FRONTIERS IN ENDOSCOPY, SERIES #33
by Truptesh H. Kothari, Paridhi Malik, Shivangi Kothari, Vivek Kaul
In this article we discuss bariatric endoscopy, a newly developing field in the management of obesity by inducing weight loss associated with a minimal complication profile. Although some therapies currently remain under FDA evaluation and trials, the emergence of endoscopic bariatric therapies holds a promising future.
Truptesh H. Kothari MD, MS Paridhi Malik MD Shivangi Kothari MD Vivek Kaul MD Division of Gastroenterology - Hepatology, University of Rochester Medical Center, Rochester NY
Obesity is defined as a complex metabolic disease of fat accumulation associated with increased risk to health. Body Mass Index (BMI) is a measure to classify obesity in adults. It is a calculated by dividing a person's weight in kilograms by the square of his height in meters (Kg/m2). According to the World Health Organization, obesity is defined as individuals with a BMI ≥ 30. Further categorization of obesity is done based on the severity of BMI over 30. Class I refers to BMI of 30-34.9, Class II refers to BMI 35-39.9, and Class III refers to BMI over 40.1 Recent statistics from a National Health and Nutrition Examination Survey (NHANES) in 2013-2014 reveal that 32.7% of adults in the U.S above the age of 20 are overweight (BMI 25-30), 37.9% are obese, and 7.7% are severely obese with BMI of more than 40.2 The reported average BMI in the year 2000 was 30 whereas it is 33.6 in 2016.
The behavioral risk factor surveillance system is an ongoing nation-wide telephone-based survey, which is conducted by the CDC. The most recent results of this study in 2015 reveals a total of 19 states with obesity rates between 25% and 30% along with four states (Alabama, Louisiana Mississippi, and West Virginia) with a prevalence of Obesity upwards of 35% of the population.3 Obesity carries a major risk to an individual's health with 55% increase in mortality, 70% increase in coronary artery disease, 75% increase in stroke risk and a 400% increase in diabetes risk. Obesity and being overweight accounts for about 2.8 million preventable deaths annually and certainly has become a global epidemic.4
Current management of obesity includes a range of interventions from lifestyle modifications and medical therapy to invasive surgical procedures (Figure 1). Weight loss is the major lifestyle modification used in controlling obesity; however, it has proven to show only moderate improvement in obesity. "An alternative approach to managing obesity is pharmacotherapy, which is considered useful as an adjunct to lifestyle modifications. This approach results in weight loss by an additional 3 to 9% in comparison to the lifestyle modification alone".5 Although anti-obesity medications assist in achieving good weight loss results, they carry a high risk of relapse and weight gain. Bariatric surgery is considered in individuals who fail to improve with lifestyle modifications and/or medications. It is also recommended for those with BMI > 40 Kg/m2 or, BMI of 35 Kg/m2 or more with comorbid conditions such as hypertension and type 2 diabetes. Some of the most commonly performed surgical weight loss procedures are Roux-en-Y gastric bypass, sleeve gastrectomy, and gastric banding. Several endoscopic (non-surgical) options have emerged for obesity management in the last decade.
Although Bariatric surgery remains an efficient and durable option for obesity management, less than 1% patients undergo bariatric surgery. The low usage of the surgery may be attributed to surgical cost, patient preference, access to care, and the mortality- morbidity associated with this procedure. Some of the major complications reported after a surgical bariatric procedure are luminal obstruction, anastomotic leak, marginal ulcer, gastrointestinal bleeding, wound related complications, and pulmonary embolism. The complication rates of bariatric surgical procedures remain high at 17%.6 The high complication rates of surgery led to the need for developing a less invasive alternative that reduces morbidity and can provide quick access to patient care. This gap in the management options has led to the evolution of bariatric endoscopy. Bariatric Endoscopy is a newly developing field in the management of obesity by inducing weight loss associated with a minimal complication profile.
Endoscopic bariatric interventions are classified based on site of intervention and can be either a Gastric or a Small Bowel intervention. Gastric interventions include space-occupying devices such as intragastric balloons, TransPyloric Shuttle, and Full Sense Device along with Aspiration therapy and Gastroplasty techniques. These devices work via different mechanisms to induce early satiety, including increasing the stimulation of mechanical and chemical receptors in the gastric tract, delaying gastric emptying and reducing luminal accommodation thus limiting food intake by inducing early satiety (Table 1).
Small bowel interventions interfere with nutritional absorption by various mechanisms depending on the technique (Table 2). Of note, currently, none of the small bowel endoscopic bariatric interventions discussed are FDA approved or commercially available in the USA.
