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New Technologies and Expert Meeting (Part 2)
Introduction (and welcome address): Time for us to change!
Although the need for innovation remains a mantra in bariatrics, we felt that a different type of organization was requested starting effectively this year 2015, for several reasons:
- Some trends are moving so fast that sometimes "wait and see" seems the appropriate action, sometimes we have to confirm data that look brilliant and advise caution.
- New technologies can be divided into three groups: the current surgical techniques and their improvements; the endoscopic field; the adjacent fields (biology, smartsensing, etc.). Each of them is equally important, since we do not know from where the light will come in the near future. The surgical field is pretty much covered by more traditional meetings, even if a focus on them is necessary every now and then; the endoscopic field is also covered since the initiative of the Spanish leader Gontrand Lopez-Nava; innovations from "outside" require finesse and expertise to be sorted out.
Finally, we broke a deal with our friend Karl Miller who has organizes for a long time the very successful Austrian expert meeting. We agreed to host each other every other year, so that both our meetings represent innovation and state of the art expertise in the same time. This way we shall ensure more industry support, and a long-term capacity to deliver news in a friendly atmosphere and contribute to highlight this more than ever thrilling field... Long live to the International "New Technologies and Expert Meeting"!
Endoscopic treatment in obesity, the past, the present and the future : Elisabeth MATHUS-VLIEGEN (The Netherlands)
The obesity epidemic asks for an active involvement of gastroenterologists because of 3 reasons: many of the co-morbidities associated with obesity involve the gastrointestinal tract; a small proportion of obese patients will need bariatric surgery and may suffer from surgical complications that may be solved by minimally invasive endoscopic techniques; and finally, the majority will not be eligible for bariatric surgery and will need some other form of treatment. The first approach should consist of an energy-restricted diet, physical exercise and behaviour modification, followed by pharmacotherapy. For patients who do not respond to medical therapy but are not or not yet surgical candidates, an endoscopic treatment might look attractive. So, endoscopic bariatric therapy has a role to play either as an alternative or adjunct to medical treatment. In the past, only intragastric balloons (IGB) were available. Although being available for 3 decades, intragastric balloon treatment is not covered by the existing evidence-based guidelines. This is partly the result of ineffective and hazardous balloons in the 1980s such as the FDA approved Garren-Edwards Gastric Bubble (GEGB). In GEGBs, deflations occurred in 31% which needed surgical interventions in 2.3%. Gastric ulcers were seen in 26% and the balloon was not tolerated in 7%. Being concerned of the design, construction and integrity of previous balloons, experts participating in the workshop “Obesity and the gastric balloon” formulated the fundamental requirements for an optimal balloon design in 1987. Intragastric balloons should be smooth, seamless and constructed of long-lasting material with a low ulcerogenic and obstructive potential. They should have a radiopaque marker to allow appropriate follow-up in case of deflation. There was uncertainty about the ideal shape, fill content and fill medium, but yet, a preference was expressed to have the ability to be adjusted to a variety of sizes and be filled with fluid rather than air. None of the existing balloons conformed to these requirements and this resulted in the withdrawal of balloons from the American market. Many years of research finally resulted in the development of a balloon (Bioenterics Intragastric Balloon, BIBÔ, Allergan intragastric balloon) that fulfilled the specified requirements. Over the last 15 years the balloon market is booming, although it has also resulted in some deceptions as with the Heliosphere Bag. New endoscopic modalities have been developed that vary in their mechanisms of action: by gastric distension and space occupation (IGB), delayed gastric emptying (IGB; BTA; ACE), gastric restriction and decreased distensibility (suturing and stapling devices), impaired gastric accommodation (Adjustable Totally Implanted Intragastric Prosthesis ATIIP; BTA; suturing and stapling devices), stimulation of antroduodenal receptors (SatiSphere), by gastric content evacuation (ABS) or by duodenal exclusion and malabsorption (DJBS). Vagal signalling to the hypothalamus and hormonal influences (IGB, ACE, DJBS) may play a role as well. One should realise that these developments are very costly and often not reimbursed. Several companies went bankrupt and many of the endoscopic tools did poorly. Furthermore, the suturing and stapling devices require high endoscopic skills. Apart from their mechanisms of action, the endoscopic interventions can be separated into early intervention in obese patients (BMI ≥ 30 kg/m2)to provide weight loss; primary intervention in subjects eligible for surgery but who refuse surgery or have no access to surgery; secondary intervention as a bridge to elective surgery in those with BMI ≥40 kg/m2 or as a bridge to bariatric surgery in those with BMI ≥50 kg/m2; metabolic intervention, primarily addressing comorbid diseases such as diabetes with a modest effect on weight.
