- Email: [email protected]
Endoscopic Options for the Treatment of Obesity
Imaging and Advanced Technology Ralf Kiesslich and Pankaj Jay Pasricha, Section Editors
Endoscopic Options for the Treatment of Obesity MOSTAFA IBRAHIM, DANIEL BLERO, and JACQUES DEVIERE Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
O
verweight and obesity are defined as abnormal or excessive fat accumulation that presents a disease with considerable morbidity and mortality.1 Management of obesity depends on body mass index (BMI) as well as the presence of comorbidities, including heart disease, diabetes, hypertension, dyslipidemia, osteoarthritis, and sleep apnea.2 Approximately 1.6 billion adults are overweight; ⱖ400 million adults are obese. The World Health Organization further projects that by 2015, approximately 2.3 billion adults will be overweight and ⬎700 million will be obese. At least 20 million children ⬍5 years old were overweight globally in 2005. Once considered a problem only in highincome countries, overweight and obesity are now dramatically on the rise in low- and middle-income countries, particularly in urban settings.3 The approach for mild obesity should consist of a combination of a calorie-restricted diet, physical activity, and behavior modification.3 The only effective therapy for morbid obesity, as defined by BMI ⱖ 40 kg/m2, or by a BMI ⱖ 35 kg/m2 in the presence of comorbidities, is currently surgery.4 It has been shown effective in the long term and significantly reduces the risk of mortality associated with this disease. In the United States, the number of indications for bariatric surgery has increased by 80% between 1998 and 20045 and, in terms of health care demand, it clearly will represent the pandemic of the 21st century. Bariatric surgery for morbidly obese patients has demonstrated significant clinical benefits. It induces and maintains satisfactory weight loss while decreasing the comorbidities associated with the patient’s overweight.6 Efficacy varies with the type of procedure, which can be divided into restrictive (gastric banding, vertical gastroplasty, sleeve gastrectomy), malabsorptive (biliopancreatic diversion), or a combination of both (gastric bypass). The first and the last type of operations are currently the most frequently performed sometimes as an optional, 2-step procedure starting with gastric restriction. Although very effective, laparoscopic and surgical bariatric procedures have complication rates of 3%– 20% and mortality rates of 1%.7 Cardiopulmonary events and anastomotic leaks are the major sources of severe morbidities. The demand for less invasive therapy for obesity in the last years lead to emergence of endoscopic technology poGASTROENTEROLOGY 2010;138:2228 –2232
tentially characterized by less invasiveness and fewer postprocedure complications. Indeed, endoluminal surgery, performed entirely through natural orifices, offers the potential for a less invasive weight loss procedure, possibly performed on an ambulatory basis, and might find its place in the current armamentarium of morbid obesity treatment, extending indication to patients with severe comorbidities, older age, or even nonmorbid obese patients. We currently review the various endoluminal techniques which are currently either in routine use or in evaluation.
Endoscopic Therapeutic Options for Endoluminal Treatment of Obesity Intragastric Balloon The use of intragastric device to induce weight loss in obese patients was first described in 1982.8 Since then, numbers of intragastric balloons have been in use worldwide, and several have been withdrawn from the market. With a spherical shape and larger capacity than earlier models, the BioEnterics Intragastric Balloon (BIB, Allergan, Irvine, CA) has been the most extensively studied. Among the recently improved minimally invasive procedures, the intragastric balloon has been 1 temporary, nonoperative option that can promote weight loss in obese patients by partially filling their stomach and inducing a sense of early satiety.9,10 One of the major drawbacks of balloon implantation is weight regain after balloon removal. In this line, 2 recent studies help to better understand what can be expected from balloon implantation. Mathus–Vliegen et al11 included patients who had participated in a randomized, controlled trial comparing balloon versus sham for a 3-month period, into an additional trial including 9 months of balloon treatment and follow-up for 1 year after removal. They excluded 8 patients who had not met the weight loss goal during the first 3 months (n ⫽ 5) or who did not tolerate the balloon (n ⫽ 3). Although there was no difference between sham and balloon during the first 3 months, after 1 year of balloon treatment, a mean weight loss of 21.3 kg (17.1%) was achieved in all patients, of © 2010 by the AGA Institute
0016-5085/$36.00 doi:10.1053/j.gastro.2010.04.030
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which 12.6 kg (9.9%) was maintained at the end of the second balloon-free year. Overall, 47% of patients sustained a 10% weight loss at the end of 2 years follow-up. Although this study could not demonstrate an independent benefit of balloon treatment beyond diet, exercise, and behavioral therapy in the first treatment, balloon treatment for 1 year, in those patients who tolerated the treatment, resulted in substantial weight loss, a significant part of which was maintained during the first year after removal of the balloon. Another recently published study looked at the long-term outcomes after treatment with an intragastric balloon for 6 months, with no structured weight maintenance program after balloon removal. One hundred consecutive, morbidly obese individuals were prospectively followed after BIB placement; 97 patients completed final follow-up at a mean of 4.8 years. Although, after 6 months, 63% of patients had ⬎10% baseline weight loss, there were only 28% at final follow-up. At that time, 35 patients had undergone bariatric surgery and 34 patients had no significant weight change from baseline.12 These studies further confirm that balloon implantation may be of some help in a minority of patients for long-term weight loss. It is a potential option for patients unwilling to undergo bariatric surgery or who are not candidates for bariatric surgery, and could also be used as a temporary measure in super obese patients, to induce weight loss and decrease the risk of complications associated with further bariatric surgery.13
Gastric Restriction Endoluminal vertical gastroplasty using EndoCinch.
