Endoscopic Methods in Obesity Treatment

Abstract

Obesity is a multifactorial, chronic disease that occurs with a pathologic increase in the body fat ratio and significantly increases mortality and morbidity. It has become a global health problem with increasing prevalence day by day. Methods used in the treatment of obesity are classified as diet, exercise, lifestyle changes, medical treatments, surgical treatments and endoscopic treatments. Endoscopic treatments are classified as intragastric balloon, transpyloric shuttle, endoscopic sleeve gastroplasty, gastric aspiration, small bowel procedures, duodenal mucosal resurfacing, intragastric botulinum toxin A injection. Although surgical procedures are known as the most effective methods in the fight against obesity today, the frequency and effectiveness of endoscopic treatments are increasing day by day. Endoscopic methods in obesity treatment are promising. There is a need for new methods with high efficacy and reliability, easy application, low complication rate and low cost in the treatment of obesity.

1. Introduction

Obesity is a multifactorial, chronic disease that occurs with a pathologic increase in the body fat ratio and significantly increases mortality and morbidity. It has become a global health problem with increasing prevalence day by day [1]. Between 1980 and 2002, the prevalence of obesity doubled in adults (aged over 19 years) and tripled in children and adolescents (aged between 6 and 19 years) [2]. Obesity has complex etiologic causes that cannot be defined as overeating alone. Genetic and environmental interactions, behavioral disorders, metabolic and endocrine disorders play an intertwined role in the etiology of obesity. Most of them occur as a result of a series of vicious cyclical events that can be explained in a cause and effect relationship. Although genetic and neuroendocrine factors are rarely encountered, environmental factors constitute the basis of the etiology of obesity [3].

In the diagnosis and evaluation of obesity, the patient’s chronological history of weight gain, the age at which the patient started to gain weight, the presence of overweight people in the family, the ages of pregnancy, child rearing and menopause, which are favorable periods for weight gain for female patients, how overweight affects the patient’s health, and the patient’s expectations from treatment should be questioned. During physical examination, diseases that may cause obesity and the main accompanying comorbidities; coronary artery disease, peripheral artery disease, type 2 diabetes mellitus, obstructive sleep apnea syndrome should be questioned [4].

Anthropometric measurements are used to define and classify obesity. These include methods such as body mass index, skinfold thickness and circumference measurements [5, 6].

2. Obesity treatment methods

2.1 Diet, exercise, lifestyle changes

First of all, realistic goals should be set. Changes should be made in the person’s eating habits and physical activity habits. In addition, activity and diet planning should be increased gradually. Access to food intake should be made difficult and self-control should be ensured. Alternative behaviors against eating stimuli should be tried to be developed. Regular weight checks should be performed and social support should be provided if necessary [7].

Diet therapy is applied to ensure a healthy and balanced diet, taking into account the gender, lifestyle, age and physical activity status of the person. It is very important in diet therapy to regulate the wrong eating habits in the process of becoming obese. After the body weight reaches the desired level in diet therapy, it is also necessary to maintain this level and to maintain eating habits for life. In diet therapy for children as well as adults, diet programs are made to maintain development and growth [8].

Exercise, which is one of the methods and essentials of effective weight loss, is one of the types of physical activity. Exercise, which is effective in the treatment of obesity, should be done at moderate intensity, on average 5 times a week and each exercise should be at least 30 minutes. Exercises that should be done in a disciplined manner can be shaped according to the age, gender, living conditions and sports history of the person [9].

In addition to moderate exercises, the person should also do resistance exercises that will work muscles such as the abdomen, hips, legs, shoulders and back. These exercises, which will help to lose weight and help the body reach the desired index, should be done 2 or 3 times a week. The energy burning of all these exercises is valid not only during the activity but also after the activity [9].

In addition to diet, weekly exercise programs are one of the factors that prevent the person from gaining weight again. Regular exercise should be continued after reaching the desired weight. In addition to weight loss, exercise also makes people feel good about themselves. Loss of confidence during obesity can be regained with exercise and it is effective in preventing many diseases. Exercise reduces the risk of many diseases such as decreased insulin resistance, cardiovascular, hypertension, diabetes [9].

Lifestyle changes supported by healthy nutrition and exercise are indispensable conditions for the treatment of obesity.

