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Gastric restriction and delayed gastric emptying may not be the keys to an effective endoscopic metabolic therapy
Letterss to the editor
associated with PEP (odds ratio [OR] of 1.95) only in the univariate analysis because those at presumably high risk for PEP received PD stent placement.1 After adjustment for other risk factors in the multivariate analysis, the OR of PD stent placement decreased to 1.04 (P Z .906). The role of PD stent placement in cases with unintentional PD guidewire insertion can be evaluated only in a prospective randomized controlled trial. Last but not least, case volume can be an important issue in terms of both success and adverse event rates in therapeutic ERCP. Although high case volume was associated with a high success rate in several studies,3-7 only one study showed a positive association of case volume with adverse events.4 However, the association was observed only in overall, cardiopulmonary adverse events and cholangitis, but not in PEP. When we analyzed our study cohort in association with case volumes, there were no correlations of case volume with PEP (R2 Z 0.049) or PD manipulation (R2 Z 0.011). This probably is because ERCPs performed by low-volume endoscopists or at low-volume centers are at lower baseline risk of PEP.8 We believe our study results were not affected much by case volume by each endoscopist; on the contrary, the involvement of multiple endoscopists can be our study strength because it allows extrapolation. Yousuke Nakai, MD, PhD Hiroyuki Isayama, MD, PhD Kazuhiko Koike, MD, PhD Department of Gastroenterology Graduate School of Medicine The University of Tokyo Tokyo, Japan
REFERENCES 1. Nakai Y, Isayama H, Sasahira N, et al. Risk factors for post-ERCP pancreatitis in wire-guided cannulation for therapeutic biliary ERCP. Gastrointest Endosc 2015;81:119-26. 2. Choudhary A, Bechtold ML, Arif M, et al. Pancreatic stents for prophylaxis against post-ERCP pancreatitis: a meta-analysis and systematic review. Gastrointest Endosc 2011;73:275-82. 3. Varadarajulu S, Kilgore ML, Wilcox CM, et al. Relationship among hospital ERCP volume, length of stay, and technical outcomes. Gastrointest Endosc 2006;64:338-47. 4. Kapral C, Duller C, Wewalka F, et al. Case volume and outcome of endoscopic retrograde cholangiopancreatography: results of a nationwide Austrian benchmarking project. Endoscopy 2008;40:625-30. 5. Testoni PA, Mariani A, Giussani A, et al. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol 2010;105:1753-61. 6. Peng C, Nietert PJ, Cotton PB, et al. Predicting native papilla biliary cannulation success using a multinational endoscopic retrograde cholangiopancreatography (ERCP) quality network. BMC Gastroenterol 2013;13:147. 7. Cote GA, Imler TD, Xu H, et al. Lower provider volume is associated with higher failure rates for endoscopic retrograde cholangiopancreatography. Med Care 2013;51:1040-7.
