Endoluminal Treatment Options for Morbid Obesity: Devices and Techniques for Natural Orifice Approaches

by Rebecca P. Petersen, MD, MSc; Bipan Chand, MD; and Aurora D. Pryor, MD

The second article in this series is written by DRs. rebecca P. Petersen and Aurora D. Pryor, from the Duke Center for Weight Loss and Metabolic Surgery, Duke University Medical Center, Durham, North Carolina; and DR. BIPAND CHAND, from the Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio. Dr. Marc Bessler, a leading authority in the surgical treatment of obesity, is the Column Editor of this series, and Surgical Director, New York-Presbyterian Hospital Center, for Obesity Surgery, and Assistant Professor of Surgery, Department of Surgery, Director of Laparoscopic Surgery, Columbia University College of Physicians and Surgeons, New York, New York.

Introduction
The prevalence of obesity is increasing and threatens to be the major public health problem in the foreseeable future. Data from the National Health and Nutritional Examination Survey (NHANES) estimated in 2005 that 24 percent of the US population was obese, defined as having a body mass index (BMI) over 30kg/m2. Current projections are that the prevalence will continue to increase, raising serious public health concerns.1,2 Obesity is associated with a variety of comorbidities, including hypertension, diabetes, dyslipidemia, and musculoskeletal disorders. For the morbidly obese, surgical techniques have demonstrated the only effective long-term weight loss and have been shown to reduce markers of serious metabolic diseases including diabetes and dyslipidemia.1

In recent years, more than 100,000 bariatric procedures were estimated to have been performed annually3 and—given the increasing prevalence of obesity—use of these procedures likely will increase. However, no optimal single procedure has been identified, and the procedures currently performed for morbid obesity have risks associated with them. For example, among patients undergoing Roux-en-Y gastric bypass procedures a recent meta-analysis found a mortality of 0.5 percent.4

Given the prevalence of the disease and the risks of conventional procedures, considerable effort has been directed toward improving current surgical techniques. Many of the advances on the horizon in bariatric medicine focus on natural orifice therapies, which are the focus of this review. Natural orifice approaches may minimize the anesthetic and wound issues associated with traditional surgical approaches.

Natural Orifice Procedures—The New Frontier
A common use of the natural orifice route may be the placement of a short-term device to reduce operative mortality or morbidity of a definitive bariatric procedure. Natural orifice approaches are also used for revisional bariatric procedures to reduce a stoma size, to repair a fistula, or to create a new anastomosis. In many cases, endoluminal revision may help minimize some of the difficulty in standard revisional surgery by avoiding adhesions in the new operative plane. Finally, de novo primary bariatric surgical procedures via a natural orifice are considered the new frontier for bariatric procedures.5, 6

Endoluminal Procedures
Several devices have been developed (and adapted) to facilitate the endoluminal approach to bariatric procedures. These devices range from simple space-occupying devices to complex suturing platforms to combine restrictive and malabsorptive devices. The most important issue in developing devices for less invasive weight loss surgery is to ensure their safety. Usage data from the intra-gastric balloon, which are discussed in this article, demonstrate that patients are willing to undergo these procedures without clinical evidence of success and moderate safety profiles. As these technologies are developed, it is important that patient safety is ensured while designing devices that are both effective and technically easy to deploy.

Endoscopic Restriction Procedures
Balloon and obstructive-based devices. One of the first endoluminal devices for morbid obesity was the Garren-Edwards bubble, a cylindrically shaped, space-occupying device placed endoscopically into the gastric lumen. The initial concept was proposed in 1982 and the device received FDA approval in 1985. The device was embraced by the clinical community and 25,000 devices were placed despite minimal clinical data to support its use. Subsequently, several sham-controlled trials showed minimal benefit of the device. Complications including ulcers and erosion were found in 40 percent of patients, small bowel obstruction in two percent of patients, and Mallory-Weiss tears in 11 percent of patients.7,8 Given poor patient tolerability and efficacy, the device was removed from the market in 1988.

