Endoscopy in the Management ofObesity

Shelby Sullivan, MD

KEYWORDS

� Weight regain � Endoscopic bariatric revision � Endoscopic bariatric therapy� Intragastric balloon � Duodenal jejunal bypass liner

KEY POINTS

� Obesity affects more than one third of adults in the United States and is associated withincreased morbidity, mortality, and health care costs.

� Current treatment options include medical management with therapeutic lifestyle changeand pharmacotherapy, as well as bariatric surgery; however, these treatments havelimitations.

� Endoscopic therapies are emerging as potential tools to address the limitations of thecurrent obesity therapies.

The latest National Health and Nutrition Examination Survey data from 2009 through2010 indicates 35.5% of adult men and 35.8% of adult women in the United Stateshave a body mass index (BMI) of >30 kg/m2.1 Obesity adversely affects every organsystem, and it increases morbidity and mortality.2–4 In addition, recent data suggeststhat there is a 2- to 3-fold increase for incremental health care costs in obese adults inthe United States compared with normal weight adults.5 Given the prevalence ofobesity and its associated morbidity, mortality, and increasing health care costs, itis imperative that the medical community addresses this disease.Unfortunately, current treatment options for obesity are limited. Therapeutic lifestyle

change (TLC) consisting of diet, exercise, and behavior modification results in up to10% short-term weight loss, but 5% or less weight loss in the long term.6 Weightloss medications increase weight loss by 3% to 5% over placebo and are more likelyto result in 10% weight loss in patients than TLC alone7; however, medical therapymust be continued long term to maintain any weight loss achieved with the medica-tion. Bariatric surgery has been shown to be superior to TLC8,9 and pharmaco-therapy10 for weight loss and weight maintenance, and remains the most effective

Disclosures: Site investigator for both ReShape Duo (ReShape Medical) and EndoBarrier(GI Dynamics).Division of Gastroenterology, Center for Human Nutrition, Washington University School ofMedicine, 660 South Euclid Avenue, Campus Box 8124, St Louis, MO 63110, USAE-mail address: ssulliva@dom.wustl.edu

Gastrointest Endoscopy Clin N Am 23 (2013) 165–175http://dx.doi.org/10.1016/j.giec.2012.10.009 giendo.theclinics.com1052-5157/13/$ – see front matter Published by Elsevier Inc.

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treatment option available for obesity. Although short-term costs for the surgery andpostoperative complications are high, long-term cost–benefit analyses favor bariatricsurgery over medical management of obesity.11 Minor postoperative complicationsoccur frequently, but serious complications occur in 5% or fewer of post bariatricsurgery patients and the mortality rate is low.12 However, 2 issues continue to plaguebariatric surgery: Failure of weight loss or weight regain and limited access to surgery.Although the number of bariatric procedures performed per year has increased from9189 in 1993 to 124,838 in 2008,13 this only represents approximately 1% of obesepersons who qualify for a bariatric surgical procedure.12 Endoscopic bariatric proce-dures have emerged as potential options that not only address both of these issues,but also have reduced associated morbidity and mortality as well.

ENDOSCOPIC THERAPY FOR WEIGHT LOSS FAILURE

Weight regain has been reported in long-term studies, capturing patient weight10 years or more after the original bariatric surgical procedure.14–16 In the SwedishObesity Study, 8.8% of Roux-en-Y gastric bypass (RYGB) patients and 25% of adjust-able gastric banding patients maintained less than 5% of their weight loss at10 years.14 Similar rates of weight loss failure at 10 or more years of follow-up, asdefined by end BMI compared with starting BMI,17 were seen in patients afterRYGB and Bilioopancreatic Diversion (BPD), but were higher in patients with higherpreoperative BMI.15,16,18