The EndoCinch Suturing System (C.R. Bard, Murray Hill, NJ) was initially designed for the endoscopic treatment of gastroesophageal reflux disease. This system allows the placement of series of stitches in the lower esophagus to create a pleat in the sphincter. This pleat alters the gateway between the stomach and esophagus and potentially prevents acid from flowing out of the stomach. Although associated with encouraging early results, the EndoCinch for the treatment of gastroesophageal reflux disease has been called into questions owing to the lack of retention of plications in the long term,14 an observation that is probably related to the fact that most of these stitches are placed in the submucosa. Fogel et al15 first described the use of this technology for the treatment of obesity in 64 patients. His technique consisted in the deployment of 7 sutures in a continuous and cross-linked design from the proximal fundus to the distal body (Figure 1A, B). The result of the treatment is suggested to be a significant decrease in distensibility of the stomach. The procedure was performed ambulatory and out of the 59 patients followed for 12 months, the percentage excess weight loss reported was 21% at 1 month and 58% at 12 months. Only a minority of patients (n ⫽ 14) underwent
Figure 1. (A) EndoCinch device fixed at the tip of the endoscope. (B) Cross-linked design of the sutures placement along the lesser curve of the stomach. Fogel R, De Fogel J, Bonilla Y, et al. Clinical experience of transoral suturing for an endoluminal vertical gastroplasty: 1-year follow-up in 64 patients. Gastrointest Endosc 2008;68:51– 8.
repeat endoscopy during follow-up. In 11, the suture line was reported as completely or partially intact. Unfortunately, limited information on endoscopic or radiologic follow-up was provided, making it difficult to understand the extent of stomach restriction. Using a modified version of the EndoCinch device, Thomson et al reported in abstract form a short-term efficacy in a group of 16 patients.16 A randomized, controlled trial is ongoing in the United States to further investigate this technique and hopefully will also provide long-term data that are the major matter of concern both clinically and anatomically. Transoral gastroplasty. Transoral gastroplasty (TOGA System; Satiety, Inc, Palo Alto, CA) recently emerged as a new and apparently safe technique for the endoluminal surgical treatment of obesity. It uses endoscopic stapling 2229
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device to create a full-thickness plication in the proximal stomach, with a strictly endoluminal approach. The purpose is, like for other restrictive procedures, to induce an early satiety owing to reduction of stomach capacity. The system consists of the TOGA Sleeve Stapler, a flexible 18-mm diameter shaft device, which rides over a guide wire for introduction (Figure 2A, B). It is specifically designed for the procedure and accommodates a standard endoscope up to an 8.6-mm diameter and creates a full-thickness plication of the anterior and posterior walls of the stomach, which are acquired using vacuum pots located parallel to the staple line (Figure 2C, D). With 2 successive applications of the stapler, a restrictive sleeve is created which extends distally from the esophagus, along the lesser curve (Figure 2E). In the first evaluation, this procedure has been completed by the placement of restriction(s) in the distal part of the sleeve, using a dedicated stapling device also based on vacuum acquisition of the tissues. Only 2 human series are currently published as full paper. The first17 was performed in 21 patients with a mean BMI of 43.3 kg/m2. The mean
excess weight loss was 16%, 23%, and 25% at 1, 3, and 6 months posttreatment. No severe adverse event was reported and, at 6-month endoscopy, gaps between the 2 staple lines were evidenced in 13 of 21 patients. After this first evaluation, the technique was improved, especially with regard to the successive application of the 2 staple lines and the device has been modified. Using this latter, a second human pilot series18 was reported in 11 patients, showing better results with mean excess weight loss of 19%, 34%, and 46% at 1, 3, and 6 months, respectively. A multicenter, randomized, sham-controlled study is ongoing in 10 centers, comparing the active and sham procedures (2:1 ratio) in a series of ⬎300 patients; inclusion of these patients has been completed. These results, as well as those of a 2-year follow-up, of a two-center European study should become available soon, and preliminary reports have shown sustained weight loss up to 2 years of follow-up.19 The interest of these studies is also to show that these transoral techniques are not more difficult to perform in heavily obese patients and, although the TOGA technique is
Figure 2. (A) Transoral gastroplasty (TOGA) device. (B) Stapling procedure. (C) Tissue acquisition into the vacuum pots. (D) TOGA system in place with sliding sail separating the anterior and posterior walls before tissue acquisition. (E) Immediate results after placement of 2 staple lines. (F) 1 month follow up after TOGa procedure. 2230
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performed under general anesthesia, recovery is very fast and the procedure could be performed on an outpatient basis. Recent studies performed in the settings of European evaluations of the technique have shown then TOGA significantly increased the insulin sensitivity while reducing fat mass.20 The revisional surgery after TOGA was also evaluated recently showing that the conversion of TOGA into a laparoscopic Roux-en-Y gastric bypass (LRYGBP) was easy and performed over the same duration as a primary LRYGBP, without the excess time and difficulty usually needed for conversion of a restrictive procedure into a LRYGBP.21 This feature, combined with the fact that the procedure can currently be performed within 30 – 45 minutes on an outpatient basis, suggests that this technique, if proven effective in the mid term, might become the ideal first step of a potential 2-step bariatric treatment strategy, starting with a restrictive procedure with the option of a LRYGBP in a second phase for those patients not loosing or regaining weight after the restrictive transoral surgery. Duodenojejunal bypass sleeve. This technique has to be put in line with the development of metabolic surgery and particularly with the clinical observation that bypassing the proximal bowel improves type 2 diabetes and induces weight loss, a feature which, at least in part, explains the greater improvement of diabetes observed in patients undergoing a LRYGBP, for the same weight