2.2 Medical treatment

Drug therapy can be used in the treatment of overweight and obese patients in addition to diet, exercise and lifestyle changes. However, problems such as the efficacy and safety of drugs, slowing and plateauing of weight loss during treatment, and weight regain when the drug is discontinued are the limiting points of drug treatment in obesity. Drug treatment can be used for those with a BMI >30 kg/m² and those with a BMI of 27–29.9 kg/m² with additional morbidity [10].

The rationality of the targets set is of great importance in the success of treatment. Targeting the ideal normal body weight is not a realistic approach. Therefore, physicians and patients should have a realistic approach to weight loss treatment at the beginning. Success in treatment is measured by the amount of weight lost and improvement in existing risk factors. Weight loss exceeding 2 kg in the first month of drug treatment, losing 5% of the basal weight in the 3rd–6th months and staying at this level can be considered an effective treatment. A 5–10% weight loss significantly reduces the risk for diabetes and cardiovascular disease [10, 11].

Drug treatment does not provide a curative result in obesity. During treatment, weight loss stops after maximal treatment response is achieved. After drug treatment is discontinued, weight gain may occur again. Obese patients with concomitant diabetes, depression and cardiovascular diseases should be advised to choose treatments that have a weight loss effect rather than weight gain when planning drug treatment for these conditions. Currently, the drugs approved by the US Food and Drug Administration (FDA) for the treatment of obesity are phentermine, diethylpropion, phendimetrazine, benzfetamine, orlistat, lorcaserin, phentermine/topiramate-Extended Release (ER) combination. Of these drugs, only orlistat, lorcaserin, phentermine/topiramate-ER are approved by the FDA for long-term use. The others are only approved for short-term (a few weeks) use. All drugs are approved for use in patients with a BMI ≥ 30 kg/m². Benzfetamine and diethylpropion can also be used in patients with a BMI ≥ 27 kg/m² and an additional obesity-related comorbidity (hypertension, diabetes). Recently, drugs with the active ingredients semaglutide and liraglutide have also been used in the treatment of obesity and show promise [12].

2.3 Surgical treatment

In 1991, the US National Institutes of Health Consensus Conference decided that surgery should be considered as a treatment in selected patients when it became clear that non-surgical treatments resulted in little weight loss and subsequent weight regain. At the same time, the committee recommended that these patients should be evaluated by a multidisciplinary team before surgery and followed up for life after the operation is performed under appropriate conditions [13, 14, 15].

If we look at the historical development of bariatric surgery, the first operations were performed in the 1950s to treat severe hyperlipidemia associated with obesity. These operations were ileocolic bypass operations to limit absorption and caused severe postoperative nutritional complications and liver failure. The jejunoileal bypass was then developed and became popular in the mid-1970s [13, 14].

In 1969, Mason and Ito performed the first gastric bypass, which they described as the connection of a jejunum ring to a transverse proximal gastric pouch. Postoperative bile reflux esophagitis was severe and Griffin et al. described the roux-n-Y modification of the gastric bypass in 1977 [14, 15, 16, 17].

In 1980, Mason performed the first VBG. This surgery initially achieved excellent weight loss with low mortality and morbidity and became the most commonly performed bariatric operation in the US in the 1980s. However, from the early 1990s, patients who underwent VBG surgery regained weight. In the long term, weight loss was small and by the 1990s, the roux-n-Y gastirk bypass became the preferred operation of bariatric surgery in the US [18, 19].

In Italy, Scopinaro developed biliopancreatic diversion in the 1980s. This operation, together with its modification including duodenal switch, has been the only malabsorptive operation with long-term success. It represents less than 5% of the operations performed in the USA [19, 21].

Laparoscopic bariatric surgery started in the 1990s. Belachew performed the first laparoscopic adjustable gastric band operation in 1994. Wittgrove and Clark performed the first laparoscopic RYGB in the same year. In 2001, the application of LAGB was approved in the USA. Its popularity increased until 2009, but has declined since then. Laparoscopic sleeve gastrectomy (LSG) has enjoyed a rapidly increasing popularity in the US and internationally since 2008 [21].

