Are endoscopists definitely stepping into the arena of weight-loss therapy?
submitted19 September 2014
accepted after revision07 October 2014
22 December 2014 (online)
Obesity, defined by a body mass index (BMI) ≥ 30 kg/m2, is a chronic, lifelong, multifactorial (including genetically-related) disease of excessive fat storage, which, in combination with the pattern of fat distribution, places the individual at increased risk of obesity-associated diseases and premature death. Almost every organ system is affected, with the gastrointestinal tract involved as well.
Gastrointestinal complaints, assessed by validated questionnaires and endoscopy, occur 1.6 – 3.1 times more frequently in obese subjects compared with those of normal weight  . Examples of obesity-associated diseases are gastroesophageal reflux disease, gallstones, pancreatitis, nonalcoholic fatty liver disease, and colonic polyps. Obese subjects are also at increased risk of gastrointestinal malignancies with a relative risk – varying according to the BMI class and the type of cancer – between 1.28 and 4.52 for men and between 1.28 and 2.76 for women . In men, the risk of liver cancer is highest, followed by colorectal, pancreatic, and esophageal cancer; in women, the risk is highest for gallbladder cancer, followed by pancreatic and colorectal cancer. Similarly, a 5-kg/m2 increase in BMI, above a BMI of 23 kg/m2, equal to a weight gain of 13 – 15 kg, resulted in an increased risk of esophageal adenocarcinoma and colorectal cancer in men and gallbladder cancer, esophageal adenocarcinoma, pancreatic cancer, and colonic cancer in women . This is the first reason why endoscopists should take care of the obese patient. Weight loss may reverse these risks.
The second reason is the burgeoning interest in bariatric surgery. Bariatric surgery involves the gastrointestinal tract and may therefore increase gastrointestinal complaints. Bariatric surgery may also result in complications that, in most cases, can be solved by minimally invasive endoscopic interventions .
Thirdly, the gastrointestinal tract is involved in the regulation of energy balance, which is where chances for the endoscopist lie. Based on evidence-based guidelines, the first approach in the treatment of obesity is an intensive lifestyle program that should consist of an energy-restricted diet, physical exercise, and behavior modification   .
When motivated patients have seriously attempted but failed to achieve weight loss, pharmacotherapy is recommended. One of the few available drugs, orlistat, acts on the digestive system by inhibiting gastric and pancreatic lipase. Pharmacotherapy is indicated in subjects with a BMI ≥ 30 kg/m2, or a BMI ≥ 27 kg/m2 in the presence of obesity-associated comorbidity. A surgical approach is restricted to very obese subjects (BMI ≥ 40 kg/m2, or BMI ≥ 35 kg/m2 with obesity-associated comorbidity). Surgeons are unable to meet the great demand and approximately 1 % only of eligible individuals with morbid obesity in the USA receive bariatric surgery . Therefore, endoscopic therapy, often labelled endoscopic bariatric therapy (EBT), has a role to play in the treatment of obesity, either as an alternative to or an adjunct to medical treatment. EBT may fill the therapeutic gap between pharmacotherapy and bariatric surgery.
Some decades ago, endoscopists had nothing to offer in this field except for intragastric balloons. Intragastric balloons appear to be safe and efficacious. Two systematic reviews and one meta-analysis have discussed newly designed balloons, mainly the Bioenterics intragastric balloon (BIB; Allergan, Irvine, California, USA)   .
Imaz et al. pooled 15 articles (3608 patients) to estimate the effectiveness of BIB . The estimates for weight lost at balloon removal after 6 months were 14.7 kg (12.2 %), 5.7 kg/m2, and 32.1 % excess weight loss (EWL). A meta-analysis of two randomized controlled trials (RCTs) that compared the use of a balloon with placebo estimated that patients with balloons lost more weight than the placebo group; differences in weight loss were 6.7 kg (1.5 %), 3.2 kg/m2, and 17.6 % EWL   .
Safety was assessed by early balloon removal in 13 articles with 3442 patients and by complications in 12 studies with 3429 patients . Early balloon removal occurred in 4.2 % of patients. Complications included gastrointestinal tract obstruction in 0.6 %, gastric perforation in 0.2 %, early deflation in 0.1 %, and gastric ulceration in 0.1 %. There were nine deaths from gastric perforation, five of which occurred in patients who had had previous gastric surgery, which is an absolute contraindication for the positioning of an intragastric balloon  .
Over the last 15 years, the balloon market has been booming. Several different balloon types are now available or being studied, including: adjustable balloons with or without a migration-preventing anchor; two separate balloons that are connected to each other to prevent balloon passage in the case of one of the two balloons deflating; balloons that occlude the pylorus; and balloons placed by the percutaneous endoscopic gastrostomy (PEG) technique and adjustable by access to a subcutaneous port. Some of these new balloons are allowed to stay in place for 12 months. In the search for minimally invasive placement and removal of intragastric balloons, orally ingested balloons that degrade spontaneously are now under investigation.