Hormonal effects of endoscopic bariatric techniques : Elisabeth MATHUS-VLIEGEN (The Netherlands)
Satiety is centrally and peripherally mediated by gastrointestinal peptides and the vagal nerve. Candidate gastrointestinal hormones are glucagon-like peptide 1 (GLP-1), cholecystokinine (CCK) and pancreatic polypeptide (PP). Also, suppression of fasting ghrelin levels and even more an enhanced meal suppression of ghrelin secretion by the gastric fundus might contribute to postponement of meals. As yet, only a few endoscopic bariatric therapies have been examined as to their hormonal effects.
Intragastric balloons : CCK and PP are satiety hormones while ghrelin is an orexigenic hormone. A reduced CCK and PP secretion after balloon positioning was an unexpected finding and may reflect delayed gastric emptying induced by the balloon. Satiety and weight loss were not adversely influenced by these hormonal changes. Improved glucose metabolism partly explained the reduced PP secretion.
Ghrelin secretion. Authors do not agree on fasting and meal-suppressed ghrelin levels which has been reported to remain unchanged (Martinez-Brocca et al., 2007), to decrease (Mion et al., 2005) or fail to increase despite weight loss (Mathus-Vliegen et al., 2014). We discovered that concentrations did not change by balloon treatment and, unexpectedly, did not rise despite substantial weight loss and negative energy balance. This suppression might be of benefit in the maintenance of weight loss but could not be ascribed to the balloon treatment. The only effect of the balloon was found when it was located in the fundus. This led to a greater suppression of ghrelin which may be related to a longer contact of ghrelin-secreting cells in the fundus with food obstructed above or adhered to the balloon as could be judged at endoscopy. Another possibility might be a mechanical compression and/or ischemia of the fundic mucosa or fundic distension as suggested by Mion et al. The absence of an effect of either sham or balloon treatment in the study of Martinez-Brocca et al. might be due to the small weight loss and the persistence of balloon-related distress at the repeat exam, already 4 weeks after balloon positioning.
Duodenojejunal bypass liner: In gastric bypass surgery, the rapid improvement of diabetes before any weight reduction has occurred, can be explained by two hypotheses. The foregut hypothesis suggests that improved glycaemic control results from a reduced secretion of diabetogenic hormones or anti-incretin factors in response to the absence of nutrients in the proximal small intestine. Intestinal glucagon synthesis and glucose-dependent insulinotropic factor (GIP) have been suggested to decrease after exclusion of the proximal small intestine. In accordance with the foregut , de Jonge et al. (2013) discovered that prevention of digestion and uptake of nutrients by the DJBS was associated with a decreased secretion of glucagon, a diabetogenic factor, as well as a decreased secretion of GIP, which is secreted in the proximal small intestine and affects glucagon secretion. The second hypothesis is the hindgut hypothesis which attributes the improved glycaemic control to the enhanced secretion of incretins such as GLP-1 in response to undigested nutrients in the distal small bowel. The observed increased GLP-1 secretion of de Jonge et al. are in agreement with the hindgut hypothesis.
Other endoscopic therapies: As yet there are no data about the effects on the gastric fundus and the ghrelin secreting cells by endoscopic procedures such as stapling and suturing, the adjustable gastric implant prosthesis or botulinum toxin injections. Also, no data are available on CCK and PP secretion. The data that are available on the effect on diabetes are merely the result of weight loss and not so much the result of changes in gastrointestinal and endocrine hormones. So, there is much room left for further hormonal investigations!
Gastric pouch reduction after gastric bypass, where are we standing? Christopher C THOMPSON (USA) has presented his current results and strategy by video-conference.