The most commonly used bariatric surgery methods today are Laparoscopic Sleeve Gastrectomy (LSG), Roux n Y Gastric Bypass (RYGB), Single Anastomosis Gastric Bypass (OAGB), Transit Bipartition (TB), Biliopancreatic diversion and duodenal switch (BPD-DS), Single Anastomosis Duodeno-ileal bypass (SADI-S), Single Anastomosis Sleeve-Ileal Bypass (SASI Bypass) [18, 19, 20, 21].

2.4 Endoscopic treatment methods

The advantages of endoscopic methods used in the treatment of obesity are that they are minimally invasive, have a reversible effect, are reproducible, are a cost-effective treatment option, and can be used for bridging before surgical treatment. Endoscopic bariatric procedures are divided into two categories: interventions in the stomach and interventions in the small bowel. Gastric interventions include gastric balloon, transpyloric shuttle, endoscopic sleeve gastroplasty, pose and gastric aspiration. Interventions in the small intestine include duodenojejunal diversion, gastroduodenojejunal bypass, jejunoileal diversion and duodenomucosal resurfacing/remodeling (Figure 1) [22].

Figure 1.

View of endoscopic treatment methods [22].

2.4.1 Intragastric balloon

Intragastric balloon application is one of the most commonly used endoscopic bariatric methods today. In 2015, it received FDA approval for use in the treatment of obesity. While the peripheral effects of intragastric balloon application are known as reducing gastric volume and slowing gastric emptying; central effects can be counted as activation of gastric tension receptors, signal transmission to the hypothalamus via vagal nerve and early satiety. In 2022, indications for use were specified in the Indications for Metabolic and Bariatric Surgery guidelines published by ASMBS and IFSO. In addition, the areas and conditions of use are also specified in the Spanish and Brazilian intragastric balloon application consensus [23, 24, 25].

According to the Brazilian intragastric balloon consensus agreement, indications are defined as being over 12 years of age (no upper age limit (signed by both parents)), body mass index over 25 and failure of diet, exercise and lifestyle changes, and bridge treatment before bariatric surgery. Contraindications were defined as the presence of active peptic ulcer, presence of gastric or esophageal varices, presence of hiatal hernia larger than 5 cm, and previous gastric surgery. According to this consensus, the intragastric balloon should be removed in case of intolerance (severe nausea and vomiting attacks, severe pain), recurrent fluid-electrolyte disturbance, balloon deflation (methylene blue—72 hours), gastrointestinal bleeding, moderate to severe pancreatitis and pregnancy (2nd trimester) during treatment [24, 25].

Ideal balloon characteristics are defined as a material with a smooth surface, made of durable material, inflatable with liquid or air, adjustable in volume, with a radio-opaque marker to facilitate follow-up [23, 24, 25]. The most commonly used intragastric balloon types today are Orbera, ReShape Duo, Obalon, Heliosphere, Spatz and Elipse. Some characteristics of intragastric balloon types are summarized in Table 1.

• Obese patients undergoing IGB treatment require concomitant dietary and lifestyle modification.

• PPI prophylaxis should be performed in individuals undergoing IGB therapy.

• Intraoperative anesthetics associated with the lowest incidence of nausea should be used during the procedure.

• A planned anti-emetic regimen is recommended for 2 weeks post-procedure.

• Multivitamin supplementation at a daily dose of 1–2 adult doses (Figure 2) [23, 24, 25].

Summary of Intragastric balloon characteristics
		FDA/CE approved			CE approved
Balloon type	Orbera	ReShape Duo	Obalon	Heliosphere	Spatz	Elipse
Manufacturer	Apollo Endosurgery	ReShape Medical	Obalon Therapeutics	Helioscopie Medical Implants	Spatz FGIA	Allurion Technologies
Filled with	Saline	Saline	Nitrogen gas	Air	Saline	Liquid
Capacity (mL)	400-700	450 × 2	250 × 3	900–1000	300–900	550
Number of balloons	1	2	Up to 3	1	1	1
Insertion	Endoscopy	Endoscopy	Swallowed	Endoscopy	Endoscopy	Swallowed
Removal	Endoscopy	Endoscopy	Endoscopy	Endoscopy	Endoscopy	Natural pass
Duration	6	6	6	6	12	4
Adjustable	No	No	No	No	Yes	No

Table 1.

Characteristics of intragastric balloon types [22].

Figure 2.

Intragastric balloon material.

