Bariatric endoscopy: from managing complications to primary metabolic procedures

Abstract

Obesity is a worldwide epidemic and is the second leading cause of preventable death. The approach to treating obesity involves a multidisciplinary approach including lifestyle interventions, pharmacological therapies, and bariatric surgery. Endoscopic interventions are emerging as important tools in the treatment of obesity with primary and revisional bariatric endoscopic therapies. These include intragastric balloons, aspiration therapy, suturing and plication, duodenal-jejunal bypass liners, endoscopic duodenal mucosal resurfacing, and incisionless magnetic anastomosis systems. Endoscopic interventions have also demonstrated efficacy in treating complications of bariatric surgery. Approaches include stenting, endoscopic internal drainage, and endoscopic vacuum-assisted closure. This review aimed to discuss the current endoscopic procedures used as primary and revisional bariatric therapy including those used for managing bariatric surgical complications.

INTRODUCTION

Obesity is estimated to affect 650 million people worldwide [1] and obesity is associated with higher morbidity and mortality [2]. To reduce and prevent morbidity, treatment for obesity requires a multimodal approach that includes lifestyle interventions, pharmacological therapies, and bariatric surgery. Although bariatric surgery is highly effective at inducing weight loss, improving comorbidities, and reducing mortality [3], only approximately 1% of eligible patients undergo bariatric surgery every year [4].

Endoscopic bariatric therapies (EBT) are emerging as an increasingly important modality in the treatment of obesity [5]. Many of these treatment approaches, such as intragastric balloons (IGBs), aspiration therapy, suturing and plication, duodenal-jejunal bypass liners (DJBLs), endoscopic duodenal mucosal resurfacing (DMR), and incisionless magnetic anastomosis systems (IMAS), are still evolving. Endoscopic approaches have also been effective in managing bariatric surgical complications [6]. These approaches include stenting, endoscopic internal drainage (EID), and endoscopic vacuum-assisted closure (E-VAC).

In this review, we aimed to discuss endoscopic therapies for the treatment of obesity and the management of complications from bariatric surgery.

MAIN SUBJECTS

Endoscopic interventions as primary metabolic therapy

EBT involves a spectrum of techniques using flexible endoscopy to manage obesity and its associated comorbidities [7]. Compared to bariatric surgery, EBT avoids operative intervention, especially in reoperative bariatric surgery, which can be both more difficult for the surgeon and higher risk for the patient [8]. EBT generally benefits from having a lower complication rate than surgery [9]. However, advanced endoscopic training for EBT can be challenging with a long learning curve, and specialized training programs may be required for some EBT procedures. Furthermore, platforms for performing EBT are continuously evolving, which in turn, demands continuous learning from the endoscopists [10].

EBT can be used for primary or revisional therapy after bariatric surgery. Endoscopic interventions can also be used as a bridging therapy to induce weight loss prior to bariatric surgery. As a primary therapy, EBT is ideal for patients who are not candidates for bariatric surgery, such as patients who cannot tolerate general anesthesia. EBT is also an option for patients who do not want surgery or who are not eligible for surgery under the current National Institutes of Health guidelines [11]. EBT as a bridging therapy can be used to increase the ease of surgery and reduce operative risks in high-risk patients, especially those with a high body mass index (BMI). EBT as a bridging intervention can also be used to improve outcomes of other operations including transplant, orthopedic, or abdominal wall surgery [12].

In 2015, the American Society for Metabolic and Bariatric Surgery and the American Society for Gastrointestinal Endoscopy (ASGE) defined the acceptable efficacy threshold of EBT as ≥25% excess weight loss (EWL) with a complication rate of ≤5%. In 2020, the ASGE and the Association for Bariatric Endoscopy released a position statement defining essential principles for training and granting privileges to ensure that patients are receiving high-quality care through EBT [13].

