- Email: [email protected]
Early Experience With Endoscopic Sleeve Gastroplasty and Hints at Mechanisms of Action
Accepted Manuscript Early Experience with Endoscopic Sleeve Gastroplasty and Hints at Mechanisms of Action Shelby Sullivan, MD, Steven A. Edmundowicz, MD FASGE
PII: DOI: Reference:
S1542-3565(16)30856-4 10.1016/j.cgh.2016.09.145 YJCGH 54933
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 23 September 2016 Please cite this article as: Sullivan S, Edmundowicz SA, Early Experience with Endoscopic Sleeve Gastroplasty and Hints at Mechanisms of Action, Clinical Gastroenterology and Hepatology (2016), doi: 10.1016/j.cgh.2016.09.145. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Early Experience with Endoscopic Sleeve Gastroplasty and Hints at Mechanisms of Action Shelby Sullivan MD, Visiting Associate Professor of Medicine University of Colorado School of Medicine and Steven A. Edmundowicz MD FASGE Visiting Professor of Medicine University of Colorado School of
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Medicine.
Dr. Shelby Sullivan Dr Steven Edmundowicz FASGE University of Colorado School of Medicine
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Mail Stop F735 Anschutz Outpatient Pavilion
Aurora Colorado 80045 Academic: (720) 848-2786 [email protected] [email protected]
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Disclosures:
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1635 Aurora Ct.
Dr. Sullivan receives research support from Aspire Bariatrics, ReShape Medical, GI Dynamics, USGI Medical, Obalon, Baronova. She is a paid consultant for 2012-2016: Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee, Center for Devices and Radiological Health,
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Food and Drug Administration, 2013-Present: USGI Medical, EnteroMedics Advisory Board, May, 2014, 2015-Present: Obalon, Takeda Pharmaceuticals, Advisory Board, September 2015, 2016-Present: Elira
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Therapeutic, 2016 SynerZ
Dr. Edmundowicz receives research support from Aspire Bariatrics, ReShape Medical, GI Dynamics, USGI Medical, and Obalon. He is a paid consultant with Boston Scientific, Olympus, Medtronic, GI Dynamics, Xlumena, Fractyl and Torax. He is a stockholder in Motus GI, SynerZ, Elira, Endostim, Check-Cap, and Freehold surgical.
ACCEPTED MANUSCRIPT
It is widely recognized that obesity is major health concern in the United States, with over 90 million Americans affected by the disease. Due to obesity related co-morbidities including but not limited to diabetes, heart disease, and cancer; the healthcare costs associated with obesity may account for up to 21% of US healthcare expenditures1, 2 . Current therapies for obesity include lifestyle therapy,
RI PT
pharmacotherapy, endoscopic bariatric therapy, and bariatric surgery. Lifestyle therapy alone is the least effective therapy, possibly due to hunger and satiety hormone changes which result in increased hunger and desire to eat with weight loss3. Bariatric surgery, namely Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, is the most effective therapy. The mechanisms for weight loss with bariatric
SC
surgery are not completely understood, but the altered anatomy changes the response of several gut hormones which have effects on hunger and satiety in addition to changes in gastric capacity, gut motility, and bile acids4, 5. Not only does this result in decreased food intake, but RYGB has also been
M AN U
shown to induce remission of food addiction6; further demonstrating the effect of this surgery on eating behaviors. Unfortunately, only 1% of patients who qualify for bariatric surgery pursue surgical options7; likely related to the risks, costs, recovery time, and food restrictions associated with bariatric surgery. There is increasing hope that minimally invasive endoscopic procedures would fill the treatment gap between medical therapies and bariatric surgery.
