- Email: [email protected]
Primum non nocere! (First do no harm!)
EDITORIAL
Primum non nocere! (First do no harm!) In this issue of Gastrointestinal Endoscopy, Betzel and colleagues1 from Rijnstate Hospital, Arnhem, the Netherlands present their safety experience with the endoscopically placed duodenal-jejunal bypass liner. They report their single-center safety experience with endoscopic implantation and removal of the GI Dynamics Endobarrier sleeve for the treatment of type II diabetes and obesity over a 7-year period. Their report highlights the known adverse events that have been previously encountered with this device. It is important to note that 80% of their patients who could be implanted with the device tolerated it with minimal descriptions of untoward symptoms. However, in 13 of the 165 patients (8%), implantation failed for purely anatomic reasons (eg, short bulb). Approximately 50% of the implanted patients had significant GI symptoms after placement of the device. This led to early explantation in 16 patients (10%). Of the 152 implanted patients, 11 had serious adverse events, including 7 with GI bleeding, 2 of whom had hypotension and required emergent interventions for arterial bleeding (1 embolization and 1 surgery). There were 2 mild cases of pancreatitis, and 1 patient experienced hepatic abscesses requiring intravenous and oral antibiotic therapy. On an intention-to-treat basis, therapy failed in 40 (24%) of the patients. Two additional patients experienced perforation of the esophagus on device removal. (The removal system has since been modified to prevent this adverse event in the future.) Although the device has been used widely outside the United States, it has not been approved to be marketed for clinical use in the United States by the U. S. Food and Drug Administration (FDA). A multicenter randomized controlled pivotal trial was initiated in the United States in 2013. However, this 21-center trial had enrollment suspended by the FDA in March 2015. According to a press release on the GI Dynamics website (www.gIdynamics. com), the trial was placed on hold when 4 cases of hepatic abscesses were noted in the 325 randomized subjects. A risk mitigation plan has been developed for presentation to the FDA. It is hoped that this plan will be accepted by the FDA and the trial will resume enrollment soon. This large blinded multicenter study will provide a better understanding of the true incidence of other adverse events in comparison with a control group.
The ASGE Bariatric Endoscopy Task Force and the ASGE Technology Committee recently completed a systematic review and meta-analysis assessing the preservation and incorporation of valuable endoscopic innovation (PIVI) thresholds for adopting endoscopic bariatric therapies into clinical practice.2 The review evaluated 271 implanted patients and reported the following. Serious adverse events included migration (4.9%), GI bleeding (3.86%), sleeve obstruction (3.4%), liver abscess (0.126%), cholangitis (0.126%), acute cholecystitis (0.126%), and esophageal perforation (0.126%) secondary to trauma from an uncovered barb at withdrawal. This report by Betzel and colleagues1 notes a similar high rate of serious adverse events. In the American Society for
In the ASGE/ASMBS joint society PIVI document, “A pathway to endoscopic bariatric therapies,” the task force felt that in addition to efficacy described as more than 25% excess weight loss, a serious adverse event rate of less than 5% was necessary before the societies could support a device for clinical use. Gastrointestinal Endoscopy (ASGE) / American Society for Metabolic and Bariatric Surgery (ASMBS) joint society PIVI document,3 “A pathway to endoscopic bariatric therapies,” the task force thought that in addition to efficacy described as more than 25% excess weight loss, a serious adverse event rate of less than 5% was necessary before the societies could support a device for clinical use. It seems that the overall reported rate of adverse events in all trials of the Endobarrier may exceed the 5% threshold. However, all individuals interested in this device are patiently waiting for the final assessment of the serious adverse events encountered in the multicenter trial in the United States. Once the results of that randomized controlled trial are tabulated, we should have a better idea of the true risk of adverse events with this unique device and whether it can be used clinically without “doing harm” to our patients. DISCLOSURE
Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2015.07.026
Dr. Edmundowicz receives consulting fees and is an advisory board member for Boston Scientific and Olympus; is a stockholder medical advisory board
www.giejournal.org
Volume 82, No. 5 : 2015 GASTROINTESTINAL ENDOSCOPY 853
Editorial
Edmundowicz
member for SynerZ Medical; receives consulting fees and is a research advisory committee member for GI Dynamics; receives consulting fees and is an advisory board member for Fractyl; is a consultant (stock/ownership interest) for Beacon Endoscopic, now acquired by Medtronic; and is site principal investigator or coinvestigator, receiving institutional research grants, from Aspire Bariatrics, US GI, ReShape Medical, Obalon, and Baranova.
Washington University School of Medicine St. Louis, Missouri REFERENCES
Steven A. Edmundowicz, MD, FASGE Professor of Medicine Chief of Endoscopy Departments of Medicine and Endoscopy
1. Betzel B, Koehestanie P, Aarts EO, et al. Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment for diabetes and obesity. Gastointest Endosc 2015;82:845-52. 2. ASGE Bariatric Endoscopy Task Force and ASGE Technology Committee; Abu Dayyeh B, Kumar N, Edmundowicz SA, et al. ASGE bariatric endoscopy task force systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting endoscopic bariatric therapies. Gastrointest Endosc 2015;82:425-38. 3. Ginsberg GG, Chand B, Cote GA, et al. A pathway to endoscopic bariatric therapies. Gastrointest Endosc 2011;74:943-53.