loss, compared with a pure restrictive procedure.22 The first strictly endoluminal device used to bypass the proximal small intestine is the duodenojejunal bypass (DJBS), also called “the EndoBarrier” (GI Dynamics Inc, Watertown, MA). It is composed of a self expanding implant that seats in the duodenum and has anti-migration features. It is attached to a 60-cm plastic sleeve that extends into the proximal jejunum and works by creating a physical barrier between food that has been ingested and both the intestinal wall and biliopancreatic secretions (Figure 3A, B). The device is left in place for a maximum of 3– 6 months and is removed with a dedicated and relatively easy system. Three trials demonstrated the potential benefit of DJBS. In the first,23 it was successfully deployed in 12 patients in ⬍30 minutes (and required approximately 40 minutes to be removed). With the exception of pain prompting early removal, it was associated with a significant drop in HbA1C, compared with a control group. A second multicenter trial, from Chile, showed, at 12 weeks, a weight loss significantly greater in 24 patients treated with the EndoBarrier system compared with the diet control group in a preoperative setting.24 The last available study is a sham-controlled trial with 21 patients treated and 26 undergoing the sham procedure, with a 12-week study design. Excess weight loss (11.9% vs 2.7%) and loss of ⬎10% excess weight (62% vs 17% of patients) were all in favor of the DJBS. However, 8 subjects terminated earlier because of gastrointestinal bleed-
Figure 3. (A) The EndoBarrier system. (B) A scheme showing the implantation of the EndoBarrier system.
ing (n ⫽ 3) or device intolerance (pain and/or vomiting; n ⫽ 4) and an unrelated preexisting illness (n ⫽ 1), showing that more technological developments are still to be done.25 Although these techniques still suffer from the need for the implantation of a foreign body and the limited duration of indwell, they clearly deserve further technical improvement and clinical investigation because they could be those impacting the most on comorbidities and might be of particular interest in diabetic obese patients.22 Other implantable devices, potentially mimicking more closely the RYGBP, are currently in development (Valentx Inc, Carpentaria, CA) but no clinical data are currently available. Transoral endoscopic restrictive implant. If the duodenojejunal sleeve may be seen as the endoscopic counterpart of RYGBP, the TOGA, as the one of sleeve sleeve gastrectomy or vertical banded gastroplasty, a recently reported endoscopic implantable device (Transoral Endoscopic Restrictive Implants System (TERIS), Barosense, Red2231
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wood City, CA) may be seen as an endoscopic equivalent to gastric banding. A phase I pilot trial has been recently reported.26 Successful placement has been achieved in 12 of 13 patients with complications (including perforation) in 3 of them. This system is obviously currently technically demanding (22 mm insertion tube, 142 min median procedural time) but an interesting excess weight loss of 28% was observed at 3 months, suggesting that provided technical improvements are made, it could become another option in the endoscopic armamentarium. This procedure is associated with the placement of an implant which means that it offers the potential advantage of being removable (the drawback being like with other implants the long-term durability of the procedure which will only be demonstrated by long-term follow-up).
Future Developments Mechanisms of bariatric procedures are complex and involve modulation of the neurohormonal mechanisms that regulate appetite, satiety, glucose metabolism, energy utilization, and feeding behavior.27 Transoral procedures offer the possibility to further unravel these mechanisms in the light of clinical observations. If restrictive surgical procedures such as gastric banding or vertical banded gastroplasty are supposed to mainly act by increasing the resistance to the passage of food and thereby inducing weight loss because of noxious symptoms; this effect is much less obvious with the endoluminal procedures performed with Endocinch and, to some extent, with the transoral stapler (TOGA). This latter technique, however, reduces the volume of the stomach in a much greater extent than vertical gastroplasty, because of the technique of tissue acquisition and suture (Figure 2F), with the potential consequence of limiting the distensibility and further modulating Ghrelin response to fasting or postprandial Ghrelin inhibition and/or stimulation of appetite frenators, such as peptide YY or glucagon-like peptide 1 (GLP-1). Understanding the physiologic effect of the new technologies at the level of neurohormonal mediators will be, in our view, among the key factors that might allow designing the most effective treatment option in the future. Other mechanisms of restrictive procedures also include delayed gastric emptying and, recently, procedures only acting on gastric emptying such as pyloric sutures have been tested in animals.28 Although this seems effective in inducing weight loss, one may question the quality of life if such technique would be translated into clinical trials. Gastric electrical stimulation via laparoscopic implantation of electrodes is another way to limit food intake by delaying the gastric emptying. It is probable that such an electrical stimulation could be implanted exclusively via endoscopy in the future, opening another area of investigation.29
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The most complex changes in neurohormonal regulation occur after RYGBP, which is also the most effective therapy for morbid obesity. This procedure is associated with a significant improvement of diabetes, which occurs within days after surgery, independent from weight loss, a feature that is also observed when preventing the proximal bowel from exposition to nutrients, whatever the technique.30,31 This further extends the potential of endoluminal surgery, not only to treat morbid obesity, but also to potentially become part of the therapeutic armamentarium in all patients, obese or not, having a type 2 diabetes. Techniques are already in development to perform anastomosis using a strictly transoral approach32,33 and devices allowing triangulation and better suturing or stapling are under development. This might be the next step of bariatric and metabolic endoluminal surgery and may become, in the near future, among the major activities of therapeutic endoscopy centers if they become organized enough to be integrated in multidisciplinary teams in charge of these patients.