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In this issue of CGH⁸, Abu Dayyeh and colleagues of the Mayo Clinic, Rochester describe their initial single center experience with Endoscopic Sleeve Gastroplasty (ESG). This endoscopic procedure uses an available endoscopic suturing device that has been approved for the general purpose of endoscopic suturing of tissues. ESG is minimally invasive and done under general anesthesia, occasionally with an
EP
overnight hospital observation stay. This procedure was devised to endoscopically achieve a change in the gastric anatomy similar to that achieved with laparoscopic sleeve gastrectomy without the surgical
AC C
resection of the fundus or body of the stomach (Figure 1)
In this early report of the first 25 patients (patients followed for a median of 9 months), the results appear encouraging with 56%+/- 23% excess weight loss at 9 months in 17 patients. The group also reports findings of physiologic and hormonal measurements in 4 patients. In these patients gastric emptying was delayed, which is opposite to the effect of sleeve gastrectomy where gastric emptying is accelerated⁹. Calorie intake to reach maximum fullness in a liquid meal test decreased by 59%. There was a trend towards a decrease in ghrelin concentrations during a meal test. Although this was not statistically significant, ghrelin is expected to increase with weight loss, so the lack of an increase with
ACCEPTED MANUSCRIPT
ESG is an interesting finding. Whole body insulin sensitivity measured by HOMA-IR improved as expected for the percent excess weight loss seen in these patients. Taken together, these limited data suggest that although gastric luminal dimensions after ESG and sleeve gastrectomy are very similar, the mechanism for weight loss may be very different. While these subgroup studies are interesting and
RI PT
seem to demonstrate possible physiologic changes induced by of ESG, they should be interpreted with caution due to the small number of subjects evaluated. Further studies with additional subjects are needed for validation of these small pilot data. Moreover, the patients included in this study had on average lower BMIs than patients undergoing sleeve gastrectomy, making true comparisons between
SC
the two procedures difficult.
Durability of ESG was also assessed in 9 patients at 3 months with repeat upper endoscopies.
M AN U
Approximately 2/3 of the had intact gastroplasties with fibrotic bands. 1/3 had partial breakdown of the gastroplasty. The group also compared their results to a similar group of patients treated at another center in Spain that had started an ESG program around the same time. They found similar results in weight loss with 53% mean excess weight loss at 6 and 12 months at both centers. However only 10 subjects from the Mayo group were evaluated at 12 months, limiting the reliability of the weight
TE D
loss durability at 12 months.
Complications were seen in this series as might be expected with any new technique or device. Modifications of the technique and awareness of the full thickness suturing that occurs with this procedure will hopefully reduce or eliminate these complications in the future.
EP
In summary ESG has the potential for providing an effective therapy for the many patients with obesity, in particular those patients with a BMI between 30 and 40 kg/m2 who may not qualify for sleeve
AC C
gastrectomy. ESG has the advantage of a single endoscopic procedure that may have effective weight control for more than a year in some patients, when compared with other clinically available endoscopic bariatric therapies. ESG in its current form is ready to be provided clinically in centers that have programs in endoscopic treatments of obesity and extensive experience with the use of the suturing device. Possible mechanisms for weight loss include a delay in gastric emptying and possible alteration in gut hormones, but further research is needed to clarify both mechanisms of action and weight loss durability.
ACCEPTED MANUSCRIPT
References
1.
Cawley J, Meyerhoefer C. The medical care costs of obesity: An instrumental variables approach. Journal of Health Economics 2012;31:219-230. Finkelstein EA, Trogdon JG, Cohen JW, et al. Annual Medical Spending Attributable To Obesity:
RI PT
2.
Payer-And Service-Specific Estimates. Health Affairs 2009;28:w822-w831. 3.
Sumithran P, Prendergast LA, Delbridge E, et al. Long-Term Persistence of Hormonal Adaptations to Weight Loss. New England Journal of Medicine 2011;365:1597-1604.
Albaugh VL, Flynn CR, Tamboli RA, et al. Recent advances in metabolic and bariatric surgery. F1000Research 2016;5:F1000 Faculty Rev-978.
5.
SC
4.
Pepino MY, Bradley D, Eagon JC, et al. Changes in taste perception and eating behavior after
6.
M AN U
bariatric surgery-induced weight loss in women. Obesity 2014;22:E13-E20. Pepino MY, Stein RI, Eagon JC, et al. Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity. Obesity 2014;22:1792-1798. 7.
Dumon KR, Murayama KM. Bariatric surgery outcomes. Surg Clin North Am 2011;91:1313-38, x.
8.
Abu Dayyeh BK, Acosta Cardenas AJ, Camilleri, M, et al. Endoscopic sleeve gastroplasty for
2016;XXXXXXXXXXX
Mans E, Serra-Prat M, Palomera E, et al. Sleeve gastrectomy effects on hunger, satiation, and gastrointestinal hormone and motility responses after a liquid meal test. The American Journal
EP
of Clinical Nutrition 2015;102:540-547.
AC C
9.
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treatment of obesity alters gastric physiology and induces body weight loss. CGH
ACCEPTED MANUSCRIPT
Figure 1 Used with permission
Figure 1A. Suturing device attached to the endoscope
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Gastrointestinal Endoscopy 2015 Volume 15 page 1076
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Figure 1B. ESG with gastric restriction using endoscopically placed sutures.