www.giejournal.org
8. Cote GA, Keswani RN, Jackson T, et al. Individual and practice differences among physicians who perform ERCP at varying frequency: a national survey. Gastrointest Endosc 2011;74:65-73 e12. http://dx.doi.org/10.1016/j.gie.2015.02.049
Gastric restriction and delayed gastric emptying may not be the keys to an effective endoscopic metabolic therapy To the Editor: We read with interest the recently published article by Verlaan and Paulus et al1 describing the use of an endoscopic stapler for gastric volume reduction in obese patients. As the authors point out, studies of several other gastric restrictive techniques have reported similar outcomes.2-5 When the outcomes of endoscopic restrictive therapies are analyzed, the reduction in obesity-related comorbidities appears to correlate with the degree of weight loss. In comparison, the benefits of vertical sleeve gastrectomy (VSG) go beyond its ability to simply produce weight loss.6 VSG is now recognized to alter critical signaling and metabolic pathways to improve the metabolic profile even before significant weight loss occurs, indicating that it is more than simply a restrictive procedure.7,8 This raises mechanistic questions as to why VSG has superior outcomes compared with endoscopic restrictive therapies. One obvious difference is the excision of 80% of the gastric mucosa in VSG. The gastric mucosa is being increasingly recognized as an important regulator of hunger and food intake.9 Therefore, if endoscopic techniques are targeted at impeding the function of the gastric mucosa, could one expect an improvement in comorbidities out of proportion to simply weight loss? A misconception held by many is that delayed gastric emptying results in reduced caloric intake. In this study, 2 plications were placed in the antrum with the specific purpose to decrease gastric emptying.1 However, gastric emptying appears to be accelerated after VSG, and this has been suggested as a mechanism for its improvement in metabolic profile.10 Understanding the mechanisms contributing to the benefits of VSG offers tremendous potential to develop an endoscopic metabolic therapy. Progress toward this goal has been hindered because many continue to ignore the true science behind the benefits of bariatric surgery, a technique that has been proved to reduce obesity-related morbidity and mortality. Vivek Kumbhari, MD Division of Gastroenterology and Hepatology Johns Hopkins Medical Institutions Baltimore, Maryland, USA Volume 82, No. 1 : 2015 GASTROINTESTINAL ENDOSCOPY 185
Letterss to the editor
Marco Heinrich, PhD Department of Cardiac Surgery University of Leipzig Leipzig, Germany Mouen A. Khashab, MD Anthony N. Kalloo, MD Division of Gastroenterology and Hepatology Johns Hopkins Medical Institutions Baltimore, Maryland, USA Andreas Oberbach, MD, PhD Department of Cardiac Surgery University of Leipzig Leipzig, Germany REFERENCES 1. Verlaan T, Paulus GF, Mathus-Vliegen EM, et al. Endoscopic gastric volume reduction with a novel articulating plication device is safe and effective in the treatment of obesity (with video). Gastrointest Endosc 2015;81:312-20. 2. Espinos JC, Turro R, Mata A, et al. Early experience with the incisionless operating platform (IOP) for the treatment of obesity: the primary obesity surgery endolumenal (POSE) procedure. Obes Surg 2013;23: 1375-83. 3. Familiari P, Costamagna G, Blero D, et al. Transoral gastroplasty for morbid obesity: a multicenter trial with a 1-year outcome. Gastrointest Endosc 2011;74:1248-58. 4. Abu Dayyeh BK, Rajan E, Gostout CJ. Endoscopic sleeve gastroplasty: a potential endoscopic alternative to surgical sleeve gastrectomy for treatment of obesity. Gastrointest Endosc 2013;78:530-5. 5. Lopez-Nava G, Galvao MP, da Bautista-Castano I, et al. Endoscopic sleeve gastroplasty for the treatment of obesity. Endoscopy. Epub 2014 Nov 7. 6. Clifton PM. Bariatric surgery: results in obesity and effects on metabolic parameters. Curr Opin Lipidol 2011;22:1-5. 7. Shah SS, Todkar JS, Shah PS, et al. Diabetes remission and reduced cardiovascular risk after gastric bypass in Asian Indians with body mass index <35 kg/m(2). Surg Obes Relat Dis 2010;6:332-8. 8. Chambers AP, Jessen L, Ryan KK, et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 2011;141:950-8. 9. Pasricha PJ. Hunger games: is your stomach making you fat? Gastroenterology 2015;148:491-3. 10. Melissas J, Daskalakis M, Koukouraki S, et al. Sleeve gastrectomy: a “food limiting” operation. Obes Surg 2008;18:1251-6.
