 24 weeks via ITT analysis, and 9.9 lb in ReShape^® group at 48 weeks. Balloon deflation occurred in 6% but without migrations, and early retrieval for nonulcer intolerance occurred in 9% of subjects. Gastric ulcers were observed, and a minor device change led to significantly reduced ulcer size and frequency (10%). Based on these data, the FDA felt the risk–benefit profile was favorable enough to grant approval.

The Obalon Gastric Balloon (Obalon Therapeutics Inc., Carlsbad, California) is a 250-mL gas-filled balloon that is packaged within a large dissolvable gelatin capsule. It is swallowed under fluoroscopic visualization but does not require endoscopic placement. A catheter, which extends through the esophagus and outside the mouth, is used to fill the balloon by using a gas-filled canister. The Obalon balloon requires endoscopic removal via puncture and forceps extraction. Up to 3 balloons can be swallowed during the same or sequential sessions, and balloons are removed endoscopically after 12–24 weeks. The target population is patients with BMI 27 or greater who have failed previous conservative measures for weight loss. Initial feasibility data demonstrated proof of concept for preliminary safety and efficacy in 17 patients [64]. Based on data from the European Union Limited Market Release (unpublished data from Obalon) from eleven centers throughout Belgium, Germany, Italy, and Spain studying 119 subjects in the absence of a control group, they found a 50.2% EWL, 8.3% %TWL, 2.8-point reduction in BMI, and mean weight loss of 8.0 ± 5.8 kg over the 3-month period. In this study, most commonly reported adverse events were nausea (10.1%), vomiting (6.7%), and 9 patients (7.6%) requested early removal of balloons mainly due to a lack of commitment to the full 3-month therapy period. One (0.8%) small (<1 cm), nonbleeding ulcer was observed during the endoscopy to remove balloons at the end of the treatment period and was reported as possibly related to the contraindicated use of NSAIDs. Finally, one esophageal laceration (0.8%) was observed after balloon removal in a patient diagnosed with eosinophilic esophagitis. While the device is currently not FDA-approved, the US Pivotal Trial for the Obalon IGB has been under way with published results awaiting release.

The Elipse™ balloon (Allurion Technologies, Wellesley, MA) is another example of an intragastric balloon. While an IGB is technically not an EBT, as novel technology is utilized eliminating endoscopy and sedation for both implantation and removal, these devices should be included under nonsurgical approaches to procedural management of obesity. The Elipse is enclosed inside a capsule and is attached to a thin, flexible catheter long enough to remain outside the patient’s mouth once the capsule is swallowed (Fig. 10.3). Once in the stomach the capsule quickly dissolves, the balloon is filled with 550 mL of fluid. When filling is complete, the detachable catheter is removed. The Elipse balloon is designed to remain within the stomach for a predetermined period of several months, at which point a valve opens based on timed-release technology, allowing the balloon to empty automatically from the stomach and be excreted spontaneously from the GI tract. In a proof-of-concept pilot study, 8 patients swallowed a smaller prototype Elipse balloon intended to remain in the stomach for 6 weeks, self-empty, and then pass [65]. There were no serious adverse events, and all balloons were swallowed as well as excreted safely. Despite not being prescribed a diet or exercise plan, all eight patients lost weight, and after 6 weeks of Elipse therapy, the mean weight loss was 2.4 kg and mean %EWL was 12.4%. In results presented at the 2015 Obesity Week conference and submitted for publication, a larger study of 34 individuals with BMI between 27 and 40 found an average weight loss of 10 kg (22 lb), 39% EWL, 10% TWL, and 8 cm off their waist circumference over the 4-month treatment period, with improvements in triglycerides, hemoglobin A1c, and quality of life. All balloons were safely and naturally excreted. In 2015, the device received European Marketing Approval and is in the planning phases for a US Pivotal Trial-seeking FDA approval.