Supplementary Material Note: The first 5 references associated with this article are available below in print. The remaining references accompanying this article are available online only with the electronic version of the article. To access the remaining references, visit the online version of Gastroenterology at www.gastrojournal.org, and at doi:10.1053/j.gastro.2010.04.030. References 1. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity. WHO/ NUT/ NCD/98.1. WHO Technical Support Series, WHO, Geneva; 1998. p. 1–276. 2. The World Health Organization 2005 data. Available at: http:// www.who.int/ncd_surveillance. Accessed September 16, 2006. 3. Glenny AM, O’Meara S, Melville A, et al. The treatment and prevention of obesity: a systematic review of the literature. Int J Obes Relat Metab Disord 1997;21:715–737. 4. Magnusson M, Freedman J, Jonas E, et al. Five-year results of laparoscopic vertical banded gastroplasty in the treatment of massive obesity. Obes Surg 2002;12:826 – 830. 5. Zhao Y, Encinosa W. Agency for health care research and quality AHRQ. Bariatric surgery utilization and outcomes. In 1998 and 2004. Statistical Brief # 23, January 2007.
Reprint requests Address requests for reprints to: Jacques Devière, MD, PhD, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium. e-mail: [email protected]. Conflicts of interest Jacques Deviere has research support and consulting fees from Satiety Inc, Palo Alto, CA. The remaining authors disclose no conflicts.
June 2010
Imaging and Advanced Technology
References (Online Only) 6. Paxton J, Matthews J. The cost effectiveness of laparoscopic versus open gastric bypass surgery. Obes Surg 2005;15:24 –34. 7. Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg 2006;16:119 –124. 8. Nieben OG, Harboe H. Intragastric balloon as an artificial bezoar for treatment of obesity. Lancet 1982;1:198 –199. 9. Evans JD, Scott MH. Intragastric balloon in the treatment of patients with morbid obesity. Br J Surg 2001;88:1245–1248. 10. Genco A, Bruni T, Doldi SB, et al. Bioenterics Intragastric Balloon: the Italian Experience with 2515 patients. Obes Surg 2005;15: 1161–1164. 11. Mathus-Vliegen EM, Tytgat GN. Intragastric balloon for treatmentresistant obesity: safety, tolerance, and efficacy of 1-year balloon treatment followed by a 1-year balloon-free follow-up. Gastrointest Endosc 2005;61:19 –27. 12. Dastis NS, François E, Deviere J, et al. Intragastric balloon for weight loss: results in 100 individuals followed for at least 2.5 years. Endoscopy 2009;41:575–580. 13. Spyropoulos C, Katsakoulis E, Mead N, et al. Intragastric balloon for high-risk super obese patients: a prospective analysis of efficacy. Surg Obes Relat Dis 2007;3:78 – 83. 14. Schwartz MP, Wellink H, Gooszen HG, et al. Endoscopic gastroplication for the treatment of gastroesophageal reflux disease: a randomized sham controlled trial. Gut 2007;56:20 –28. 15. Fogel R, De Fogel J, Bonilla Y, et al. Clinical experience of transoral suturing for an endoluminal vertical gastroplasty: 1-year follow-up in 64 patients. Gastrointest Endosc 2008;68:51–58. 16. Thompson CC, Brethauer SA, Chand B, et al. M1259 Transoral Gastric Volume Reduction as an Intervention for Weight Management (TRIM) Multicenter Feasibility Study: a report of early outcomes. Gastroenterology 2009;136:A-384. 17. Deviere J, Ojeda Valdes G, Cuevas Herrera L, et al. Safety, feasibility and weight loss after transoral gastroplasty: first human multicenter study. Surg Endosc 2008;22:589 –598. 18. Moreno C, Closset J, Dugardeyn S, et al. Transoral gastroplasty is safe, feasible, and induces significant weight loss in morbidly obese patients: results of the second human pilot study. Endoscopy 2008;40:406 – 413. 19. Deviere J. Transoral gastroplasty for obesity. Proceedings of the IFSO meeting, Paris 2009. Available at: www.ifso2009.com. 20. Chiellini C, Iaconelli A, Familiari P, et al. Study of the effects of transoral gastroplasty on insulin sensitivity and secretion
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in obese subjects. Nutr Metab Cardiovasc Dis 2010;20: 202–207. Closset J, Germanova D, Loi P, et al. Laparoscopic Gastric Bypass as a Revision Procedure After Transoral Gastroplasty. Obes Surg 2009 Dec 10 [Epub ahead of print]. Rubino F, Cohen RV, Schiavon CA, et al. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases. Surg Obes Relat Dis 2007;3:195–197. Rodriguez-Grunert L, Galvao Neto MP, Alamo M, et al. First human experience with endoscopically delivered and retrieved duodenal-jejunal bypass sleeve. Surg Obes Relat Dis 2008;4: 55–59. Tarnoff M, Rodriguez L, Escalona A, et al. Open label, prospective, randomized controlled trial of an endoscopic duodenal-jejunal bypass sleeve versus low calorie diet for pre-operative weight loss in bariatric surgery. Surg Endosc 2009;23:650 – 656. Gersin KS, Rothstein RI, Rosenthal RJ, et al. Open-label, shamcontrolled trial of an endoscopic duodenojejunal bypass liner for preoperative weight loss in bariatric surgery candidates. Gastrointest Endosc 2010 Mar 19 [Epub ahead of print]. De Jong K, Mathus–Vliegen EMH, Weldhuyzen EAML, et al. Shortterm safety and efficacy of the transoral endoscopic restrictive implant system for the treatment of obesity. Gastrointest Endosc [in press]. Wren AM, Bloom SR. Gut hormones and appetite control. Gastroenterology 2007;132:2116 –2130. Vegesna AK, Korimilli A, Besetty R, et al. Endoscopic pyloric suturing to facilitate weight loss (a canine model). Gastrointest Endosc 2010. Forthcoming. Liu J, Hou X, Song G, et al. Gastric electrical stimulation using endoscopically placed mucosal electrodes reduces food intake in humans. Am J Gastroenterol 2006;101:798 – 803. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology to diabetes. Ann Surg 2006;244:741–749. Aguirre V, Stylopoulos N, Grinbaum R, et al. An endoluminal sleeve induces substantial weight loss and normalises glucose homeostasis in rats with diet induced obesity. Obesity 2008;16: 2585–2592. Kantsevoy SV, Jagannath SB, Niiyama H, et al. Endoscopic gastrojejunostomy with survival in a porcine model. Gastrointest Endosc 2005;62:287–292. Chopita N, Vaillaverde A, Cope C, et al. Endoscopic gastroenteric anastomosis using magnets. Endoscopy 2005;37:313–317.
Endoscopic Options for the Treatment of Obesity MOSTAFA IBRAHIM, DANIEL BLERO, and JACQUES DEVIERE Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
O
verweight and obesity are defined as abnormal or excessive fat accumulation that presents a disease with considerable morbidity and mortality.1 Management of obesity depends on body mass index (BMI) as well as the presence of comorbidities, including heart disease, diabetes, hypertension, dyslipidemia, osteoarthritis, and sleep apnea.2 Approximately 1.6 billion adults are overweight; ⱖ400 million adults are obese. The World Health Organization further projects that by 2015, approximately 2.3 billion adults will be overweight and ⬎700 million will be obese. At least 20 million children ⬍5 years old were overweight globally in 2005. Once considered a problem only in highincome countries, overweight and obesity are now dramatically on the rise in low- and middle-income countries, particularly in urban settings.3 The approach for mild obesity should consist of a combination of a calorie-restricted diet, physical activity, and behavior modification.3 The only effective therapy for morbid obesity, as defined by BMI ⱖ 40 kg/m2, or by a BMI ⱖ 35 kg/m2 in the presence of comorbidities, is currently surgery.4 It has been shown effective in the long term and significantly reduces the risk of mortality associated with this disease. In the United States, the number of indications for bariatric surgery has increased by 80% between 1998 and 20045 and, in terms of health care demand, it clearly will represent the pandemic of the 21st century. Bariatric surgery for morbidly obese patients has demonstrated significant clinical benefits. It induces and maintains satisfactory weight loss while decreasing the comorbidities associated with the patient’s overweight.6 Efficacy varies with the type of procedure, which can be divided into restrictive (gastric banding, vertical gastroplasty, sleeve gastrectomy), malabsorptive (biliopancreatic diversion), or a combination of both (gastric bypass). The first and the last type of operations are currently the most frequently performed sometimes as an optional, 2-step procedure starting with gastric restriction. Although very effective, laparoscopic and surgical bariatric procedures have complication rates of 3%– 20% and mortality rates of 1%.7 Cardiopulmonary events and anastomotic leaks are the major sources of severe morbidities. The demand for less invasive therapy for obesity in the last years lead to emergence of endoscopic technology poGASTROENTEROLOGY 2010;138:2228 –2232
tentially characterized by less invasiveness and fewer postprocedure complications. Indeed, endoluminal surgery, performed entirely through natural orifices, offers the potential for a less invasive weight loss procedure, possibly performed on an ambulatory basis, and might find its place in the current armamentarium of morbid obesity treatment, extending indication to patients with severe comorbidities, older age, or even nonmorbid obese patients. We currently review the various endoluminal techniques which are currently either in routine use or in evaluation.