gastric emptying, that delayed gastric emptying is linked with increased feelings of satiety, and that another effective minimally invasive restrictive therapydthe intragastric balloondis accompanied by delayed gastric emptying.2-5 Therefore, we cannot agree with the statement by Kumbhari et al that this is a misconception. The simple fact that, in some studies, the gastric emptying rate is increased after laparoscopic sleeve gastrectomy (LSG) does not mean that this solely enhances weight loss. Because a large portion of the stomach is removed, one could also argue that LSG is effective despite an enhanced gastric empting rate because of the extreme effects of volume reduction and removal of ghrelinproducing cells. Endoscopic gastroplication of the fundus aims to reduce the capacity of the stomach, thereby interfering with gastric accommodation and relaxation after meal ingestion, contributing to a sense of fullness. Plicating the antrum in our procedure aims to limit enhanced gastric emptying caused by the gastric volume reduction. The procedure is minimally invasive and has an exceptional safety profile compared with LSG.6 Because bariatric surgery should be applied only if the expected health improvement outweighs the risk of surgery, a safer risk profile makes endoscopic techniques accessible to a broader group of patients. To understand the exact mechanisms behind weight loss after endoscopic gastroplication, we additionally studied gastric emptying, GI hormone changes, and feelings of hunger and satiety in a subgroup of 10 patients. The results of this study will be submitted for publication soon and will demonstrate short-term and long-term changes that are not explained by weight loss alone.
We thank Kumbhari et al for their interest in our recent publication “Endoscopic gastric volume reduction with a novel articulating plication device is safe and effective in the treatment of obesity” in Gastrointestinal Endoscopy,1 but we believe a reply to their letter is justified. We support the statement that understanding the mechanisms behind obesity and weight loss surgery will contribute to the development and improvement of new techniques. Gastric emptying rate is clearly a piece of this puzzle and is exactly the reason why plications were also created in the antrum. Several studies have investigated the role of gastric emptying in the development of obesity and have found that obese people have enhanced
Givan F. Paulus, MD Department of Surgery Maastricht University Medical Center Maastricht, The Netherlands Department of Surgery Kennemer Gasthuis Haarlem, The Netherlands Mark van Avesaat, MD Department of Gastroenterology and Hepatology Maastricht University Medical Center Maastricht, The Netherlands Elisabeth M. H. Mathus-Vliegen, MD, PhD Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam, The Netherlands Nicole D. Bouvy, MD, PhD Department of Surgery Maastricht University Medical Center Maastricht, The Netherlands Paul Fockens, MD, PhD Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam, The Netherlands
186 GASTROINTESTINAL ENDOSCOPY Volume 82, No. 1 : 2015
www.giejournal.org
http://dx.doi.org/10.1016/j.gie.2015.01.058
Response:
associated with PEP (odds ratio [OR] of 1.95) only in the univariate analysis because those at presumably high risk for PEP received PD stent placement.1 After adjustment for other risk factors in the multivariate analysis, the OR of PD stent placement decreased to 1.04 (P Z .906). The role of PD stent placement in cases with unintentional PD guidewire insertion can be evaluated only in a prospective randomized controlled trial. Last but not least, case volume can be an important issue in terms of both success and adverse event rates in therapeutic ERCP. Although high case volume was associated with a high success rate in several studies,3-7 only one study showed a positive association of case volume with adverse events.4 However, the association was observed only in overall, cardiopulmonary adverse events and cholangitis, but not in PEP. When we analyzed our study cohort in association with case volumes, there were no correlations of case volume with PEP (R2 Z 0.049) or PD manipulation (R2 Z 0.011). This probably is because ERCPs performed by low-volume endoscopists or at low-volume centers are at lower baseline risk of PEP.8 We believe our study results were not affected much by case volume by each endoscopist; on the contrary, the involvement of multiple endoscopists can be our study strength because it allows extrapolation. Yousuke Nakai, MD, PhD Hiroyuki Isayama, MD, PhD Kazuhiko Koike, MD, PhD Department of Gastroenterology Graduate School of Medicine The University of Tokyo Tokyo, Japan
REFERENCES 1. Nakai Y, Isayama H, Sasahira N, et al. Risk factors for post-ERCP pancreatitis in wire-guided cannulation for therapeutic biliary ERCP. Gastrointest Endosc 2015;81:119-26. 2. Choudhary A, Bechtold ML, Arif M, et al. Pancreatic stents for prophylaxis against post-ERCP pancreatitis: a meta-analysis and systematic review. Gastrointest Endosc 2011;73:275-82. 3. Varadarajulu S, Kilgore ML, Wilcox CM, et al. Relationship among hospital ERCP volume, length of stay, and technical outcomes. Gastrointest Endosc 2006;64:338-47. 4. Kapral C, Duller C, Wewalka F, et al. Case volume and outcome of endoscopic retrograde cholangiopancreatography: results of a nationwide Austrian benchmarking project. Endoscopy 2008;40:625-30. 5. Testoni PA, Mariani A, Giussani A, et al. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol 2010;105:1753-61. 6. Peng C, Nietert PJ, Cotton PB, et al. Predicting native papilla biliary cannulation success using a multinational endoscopic retrograde cholangiopancreatography (ERCP) quality network. BMC Gastroenterol 2013;13:147. 7. Cote GA, Imler TD, Xu H, et al. Lower provider volume is associated with higher failure rates for endoscopic retrograde cholangiopancreatography. Med Care 2013;51:1040-7.