Although multiple factors likely play a role in weight regain, the factors that may betreated by endoscopists include gastro-gastric fistulas, stoma dilation, and pouch dila-tion. Some controversy exists regarding the role of stoma and pouch dilation in weightregain. Multiple early studies did not show a correlation between pouch diameter andweight loss19–24; however, some early studies did show a correlation,25 even in thesetting of extensive behavior modification therapy.26 More recently, both pouch size27

and stoma diameter have been shown to be significantly correlated with weight lossfailure or weight regain in both univariate and multivariate analyses,28,29 but not in allstudies.30 Heneghan and colleagues29 found small, but significant differences pouchlength (5.0 � 2.4 vs 5.8 � 2.6 cm; P 5 .005) and stoma diameter (2.1 � 0.8 vs 2.5 �1.0 cm; P<.001) in the control (no weight regain) compared with weight regain groups,respectively. Failure to loseweight orweight regain hasbeen treatedbybariatric surgicalrevision with mixed outcomes. Weight loss has been demonstrated, but the surgicalcomplication rates are higher than with the index procedure.31–34 Given the risk of revi-sional surgery, endoscopic approaches including the use of sclerosants to decreasestoma diameter, as well as decreasing stoma and pouch size with suturing, tissue plica-tion, or clips have been investigated as safer options compared with surgery.Sclerotherapy of dilated gastrojejunostomies was first described in 2003,35 and

since then a number of series using sclerotherapy for dilated stomas have been pub-lished with weight loss or weight stabilization in 50% to 91.6% of patients at1 year.36–40 The largest of these series included 231 patients with weight regain andan average baseline gastrojejunostomy stoma diameter that was 19 mm. Thesepatients were treated with an average of 2 sclerotherapy sessions and 16 mL ofsodium morrhuate injected at each session.40 The average weight loss 6 months aftersclerotherapy was 18% of the weight that had been regained, and 76% of patients lostmore weight or maintained their 6-month weight loss at 12 months. Complicationsincluded bleeding (2.4% immediate and 0.2% delayed), abdominal pain requiringadmission (0.5%), and small ulcers on repeat endoscopy (1%). Baseline stoma diam-eter was not a predictor of response to sclerotherapy.

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The Endocinch Suturing System (C.R. BARD Inc, Murray Hill, NJ, USA) was pilotedby Thompson and colleagues41 in 2006. The authors used a technique of mucosalablation with argon plasma coagulation followed by placement of 2 sutures onaverage and then tightening the sutures to form tissue plications. The average stomadiameter was reduced to 10 mm (68% reduction), and patients had an average excessweight loss of 23.4%. This device has also been studied in a randomized, double-blinded, sham-controlled, multicenter trial of 77 patients. Patients included in thestudy had baseline stoma diameters of more than 20mm. The authors achieved a gas-trojejunostomy of 10 mm or less in 89% of patients randomized to the treatment armwith an average number of 4 sutures placed. A trend was seen in the intention-to-treatanalysis with more weight loss in the treatment group compared with the control group(4.2 � 5.4% and 1.9 � 5.2%; P 5 .066) at 6 months.42

The Incisionless Operating Platform (USGI Medical, San Clemente, CA, USA) isa tissue plication system that places expandable tissue anchors to hold tissuetogether. Two small pilot studies of decreasing stoma diameter and pouch length inpatients with weight regain after RYGB demonstrated short-term weight loss of 7.8to 8.8 kg at 3 months.43,44 Data from a multicenter registry of 116 patients reported32% (6.5 � 6.5 kg) of the regained weight was lost at 6 months with stoma diameterreduced by 50% to 11.5 mm, and pouch length reduced by 44% to 3.3 cm.45 At12 months post-procedure, 73 of 112 subjects with successful procedures had a totalweight loss of 5.9 � 1.1 kg.46

The StomaphyX device (EndoGastric Solutions Inc, Redmond, WA, USA) is a tissueplication device that uses polypropylene H-fasteners to approximate serosal surfaces.This device was first used to treat weight regain with 39 patients who were at least2 years out from RYGB and had gained at least 10% of their lowest weight.47 Excessbody weight loss was 19.5% 12 months post-procedure; however, only 6 of39 patients returned for the 12-month follow-up. Another study of 64 patients usedan average of 23 H-fasteners and reported a 33% decrease in gastric pouch lengthand the stoma was reduced from 22 to 9 mm.48 The average weight loss was7.3 kg, but the mean follow-up was only 5.8 months. Two other small studies haveshown weight loss after endoscopic revision with StomaphyX.49,50