Endoscopic Therapeutic Options for Endoluminal Treatment of Obesity Intragastric Balloon The use of intragastric device to induce weight loss in obese patients was first described in 1982.8 Since then, numbers of intragastric balloons have been in use worldwide, and several have been withdrawn from the market. With a spherical shape and larger capacity than earlier models, the BioEnterics Intragastric Balloon (BIB, Allergan, Irvine, CA) has been the most extensively studied. Among the recently improved minimally invasive procedures, the intragastric balloon has been 1 temporary, nonoperative option that can promote weight loss in obese patients by partially filling their stomach and inducing a sense of early satiety.9,10 One of the major drawbacks of balloon implantation is weight regain after balloon removal. In this line, 2 recent studies help to better understand what can be expected from balloon implantation. Mathus–Vliegen et al11 included patients who had participated in a randomized, controlled trial comparing balloon versus sham for a 3-month period, into an additional trial including 9 months of balloon treatment and follow-up for 1 year after removal. They excluded 8 patients who had not met the weight loss goal during the first 3 months (n ⫽ 5) or who did not tolerate the balloon (n ⫽ 3). Although there was no difference between sham and balloon during the first 3 months, after 1 year of balloon treatment, a mean weight loss of 21.3 kg (17.1%) was achieved in all patients, of © 2010 by the AGA Institute
0016-5085/$36.00 doi:10.1053/j.gastro.2010.04.030
Imaging and Advanced Technology continued
which 12.6 kg (9.9%) was maintained at the end of the second balloon-free year. Overall, 47% of patients sustained a 10% weight loss at the end of 2 years follow-up. Although this study could not demonstrate an independent benefit of balloon treatment beyond diet, exercise, and behavioral therapy in the first treatment, balloon treatment for 1 year, in those patients who tolerated the treatment, resulted in substantial weight loss, a significant part of which was maintained during the first year after removal of the balloon. Another recently published study looked at the long-term outcomes after treatment with an intragastric balloon for 6 months, with no structured weight maintenance program after balloon removal. One hundred consecutive, morbidly obese individuals were prospectively followed after BIB placement; 97 patients completed final follow-up at a mean of 4.8 years. Although, after 6 months, 63% of patients had ⬎10% baseline weight loss, there were only 28% at final follow-up. At that time, 35 patients had undergone bariatric surgery and 34 patients had no significant weight change from baseline.12 These studies further confirm that balloon implantation may be of some help in a minority of patients for long-term weight loss. It is a potential option for patients unwilling to undergo bariatric surgery or who are not candidates for bariatric surgery, and could also be used as a temporary measure in super obese patients, to induce weight loss and decrease the risk of complications associated with further bariatric surgery.13
Gastric Restriction Endoluminal vertical gastroplasty using EndoCinch.
The EndoCinch Suturing System (C.R. Bard, Murray Hill, NJ) was initially designed for the endoscopic treatment of gastroesophageal reflux disease. This system allows the placement of series of stitches in the lower esophagus to create a pleat in the sphincter. This pleat alters the gateway between the stomach and esophagus and potentially prevents acid from flowing out of the stomach. Although associated with encouraging early results, the EndoCinch for the treatment of gastroesophageal reflux disease has been called into questions owing to the lack of retention of plications in the long term,14 an observation that is probably related to the fact that most of these stitches are placed in the submucosa. Fogel et al15 first described the use of this technology for the treatment of obesity in 64 patients. His technique consisted in the deployment of 7 sutures in a continuous and cross-linked design from the proximal fundus to the distal body (Figure 1A, B). The result of the treatment is suggested to be a significant decrease in distensibility of the stomach. The procedure was performed ambulatory and out of the 59 patients followed for 12 months, the percentage excess weight loss reported was 21% at 1 month and 58% at 12 months. Only a minority of patients (n ⫽ 14) underwent
Figure 1. (A) EndoCinch device fixed at the tip of the endoscope. (B) Cross-linked design of the sutures placement along the lesser curve of the stomach. Fogel R, De Fogel J, Bonilla Y, et al. Clinical experience of transoral suturing for an endoluminal vertical gastroplasty: 1-year follow-up in 64 patients. Gastrointest Endosc 2008;68:51– 8.