854 GASTROINTESTINAL ENDOSCOPY Volume 82, No. 5 : 2015
www.giejournal.org
Primum non nocere! (First do no harm!) In this issue of Gastrointestinal Endoscopy, Betzel and colleagues1 from Rijnstate Hospital, Arnhem, the Netherlands present their safety experience with the endoscopically placed duodenal-jejunal bypass liner. They report their single-center safety experience with endoscopic implantation and removal of the GI Dynamics Endobarrier sleeve for the treatment of type II diabetes and obesity over a 7-year period. Their report highlights the known adverse events that have been previously encountered with this device. It is important to note that 80% of their patients who could be implanted with the device tolerated it with minimal descriptions of untoward symptoms. However, in 13 of the 165 patients (8%), implantation failed for purely anatomic reasons (eg, short bulb). Approximately 50% of the implanted patients had significant GI symptoms after placement of the device. This led to early explantation in 16 patients (10%). Of the 152 implanted patients, 11 had serious adverse events, including 7 with GI bleeding, 2 of whom had hypotension and required emergent interventions for arterial bleeding (1 embolization and 1 surgery). There were 2 mild cases of pancreatitis, and 1 patient experienced hepatic abscesses requiring intravenous and oral antibiotic therapy. On an intention-to-treat basis, therapy failed in 40 (24%) of the patients. Two additional patients experienced perforation of the esophagus on device removal. (The removal system has since been modified to prevent this adverse event in the future.) Although the device has been used widely outside the United States, it has not been approved to be marketed for clinical use in the United States by the U. S. Food and Drug Administration (FDA). A multicenter randomized controlled pivotal trial was initiated in the United States in 2013. However, this 21-center trial had enrollment suspended by the FDA in March 2015. According to a press release on the GI Dynamics website (www.gIdynamics. com), the trial was placed on hold when 4 cases of hepatic abscesses were noted in the 325 randomized subjects. A risk mitigation plan has been developed for presentation to the FDA. It is hoped that this plan will be accepted by the FDA and the trial will resume enrollment soon. This large blinded multicenter study will provide a better understanding of the true incidence of other adverse events in comparison with a control group.
The ASGE Bariatric Endoscopy Task Force and the ASGE Technology Committee recently completed a systematic review and meta-analysis assessing the preservation and incorporation of valuable endoscopic innovation (PIVI) thresholds for adopting endoscopic bariatric therapies into clinical practice.2 The review evaluated 271 implanted patients and reported the following. Serious adverse events included migration (4.9%), GI bleeding (3.86%), sleeve obstruction (3.4%), liver abscess (0.126%), cholangitis (0.126%), acute cholecystitis (0.126%), and esophageal perforation (0.126%) secondary to trauma from an uncovered barb at withdrawal. This report by Betzel and colleagues1 notes a similar high rate of serious adverse events. In the American Society for
In the ASGE/ASMBS joint society PIVI document, “A pathway to endoscopic bariatric therapies,” the task force felt that in addition to efficacy described as more than 25% excess weight loss, a serious adverse event rate of less than 5% was necessary before the societies could support a device for clinical use. Gastrointestinal Endoscopy (ASGE) / American Society for Metabolic and Bariatric Surgery (ASMBS) joint society PIVI document,3 “A pathway to endoscopic bariatric therapies,” the task force thought that in addition to efficacy described as more than 25% excess weight loss, a serious adverse event rate of less than 5% was necessary before the societies could support a device for clinical use. It seems that the overall reported rate of adverse events in all trials of the Endobarrier may exceed the 5% threshold. However, all individuals interested in this device are patiently waiting for the final assessment of the serious adverse events encountered in the multicenter trial in the United States. Once the results of that randomized controlled trial are tabulated, we should have a better idea of the true risk of adverse events with this unique device and whether it can be used clinically without “doing harm” to our patients. DISCLOSURE
Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2015.07.026
Dr. Edmundowicz receives consulting fees and is an advisory board member for Boston Scientific and Olympus; is a stockholder medical advisory board
www.giejournal.org
Volume 82, No. 5 : 2015 GASTROINTESTINAL ENDOSCOPY 853
Editorial
Edmundowicz
member for SynerZ Medical; receives consulting fees and is a research advisory committee member for GI Dynamics; receives consulting fees and is an advisory board member for Fractyl; is a consultant (stock/ownership interest) for Beacon Endoscopic, now acquired by Medtronic; and is site principal investigator or coinvestigator, receiving institutional research grants, from Aspire Bariatrics, US GI, ReShape Medical, Obalon, and Baranova.
Washington University School of Medicine St. Louis, Missouri REFERENCES
Steven A. Edmundowicz, MD, FASGE Professor of Medicine Chief of Endoscopy Departments of Medicine and Endoscopy
1. Betzel B, Koehestanie P, Aarts EO, et al. Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment for diabetes and obesity. Gastointest Endosc 2015;82:845-52. 2. ASGE Bariatric Endoscopy Task Force and ASGE Technology Committee; Abu Dayyeh B, Kumar N, Edmundowicz SA, et al. ASGE bariatric endoscopy task force systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting endoscopic bariatric therapies. Gastrointest Endosc 2015;82:425-38. 3. Ginsberg GG, Chand B, Cote GA, et al. A pathway to endoscopic bariatric therapies. Gastrointest Endosc 2011;74:943-53.
854 GASTROINTESTINAL ENDOSCOPY Volume 82, No. 5 : 2015
www.giejournal.org