Endo-Aspire as a sole obesity treatment / study in Super-obese patients : Shelby SULLIVAN (USA)
The use of endoscopic aspiration therapy for obesity has been evaluated in a US study. It consists of an endoscopically-placed gastrostomy tube PEG (A-TubeTM) and siphon assembly. The food is conveniently stored and then flushed. With the AspireAssist, patients aspirate gastric contents 20 min after meal consumption, removing about 30% of ingested calories.Aspiration therapy involves endoscopic placement of a gastrostomy tube (A-Tube) and the AspireAssist siphon assembly (Aspire Bariatrics, King of Prussia, PA) to aspirate gastric contents 20 minutes after meal consumption. A pilot study was implemented, with 18 obese subjects who were randomly assigned (2:1) to groups that underwent aspiration therapy for 1 year plus lifestyle therapy (n ¼ 11; mean body mass index, 42.6 +/-1.4 kg/m2) or lifestyle therapy only (n ¼ 7; mean body mass index, 43.4 +/- 2.0 kg/m2). Lifestyle intervention comprised a 15-session diet and behavioral education program. Results: Ten of the 11 subjects who underwent aspiration therapy and 4 of the 7 subjects who underwent lifestyle therapy completed the first year of the study. After 1 year, subjects in the aspiration therapy group lost 18.6% +/- 2.3% of their body weight (49.0% +/- 7.7% of excess weight loss [EWL]) and those in the lifestyle therapy group lost 5.9% +/- 5.0% (14.9% +/- 12.2% of EWL) (P < .04). Seven of the 10 subjects in the aspiration therapy group completed an additional year of therapy and maintained a 20.1% +/- 3.5% body weight loss (54.6% +/- 12.0% of EWL). There were no adverse effects of aspiration therapy on eating behavior and no evidence of compensation for aspirated calories with increased food intake. No episodes of binge eating in the aspiration therapy group or serious adverse were reported. Conclusions: In a pilot study, aspiration therapy appears to be a safe and effective long-term weight loss therapy for obesity. 11 patients (1 dropped out) Vs 7 control patients. The aspiration should occur 2-3 times a day, takes 10 minutes on average, removing 25-30% of the ingested calories, if performed 20 minutes after the meal. 10 patients have reached 52 weeks, 7 till 104 weeks. Treated patients had 20% WL, control patients 5%. Calorie aspiration actually accounts for 80% of the weight-loss (Pendigton analysis of WL according to calorie restriction). The European single arm trial has involved 25 patients in Sweden, with 3 dropping out. Pain occurred in 10 patients, peristomial dermatitis (6/9), minimal leakage (1), bleeding (5/9), infection (3), persistent fistula after removal (1), hypokalemia (1). Quality of life increased, anxiety during meals decreased, water consumption during the meals and chewing time increased. No binge eating or excessive eating has been reported, as well as no adverse effect on dietary restraint, body image, etc.
The "Superobese Trial", led by Evzen MACHYTKA (Ostrava, Czech Republic), (BMI>55), has involved three centers, and included 30 patients in the first center (Czech Republic). It seems that higher BMI-patients could benefit the most from this procedure according to social standards. One can view it as a possible gold standard in the future for super-obese subjects, either as a definitive therapy or as a bridge to surgery.
Technical aspects of the Endo-Barrier : Amador GARCIA RUIZ (Spain)
Preliminary results of the French Endo-Barrier trial ENDOMETAB : Gregory BAUD (France)
The French Ministry of Health has approved a large, randomized, multi-center clinical utility study of EndoBarrier® Therapy, a novel, non-surgical treatment for type 2 diabetes and/or obesity. The study, called ENDOMETAB, is coordinated by the University Hospital of Lille over a two-year period. The protocol should enroll 174 subjects at leading academic centers throughout France, and will evaluate the impact and cost of 12 months of treatment with EndoBarrier Therapy compared to 12 months of conventional treatment (dietary counseling, physical activity and lifestyle changes) on metabolic syndrome in patients suffering from obesity, both with and without diabetes. EndoBarrier is a thin, flexible, tube-shaped liner that forms a physical barrier between food and a portion of the wall of the intestine. It has been proven to lower HbA1c (blood glucose) to healthy levels and achieve weight loss of approximately 20 percent within one year. So far, the study has included 64 patients with BMI>30 and the presence of a metabolic syndrome, 40 had the Endobarrier. There were 7 major adverse events: migration (3), acute pancreatitis (1), pain and removal (1), bowel obstruction (1).