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M AN U
SC
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ACCEPTED MANUSCRIPT
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M AN U
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ACCEPTED MANUSCRIPT
PII: DOI: Reference:
S1542-3565(16)30856-4 10.1016/j.cgh.2016.09.145 YJCGH 54933
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 23 September 2016 Please cite this article as: Sullivan S, Edmundowicz SA, Early Experience with Endoscopic Sleeve Gastroplasty and Hints at Mechanisms of Action, Clinical Gastroenterology and Hepatology (2016), doi: 10.1016/j.cgh.2016.09.145. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Early Experience with Endoscopic Sleeve Gastroplasty and Hints at Mechanisms of Action Shelby Sullivan MD, Visiting Associate Professor of Medicine University of Colorado School of Medicine and Steven A. Edmundowicz MD FASGE Visiting Professor of Medicine University of Colorado School of
RI PT
Medicine.
Dr. Shelby Sullivan Dr Steven Edmundowicz FASGE University of Colorado School of Medicine
SC
Mail Stop F735 Anschutz Outpatient Pavilion
Aurora Colorado 80045 Academic: (720) 848-2786 [email protected] [email protected]
TE D
Disclosures:
M AN U
1635 Aurora Ct.
Dr. Sullivan receives research support from Aspire Bariatrics, ReShape Medical, GI Dynamics, USGI Medical, Obalon, Baronova. She is a paid consultant for 2012-2016: Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee, Center for Devices and Radiological Health,
EP
Food and Drug Administration, 2013-Present: USGI Medical, EnteroMedics Advisory Board, May, 2014, 2015-Present: Obalon, Takeda Pharmaceuticals, Advisory Board, September 2015, 2016-Present: Elira
AC C
Therapeutic, 2016 SynerZ
Dr. Edmundowicz receives research support from Aspire Bariatrics, ReShape Medical, GI Dynamics, USGI Medical, and Obalon. He is a paid consultant with Boston Scientific, Olympus, Medtronic, GI Dynamics, Xlumena, Fractyl and Torax. He is a stockholder in Motus GI, SynerZ, Elira, Endostim, Check-Cap, and Freehold surgical.
ACCEPTED MANUSCRIPT
It is widely recognized that obesity is major health concern in the United States, with over 90 million Americans affected by the disease. Due to obesity related co-morbidities including but not limited to diabetes, heart disease, and cancer; the healthcare costs associated with obesity may account for up to 21% of US healthcare expenditures1, 2 . Current therapies for obesity include lifestyle therapy,
RI PT
pharmacotherapy, endoscopic bariatric therapy, and bariatric surgery. Lifestyle therapy alone is the least effective therapy, possibly due to hunger and satiety hormone changes which result in increased hunger and desire to eat with weight loss3. Bariatric surgery, namely Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, is the most effective therapy. The mechanisms for weight loss with bariatric
SC
surgery are not completely understood, but the altered anatomy changes the response of several gut hormones which have effects on hunger and satiety in addition to changes in gastric capacity, gut motility, and bile acids4, 5. Not only does this result in decreased food intake, but RYGB has also been
M AN U
shown to induce remission of food addiction6; further demonstrating the effect of this surgery on eating behaviors. Unfortunately, only 1% of patients who qualify for bariatric surgery pursue surgical options7; likely related to the risks, costs, recovery time, and food restrictions associated with bariatric surgery. There is increasing hope that minimally invasive endoscopic procedures would fill the treatment gap between medical therapies and bariatric surgery.
TE D
In this issue of CGH⁸, Abu Dayyeh and colleagues of the Mayo Clinic, Rochester describe their initial single center experience with Endoscopic Sleeve Gastroplasty (ESG). This endoscopic procedure uses an available endoscopic suturing device that has been approved for the general purpose of endoscopic suturing of tissues. ESG is minimally invasive and done under general anesthesia, occasionally with an
EP
overnight hospital observation stay. This procedure was devised to endoscopically achieve a change in the gastric anatomy similar to that achieved with laparoscopic sleeve gastrectomy without the surgical
AC C
resection of the fundus or body of the stomach (Figure 1)
In this early report of the first 25 patients (patients followed for a median of 9 months), the results appear encouraging with 56%+/- 23% excess weight loss at 9 months in 17 patients. The group also reports findings of physiologic and hormonal measurements in 4 patients. In these patients gastric emptying was delayed, which is opposite to the effect of sleeve gastrectomy where gastric emptying is accelerated⁹. Calorie intake to reach maximum fullness in a liquid meal test decreased by 59%. There was a trend towards a decrease in ghrelin concentrations during a meal test. Although this was not statistically significant, ghrelin is expected to increase with weight loss, so the lack of an increase with
ACCEPTED MANUSCRIPT
ESG is an interesting finding. Whole body insulin sensitivity measured by HOMA-IR improved as expected for the percent excess weight loss seen in these patients. Taken together, these limited data suggest that although gastric luminal dimensions after ESG and sleeve gastrectomy are very similar, the mechanism for weight loss may be very different. While these subgroup studies are interesting and
RI PT
seem to demonstrate possible physiologic changes induced by of ESG, they should be interpreted with caution due to the small number of subjects evaluated. Further studies with additional subjects are needed for validation of these small pilot data. Moreover, the patients included in this study had on average lower BMIs than patients undergoing sleeve gastrectomy, making true comparisons between
SC
the two procedures difficult.