The bypass of duodenum and proximal jejunum by the duodenojejunal bypass liner (GI Dynamics Inc., Watertown, Mississippi, USA) is a totally different concept. It consists of an impermeable Teflon sleeve which runs from the post-pyloric region to the proximal jejunum. A self-expanding nitinol stent released into the duodenal bulb holds the device in place. To some extent it mimics a surgical gastric bypass procedure by creating a physical barrier that allows food to bypass the duodenum and proximal jejunum without mixing with bile and pancreatic enzymes until later in the gut, thereby potentially altering the incretin pathways and the enteroinsular axis. Indeed, improved glycemic control could be attributed to decreased secretion of glucagon and gastric inhibitory peptide (GIP) and enhanced secretion of glucagon-like peptide-1 (GLP-1) .
A meta-analysis evaluated the clinical effectiveness of this device in four RCTs . In patients with a BMI of 30 – 34.9 kg/m2 and type 2 diabetes, there was a marginally greater reduction in weight loss with the use of the duodenojejunal bypass liner than was seen for subjects treated by diet or a sham procedure. In patients with a BMI of 35 – 39.9 kg/m2 plus comorbidities, a significant and clinically relevant reduction in excess weight (12 % – 22 %) was seen up to 12 weeks, but effects on metabolic function expressed in terms of HbA1c and fasting blood glucose were unclear. Four RCTs and six non-RCTs were included in a safety analysis with in total 282 patients . Positioning of the device failed in 18 and succeeded only after several attempts in five patients. There were 60 early explantations because of migration or rotation, dislocation, obstruction, bleeding, and intolerance. At present, the device has been launched as a metabolic intervention for a duration of 12 months for those with a BMI > 30 kg/m2 and type 2 diabetes.
The youngest sprig in the armamentarium of the endoscopist is the AspireAssist aspiration therapy system (Aspire Bariatrics, King of Prussia, Pennsylvania, USA), discussed by Forssell and Norén in this issue . Endoscopic aspiration therapy involves the placement of a gastrostomy tube via the pull technique for PEG placement and an AspireAssist siphon assembly to aspirate gastric contents 20 minutes after a meal. In a per protocol analysis, body weight loss after a 4-week run-in period of a very low calorie diet and 6 months of aspiration therapy was 16.5 % of initial weight and 40.8 % of excess weight, which is in line with the 12-month data of Sullivan et al. , who showed a 18.6 % weight loss and 49.0 % EWL in the aspiration plus lifestyle-therapy group compared with 5.9 % weight loss and 14.9 % EWL in the lifestyle group. In each study, three patients discontinued therapy: because of relocation, pain, and personal life issues in Sullivan’s study, and because of inability or unwillingness to spend 45 minutes per day on aspiration therapy in the study by Forssell and Norén  .
It would have been interesting to see whether the patients later regained weight or were able to put into practice the lessons of adequate chewing, drinking large amounts of water at meals, and avoiding snacking between meals that were required for successful aspiration and are key elements of behavior-modification therapy. In contrast to Sullivan et al., no prophylactic proton pump inhibitors (PPIs) or potassium supplements were given by Forssell and Norén, apparently without any important changes being seen in the electrolytes  .
Notwithstanding a PEG failure rate of 3 % that is reported in overweight and obese patients , they had the guts to include seven patients with (mild) type 2 diabetes, of whom one patient used insulin and four metformin. Unfortunately, we are not informed whether the adverse events, which included aseptic fluid collection, skin breakdown, and skin infection at the ostomy site, occurred in these seven patients.
To meet criticism of creating eating disorders, both studies offered lifestyle therapy or cognitive behavioral therapy. The claim of inducing adverse eating behaviors could not be substantiated by Sullivan et al. . As yet, is it unknown whether regular meal aspiration affects satiation and satiety differently and whether an eating pattern of whole-day grazing and snacking will impact upon the results. To safeguard long-term unsupervised and overzealous use, the connector, which opens the valve to allow aspiration of gastric contents, contains a counter, which locks after 115 aspiration cycles. After this, patients have to return for a new connector.
Some endoscopists may be reluctant to accept the idea of this approach, as patients may continue their bad eating habits, whilst having a safe haven in case of food indulgence. Proponents will argue that this therapy will not absolve patients from taking responsibility for their own lifestyle and that there is only a gradual shift from active removal of food by aspiration to passive bowel movement of undigested and malabsorbed food after malabsorptive bariatric surgery.
My answer to the question “Are endoscopists definitely stepping into the arena of weight-loss therapy?” is: “I hope they will and I think they should.” The health implications of obesity are substantial, and beneficial changes are seen with a 5 % – 15 % weight loss in the less severely obese patient and with a 15 % – 25 % weight loss in morbidly obese subjects .
Until recently, endoscopists did not have many options but, in search of less invasive interventions for obesity and morbid obesity, several endoscopic techniques have been developed and most are at the disposal of, and practicable for, endoscopists . They promise the level of weight loss that is required for health benefits.
Endoscopic treatment has the advantage of being cheap, minimally invasive, moderately time-consuming, reversible, and feasible as an ambulant procedure, without a steep learning curve as is the case with bariatric surgery. It has the disadvantage of limited durability. But this is only the beginning. By using gastric sutures and gastric stapling techniques, endoscopic procedures may mimic bariatric surgical interventions such as the vertical banded gastroplasty, sleeve gastrectomy, and the gastric band. Gastric volume reduction devices require high endoscopic skills and significant time and are still in their infancy in terms of development, but certainly, this is a fascinating area. Obesity is a global epidemic and, at the global level, the future is bright for the endoscopist!
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