repeat endoscopy during follow-up. In 11, the suture line was reported as completely or partially intact. Unfortunately, limited information on endoscopic or radiologic follow-up was provided, making it difficult to understand the extent of stomach restriction. Using a modified version of the EndoCinch device, Thomson et al reported in abstract form a short-term efficacy in a group of 16 patients.16 A randomized, controlled trial is ongoing in the United States to further investigate this technique and hopefully will also provide long-term data that are the major matter of concern both clinically and anatomically. Transoral gastroplasty. Transoral gastroplasty (TOGA System; Satiety, Inc, Palo Alto, CA) recently emerged as a new and apparently safe technique for the endoluminal surgical treatment of obesity. It uses endoscopic stapling 2229
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device to create a full-thickness plication in the proximal stomach, with a strictly endoluminal approach. The purpose is, like for other restrictive procedures, to induce an early satiety owing to reduction of stomach capacity. The system consists of the TOGA Sleeve Stapler, a flexible 18-mm diameter shaft device, which rides over a guide wire for introduction (Figure 2A, B). It is specifically designed for the procedure and accommodates a standard endoscope up to an 8.6-mm diameter and creates a full-thickness plication of the anterior and posterior walls of the stomach, which are acquired using vacuum pots located parallel to the staple line (Figure 2C, D). With 2 successive applications of the stapler, a restrictive sleeve is created which extends distally from the esophagus, along the lesser curve (Figure 2E). In the first evaluation, this procedure has been completed by the placement of restriction(s) in the distal part of the sleeve, using a dedicated stapling device also based on vacuum acquisition of the tissues. Only 2 human series are currently published as full paper. The first17 was performed in 21 patients with a mean BMI of 43.3 kg/m2. The mean
excess weight loss was 16%, 23%, and 25% at 1, 3, and 6 months posttreatment. No severe adverse event was reported and, at 6-month endoscopy, gaps between the 2 staple lines were evidenced in 13 of 21 patients. After this first evaluation, the technique was improved, especially with regard to the successive application of the 2 staple lines and the device has been modified. Using this latter, a second human pilot series18 was reported in 11 patients, showing better results with mean excess weight loss of 19%, 34%, and 46% at 1, 3, and 6 months, respectively. A multicenter, randomized, sham-controlled study is ongoing in 10 centers, comparing the active and sham procedures (2:1 ratio) in a series of ⬎300 patients; inclusion of these patients has been completed. These results, as well as those of a 2-year follow-up, of a two-center European study should become available soon, and preliminary reports have shown sustained weight loss up to 2 years of follow-up.19 The interest of these studies is also to show that these transoral techniques are not more difficult to perform in heavily obese patients and, although the TOGA technique is
Figure 2. (A) Transoral gastroplasty (TOGA) device. (B) Stapling procedure. (C) Tissue acquisition into the vacuum pots. (D) TOGA system in place with sliding sail separating the anterior and posterior walls before tissue acquisition. (E) Immediate results after placement of 2 staple lines. (F) 1 month follow up after TOGa procedure. 2230
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performed under general anesthesia, recovery is very fast and the procedure could be performed on an outpatient basis. Recent studies performed in the settings of European evaluations of the technique have shown then TOGA significantly increased the insulin sensitivity while reducing fat mass.20 The revisional surgery after TOGA was also evaluated recently showing that the conversion of TOGA into a laparoscopic Roux-en-Y gastric bypass (LRYGBP) was easy and performed over the same duration as a primary LRYGBP, without the excess time and difficulty usually needed for conversion of a restrictive procedure into a LRYGBP.21 This feature, combined with the fact that the procedure can currently be performed within 30 – 45 minutes on an outpatient basis, suggests that this technique, if proven effective in the mid term, might become the ideal first step of a potential 2-step bariatric treatment strategy, starting with a restrictive procedure with the option of a LRYGBP in a second phase for those patients not loosing or regaining weight after the restrictive transoral surgery. Duodenojejunal bypass sleeve. This technique has to be put in line with the development of metabolic surgery and particularly with the clinical observation that bypassing the proximal bowel improves type 2 diabetes and induces weight loss, a feature which, at least in part, explains the greater improvement of diabetes observed in patients undergoing a LRYGBP, for the same weight loss, compared with a pure restrictive procedure.22 The first strictly endoluminal device used to bypass the proximal small intestine is the duodenojejunal bypass (DJBS), also called “the EndoBarrier” (GI Dynamics Inc, Watertown, MA). It is composed of a self expanding implant that seats in the duodenum and has anti-migration features. It is attached to a 60-cm plastic sleeve that extends into the proximal jejunum and works by creating a physical barrier between food that has been ingested and both the intestinal wall and biliopancreatic secretions (Figure 3A, B). The device is left in place for a maximum of 3– 6 months and is removed with a dedicated and relatively easy system. Three trials demonstrated the potential benefit of DJBS. In the first,23 it was successfully deployed in 12 patients in ⬍30 minutes (and required approximately 40 minutes to be removed). With the exception of pain prompting early removal, it was associated with a significant drop in HbA1C, compared with a control group. A second multicenter trial, from Chile, showed, at 12 weeks, a weight loss significantly greater in 24 patients treated with the EndoBarrier system compared with the diet control group in a preoperative setting.24 The last available study is a sham-controlled trial with 21 patients treated and 26 undergoing the sham procedure, with a 12-week study design. Excess weight loss (11.9% vs 2.7%) and loss of ⬎10% excess weight (62% vs 17% of patients) were all in favor of the DJBS. However, 8 subjects terminated earlier because of gastrointestinal bleed-
Figure 3. (A) The EndoBarrier system. (B) A scheme showing the implantation of the EndoBarrier system.