Durability of ESG was also assessed in 9 patients at 3 months with repeat upper endoscopies.
M AN U
Approximately 2/3 of the had intact gastroplasties with fibrotic bands. 1/3 had partial breakdown of the gastroplasty. The group also compared their results to a similar group of patients treated at another center in Spain that had started an ESG program around the same time. They found similar results in weight loss with 53% mean excess weight loss at 6 and 12 months at both centers. However only 10 subjects from the Mayo group were evaluated at 12 months, limiting the reliability of the weight
TE D
loss durability at 12 months.
Complications were seen in this series as might be expected with any new technique or device. Modifications of the technique and awareness of the full thickness suturing that occurs with this procedure will hopefully reduce or eliminate these complications in the future.
EP
In summary ESG has the potential for providing an effective therapy for the many patients with obesity, in particular those patients with a BMI between 30 and 40 kg/m2 who may not qualify for sleeve
AC C
gastrectomy. ESG has the advantage of a single endoscopic procedure that may have effective weight control for more than a year in some patients, when compared with other clinically available endoscopic bariatric therapies. ESG in its current form is ready to be provided clinically in centers that have programs in endoscopic treatments of obesity and extensive experience with the use of the suturing device. Possible mechanisms for weight loss include a delay in gastric emptying and possible alteration in gut hormones, but further research is needed to clarify both mechanisms of action and weight loss durability.
ACCEPTED MANUSCRIPT
References
1.
Cawley J, Meyerhoefer C. The medical care costs of obesity: An instrumental variables approach. Journal of Health Economics 2012;31:219-230. Finkelstein EA, Trogdon JG, Cohen JW, et al. Annual Medical Spending Attributable To Obesity:
RI PT
2.
Payer-And Service-Specific Estimates. Health Affairs 2009;28:w822-w831. 3.
Sumithran P, Prendergast LA, Delbridge E, et al. Long-Term Persistence of Hormonal Adaptations to Weight Loss. New England Journal of Medicine 2011;365:1597-1604.
Albaugh VL, Flynn CR, Tamboli RA, et al. Recent advances in metabolic and bariatric surgery. F1000Research 2016;5:F1000 Faculty Rev-978.
5.
SC
4.
Pepino MY, Bradley D, Eagon JC, et al. Changes in taste perception and eating behavior after
6.
M AN U
bariatric surgery-induced weight loss in women. Obesity 2014;22:E13-E20. Pepino MY, Stein RI, Eagon JC, et al. Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity. Obesity 2014;22:1792-1798. 7.
Dumon KR, Murayama KM. Bariatric surgery outcomes. Surg Clin North Am 2011;91:1313-38, x.
8.
Abu Dayyeh BK, Acosta Cardenas AJ, Camilleri, M, et al. Endoscopic sleeve gastroplasty for
2016;XXXXXXXXXXX
Mans E, Serra-Prat M, Palomera E, et al. Sleeve gastrectomy effects on hunger, satiation, and gastrointestinal hormone and motility responses after a liquid meal test. The American Journal
EP
of Clinical Nutrition 2015;102:540-547.
AC C
9.
TE D
treatment of obesity alters gastric physiology and induces body weight loss. CGH
ACCEPTED MANUSCRIPT
Figure 1 Used with permission
Figure 1A. Suturing device attached to the endoscope
RI PT
Gastrointestinal Endoscopy 2015 Volume 15 page 1076
AC C
EP
TE D
M AN U
SC
Figure 1B. ESG with gastric restriction using endoscopically placed sutures.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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M AN U
SC
RI PT
ACCEPTED MANUSCRIPT