Clinical evaluation of the Orbera device was performed in a prospective randomized controlled, comparative clinical study using 125 subjects in the treatment group and 130 subjects in the control group with BMI of 30 - 40 Kg/m2. The treatment group underwent Orbera placement followed by removal after six months. Both groups participated in a twelve-month behavioral modification program. The effectiveness of the study was measured with two co-primary endpoints. This included first, the mean percent excess weight loss (EWL) at nine months (3 months after the balloon was removed) and secondly, if >30% of Orbera-treated subjects achieved significantly greater (>15% estimated weight loss) weight loss over the mean %EWL of the control group. The study did not meet its first co-primary endpoints as the mean %EWL did not meet the 95% lower bound confidence interval, although the study did satisfy the second co- primary endpoint with 45.6% Orbera treated patients exceeding 15% mean EWL over the control subjects. Total body weight loss in the Orbera group was noticed to be a mean of 10.2% and 9.1% at 6 and 9 months after balloon insertion respectively. Significant weight loss was observed within the Orbera group as compared to the control group with a mean % excess weight loss with ideal weight defined as BMI of 25. It was found to be 38.4% at month 6, 34.6% at month 9, 29% at month 12 as compared to 12.1%, 12.3% and 11.1% in the control group with a p-value of <0.001. % Total body weight loss of 10.2, 9.1, 7.6 % in the Orbera and 3.3, 3.4, 3.1 % in the control group at 6, 9 and 12 months after the insertion of the balloon with a p-value of <0.001. Secondary effectiveness of the intervention was measured by the impact of treatment on comorbid conditions such as Hypertension, Type 2 Diabetes and dyslipidemia at months 6, 9 and 12. It was noticed that both groups experienced a comparable decrease in the severity of the comorbid conditions, which may be as a result of a common factor in both groups such as diet and exercise. P-values were not statistically significant to prove a difference between the Orbera and control group when comparing the decrease in severity of hypertension, diabetes and dyslipidemia. Orbera pivotal trial revealed that patients could expect to achieve three times the weight loss at six months as compared to diet and exercise alone, majority of which is lost in the first three months (Figure 2.a., 2.b., 2.c.).
A longitudinal and interventional study was performed in obese patients over six months after placement of an intragastric balloon aimed to study the effect of the treatment on lung function, BMI, and DXA parameters. It was noted that lung volumes were significantly reduced at six months after balloon placement. A drop in BMI was also noticed from 39.1 Kg/m2 to 34.5 Kg/m2. Considerable improvement in body fat distribution was also reported using DXA measurements of body fat.7
A randomized clinical study was performed to evaluate the safety and efficacy of the ReShape dual balloon system (DBS) by comparing two groups of patients: one with DBS treatment along with diet and exercise and one that was a control group with diet and exercise only (Figure 3). The study included a total of 326 individuals with 187 in the DBS group and 139 in the control group. The BMI of the targeted patient population was between 30-40 Kg/m7. The study revealed a significant effect in the DBS group as compared to control. The effectiveness was measured using two co-primary endpoints. The first primary endpoint was defined by the percent excess weight loss (%EWL) and the second primary endpoint measured if more than 35% achieved a 25% EWL in the treatment group at 24 weeks when the dual balloon system was retrieved. This pivotal trial successfully met both the co-primary endpoints. It was found that the weight loss was more than double as compared to the control group along with a %EWL of 25.1% in the DBS group (intention-to-treat). This is significantly greater than the control group with a %EWL of 11.3%. The second primary endpoint was also met as there was a 49.1% difference in the treatment group who achieved a 25% EWL, this was considerably over the 35% response rate.8
A prospective study of 150 patients was performed in patients who regained weight post-Roux-en-Y gastric bypass (RYGB) surgery. The targeted patient population included patients with Gastrojejunal anastomosis (stoma) aperture larger than 15mm. This study aimed to recognize the long-term benefits of management of dilated anastomosis aperture post-RYGB using an endoscopic procedure called Transoral Outlet Reduction (TORe). The study focused on trending weight loss at 3, 6, 12, 24, and 36 months after completion of the TORe procedure. It was reported that a weight loss of 9 to 11 kg and a BMI loss of 3 Kg/m2 was achieved as a result. This was as a result of a decrease in aperture size from 24.1 + 1mm to 9.0 + 0.2mm. The adverse effects were limited to abdominal pain in 4% patients, gastrointestinal bleeding in 3.3% and nausea in 2.0%. It was shown that a greater reduction in anastomotic aperture was associated with a greater post-procedural weight reduction.9 TORe, being less invasive, is a safe and reliable alternative in the treatment of post-surgical complications of RYGB.
Obesity is one of the leading health problems in the United Status today and is becoming very challenging to manage. Despite numerous management options varying from lifestyle modifications to bariatric surgery, obesity remains a problem unsolved. It comes with its wide array of comorbidities increasing the financial burden of this widespread epidemic even further. As a result, it has become one of the top priorities in today's healthcare. Endoscopic techniques allow for the management of obesity in a less-invasive manner and help prevent the associated risks of the bariatric surgical procedures. It also allows for a holistic approach to manage obesity with endoscopic intervention being the primary tool complemented by its behavioral modification program and comprehensive follow-up strategies. Although some of the therapies currently remain under FDA evaluation and trials, the emergence of endoscopic bariatric therapies holds a promising future in the way obesity will be managed. This is indeed a revolutionary step towards medical and surgical management of obesity.
See the article Tables, Images and References in the PDF