Intragastric balloons

The first EBT therapy, developed in 1985, was the Garren Edwards Bubble, which was the earliest form of IGBs [14]. However, it was discontinued in 1988 due to serious complications but reapproved by the U.S. Food and Drug Administration (FDA) in 2015 for weight loss. IGBs are currently indicated for use in patients with a BMI of ≥30 kg/m² in the United States. They are either placed endoscopically or swallowed and removed at 6 to 12 months. The current FDA-approved IGBs include the Orbera (Apollo Endosurgery), Spatz (Spatz Medical), Reshape Duo (Apollo Endosurgery), and the Obalon (Obalon Balloon System). Uniquely, the Allurion Elipse balloon deflates on its own at 4 months and does not require endoscopic removal but is not currently approved by the FDA [14].

A meta-analysis of randomized controlled trials (RCT) of IGBs included 13 studies and demonstrated a mean difference in the percentage of EWL (%EWL) of 18.0% and a percentage total body weight loss (%TBWL) of 4.4% at follow-up compared to lifestyle interventions or sham treatment [15]. In this analysis, IGBs resulted in a %TWBL of approximately 7% to 15% compared to 3% to 9% for lifestyle interventions or sham treatment. The duration of balloon use ranged from 3 to 8 months. The rate of serious adverse events following IGBs is low [15]. However, weight recurrence is commonly observed after removal, with patients regaining up to half of their original weight [16]. Despite weight recurrence, there is persistent improvement in metabolic syndrome and diabetes 1 year after IGB therapy [17]. IGB is also useful as a bridging intervention for bariatric surgery in patients with a higher BMI [18].

Suturing and plication

Endoscopic sleeve gastroplasty (ESG) and the primary obesity surgery endoluminal (POSE) procedure are the leading suturing and plication techniques. These procedures are nonoperative counterparts of sleeve gastrectomy. They function by reducing gastric volume, reducing gastric motility and emptying, and inducing satiety. ESG is typically performed using an endoscopic suturing device, such as the OverStitch (Apollo Endosurgery), to imbricate the greater curvature, resulting in a tubularized stomach [9]. The POSE procedure is a technique that combines a multi-lumen device with a tissue approximator that incorporates snowshoe anchors that allows for the placement of durable intragastric sutured plications both in the fundus and at the gastric antral inlet [19].

The MERIT (Multicentre ESG Randomised Interventional) trial is the largest ESG trial to date in patients with class 1 and 2 obesity [9]. ESG resulted in a mean %EWL of 49.2% compared with 3.2% in the control group at 1-year follow-up. The %TBWL was 13.6% for ESG compared with 0.8% for controls. There was a significantly greater improvement in metabolic comorbidities in the ESG cohort. At 104 weeks, the majority (68%) maintained a %EWL of ≥25%. Adverse events occurred in 2% of patients including abdominal abscess, bleeding, and malnutrition [9]. Overall, ESG demonstrated excellent efficacy and safety for the treatment of obesity.

Outcomes for the POSE procedure have been less promising. The ESSENTIAL trial was a multicenter, blinded RCT which evaluated 221 patients in the United States. The POSE procedure had a higher %TBWL of 5.0% at 1 year compared with 1.4% in the sham cohort, but the trial did not reach its predefined endpoint [20]. This led to the development of the modified POSE procedure (POSE 2.0) which adds additional plications to the gastric body. In a multicenter prospective trial, POSE 2.0 demonstrated a %TBWL of 15.7% at 1 year [19]. However, in the future, more RCTs are required to further evaluate POSE 2.0 as a treatment for obesity.

Fayad et al. [21] compared ESG with laparoscopic sleeve gastrectomy (LSG) and found that, at 6 months, the %TBWL was higher after LSG (23.6% vs. 17.6%). However, there were also higher adverse events with LSG (16.9% vs. 5.2%). This adverse event rate appears higher than expected because the study included mild adverse events, such as abdominal pain, nausea, vomiting, and dehydration [21].

Suturing and plication techniques are also useful as interventions for weight recurrence after laparoscopic Roux-en-Y gastric bypass (LRYGB) or LSG. These are discussed below.