ing (n ⫽ 3) or device intolerance (pain and/or vomiting; n ⫽ 4) and an unrelated preexisting illness (n ⫽ 1), showing that more technological developments are still to be done.25 Although these techniques still suffer from the need for the implantation of a foreign body and the limited duration of indwell, they clearly deserve further technical improvement and clinical investigation because they could be those impacting the most on comorbidities and might be of particular interest in diabetic obese patients.22 Other implantable devices, potentially mimicking more closely the RYGBP, are currently in development (Valentx Inc, Carpentaria, CA) but no clinical data are currently available. Transoral endoscopic restrictive implant. If the duodenojejunal sleeve may be seen as the endoscopic counterpart of RYGBP, the TOGA, as the one of sleeve sleeve gastrectomy or vertical banded gastroplasty, a recently reported endoscopic implantable device (Transoral Endoscopic Restrictive Implants System (TERIS), Barosense, Red2231
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wood City, CA) may be seen as an endoscopic equivalent to gastric banding. A phase I pilot trial has been recently reported.26 Successful placement has been achieved in 12 of 13 patients with complications (including perforation) in 3 of them. This system is obviously currently technically demanding (22 mm insertion tube, 142 min median procedural time) but an interesting excess weight loss of 28% was observed at 3 months, suggesting that provided technical improvements are made, it could become another option in the endoscopic armamentarium. This procedure is associated with the placement of an implant which means that it offers the potential advantage of being removable (the drawback being like with other implants the long-term durability of the procedure which will only be demonstrated by long-term follow-up).
Future Developments Mechanisms of bariatric procedures are complex and involve modulation of the neurohormonal mechanisms that regulate appetite, satiety, glucose metabolism, energy utilization, and feeding behavior.27 Transoral procedures offer the possibility to further unravel these mechanisms in the light of clinical observations. If restrictive surgical procedures such as gastric banding or vertical banded gastroplasty are supposed to mainly act by increasing the resistance to the passage of food and thereby inducing weight loss because of noxious symptoms; this effect is much less obvious with the endoluminal procedures performed with Endocinch and, to some extent, with the transoral stapler (TOGA). This latter technique, however, reduces the volume of the stomach in a much greater extent than vertical gastroplasty, because of the technique of tissue acquisition and suture (Figure 2F), with the potential consequence of limiting the distensibility and further modulating Ghrelin response to fasting or postprandial Ghrelin inhibition and/or stimulation of appetite frenators, such as peptide YY or glucagon-like peptide 1 (GLP-1). Understanding the physiologic effect of the new technologies at the level of neurohormonal mediators will be, in our view, among the key factors that might allow designing the most effective treatment option in the future. Other mechanisms of restrictive procedures also include delayed gastric emptying and, recently, procedures only acting on gastric emptying such as pyloric sutures have been tested in animals.28 Although this seems effective in inducing weight loss, one may question the quality of life if such technique would be translated into clinical trials. Gastric electrical stimulation via laparoscopic implantation of electrodes is another way to limit food intake by delaying the gastric emptying. It is probable that such an electrical stimulation could be implanted exclusively via endoscopy in the future, opening another area of investigation.29
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The most complex changes in neurohormonal regulation occur after RYGBP, which is also the most effective therapy for morbid obesity. This procedure is associated with a significant improvement of diabetes, which occurs within days after surgery, independent from weight loss, a feature that is also observed when preventing the proximal bowel from exposition to nutrients, whatever the technique.30,31 This further extends the potential of endoluminal surgery, not only to treat morbid obesity, but also to potentially become part of the therapeutic armamentarium in all patients, obese or not, having a type 2 diabetes. Techniques are already in development to perform anastomosis using a strictly transoral approach32,33 and devices allowing triangulation and better suturing or stapling are under development. This might be the next step of bariatric and metabolic endoluminal surgery and may become, in the near future, among the major activities of therapeutic endoscopy centers if they become organized enough to be integrated in multidisciplinary teams in charge of these patients.
Supplementary Material Note: The first 5 references associated with this article are available below in print. The remaining references accompanying this article are available online only with the electronic version of the article. To access the remaining references, visit the online version of Gastroenterology at www.gastrojournal.org, and at doi:10.1053/j.gastro.2010.04.030. References 1. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity. WHO/ NUT/ NCD/98.1. WHO Technical Support Series, WHO, Geneva; 1998. p. 1–276. 2. The World Health Organization 2005 data. Available at: http:// www.who.int/ncd_surveillance. Accessed September 16, 2006. 3. Glenny AM, O’Meara S, Melville A, et al. The treatment and prevention of obesity: a systematic review of the literature. Int J Obes Relat Metab Disord 1997;21:715–737. 4. Magnusson M, Freedman J, Jonas E, et al. Five-year results of laparoscopic vertical banded gastroplasty in the treatment of massive obesity. Obes Surg 2002;12:826 – 830. 5. Zhao Y, Encinosa W. Agency for health care research and quality AHRQ. Bariatric surgery utilization and outcomes. In 1998 and 2004. Statistical Brief # 23, January 2007.
Reprint requests Address requests for reprints to: Jacques Devière, MD, PhD, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium. e-mail: [email protected]. Conflicts of interest Jacques Deviere has research support and consulting fees from Satiety Inc, Palo Alto, CA. The remaining authors disclose no conflicts.
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