Metabolic aspects of the Endo-Barrier : Jan GREVE (The Netherlands)
J GREVE has reviewed the metabolic effects of the endoscopic duodenal-jejunal bypass liner, that rapidly improves type 2 diabetes. The current anchor is meant to last one year. In a non randomized study, single center, 22 patients, HBA1c dropped from 8.8% to 6.5% at 52 months and 6.6% at 72 months. Factors regulating glucose homeostasis in patients with type 2 diabetes treated with endoscopic duodenal-jejunal bypass liner (DJBL) have been investigated. Seventeen obese patients (BMI 30-50) with type 2 diabetes received the DJBL for 24 weeks. More than 2000 devices have been placed today; the average HbA1c rate reduction is 1.5. From 2009 to 2015, the cumulated adverse events have been: migration (39), pancreatitis (15), perforation (7), major bleeding (50), obstruction (26), abscess (22), total 169 (5.82%).
ValenTx Endoscopic Gastro-Jejunal Bypass : Laurent BIERTHO (Canada)
L BIERTHO has presented his experience with the ValentX system (Boston Scientific) The principle is a 1.2 m sleeve-tube that is attached to the eso-gastric junction, with a small reservoir at the top of the gastric lumen. A safety and efficacy study has been implemented, with 3 centers in Northern America and 32 patients, starting in February 2014. Mean BMI was 42.5, weight 118 kg. 26 patients have reached 9 months FU, with 47% EWL. 5 adverse events have been reported.
Endoplication, interim results of the MILEPOST Study : Karl MILLER (Austria)
Endoplication, technical aspects : Roman TURRO-ARAU (Spain)
Roman TURRO-ARAU has reported the current experience with the per-oral Incisionless Operating Platform™ (IOP) (USGI Medical) in Spain. It places transmural plications in the gastric fundus and distal body using specialized suture anchors (the Primary Obesity Surgery Endoluminal [POSE] procedure). It allows fundus restriction and dismotility in the antrum.The POSE Milepost study has been randomized and blinded, with 3 centers in Austria, Spain and the Netherlands. More than 3500 cases have been performed since 2009, including 177 patients at the Teknon Institute in Barcelona. 56% EWL has been achieved on average at 12 months
Spanish results with the DUO-Balloon : Gontrand LOPEZ-NAVA (Spain)
US results with the DUO-Balloon : Shelby SULLIVAN (USA)
G LOPEZ-NAVA and S SULLIVAN have presented the results of the DUO-balloon (Duoshape, US). It is a CE approved device, with pending FDA authorization. This 900 cc dual balloon has a “natural curvature” that improves post-implant comfort, and the dual shape reduces the risks of migration and obstruction. A US pilot trial has been conducted on 30 patients, then a US pivotal trial (326 patients), and a trial in Madrid (60 patients). The pilot trial has involved 21 treated patients and 9 control patients, EWL was 32% at removal. The pivotal trial has been randomized, with a sham group, and met study efficacy according to the FDA requirements (2013). In the Madrid experience, there were 1 deflation (1.6%), 11 gastric erosions (8.3%), 3 early explants (1 for gastric perforation, 2 for vomiting). Total WL has been 15% at 6 months.
Reduce pivotal trial in the US: it was a randomized double-blinded study, with a sham group, BMI range 30-40. The difference between DUO and diet alone was supposed to be more than 7.5%, and 35% of the patients had to obtain more than 25% EWL. The objective was to maximize the difference between the sham group and the active group, not to maximize weight-loss. 326 patients have been enrolled, 187 DUO and 139 Diet alone. 77 patients from the sham group benefited from a crossover to the DUO group (total 264). 24 months EWL was 25,1% Vs 11.3% in the control group, and 48.8% had more than 25% EWL. There were 87% vomiting, 61% nausea, pain in 55%, 6% early deflation and 15% early retrieval .