2.4.2 Trans Pyloric Shuttle

Trans Pyloric Shuttle (TPS) is an endoscopic, minimally invasive method for the treatment of obesity. The TPS is an apparatus that has two ends and is connected to each other with flexible silicone. When the larger part is inflated and filled, it takes the shape of a bulb. The large part of the TPS apparatus, which is delivered to the stomach with an endoscopic application device, is inflated and filled with a coil-like mechanism. After the TPS is endoscopically inserted into the stomach, it remains free in the stomach. Since the small part can easily pass through the pylorus, it passes through the pylorus with peristaltic movements and delays gastric emptying due to the intermittent formation of the large part in the pylorus and at the same time accelerates the filling time of the stomach. This device can stay in the stomach for 12 months and at the end of this period, the internal coil in the large bulb-like part of the TPS is unlocked endoscopically, the part inside the coil is removed first, and the large part is taken out of the stomach after it is narrowed (Figures 3 and 4).

Figure 3.

Transpyloric shuttle [26].

Figure 4.

Image of the transpyloric shuttle in the stomach [26].

After the results of the Endobesity II study were published, TPS received FDA approval in 2019. According to this study, TWL was 9.5% in patients who underwent TPS and 2.8% in the control group after 12 months of follow-up. In terms of serious side effects, 4.69% of patients who underwent TPS experienced side effects, while this rate was 1.12% in the control group [26].

2.4.3 Endoscopic sleeve gastroplasty

Endoscopic sleeve gastropilasty (ESG) is a globally accepted method for the treatment of obesity. Although bariatric surgery is the most effective method in the treatment of obesity, many patients avoid surgery because it is perceived as invasive and fear of complications. ESG is a less invasive and organ-sparing option in the treatment of obesity. Endoscopic gastroplasty alters the anatomy and physiology of the stomach by folding the gastric walls and reducing the intragastric volume by up to 75%. Functional exclusion of part of the stomach results in a reduction of both gastric volume and motility [27].

ESG is performed with two types of FDA-approved devices: Overstitch platform (Apollo Endosurgery, Austin, TX), Primary Obesity Surgery Endoluminal (POSE) (USGI Medical, San Clemente, CA).

The Overstitch platform (Apollo Endosurgery, Austin, TX) is used to endoscopically perform gastroplasty with full-thickness suturing and plication of the greater curvature from the inside. This procedure is the most commonly performed endoscopic gastroplasty in recent years. ESG has been shown to be beneficial for weight loss by both reducing gastric volume and gastric emptying [27]. It also has effects on gut hormones and has been shown to reduce ghrelin levels [27]. The most common side effects are nausea and vomiting and abdominal pain. Leakage and free fluid around the stomach, gastric bleeding, some cases of venous thromboembolism and other complications such as pneumotrax, pneumperitnyum have also been seen [27, 28].

Contraindications for ESG, as with other endoscopic options for the treatment of obesity, include large hiatal hernia, gastric ulcer, gastric tumors or intestinal metaplasia, previous surgical procedure, pregnancy, continuous monitoring and anticoagulant use [27, 28].

There are many studies in the literature on this technique. Seven studies including 6775 patients (3413 with ESG and 3362 with LSG) were included in Beran et al. ESG and LSG were compared in the short and long term and significant differences in TBWL% were seen in favor of LSG. The trend towards a lower incidence of adverse events in ESG compared with LSG did not reach statistical significance (RR 0.51, 95% CI 0.23–1.11, P = 0.09). The incidence of new-onset gastroesophageal reflux disease (GERD) was significantly lower after ESG compared to LSG, 1.3% versus 17.9%, respectively (RR 0.10, 95% CI 0.02–0.53, P = 0.006). ESG provided clinically adequate but lower short- and medium-term weight loss and resulted in fewer adverse events, including GERD, compared to LSG. Given the gastroprotective nature of ESG and its acceptable safety profile, it may be considered as an alternative to LSG for patients with mild to moderate obesity [28].

In a study by Lopez-Nava et al. with 248 patients, TBWL was 18.5% after 24 months of follow-up in patients who underwent ESG [29].

In the 91-patient study by Sharaiha et al. TBWL was 17.6% after 1-year follow-up (76% patient follow-up rate). At the same time, the reduction in medical comorbidities, HgA1 C, Blood Pressure, Triglyceride and ALT values were statistically significant [30].