Bypass liners

DJBLs were designed to mimic the effects of LRYGB by bypassing the duodenum and proximal jejunum. DJBLs are placed endoscopically and removed after 12 to 52 weeks [22]. The most well-known device is the Endobarrier (GI Dynamics) which is 60 cm long. There is also the ValenTx (Valentx Inc.) device 120 cm long, which is designed to also bypass the stomach. The ValenTx device is less studied [23]. A meta-analysis of DJBLs found that at the time of explant, patients with a DJBL had a greater hemoglobin A1c (HbA1c) reduction compared to controls. This difference persisted 6 months after explantation. At the time of explantation, patients also had a BMI reduction of 4.1 kg/m².

Ruban et al. [24] performed the largest RCT to date on DJBLs with 113 participants. In the DJBL group, 24.2% of participants achieved over 15% weight loss compared to the 3.7% in the control group. The DJBL group also experienced a statistically significant reduction in blood pressure and total cholesterol. However, these effects only lasted for the duration of the DJBL implantation and failed to show a difference 1 year after explantation. Patients with a DJBL also experienced a variety of adverse events, ranging from abdominal pain (11%) and device malfunction (9%) to upper gastrointestinal hemorrhage (2%). Ruban et al. [24] demonstrated that while DJBLs may have promising effects while implanted, the risks must be weighed against the temporary benefits.

Endoscopic duodenal mucosal resurfacing

DMR is an endoscopic technique that was developed to reproduce the positive effects that upper gastrointestinal bypass surgery had on type 2 diabetes mellitus (T2DM) [25,26]. The duodenum has downstream effects on glucose homeostasis, a process that is dysfunctional in patients with T2DM. By undergoing DMR, a patient’s duodenal mucosal layer is hydrothermally ablated, prompting mucosal healing, and resurfacing, thus, altering the metabolic downstream signaling pathways. Rajagopalan et al.’s study [27] revealed a statistically significant reduction in HbA1c of 1.2% in 39 patients, 6 months after DMR. Patients who underwent long-segment DMR experienced more dramatic decreases in HbA1c compared to those who had short-segment DMR. This improvement occurred even with the reduction in oral antidiabetic agents in the long-segment DMR subgroup. Additionally, there were no lasting adverse events reported. Repeat endoscopy showed full mucosal healing in all patients. Three patients were reported to have duodenal strictures 2 to 6 weeks after the procedure. However, all were successfully treated with endoscopic balloon dilation with full recovery. Overall, these results suggest that DMR is a well-tolerated, safe, and effective endoscopic treatment for patients with T2DM, but further research studies with larger sample sizes are warranted [27].

In terms of longer-term effects, van Baar et al. [28] treated 37 participants with long-segment DMR and followed up for 12 months. The study found lasting improvements in HbA1c, fasting plasma glucose, insulin resistance, and transaminase levels in those with non–insulin-dependent T2DM. There were several procedure-related adverse events, such as diarrhea, nausea, and fatigue, but 81% of these were mild, and none were severe. Early studies demonstrate that DMR is a safe procedure for patients with T2DM treated with oral medications and is beneficial in regulating blood glucose for at least 1 year [28].

Incisionless magnetic anastomosis system

IMAS is a more invasive but promising endoscopic procedure designed to create an enteral diversion to circumvent a large portion of the small bowel. The first and only article to report on the effect of IMAS in humans was a pilot study of 10 patients, published in 2017 [29]. Self-assembling magnets were placed proximally in the jejunum via an enteroscope and distally in the terminal ileum via a colonoscope. Correct placement and confirmation of the magnet connection was performed with a laparoscope at the time of deployment and an abdominal X-ray 48 hours after the procedure. The magnetic connection and the subsequent compression of tissues can cause necrosis and fistulization of the jejunum to the ileum. Passage of the magnets through the rectum occurred in all patients with no serious adverse events. Follow-up endoscopy was completed at increasing intervals for 12 months to confirm patency of the jejunoileal anastomosis. On average, patients experienced a %TWBL of 14.6%, a 1.9% reduction in HbA1c, and a lowering of their fasting blood glucose up to 12 months after the procedure. However, the sample size was small and further research is warranted before it can be considered for mainstream use.

Endoscopic interventions for weight recurrence

Bariatric surgery, though highly successful for weight loss, has a high rate of weight recurrence in the long term. Keeping in mind that the definition of weight recurrence is variable across different studies [26,30–33], an international study found that 40% to 64% of patients experienced weight recurrence 5 years after LSG. Weight recurrence was similarly high for patients who underwent LRYGB 5 years prior (about half of the patients experienced weight recurrence) [31].

Eating habits and psychosocial factors are not the only reasons people regain weight. Surgically modifiable risk factors, including larger gastrojejunal stoma diameter and post-sleeve gastrectomy gastric volumes, have statistically significant correlations with increased weight recurrence [30,34–36]. Traditionally, patients could undergo corrective or conversion operations to address these anatomic factors, but revisional surgeries carry a higher risk of morbidity than primary bariatric surgery [37]. Comparatively, endoscopic procedures have a minimal risk of serious adverse events and have shown to be reasonably effective [38–42].

Transoral outlet reduction

Post-LRYGB gastrojejunal aperture (GJA) diameters larger than 25 mm had a 75% positive predictive value of weight recurrence [34]. To treat GJA dilation, transoral outlet reduction (TORe) is an umbrella term that refers to endoscopic techniques that reduce stoma size through endoscopic suturing, mucosal cryoablation, or argon plasma coagulation (APC).

Endoscopic suturing

Of the various TORe methods, endoscopic suturing is the most researched. The RESTORe (Randomized Evaluation of Endoscopic Suturing Transorally for Anastomotic Outlet Reduction) trial is a multicenter, blinded, RCT that used endoscopic suturing to narrow the GJA in patients with a GJA greater than 20 mm and suboptimal weight loss or weight recurrence after LRYGB. After 6 months, 96% of patients with TORe experienced weight stabilization or weight loss relative to the baseline, compared to 77.8% of patients with sham treatment. However, there was no statistically significant difference for >15% EWL. There were also no severe adverse events in either group, demonstrating the safety of this intervention [39]. Subsequent TORe studies have also shown sustained and continued weight loss 3 to 5 years after TORe for weight recurrence after LRYGB [41–43]. A 2020 study also found that a modified endoscopic submucosal dissection around the GJA prior to endoscopic suturing increases weight loss compared to the APC-TORe procedure [44].

A 2016 study comparing endoscopic suturing to sclerotherapy showed that not only was endoscopic suturing more effective at narrowing the GJA but it also had a greater effect on cognitive restraint from eating and weight loss despite an increase in ghrelin levels 3 months after the intervention. However, the suturing arm and the sclerotherapy arm had a large discrepancy in the number of participants (9 and 34, respectively) as well as a statistically significant difference in ghrelin prior to intervention. This difference convolutes the comparisons made at 3 months [40].

In addition to the effects endoscopic suturing has on weight recurrence, it is also a useful alternative to revisional bariatric surgery for symptoms of medically refractory dumping syndromes (see the section of ‘Endoscopic interventions for dumping syndrome’) [45].

Cryoballoon ablation

Like endoscopic suturing, cryoballoon ablation aims to reduce the GJA size by inducing an inflammatory response that leads to fibrosis and stricturing. One retrospective pilot study performed cryoablation in 22 patients with weight recurrence post-LRYGB. The GJA size was successfully reduced from 24.1 mm to 17.1 mm in 89.5% of patients, which correlated with a %TBWL of 8.1% after 8 weeks [46]. The results, though promising, are still not well established and further research is essential.

Argon plasma coagulation

APC is another tool for TORe. Using high-frequency electrical current conducted through argon gas, a focused area can be coagulated. In the setting of TORe, APC can be performed at the GJA to induce stricturing. Jirapinyo et al. [47] performed a retrospective study on 217 patients looking at the effects on weight loss with high-dose APC vs. low-dose APC. High-dose APC was not only correlated with a greater %TBWL (8.1%) at 6 months compared to low-dose APC but was also a predictor of greater weight loss at 1 year (9.7% vs 5.1% TBWL). However, 8% of patients experienced adverse events, such as stenosis and gastrointestinal bleeding, requiring additional endoscopy with intervention. One patient required endoscopic incisional intervention to resolve the stenosis [47].

Baretta et al. [48] published a study in 2015 that also demonstrated favorable results. The study reported an average of 15.5 kg weight loss 2 years after three APC treatments for weight recurrence in post-LRYGB. The weight loss achieved was close to the patient’s nadir weight. APC was also able to maintain a 66.9% GJA reduction in that time. Overall, APC appears to be an effective technique for inducing weight loss in patients with a large GJA. However, patients may require multiple sessions and there is a small risk of complications.

Revisional endoscopic sleeve gastroplasty

In patients who underwent LSG, weight recurrence is correlated with larger residual gastric volumes among other psychosocial, metabolic, and dietary factors [26,30,31]. To combat increased gastric volumes, an endoscopic suture and plication procedure, the revisional ESG (R-ESG), was developed and is considered effective and safe [49,50].

Maselli et al. [49] performed a multicenter, prospective study involving 82 adults with weight recurrence after LSG. Using the OverStitch system, endoscopists reduced the gastric volume and length according to the degree of sleeve dilation, tissue configuration, and endoscopist discretion. A large majority of patients achieved over 10% TBWL after 6 and 12 months, and 52.4% achieved over 15% TBWL at the 12-month mark. The study reported one moderate adverse event in the form of gastroesophageal junction stenosis that was successfully treated with endoscopic dilation. Overall, R-ESG is a safe and effective procedure for weight recurrence in post-bariatric surgery patients with weight loss seen consistently over a year.

Endoscopic interventions for dumping syndrome

A known and problematic complication of LRYGB is dumping syndrome, either early or late. Although it is a rare complication of bariatric surgery, it most commonly occurs in patients who have undergone LRYGB. The pathophysiology for early dumping syndrome is usually explained by a hyperosmotic bolus, which draws water into the alimentary tract causing hypotension. This can be addressed with dietary changes. However, the pathophysiology of late dumping syndrome is not well understood and management initially consists of dietary changes and medical therapy. If patients are refractory following medications, they are recommended a gastrostomy feeding tube or revisional bariatric surgery. A less invasive alternative to surgery is endoscopic gastrojejunostomy revision, which aims to narrow the GJA using endoscopic suturing [45,51,52].

Bazarbashi et al. [52] performed a meta-analysis investigating the effects of TORe endoscopic suturing on symptoms of dumping syndrome. This meta-analysis included six studies and 263 patients. The results showed that 89.5% had clinical improvement of symptoms over an average of 8 months. There was a 2.4% rate of intraprocedural adverse events and 11.5% of patients needed reintervention. Based on the findings of this meta-analysis, TORe endoscopic suturing is effective and safe for dumping syndrome for at least the short term.

The longest study to date that has demonstrated the effectiveness of TORe endoscopic suturing for late dumping syndrome included 98 patients. The GJA was suture plicated with figure-of-eight stitches to decrease the diameter to 15 mm. One month after the procedure, 100% of patients experienced resolution of symptoms. Seventy-seven patients followed up 3 years after the procedure, and 84% of patients reported continued resolution of their symptoms over the long term. Additionally, the intervention was 70% effective in patients classified with severe dumping syndrome, which was defined as having three or more symptoms of late dumping. Of note, patients who had preprocedural gastroesophageal reflux disease (GERD) had a statistically significant recovery from dumping symptoms compared to those who did not have GERD prior to the suturing. One patient required hospital admission within 30 days due to an anastomotic ulcer bleeding. There were no other serious adverse events [45].

Endoscopic management of complications of bariatric surgery

Bariatric surgery is an overall low-risk surgery. The risk of mortality is 0.1%. However, not all intraabdominal complications require reoperation or surgical intervention as they carry high risks for subsequent complications [53]. With advances in endoscopic techniques and technology, many of these complications can now be managed safely with endoscopic approaches including stents, EID, and E-VAC.

Stents

Endoscopic self-expanding stents are indicated for leaks and fistulas [54,55] as they can direct gastrointestinal contents past the mucosal defect to allow for healing and enteral nutrition. Studies suggest that stents are a reasonable option for patients with leaks as they have an 88% to 92% success rate. However, practitioners must be aware that stent migration occurs in 17% to 23% of patients and that stent migration requires additional endoscopy for retrieval or repositioning [55,56]. This can be a serious problem in post-LRYGB patients who have a higher risk of migration into the distal small bowel, requiring surgical removal. However, the use of partially covered stents or securing the stent proximally with sutures or clips can reduce the risk of migration [57]. Stents can cause pain and worsen reflux and may be poorly tolerated by some patients [54]. Overall, stenting is a reasonable first-line option for leaks and fistulas after bariatric surgery despite the risk of migration and reflux.

Endoscopic internal drainage

EID is used for postoperative fluid collections, leaks, and fistulas. EID uses endoscopy to place one or more double pigtail stents (DPS) across the defect or into an intraabdominal fluid collection to allow for low-resistance, controlled drainage of the fluid collection. Donatelli et al. [58] found a success rate of 89.5% for leaks, 78.5% for fistulas, and 90% for intraabdominal fluid collections. While the success rate is high, there are significant, albeit rare, risks. Fifteen out of 614 patients had associated bleeding, some requiring interventional radiology embolization. Four of these patients underwent splenectomy for splenic artery pseudoaneurysm. The other adverse events, such as air embolism, migration of DPS into the spleen, occurred in less than 1% of patients, and there was one nonfatal myocardial infarction. Additionally, 13.6% of patients had to undergo revisional surgery because the EID did not resolve the original complication. The most prevalent predictor of EID failure was emergent surgery prior to the endoscopy. While this technique is largely successful, there are serious adverse events associated with the technique. A discussion with patients regarding these risks and potential complications is paramount before undergoing EID.

Endoscopic vacuum-assisted closure

E-VAC is particularly useful for leaks following bariatric surgery. The first to describe this technique was Markus et al. [59] in 2022 and was an adaptation from esophageal leak closures. E-VAC involves placing an endosponge fit to the size of the defect, which is then connected to a continuous suction with a negative pressure of 75 to 120 mmHg depending on the size of the cavity. The endosponge is then changed every 2 to 3 days until the abscess cavity is smaller than 2 × 2 cm in diameter and depth. E-VAC was originally implemented after a persistent leak following revisional surgery. In four cases, E-VAC was performed as first-line treatment. A 90% success rate with no complications at 1-year follow-up was reported [59]. Since then, a meta-analysis reviewing E-VAC has shown a similar success rate of 87.2%. However, the same meta-analysis reported the risks of moderate adverse events (6%), dislodgements (12.5%), and longer hospital stays. The technique was recently applied to leaks from bariatric surgeries but there is little data to date. Based on available data, E-VAC is safe and effective. However, more studies are needed to support its use for bariatric complications [60].

CONCLUSIONS

Bariatric endoscopy is a versatile tool that has multiple benefits for bariatric patients. It can safely and effectively be used for the treatment of obesity and metabolic disease as a part of multimodal therapies that include medical and surgical options. With only 1% of patients undergoing bariatric surgery, endoscopy can provide access to more patients [4]. It can also help treat weight recurrence and manage bariatric surgical complications. With further technological advancements, bariatric endoscopic techniques are continually improving and have the potential to be increasingly utilized in managing obesity and bariatric complications.