The Spatz3 Adjustable Balloon System^® (Spatz Medical, Great Neck, NY) is an endoscopically placed IGB that is filled with saline. It has an extractable inflation tube allowing for variable volume adjustment while the balloon remains in the stomach. Balloon volume may be increased to enhance the efficacy or decreased to improve the patient tolerance and is approved for 12-month implantation outside of the USA. Regarding efficacy data, two small observational studies evaluated weight-loss outcomes after Spatz3 Adjustable Balloon^® deployment in 94 obese patients. At 12 months, when the balloon was removed, %EWL was 46% [66, 67]. Finally, a case–control study comparing Spatz3^® to Orbera™ balloons found no difference in weight-loss outcomes at 12 months. The study evaluated 80 patients who had sequential placement of two Orbera balloons (6 months each) to 40 patients with the Spatz3 adjustable balloon for 12 months; however, 15% of the Spatz devices were removed due to complications related to device hardware and migration [68]. Newer versions of the Spatz3 balloon are addressing these engineering challenges.

Endoscopic sleeve gastroplasty (ESG) is a transoral endoscopic gastric volume reduction procedure that reduces gastric capacity in a similar fashion to sleeve gastrectomy without the need for gastric surgery. The Apollo OverStitch™ device (Apollo Endosurgery, Austin, TX), which is FDA-approved, allows placement of full-thickness sutures in a variety of interrupted or running patterns using a double-channel therapeutic gastroscope (Fig. 10.4a). ESG is accomplished by placing these full-thickness sutures through the gastric wall utilizing a tissue helix device to capture tissue extending from the prepyloric antrum to the gastroesophageal junction reducing the entire stomach along the greater curvature (Fig. 10.4b). Increasing data have been published showing the safety and efficacy of ESG. A 20-subject trial from Spain, in subjects with a mean baseline BMI of 38.5 kg/m², demonstrated a mean body weight reduction of 19.3 ± 8.9 kg at 6 months (17.8% TWL). In a New York study, ESG was performed on 10 subjects with a mean BMI of 45.2 kg/m² and reported no significant adverse events [69]. After 1 month, 3 months, and 6 months, excess weight loss of 18, 26, and 30% and mean weight loss of 11.5, 19.4, and 33.0 kg, respectively, were observed. In a 1-year follow-up study from Spain with 25 patients, there were no major intraprocedural, early, or delayed adverse events from ESG, and mean %TWL was 18.7 ± 10.7 at 1 year. In regression analysis, predictors of successful weight loss were the number of nutritional and psychological contacts each patient had. Notably, at 1-year follow-up, only one patient underwent a revision partial gastroplasty because of loosened applications, demonstrating significant durability of ESG suture lines. Finally, a Mayo Clinic series of 25 patients with mean BMI of 35.5 ± 2.6 kg/m² has been released [70]. After 6, 9, 12, and 20 months, subjects had lost 53 ± 17%, 56 ± 23%, 54 ± 40%, and 45 ± 41% of excess body weight, respectively, after the procedure. Endoscopy at 3 months showed intact gastroplasty in all subjects. Physiological analyses of 4 patients showed that ESG delays gastric emptying and induces early satiety. Finally, 3 subjects had serious adverse events (a perigastric inflammatory collection, a pulmonary embolism, and a small pneumothorax) but made full recoveries without surgical intervention.

These studies suggest that ESG is a promising procedure for significant weight loss in patients seeking endoscopic alternatives to sleeve gastrectomy. However, more data are needed to evaluate long-term durability and safety of the endoscopic gastroplasty procedure. As with any stomach-excluding procedure, the risk of disease such as ulcers or gastric cancer in the remnant stomach remains. The Primary Obesity Multicenter Incisionless Suturing Evaluation (PROMISE) trial (NCT01662024) to study efficacy of ESG using OverStitch™ has been completed in the USA, but the results are not yet available. Finally, as with other EBTs, USA insurance companies do not yet cover this procedure, and thus, costs can be significant to the patient.