In another study of 148 patients, endolumenal sleeve gastrolasty resulted in a TWBL of 17.53 ± 7.57% at 1 year and 18.5 ± 9% at 18 months. Leptin hormone levels unexpectedly decreased in every patient. As a complication, only 1 patient had a hemorrhage during the passage of the suture helix, which was resolved by sclerotherapy. In this study by Moreles et al., a continuous suture line was created using 4 parallel “Z” suture patterns to minimize the gastric cavity. The suture pattern aimed to eliminate the effect of the distorting force on the suture and to provide a homogeneous distribution between all suture points [31].

Comparison of ESG studies is very difficult due to the difference in technical procedures. However, many studies have been conducted by describing continuous sutures.

Primary obesity surgery endoluminal (POSE) uses an incisionless surgical system to create full-thickness plications in the gastric fundus and body. Many studies have demonstrated the safety and efficacy of the original POSE for the treatment of obesity.

In the meta-analysis by Singh et al. 7 studies were included, 2 of these studies were randmized controlled studies while the others were observational studies. At the end of 12–15 months follow-up, EWL was 48.86% and TWL was 12.68%. Serious adverse events included GI bleeding, extra-gastric bleeding, hepatic abscess, severe pain, severe nausea and severe vomiting; the overall incidence of these serious adverse events was only 2.84% [32] (Figure 5).

Figure 5.

Illustration showing the differences between the POSE 1 and POSE 2 procedures.

POSE 1 anatomically reduces the gastric fundus and places a plication line horizontally into the distal gastric body. In POSE 2, by placing plications in the greater curvature of the stomach starting from the level of the incisura and extending proximally to the corpus, the volume of the stomach is reduced so that a small reservoir of food remains in the fundus and the stomach is somewhat reduced and shortened. Both ESG and POSE have shown both gastric volume reduction and hormonal efficacy when compared with other endoscopic procedures. In addition, both ESG and POSE procedures have similar efficacy [33].

2.4.4 Gastric aspiration therapy

The AspireAssist device (Aspire Bariatrics, King of Prussia, PA) is a type of endoscopic gastrostomy tube. It works by partially aspirating ingested food. It is reversible and does not cause significant changes in the anatomy of the stomach. First, the AspireAssist device is inserted. Gastric content is aspirated by feeding water through the part connected to the external apparatus.

In the pilot study conducted by Sullivan et al. in 18 individuals with obesity, 11 patients randomly assigned to aspiration therapy and lifestyle therapy, and 7 patients to lifestyle therapy only. Lifestyle therapy consisted of a 15-session dietary and behavioral education program. After 1 year, TBWL % was 18.6% ± 2.3% in the aspiration therapy group and TWBL % was 5.9% ± 5.0% in the lifestyle therapy group. There was no significant difference between the two groups (p < 0.4) (Figure 6) [34].

Figure 6.

Aspire Bariatrics AspireAssist. Notes: (A) aspiration tube and skin port in place and (B) external device connected for aspiration [34].

2.4.5 Small bowel procedures

Duodenal bypass sheaths are closed sheaths placed between the mucosa and the GI lumen to block the digestion and absorption of nutrients. Currently, these devices are not FDA approved. Most of the literature mentions the EndoBarrier, a duodenal-jejunal bypass sleeve (DJBS) with a length of 60 cm. During insertion, a self-expanding nitinol anchor is placed inside the duodenal bulb and an impermeable fluoropolymer liner is placed distal to the proximal jejunum. Similarly, the ValenTx is a 120 cm gastro-duodenal-jejunal bypass that is fixed at the gastroesophageal junction and extends into the jejunum. Laparoscopic assistance is required for the placement of this second device [35, 36, 37, 38].

A rapid improvement in T2DM and glycemic control, as well as hormonal changes, has been noted after DJBS implantation [39, 40]. Munoz et al. [41] suggest additional weight-independent glycemic control mechanisms. Jirapinyo et al. [42] published a meta-analysis of 4 RCTs showing a 1.3% reduction in HbA1c and a significant reduction of 0.9% compared to control. This reduction was maintained after 6 months. Pooled data from observational and RCTs showed a TWL of 18% that remained significant after 1 year; GLP-1, PYY and ghrelin increased while glucose-dependent insulinotropic polypeptide decreased [41, 42].