BioEnterics Corporation (Carpinteria, California) worked to develop an improved version of the Garren-Edwards Bubble and released the BioEnterics Intragastic Balloon (BIB) system in the mid-1990s.9 The device is available internationally but currently is not FDA approved for use in the United States (US). However, clinical trials are currently underway in the US. Several case studies have demonstrated good short- to mid-term results with the device, suggesting that this can be successfully delivered and is associated with weight loss. A clinical trial randomized 43 patients to the BIB or a sham procedure for three months, followed by balloon placement and exchange every three months for an additional nine months. Patients were then followed for 12 months after BIB removal. Overall, patients in the study lost 30 percent excess weight and had some sustained weight loss at one year after removal. However, both the sham and BIB groups lost weight and no significant difference was appreciated between groups. Patients in both groups experienced frequent symptoms with the BIB in place, including nausea, vomiting, and pyrosis occurring over 50 percent of follow-up days. All of these complaints were more prevalent in the group that had the sham procedure before BIB placement. The authors concluded that the BIB was safe, though patients had frequent complaints, but the benefit of balloon over sham was not proven. Subsequent reports have found that the BIB can be deployed for up to six months without significant morbidity.10

More recently, the gastric retention technologies group of BaroNova Therapeutics, Inc. (Foster City, California) has developed a polymer pill that expands to take up space in the stomach for one week after ingestion or delivery. In theory, this pill would degrade and pass through the gastrointestinal (GI) system and can be taken at regular intervals and titrated based upon response.11 While this technology has not yet been clinically tested, it appears promising.

Suture and staple-based devices. Many manufacturers have attempted to develop endoscopic suturing and stapling devices to promote volume reduction as well as add possible elements of malabsorption. Concepts have included endoluminal gastroplasties, restrictive valves, and combined approaches to restriction and malabsorption. While many of these devices are promising for endoluminal approaches to bariatric surgery, few of the devices or techniques are proven in terms of efficacy or safety.

An endoscopic vertical banded gastroplasty (VBG) has been reported and uses a vertical ring gastroplasty created with an endoscopic sewing machine (Endoscopic Sewing Machine; CR Bard, Inc., Murray Hill, New Jersey) mounted at the tip of a flexible endoscope. This procedure utilizes a 3cm plastic ring sutured to the lesser curvature of the stomach 8cm from the gastroesophageal junction. Next, an 8cm-long tube is created along the lesser curvature by suturing the anterior and posterior walls of the stomach with the endoscopic sewing machine. Survival studies have not shown this to be durable or effective.12

Other suturing devices are in various stages of development. Satiety (Palo Alto, California) has developed The TOGATM System transoral gastroplasty (Figures 1-3). A safety trial in 21 patients was successfully completed. In this group, at six months patients had lost an average of 26.5 pounds and 24.4 percent of their excess body weight.13 The side effects of the procedures were transient and included nausea, vomiting, dysphagia, and pain. There were no serious adverse events. At the six-month follow-up endoscopy, however, there was some staple-line disruption in 13 patients. Despite these shortcomings, this is the most promising of the gastric restrictive devices to date.

The Eagle Claw prototype endoscopic suturing device (Olympus Corporation, Tokyo, Japan) has been used in a porcine model to create a gastric pouch entirely from within the gastric lumen.14 While no survival studies with this approach have been published, work is ongoing to refine and perfect the technique in animal models. The SafeStitch device may also be used for an endoluminal gastroplasty (Figures 4-5). This device uses a suction-facilitated endoluminal mucosectomy followed by suture placement to create a gastric pouch while excluding mucosa from the suture line. Clinical trials are starting this year.

Endoluminal placement of intragastric mesh has also been attempted. In this procedure, mesh was passed transorally and secured with laparoscopic intragastric suturing. The final outcome was a 30ml to 50ml gastric reservoir emptying through a 1.5cm central aperture. Two of 10 dogs in the study had 100-percent adherence of the mesh. Four of 10 had some adherence. This left 4 of the 10 with no mesh adherence, suggesting that this approach is not conducive to broader therapeutic applications without novel ways to increase mesh adherence.15

Other devices have been developed that may have use in endoluminal restrictive procedures. Power Medical (Power Medical Interventions, Inc., Langhorne, Pennsylvania) has recently released a transoral stapling device that can provide endoluminal stapling. The Endoscopic Suturing Device by Wilson-Cook (Wilson-Cook Medical, Winston-Salem, North Carolina) could also be applied for this technique. While these devices have not yet been studied specifically in endoluminal restrictive procedures, they may facilitate some transoral procedures involving gastric restriction.