The incisionless operating platform (IOP) used to perform the primary obesity surgery endoluminal (POSE) procedure uses a per-oral incisionless operating platform (USGI Medical, San Clemente, CA) to place 8–10, full-thickness, tissue anchor applications that reduce accommodation of the gastric fundus. Several applications are also placed in the distal gastric body to delay gastric emptying (Fig. 10.5a, b). The large overtube-style platform of the IOP is the TransPort^®, which is steerable in 4 directions, with 4 working channels that accommodate a slim 4.9-mm endoscope and 3 specialized instruments. These include the g-Prox^®, a flexible endoscopic grasper with a jawed gripper for creating serosa-to-serosa tissue folds and able to cut suture, the g-Lix™, a flexible tissue grasper with a distal helical tip designed to assist the g-Prox^® in capturing target tissue for a full-thickness plication, and the g-Cath™, a suture–anchor delivery catheter system with a needle at its distal tip that, after advancement through the lumen of the g-Prox^®, penetrates the target tissue deploying a pair of preloaded tissue anchors joined by suture material which holds the plication until serosal fusion occurs. A single-center, open-label, prospective trial from Spain enrolling 45 obese patients with mean BMI of 36.7 kg/m² demonstrated the feasibility and safety of the POSE procedure [71]. At 6 months, BMI decreased by 5.8 kg/m², %EWL was 49.4%, and %TWL was 15.5% without any operative morbidity or mortality. Subjects reported less hunger and earlier satiety post-procedure. Liquid intake began 12 h post-procedure, with full solids by 6 weeks. The ESSENTIAL Trial (NCT01958385) is a US multicenter, randomized, sham-controlled, pivotal trial of the POSE procedure which has enrolled 332 subjects for goal follow-up of 12 months to evaluate safety and efficacy endpoints. Results of this trial are expected to be released shortly.

The EndoBarrier^® (GI Dynamics, Lexington, MA) is a duodenojejunal bypass sleeve (DJBS) consisting an impermeable sleeve of Teflon anchored in the bulb of the duodenum by a nitinol crown with barbs. The 65-cm sleeve and anchoring device are restrained within a delivery capsule that is advanced to the duodenal bulb over a stiff wire under endoscopic and fluoroscopic guidance and subsequently deployed. The sleeve extends into the jejunum and prevents food contents from contacting the mucosa of the proximal small intestine, allowing food to reach the mid-jejunum earlier. However, the sleeve allows pancreaticobiliary secretions to move along the outside of the device to the jejunum. The EndoBarrier^® is removed endoscopically after 12 months via a custom device retrieval hood to help avoid trauma to the stomach or esophagus upon explantation. Out of seven studies involving EndoBarrier, the %EWL ranged between 12% and 22% at 12 weeks, 24 and 32% at 24 weeks, and 30 and 47% at 52 weeks [75–81]. A meta-analysis of four RCTs from these studies compared 12–24 weeks of treatment with the EndoBarrier^® DJBS (90 patients) with a sham or control arm (84 patients). The mean %EWL difference compared with a control group was significant at 9.4% (95% CI, 8.26–10.65) [46]. Improvement in % hemoglobin A1c was significant compared with sham or control diabetic group, where the EndoBarrier^® DJBS resulted in an additional 1% reduction compared to controls [46]. Regarding the safety profile of the EndoBarrier^®, this same meta-analysis reviewed the 271 implantations in the literature and found a pooled early device removal rate of 18.4%. Serious adverse events included migration (4.9%), GI bleeding (3.86%), sleeve obstruction (3.4%), liver abscess (0.126%), cholangitis (0.126%), acute cholecystitis (0.126%), and esophageal perforation (0.126%) secondary to trauma from an uncovered barb at withdrawal. Notably, the multicenter US Pivotal ENDO Trial (NCT01728116) was placed on hold in March 2015 by the FDA after reports of 7 cases of hepatic abscess among the 325 patients already enrolled of the 500 initial sample size. Thus, the future clinical use of EndoBarrier in the USA is uncertain.