There are still safety issues in using these methods that need to be addressed. Betzel et al. [43] published a systematic review of 1057 patients, of whom 33 had serious adverse events, or 3.7%. These included 11 hepatic abscesses, 8 gastrointestinal bleeding, 4 esophageal perforation and 3 acute pancreatitis. 8 patients required surgery but no deaths were reported. Despite these risks, Laubner et al. [44] showed a possible positive risk-benefit ratio in favor of DJBL for the treatment of T2DM.

Currently, bypass procedures are performed laparoscopically with stapler or manual anastomosis. Similarly, performing anastomoses is endoscopically challenging. For the treatment of obesity, type II diabetes and malignant obstructions, a completely endoscopic method of creating a durable reliable bowel bypass is desirable [45, 46, 47].

Ryou et al. performed endoscopic jejuno-ileal anastomosis in an animal experiment on 8 pigs. Since the anatomy of the pigs was not suitable, ileal magnets were placed laparoscopically and anastomoses were checked after 3 months in 8 pigs and it was observed that the anastomoses were successful [48]. In the pilot study conducted by Sullivan et al., enteroscopy and colonoscopy were performed in 10 people with obesity and magnets were placed in jejunum and ileum. With the help of laparoscopy, the correct position of the magnets was controlled and adhesion was assisted. Successful anastomoses were performed in normal form. Common side effects were vomiting and diarrhea. At the end of 6 months, TWL was 10.6% (EWL was 28%). HbA1C levels decreased in 4 patients with diabetes [49].

2.4.6 Dudenal mucosal surfacing

Duodenal mucosal resurfacing is performed using specially designed catheters (Fractyl Laboratories) advanced through a guidewire next to the endoscope. Duodenal mucosal resurfacing (DMR) is a single, minimally invasive endoscopic procedure that involves circumferential hydrothermal ablation of the duodenal mucosa followed by regeneration of the mucosa. Before ablation, the mucosa is removed with saline to protect the outer layers of the duodenum. A first-in-human study showed significant improvements in glycemia in T2D patients after DMR and suggested a positive correlation between the length of the ablated segment and efficacy [50]. Baar et al. evaluated 36 patients and found that DMR is a feasible and safe endoscopic procedure that provides durable glycemic improvement in suboptimally controlled T2D patients on oral glucose-lowering medication regardless of weight loss [51].

2.4.7 Intragastric botulinum toxin a (BTA) injection

Botulinum toxin A (BTA) injection may temporarily inhibit gastric peristalsis by paralyzing the muscular layer of the stomach. This can delay gastric emptying and prolong the duration of satiety. Conflicting evidence on efficacy has been published. Early studies showed weight loss through delayed gastric emptying without side effects [52, 53, 54]. In 2015, a meta-analysis of 8 studies concluded that BTA is effective in the treatment of obesity [55]. A recent meta-analysis concluded that intragastric BTA injection is not effective [56]. In another study, intragastric injection of BTX-A does not seem to be an effective method to achieve preoperative weight loss in super obese patients [57]. In a systemic meta-analysis conducted by Yen et al. [58], 192 individuals were evaluated in 6 randomized controlled studies. Intragastric BTA injection was found to be effective in the treatment of obesity, adequate dose (≥200 U), multiple gastric injection sites and combined diet control are very important. However, caution should be exercised due to the small sample size and limited power (Figure 7) [58].

Figure 7.

Endoscopic interventions for obesity and dysmetabolic conditions. Endoscopic interventions: (a) duodenal mucosa resurfacing, (b) intragastric botox injection, (c) gas-filled intragastric balloon, (d) liquid-filled intragastric balloon, (e) transpyloric shuttle, (f) duodenal-jejunal bypass liner, (g) gastro-duodenal-jejunal bypass liner, (h) endoscopic sleeve gastroplasty, (i) primary obesity surgery endoluminal, (l) aspiration therapy, and (m) partial jejunal diversion [36].

3. Conclusion

Although surgical procedures are known as the most effective methods in the fight against obesity today, the frequency and effectiveness of endoscopic treatments are increasing day by day. Endoscopic methods in obesity treatment are promising. There is a need for new methods with high efficacy and reliability, easy application, low complication rate and low cost in the treatment of obesity.