Over-The-Scope-Clips (Ovesco, Tubingen, Germany) have also been used toreduce stoma diameter to treat weight regain after bariatric surgery. One study re-ported 94 subjects whose stoma diameter was reduced from 35 to 8 mm with place-ment of up to 2 Over-The-Scope-Clips placed on opposite sides of the stoma.51 MeanBMI decreased from 32.8� 1.9 to 27.4� 3.8 kg/m2 at 12 months; however, 2 patientsrequiring dilation of the stoma to 12 mm owing to persistent dysphagia.Although these case series are encouraging, further research in endoscopic therapy

of weight regain after bariatric surgery is needed. First, only one endoscopic bariatricrevision procedure has been studied in a randomized, double-blind, sham-controlledstudy, and only a trend was seen toward more weight loss in the treatment group.42

This may in part be due to either patient selection or the underlying cause for thestoma and pouch dilation, which has yet to be determined. Based on the variabilityin the pre-endoscopic revision stoma and pouch diameter seen in these cases seriesas well as the study by Heneghan and colleagues demonstrating statistically differentbut clinically similar stoma diameter between patients with weight regain and thosemaintaining their weight loss, it is unclear which patients are most likely to benefitfrom these procedures. However, given the weight loss seen in many patients andthe significantly decreased risks associated with endoscopic stoma and pouch revi-sion compared with surgical revision, endoscopic treatment of weight regain afterbariatric surgery remains a promising therapeutic option.

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PRIMARY ENDOSCOPIC BARIATRIC THERAPY

Endoscopic bariatric therapy (EBT) is still in its infancy, and currently no EBT deviceshave been approved for use in the United States; however, there are many advantagesto EBT compared with traditional bariatric surgery. First, although weight loss withEBT is likely to be less than most bariatric surgical procedures, EBT is associatedwith lower complication rates and shorter recovery times than bariatric surgery.Both the lower risk profile and decreased recovery time may increase the number ofpatients willing to undergo a weight loss procedure. In addition, because most EBTonly require conscious sedation, sicker patients who may not be good candidatesfor surgery may still qualify for endoscopic placement of a device. Further, althoughbariatric surgery is the most effective therapy for weight loss at the patient level, itis limited by the number of patients who can be treated per year, restricting its effecton obesity treatment at the population level. Owing to both the number of practicinggastroenterologists and the short amount of time required for these procedurescompared with bariatric operative procedures, the number of patients who couldundergo EBT potentially dwarfs the number of patients who are able to undergo bari-atric surgery per year, making more of an impact on obesity at the population level.Multiple devices have been or are currently in the development and testing stagesfor EBT; however, for the purposes of this review, only technologies that have pub-lished data and are still viable are discussed.

INTRAGASTRIC BALLOON

The intragastric balloon (IGB) is a device that was designed to occupy space andcause gastric distension with the goal of decreasing food intake. The first IGB device,the Garren-Edwards Gastric Bubble, was approved for use by the US Food and DrugAdministration in 1985; however, it was taken off of the market in 1992 owing to bothcomplications (including damage to the gastric mucosa and balloon deflation withsubsequent small bowel obstruction) and lack of difference between the device andTLC in sham-controlled trials.52–59 These 2 issues were thought to be related to thedesign of the device itself. First, the device volume was only 220 mL when distended,and evidence suggests that a volume of at least 400 mL is needed for a reduction offood intake,60 and the device had a cylindrical shape with edges, which damaged themucosa. In addition, it was made from polyurethane that was too easily deflated.Several new designs including the BioEnterics IGB (BIB; Allergan, Irvine, CA, USA),ReShape Duo (ReShape Medical, San Clemente, CA, USA; Fig. 1.), the HeliosphereIGB (Helioscopie, Vienne, France), and the Spatz Adjustable Balloon System (SpatzFGIA, Jericho, NY, USA) have been developed and address the issues surroundingthe failure of the Garren-Edwards gastric bubble. Although these devices havedifferent designs to decrease balloon rupture and migration, they all have eliminatededges to reduce mucosal damage and have increased device volume to induce aneffect on food intake.Data suggest the current IGBs are effective at inducing weight loss significantly

greater than lifestyle therapy alone or pharmacotherapy. A randomized, controlled,cross-over trial demonstrated superiority of IGBs to pharmacotherapy with sibuatr-amine (14.5 � 1.2% compared with 9.1 � 1.5% total body weight loss; P<.05).61

Imaz and colleagues62 performed a meta-analysis on 15 studies with a total of 3608subjects receiving the BIB. Mean weight loss across studies was 14.7 kg or 12.2%of total body weight. Only 2 randomized controlled trials were included; however,these 2 studies attributed 6.7-kg of the weight loss to the BIB. Complications wererare, but included 26 cases of obstruction in the gastrointestinal tract, 4 cases of

Fig. 1. Illustration of the ReShape Duo in the stomach after being filled with 450 mL ofsaline in each of the balloons. (Courtesy of ReShape Medical, Inc, San Clemente, CA, USA;with permission.)

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gastric perforation, and 2 deaths related to gastric perforations. Four percent ofsubjects underwent early removal of the BIB. These studies did not have longfollow-up; however, a subsequent study of 195 subjects who completed 60 monthsof follow-up demonstrated a 13% excess weight loss with 23% of subjects maintain-ing more than 20% excess weight loss.63 In addition, IGBs have been evaluated forshort-term weight loss before surgeries such as laparoscopic gastric bypass witha significant decrease in weight compared with control subjects and a 75% reductionin the composite endpoint of conversion to open gastric bypass, intensive care stay oflonger than 2 days, or hospital stay of longer than 2 weeks (P 5 .031).64

Studies have also investigated the repeated use of IGB for long-term weight losstherapy. Genco and colleagues65 reported 100 obese patients who were randomizedto receive the IGB for 6 months followed by lifestyle therapy alone or IGB followed byanother IGB placement 1 month later for 6 months. At 6 months, the percent excessweight loss was the same in the 2 groups (43.5 � 21.1% and 45.2 � 22.5%, respec-tively); however, at 13 months the percent excess weight loss was greater in patientsreceiving 2 consecutive IGB placements compared with the patients receiving 1 IGBplacement followed by lifestyle therapy (51.9 � 24.6% and 25.1 � 26.2%, respec-tively). Another study with 5-year follow-up compared patients who requestedrepeated IGB compared with patients who had only 1 IGB placement and found nodifference in percent of subjects with at least 10% total body weight loss at 5 years.66

Taken together, these data suggest that the current generation of IGBs have lowercomplication rates than the first generation of IGB. IGB placement is an effective toolfor short-term weight loss, and preoperative weight loss with IGB may decreasecomplications in surgeries, such as bariatric surgery. Furthermore, some patientsmay be able to maintain a portion of the weight loss achieved with the IGB withoutfurther intervention, whereas some patients may benefit from further IGB placement.Additional research is needed to address these long-term management questions.

DUODENAL JEJUNAL BYPASS LINER

The duodenal jejunal bypass liner (DJBL; EndoBarrier, GI Dynamics, Boston, MA,USA; Fig. 2) is an endoscopically placed and retrieved impermeable liner that anchorsin the duodenal bulb and extends 60 cm into the small bowel. The device is meant tomimic the effects of bypassing the duodenum in bariatric surgery. Although human

Fig. 2. Photograph of the EndoBarrier, a duodenal jejunal bypass liner. (Courtesy of GIDynamics, Inc, Lexington, MA, USA; with permission.)

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data examining the effects of bariatric surgery on glucose metabolism andmulti-organinsulin sensitivity independent of weight loss are limited, recent data from animalmodels suggest that jejunal nutrient sensing after duodenal exclusion plays a role inthe early improvement in glycemic control after duodenal jejunal bypass surgery.67

The first human experience with the DJBL was published in 2008 with 12 subjects ina 12-week, open-label, prospective study.68 Although 2 subjects underwent explant at9 days (owing to the position of the device placement), no serious adverse eventsoccurred. Subjects lost 23.6% excess weight loss at 12 weeks and reportedly 4subjects who had type 2 diabetes before device placement attained normal fastingserum glucose concentrations off of oral hypoglycemic medications, although theserum glucose concentrations were not reported. Since then, a few studies havebeen published for preoperative weight loss in patients who are candidates for bariat-ric surgery. A single-center, 12-week, randomized, controlled trial demonstrateda 22.1 � 8% (n 5 20) compared with 5.3% � 6.6% (n 5 4) excess weight loss inthe DJBL compared with control groups (P 5 .02),69 and a 12-week, multicenter,randomized, controlled trial with extension to 24 weeks in 3 subjects in the DJBLgroup, revealed a similar weight loss of 19.0 � 10.9% compared with 6.9 � 6.1%excess weight loss in the DJBL (n 5 24) and control groups (n 5 11; P<.002). Asham-controlled trial for preoperative weight loss, however, demonstrated 11.9 �1.4% compared with 2.7 � 2% excess weight loss in the DJBL (n 5 13) and controlgroups (n 5 24), respectively (P<.05).70 A 24-week, randomized, sham-controlled trialalso demonstrated superiority of the DJBL over sham control for decreasing HbA1c inpatients with type 2 diabetes (–2.4 � 0.7% and –0.8 � 0.4% in the DJBL and controlgroups respectively; P<.05).71 In addition, an open-labeled study revealed a decreasein HbA1c (–2.3 � 0.3%) in 13 subjects who completed 52 weeks of treatment with theDJBL.72 It is important to note that 17% to 40% of subjects enrolled in these studieshad early device removal predominantly due to gastrointestinal bleeding, abdominalpain, nausea and vomiting, anchor migration, or obstruction. However, few seriousadverse events have been reported and no surgical interventions or deaths havebeen reported in relation to the DJBL.

TRANSORAL GASTRIC VOLUME REDUCTION

Transoral gastric volume reduction (Fig. 3) uses endoluminal suturing devices toreduce gastric volume to limit food intake; to date, 1 pilot study—the TRIM trial—has been reported.73 The TRIM trial was an open-label, prospective, multicenter,single-arm feasibility study using the RESTORe Suturing System (Bard/Davol,

Fig. 3. Panel A Illustration of sutures being tightened with the RESTORe Suturing System.Panel B Illustration of a completed plication approximating the anterior and posterior wallsof the stomach. (From Brethauer SA, Chand B, Schauer PR, et al. Transoral gastric volumereduction as intervention for weight management: 12-month follow-up of TRIM trial.Surg Obes Relat Dis 2012;8(3):296–303; with permission.)

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Warwick, RI, USA) to plicate the anterior and posterior walls of the stomach, resultingin reduced gastric volume owing to the approximation of the anterior and posteriorgastric walls. A total of 18 patients received an average of 6 plications; however,only 14 subjects completed 12 months of follow-up demonstrating a weight changeof –11.0 � 10.0 kg and 27.7 � 21.9% excess weight loss. No serious adverse eventsoccurred, but plication was only successful in 16 patients and at 12-month endoscopyall sutures had spontaneously released in 5 subjects.

SUMMARY

Endoscopic therapies for both primary treatment of obesity and weight regain afterbariatric surgery have made significant advances. Although further research is neces-sary, these emerging technologies are poised to providemuch needed additional toolsfor the management of obesity. This will allow endoscopists to fill an important void inthe current spectrum of obesity therapy.

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