www.giejournal.org
8. Cote GA, Keswani RN, Jackson T, et al. Individual and practice differences among physicians who perform ERCP at varying frequency: a national survey. Gastrointest Endosc 2011;74:65-73 e12. http://dx.doi.org/10.1016/j.gie.2015.02.049
Gastric restriction and delayed gastric emptying may not be the keys to an effective endoscopic metabolic therapy To the Editor: We read with interest the recently published article by Verlaan and Paulus et al1 describing the use of an endoscopic stapler for gastric volume reduction in obese patients. As the authors point out, studies of several other gastric restrictive techniques have reported similar outcomes.2-5 When the outcomes of endoscopic restrictive therapies are analyzed, the reduction in obesity-related comorbidities appears to correlate with the degree of weight loss. In comparison, the benefits of vertical sleeve gastrectomy (VSG) go beyond its ability to simply produce weight loss.6 VSG is now recognized to alter critical signaling and metabolic pathways to improve the metabolic profile even before significant weight loss occurs, indicating that it is more than simply a restrictive procedure.7,8 This raises mechanistic questions as to why VSG has superior outcomes compared with endoscopic restrictive therapies. One obvious difference is the excision of 80% of the gastric mucosa in VSG. The gastric mucosa is being increasingly recognized as an important regulator of hunger and food intake.9 Therefore, if endoscopic techniques are targeted at impeding the function of the gastric mucosa, could one expect an improvement in comorbidities out of proportion to simply weight loss? A misconception held by many is that delayed gastric emptying results in reduced caloric intake. In this study, 2 plications were placed in the antrum with the specific purpose to decrease gastric emptying.1 However, gastric emptying appears to be accelerated after VSG, and this has been suggested as a mechanism for its improvement in metabolic profile.10 Understanding the mechanisms contributing to the benefits of VSG offers tremendous potential to develop an endoscopic metabolic therapy. Progress toward this goal has been hindered because many continue to ignore the true science behind the benefits of bariatric surgery, a technique that has been proved to reduce obesity-related morbidity and mortality. Vivek Kumbhari, MD Division of Gastroenterology and Hepatology Johns Hopkins Medical Institutions Baltimore, Maryland, USA Volume 82, No. 1 : 2015 GASTROINTESTINAL ENDOSCOPY 185
Letterss to the editor
Marco Heinrich, PhD Department of Cardiac Surgery University of Leipzig Leipzig, Germany Mouen A. Khashab, MD Anthony N. Kalloo, MD Division of Gastroenterology and Hepatology Johns Hopkins Medical Institutions Baltimore, Maryland, USA Andreas Oberbach, MD, PhD Department of Cardiac Surgery University of Leipzig Leipzig, Germany REFERENCES 1. Verlaan T, Paulus GF, Mathus-Vliegen EM, et al. Endoscopic gastric volume reduction with a novel articulating plication device is safe and effective in the treatment of obesity (with video). Gastrointest Endosc 2015;81:312-20. 2. Espinos JC, Turro R, Mata A, et al. Early experience with the incisionless operating platform (IOP) for the treatment of obesity: the primary obesity surgery endolumenal (POSE) procedure. Obes Surg 2013;23: 1375-83. 3. Familiari P, Costamagna G, Blero D, et al. Transoral gastroplasty for morbid obesity: a multicenter trial with a 1-year outcome. Gastrointest Endosc 2011;74:1248-58. 4. Abu Dayyeh BK, Rajan E, Gostout CJ. Endoscopic sleeve gastroplasty: a potential endoscopic alternative to surgical sleeve gastrectomy for treatment of obesity. Gastrointest Endosc 2013;78:530-5. 5. Lopez-Nava G, Galvao MP, da Bautista-Castano I, et al. Endoscopic sleeve gastroplasty for the treatment of obesity. Endoscopy. Epub 2014 Nov 7. 