Endoscopic revision procedures. Several devices have been developed to facilitate endoscopic revision of prior bariatric procedures. The Stomaphyx device is currently available for the treatment of a dilated gastric pouch following gastric bypass. This device uses T-fasteners to create endoluminal plications that will decrease pouch size. The morbidity of this procedure appears minimal, but the benefit has yet to be proven. The Endocinch device (CR Bard, Inc., Murray Hill, New Jersey) has been successfully used for treatment of gastro-gastric fistulae and management of anastomotic dilatation.16 The company has launched a multi-center, randomized, controlled trial to determine if stoma reduction with the Endocinch device promotes additional weight loss in patients that have had gastric bypass. Results are to be announced in the end of 2008. Others have also reported success with this device for endoscopic management of gastrojejunal anastomotic dilation.17,18

The G-prox device (USGI, Inc., San Clemente, California), which can be used for mucosectomy and gastric plication or pouch formation, has received 510k approval and is currently being studied. Other companies are developing similar devices as the endoscopic approach to surgical revision is very appealing. The NDO Plicator (NDO Surgical, Inc., Mansfield, Massachusetts) also may have bariatric applications, but case reports with this device are limited.

Endoscopic Malabsorptive Procedures
An endoluminal bariatric sleeve has been developed by GI Dynamics (GI Dynamics, Newton, Massachusetts). This device is a flexible, endoscopically placed sleeve that is open at both ends and can be positioned in the duodenum past the ligament of Trietz. The sleeve allows food to pass while preventing duodenal mixing of chyme with biliary and pancreatic secretions. This is intended to mimic the duodenal and proximal jejunal bypass impact of a Roux-en-Y gastric bypass. The device is anchored past the duodenal bulb and can be endoscopically removed, allowing for relatively easy reversibility. In addition to weight loss, this device may also have value in the management of type 2 diabetes.19 The endoluminal sleeve has been tested in clinical trials with 10 successfully placed sleeves in 12 patients. Average percent of excess weight loss (%EWL) at 12 weeks was 23.6 percent, with all patients experiencing at least 10%EWL. The four diabetic patients were successfully managed off medication with normal fasting blood-glucose levels. There were two pharyngeal tears at extraction and some GI symptoms within the first two weeks of deployment.20 This device shows much promise for both weight and metabolic management.

Endoscopic Combined Restrictive and Malabsorptive Procedures
More complex devices have been developed to allow for surgical techniques that employ multiple modalities to promote weight loss. Many of these techniques involve restrictive, malabsorptive, and neurohormonal physiologic manipulations. While these devices are considerably more complex than some endoluminal devices, they are appealing as they provide combined approaches to promote satiety, and, hence, are more appealing for long-term success. As with many of the endoluminal therapies, these devices are in varying stages of development; none of the techniques using these devices have been demonstrated to be efficacious. However, studies evaluating safety are ongoing for some of the devices.

One technology company that may offer a combined approach to bariatric procedures is BaroSense (Menlo Park, California). They are developing techniques for transoral procedures for gastric restriction with or without combined malabsorptive devices for surgical weight loss.

Neurologic and Electromotor Techniques
Gastric pacing has been shown to have effect as a weight loss procedure in some patients.21 Several companies are working to develop endoscopically-placed pacing systems. Some of the devices include the Medtronic Implantable Gastric Stimulator (IGS), the Tantalus Meal activated device, and Intrapace. All of these procedures are being studied, but there is currently no published data available. Laparoscopic truncal vagotomy (and/or blockade) has been suggested as a less invasive approach to morbid obesity.11 Historically, it has been demonstrated that patients with peptic ulcer disease temporarily lose weight after gastrectomy and truncal vagotomy. As ghrelin is reduced after this operation, so is the appetite-stimulating effect, thereby making the neurohormonal mechanism of satiety appealing.22 There are pre-clinical publications in this area,23 but no clinical work has been published in this area. Devices of interest include the Valen TX, VBLOC, and TEVX by EndoVx. A large, multi-center study is currently being performed to evaluate vagal blockade (Empower Study) as a means to promote weight loss (Figures 6-7). Outcomes studies of endoscopic vagotomy or pacing are appropriate targets for future research.

Looking Inward for Future Surgical Options
The future possibilities of bariatric surgery are rich as many new techniques and devices for weight loss surgery are being developed and employed. In general, the majority of these techniques focus on proven surgical concepts of restriction and malabsorption, but with a less invasive approach. Fueling development of these advances is the tremendous need for safer, more effective, and lower cost treatments for the millions of people afflicted with obesity and its confounding medical illnesses. Surgical approaches will continue to be an important treatment modality given the poor record of non-surgical treatments for this complex disease. Adoption and implementation of any new technology should be based on safety, efficacy, and benefit over existing procedures. Nevertheless, techniques for endoluminal approaches are developing quickly, suggesting that the future of bariatric surgery can be appreciated by “looking inward.”

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Address for correspondence:
Aurora D. Pryor, MD, 3116 N. Duke St., Durham, NC 27704; Phone: (919) 660-2229; Fax: 919-660-2256; E-mail: [email protected].

Category: Emerging Technologies, Past Articles