SPATZ adjustable balloon, latest data on adjustments : Jeffrey BROOKS (USA)
The Spatz Adjustable Balloon System was developed to provide an adjustable intragastric balloon approved for 1 year implantation. Weight loss results of more than 20 kg/year have been reported in the literature. The question is whether a treatment with this gastric balloon also leads to better weight loss maintenance after balloon removal. A prospective study on the BIB balloon has reported maintenance of > 10% weight loss in 25% of patients for up to 2.5 years after BIB balloon removal. The Spatz 3 is implanted without guide-wire, it has an easy-grasp and an easy-extract system. 187 patients in 7 centers had 48.1% EWL at 12 months, 4.9 at 9, 35.2 at 6. The initial volume is 500 cc, there have been 11 down adjustments (100cc) and 38 upward adjustments (327 cc, range 150-500). 76% maintained the WL >10% versus 25% with BIB. Available data suggest a long term benefit to longer implantation time and/or adjustable balloon function.
Swallowable balloons and repeated balloons : Alfredo GENCO (Italy)
Follow-up on the strategy to treat morbid obese patients refusing surgery, using long-term repeated multiple Balloons.
Intragastric balloon is a valuable treatment in the short-term, and multiple balloon treatment has been shown to be effective in the medium term. The aim of this study was to investigate the efficacy of multiple balloon treatment in the long-term (6 years) in terms of weight loss, influence on co-morbidities, and quality of life in patients refusing surgery. Methods: Eighty-three patients with body mass index (BMI)>40, good candidates for surgery but refusing it, were enrolled in a clinical treatment protocol involving multiple intragastric balloon placement. After removing the first balloon, a second balloon was placed when the patients had regained ≥ 50% of the weight loss achieved with previous balloon. Weight, co-morbidities parameters, and quality of life test were recorded during a follow-up of 72 months. Results: All patients experienced a second balloon placement; 22.2% had a third device placed and 1 patient had a fourth device placed. At 76 months follow-up, mean BMI was 37.6 kg/m(2) (P < .001); weight cycling periods were observed. Significant difference was recorded in the presence of co-morbidities at baseline (80% of the patients) and follow-up (30%). Quality of life test in the follow-up indicated better scores than those at baseline. Conclusion: Despite the weight cycling, in patients refusing surgery, multiple intragastric balloon is the recommended treatment, allowing the patients to achieve a good weight loss, better control of co-morbidities, and better quality of life than at baseline.
Alfredo GENCO (Italy) has also presented the current results of the swallowable balloon. This new device, made by the US company OBALON, avoids endoscopy and anaesthesia during its placement. Early results are promising in terms of morbidity and weight-loss. There have been two US studies: one with a single arm, one with a randomized control design. Patients with BMI>27 should be considered. The absence of preoperative endoscopy is acceptable for young patients. HP is neither treated nor detected before implant; PPI is routinely given after implant, 40 mg omeprazole for one month, then 20 mg for the remaining two months. Large hiatal hernia (>5 cm) is a contra-indication. 138 patients have been treated with OBALON since May 2014 in Rome. There was 30.4% EWL at 3 months, 2.9% early deflation, 2 symptomatic subocclusions, 10 cases of erosion or ulcer. The treatment suggestion remains: one balloon in overweight patients, 2 in obesity class I-II, 3 in obesity class III.
Update on the Elipse, the first procedureless Intra Gastric Balloon : Ram CHUTTANI (USA)
Balancing Risks and Reward: A Critical Review of the Intragastric Balloon for Weight Loss : Ram CHUTTANI (USA)
The First human experience with the Elipse™ has been made in Czech Republic one year ago and presented at the Non Inva meeting in 2014: A novel, swallowed, self-emptying, and excreted intragastric balloon for weight loss (Allurion Technologies Inc., USA). The key intellectual property lies in the release valve, only exposed to the inside of the device, which weakens over time, an opens automatically. The balloon takes 7 min to fill. It is 85% thinner than the average silicone balloon, and is specifically designed to pass the GI tract. It can be folded into a capsule.
8 patients had been enrolled in the pilot study, with a 6 weeks prototype (proof of concept and safety study), after Ethics Committee approval. Each patient swallowed one Elipse™ device which was filled with 450mL bacteriostatic water through a delivery catheter, then removed. Each device was designed to remain in the stomach for 6 weeks, empty, and pass in the stool. Mean baseline patient characteristics were BMI 31.0 (27.1-35.5), total body weight 88.4 kg (range: 75.0-113.0), and excess weight 28.7 kg (18.6-47.3). Results: All 8 patients successfully swallowed the Elipse™ capsule. Six week post-treatment day data demonstrate a mean total body weight loss of 3.0 kg (1.2-6.8) and mean % excess weight loss of 13% (5%-33%). In one patient, the balloon appeared partially collapsed on ultrasound after 11 days of therapy. The balloon was endoscopically punctured and passed in the stool after 4 days. One asymptomatic patient elected to have the balloon endoscopically punctured after 19 days, and the balloon passed in the stool after 4 days. In both cases, careful endoscopic examination of the upper GI tract showed no abnormalities. In the remaining 6 patients, the balloon emptied and passed in the stool without endoscopic intervention after having remained in the stomach for 6 weeks. Consecutively, 50 patients have been enrolled in a multicenter study, 16 already included, BMI 27-40, current WL was 6.1 kg, 21.4% EWL, 6% WL.
A new Australian balloon, "Swallow it and forget it" : Tony KIERATH (Australia)
The early idea of a balloon with a foam filling agent has been presented, there is no prototype for the time being.
Preoperative weight-loss and Intragastric balloon, the BIGPOM study : Benoit COFFIN (France)
The BIGPOM study has been implemented in France and presented by Benoit COFFIN. Three prospective studies had been previously published concerning WL with IGB before surgery. Surprisingly, the French results did not demonstrate the benefits of this strategy. Patients were randomized in two groups: IGB versus conventional diet. The study has involved patients with BMI>45 expecting RYGBP. Bypass was performed at 6 months, i.e. at the time of balloon removal. Enrolment has lasted two years. The rate of complications has actually been higher in the IGB group. 115 patients were included, 55 in the IGB group, WL has been 3+/-7.3 kg in the IGB group, 10.3+/-8.5 kg in the control group (P<0.0001), 3 complications have been associated with balloon removal. Mean duration of GBP has been 175+/- 75 minutes in the control group Vs 188 +/- 98 min in the IGB group; weight-loss at 6 months has been 38 +/-12.1 kg Vs 40.7+/-11.7. IGB has increased the post-op complication rate. Hospital stay was respectively 6.3 +/-6.3 Vs 6.8+/-4.6 . Mean weight-loss between MO and M12 has been similar.
Obendo 2 and 3 study on Hyaluronic Acid Injection at the GE Junction, a closer look at the trajectory effect : Jerome DARGENT (France)
The final results of the OBENDO study regarding Hyaluronic Acid injection at the GE junction have been outlined, versus or in combination with Intragastric Balloon. Research into minimally invasive techniques is mandatory for greater acceptance in bariatric surgery, a useful first step being to evaluate the combination of these with current procedures. We suggested that intragastric balloon (IGB) can be performed with hyaluronic acid (HA) injections at the level of the gastro-esophageal junction. Methods: A sub-mucosal restriction is created by circular injection of an absorbable material within a defined area based on endoscopic anatomy. We included 101 patients in a prospective multi-center randomized trial, with average body mass index (BMI) 33.8 (range 27-43.6), treated from April 2010 to April 2012 by IGB and/or HA injection, sequentially, and followed for two more years. Patients were divided into group 1 (IGB alone), group 2 (IGB followed by HA at IGB removal, at 6 months), and group 3 (HA, and IGB at 6 months). Results: BMI loss at 6 months was inferior in the HA group (32 patients) compared with the IGB groups (68 patients): 2.1± 0.4 vs. 3.4±0.3, p<0.05). The efficacy of IGB alone compared with combined treatments (groups 2 and 3) was significantly inferior at 18 months only, but the impact of the treatment sequence (HA before or after IGB) on BMI loss was not statistically significant, although in favor of HA first. 21 patients had an erratic weight-loss trajectory. Patients with a history of psychiatric disorders or severe alimentory troubles having been ruled out, it did not appear that particular events played a specific role.