6. Clifton PM. Bariatric surgery: results in obesity and effects on metabolic parameters. Curr Opin Lipidol 2011;22:1-5. 7. Shah SS, Todkar JS, Shah PS, et al. Diabetes remission and reduced cardiovascular risk after gastric bypass in Asian Indians with body mass index <35 kg/m(2). Surg Obes Relat Dis 2010;6:332-8. 8. Chambers AP, Jessen L, Ryan KK, et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 2011;141:950-8. 9. Pasricha PJ. Hunger games: is your stomach making you fat? Gastroenterology 2015;148:491-3. 10. Melissas J, Daskalakis M, Koukouraki S, et al. Sleeve gastrectomy: a “food limiting” operation. Obes Surg 2008;18:1251-6.
gastric emptying, that delayed gastric emptying is linked with increased feelings of satiety, and that another effective minimally invasive restrictive therapydthe intragastric balloondis accompanied by delayed gastric emptying.2-5 Therefore, we cannot agree with the statement by Kumbhari et al that this is a misconception. The simple fact that, in some studies, the gastric emptying rate is increased after laparoscopic sleeve gastrectomy (LSG) does not mean that this solely enhances weight loss. Because a large portion of the stomach is removed, one could also argue that LSG is effective despite an enhanced gastric empting rate because of the extreme effects of volume reduction and removal of ghrelinproducing cells. Endoscopic gastroplication of the fundus aims to reduce the capacity of the stomach, thereby interfering with gastric accommodation and relaxation after meal ingestion, contributing to a sense of fullness. Plicating the antrum in our procedure aims to limit enhanced gastric emptying caused by the gastric volume reduction. The procedure is minimally invasive and has an exceptional safety profile compared with LSG.6 Because bariatric surgery should be applied only if the expected health improvement outweighs the risk of surgery, a safer risk profile makes endoscopic techniques accessible to a broader group of patients. To understand the exact mechanisms behind weight loss after endoscopic gastroplication, we additionally studied gastric emptying, GI hormone changes, and feelings of hunger and satiety in a subgroup of 10 patients. The results of this study will be submitted for publication soon and will demonstrate short-term and long-term changes that are not explained by weight loss alone.
We thank Kumbhari et al for their interest in our recent publication “Endoscopic gastric volume reduction with a novel articulating plication device is safe and effective in the treatment of obesity” in Gastrointestinal Endoscopy,1 but we believe a reply to their letter is justified. We support the statement that understanding the mechanisms behind obesity and weight loss surgery will contribute to the development and improvement of new techniques. Gastric emptying rate is clearly a piece of this puzzle and is exactly the reason why plications were also created in the antrum. Several studies have investigated the role of gastric emptying in the development of obesity and have found that obese people have enhanced
Givan F. Paulus, MD Department of Surgery Maastricht University Medical Center Maastricht, The Netherlands Department of Surgery Kennemer Gasthuis Haarlem, The Netherlands Mark van Avesaat, MD Department of Gastroenterology and Hepatology Maastricht University Medical Center Maastricht, The Netherlands Elisabeth M. H. Mathus-Vliegen, MD, PhD Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam, The Netherlands Nicole D. Bouvy, MD, PhD Department of Surgery Maastricht University Medical Center Maastricht, The Netherlands Paul Fockens, MD, PhD Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam, The Netherlands
186 GASTROINTESTINAL ENDOSCOPY Volume 82, No. 1 : 2015
www.giejournal.org
http://dx.doi.org/10.1016/j.gie.2015.01.058
Response: