Society: ASGE

Background: Gastric sleeve stenosis (GSS) is an increasingly common adverse event following sleeve gastrectomy (SG) and thought to result from progressive rotation and/or scarring of the sleeve. Objective diagnostic criteria for this condition are lacking. Given the increasing prevalence of SG procedures being performed and the rising incidence of GSS, the diagnosis of GSS is critical to expedite management and reduce patient suffering. Endoluminal impedance planimetry measurements including diameter and distensibility indices (DI) show promise in characterizing GSS, though normal and abnormal benchmark values have never been established.
Aims: To (1) establish benchmark values for the distribution of diameter and DI for normal gastric sleeve anatomy and across GSS severity, and (2) determine if impedance planimetry measurements can be used to characterize the severity of GSS.
Methods: This was a retrospective analysis of a prospective database of patients who underwent upper endoscopy with impedance planimetry for suspected GSS between 8/2018 and 11/2022. All upper endoscopies were performed by a single trained bariatric endoscopist who assessed the presence and severity of luminal narrowing and was blinded to impedance planimetry measurements. Endoscopist description of endoluminal narrowing was reported as normal [0], mild [1], moderate [2], or severe [3]. Impedance planimetry measurements were obtained by advancing the catheter across the GSS. Measurements were monitored for 60 seconds with 3 different balloon volumes (30ml, 40ml, and 50ml) and diameter and distensibility index (DI) were recorded. Primary outcome included luminal diameter and DI. Secondary outcomes included presence and severity of GSS on endoscopy.
Results: A total of 110 endoscopic procedures were included. No luminal narrowing was seen in 19 (17%). Luminal narrowing was graded as mild, moderate, and severe in 27 (25%), 34 (30%), and 30 (27%) of procedures, respectively. When stratified by severity, there was significant difference between impedance planimetry measurements of diameter and DI in all four categories using all 3 balloon volumes (Figure 1). In the group without luminal narrowing, mean (±SD) diameter and DI measurements using consecutive balloon volumes ranged from 19.1 (±5.5) to 23.2 (±1.7) and 16.8 (±4.9) to 23.1 (±10.9), respectively. Comparatively, in severe narrowing, mean (±SD) diameter and DI measurements ranged from 10.3 (±3.0) to 16.6 (±2.1) and 7.5 (±7.1) to 7.7 (±4.3), respectively. Representative images of impedance planimetry for no luminal narrowing and mild, moderate, and severe stenosis are shown in Figure 2.
Conclusion: Impedance planimetry measurements provide objective assessment in the diagnosis of GSS and correlate with luminal narrowing. This study provides new benchmark values for the diagnosis and severity of GSS.

Background
Type 2 diabetes (T2D) affects 462 million people worldwide. Non-pharmacological interventions that can improve glycemic control in patients inadequately controlled with glucose-lowering medications (GLMs) have a potential to delay insulin initiation and modify disease progression. Duodenal mucosal regeneration (DMR) induced by thermal ablation has been associated with improved glycemic control in T2D patients.

Pulsed electric field (PEF) is a unique non-thermal modality that can selectively affect cells via electroporation. This first-in-human study evaluates the safety, feasibility and preliminary efficacy of endoscopic application of PEF to elicit DMR in T2D patients inadequately controlled on GLMs and is the first PEF application in gastrointestinal tract.

Method
This is an ongoing multicenter, open-label, treatment-only study. Key eligibility criteria are 18-70 years of age, history of T2D for ≤10 years, HbA1c of 7.5%-11.0%, BMI of 24 – 40 kg/m2, C-peptide ≥ 333 pmol/l, and on 1-4 non-insulin GLMs. The primary endpoint is the incidence of device- or procedure-related serious adverse events (SAEs) at 12 wks. Secondary endpoints include technical success and changes in glycemic control at 24 wks. The procedure is performed endoscopically using the ReCET™ device (Endogenex Inc.). Patients are followed for 48 wks, with endoscopic follow up at 4 wks. The GLMs are maintained stable for ≥12 wks before and ≥24 wks after the procedure.

Results
To date, 30 patients have been enrolled (Table 1). Technical success was 100%, with a mean treated length of 11.0 ± 1.9 cm, and median procedure time of 59 min (IQR 42 – 78). No device/procedure-related SAEs occurred. Forty-five device/procedure-related adverse events (AEs) were reported in 23/30 patients. Most reported AEs were sore throat (17/30) and transient diarrhea (9/30). AEs were mild (80%) or moderate (20%) in severity. At 4 wks, the treated areas showed complete healing, mostly unidentifiable endoscopically, with no signs of stricture, ulceration, or other significant findings.

The first 12 patients were treated with single energy application (single Tx). The subsequent 18 patients received double energy application (double Tx) and 14 have reached 24 wks. Clinically significant improvements in glycemic control were observed in these 14 patients. At 24 wks, mean HbA1c was 7.5% ± 1.1% vs. 8.4% ± 1.0% at baseline (p<0.01), FPG 7.5 ± 1.7 mmol/l vs. 9.8 ± 2.2 mmol/l (P<0.01), and HOMA-IR 4.5 ± 3.6 vs. 7.4 ± 3.3 (p<0.01). Weight loss was 5.1% ± 4.1% (p<0.01) at 24 wks. An energy dose-response relationship was observed between the single Tx and double Tx dose levels (P < 0.05) (Figure 1).

Conclusions
This first GI application of PEF in human demonstrated that the technology is feasible, safe, well tolerated by patients, and is associated with clinically meaningful improvement in glycemic control.

Background: Currently, there are several endoscopic procedures for the treatment of weight regain following Roux-en-Y gastric bypass (RYGB). These include argon plasma coagulation (APC), transoral outlet reduction via suturing (S-TORe) or plication (P-TORe). These procedures focus on reducing the size of the gastrojejunal anastomosis (GJA) and/or pouch. While their safety and efficacy have been established, there is no personalized approach to assist with procedure selection.

Aim: 1) To assess the efficacy of different endoscopic gastric bypass revision (EGBR) procedures 2) To construct an anatomy-based algorithm for the treatment of weight regain to optimize weight loss.

Methods: This is a single-center retrospective study of patients who underwent APC, S-TORe or P-TORe for the treatment of weight regain following RYGB. Patients who underwent EGBR using older suturing or plication platforms were excluded. Sensitivity analyses were performed to compare percent total weight loss (%TWL) at 12 months of different EGBR procedures at different GJA sizes. For pouch ≤ 5 cm, APC and S-TORe were compared as P-TORe is not typically performed given the length of the plication device. For pouch > 5 cm, S-TORe and P-TORe were compared as APC is not typically performed to reduce pouch volume. ANOVA was used for three group comparison and Student’s t-test for sensitivity analyses.

Results: 742 RYGB patients underwent 900 EGBR procedures. Of these, 191 (21%), 591 (66%) and 118 (13%) were APC, S-TORe and P-TORe, respectively. Baseline characteristics are shown in Table 1. At 12 months, patients in the APC, S-TORe and P-TORe experienced 8.1 ± 7.1 %TWL, 9.5 ± 8.7% TWL and 10.0 ± 8.5% TWL, respectively (p =0.25), with 70%, 72% and 63% experiencing at least 5% TWL (p = 0.50). There were no SAEs. Pouch ≤ 5 cm (APC vs S-TORe): On sensitivity analyses, with GJA < 18 mm, there was no difference in %TWL between APC and S-TORe (6.7 ± 7.7 %TWL vs 10.7 ± 11.1 %TWL, p=0.31). With GJA ≥ 18 mm, S-TORe yielded greater weight loss than APC (9.2 ± 8.2% TWL vs 5.3 ± 5.5% TWL, p=0.05). Pouch > 5 cm (S-TORe vs P-TORe): On sensitivity analyses, with GJA ≤ 25 mm, P-TORe yielded greater weight loss compared to S-TORe (13.2 ± 7.5%TWL vs 9.5 ± 9.1% TWL, p=0.04). With GJA > 25 mm, S-TORe yielded greater weight loss compared to P-TORe (17.1 ± 17.5% TWL vs -0.2 ± 7.5% TWL, p=0.03). Using results of the sensitivity analyses at different GJA size, an algorithm for the management of weight regain is constructed (Figure 1).

Conclusion: Endoscopic revision of RYGB in the treatment of weight regain can be individualized based on patient anatomy. For pouch ≤ 5 cm, S-TORe should be considered when GJA ≥ 18 mm, while either S-TORe or APC can be offered when GJA < 18 mm. For pouch > 5 cm, S-TORe should be considered when GJA > 25 mm, with P-TORe being offered when GJA ≤ 25 mm.

<b>Table 1</b>. Baseline characteristics of RYGB patients with weight regain who underwent endoscopic gastric bypass revision (EGBR).

Table 1. Baseline characteristics of RYGB patients with weight regain who underwent endoscopic gastric bypass revision (EGBR).

<b>Figure 1</b>. An anatomy-based algorithm for the treatment of weight regain following Roux-en-Y gastric bypass. APC: argon plasma coagulation; S-TORe: suturing transoral outlet reduction; P-TORe: plication transoral outlet reduction; %TWL: percent total weight loss at 12 months. Bold font with * indicates statistical significance.

Figure 1. An anatomy-based algorithm for the treatment of weight regain following Roux-en-Y gastric bypass. APC: argon plasma coagulation; S-TORe: suturing transoral outlet reduction; P-TORe: plication transoral outlet reduction; %TWL: percent total weight loss at 12 months. Bold font with * indicates statistical significance.

Introduction: Super-Obese patients presenting several comorbidities put foward a dilemma due to high perioperative adverse event rates. Although bariatric surgery remains to this moment the Gold standard of treatment while approaching those patients, not only as weight loss tools, but regarding their impact as metabolic procedures, only a small parcel accepts this option. Fear of complications even in then presence of extensive detailment opens a possibility for other solutions. Bariatric endoscopy proposes minimally invasive proceedings that can be an alternative not merely regarding weight loss but to the amelioration of comorbidities. Hence, it can postpone or even bypass surgery.
Objectives:
Methods: A cohort of 76 patients( mean age 43±7) with a BMI above 50 (51-63)was prospecticaly recruited and analysed retrospectively from February 2018 to January 2021. They were engaged to accomplish two consecutive endobariatric approaches. Firstly, a six-month nonadjustable intragastric balloon was placed, and at the time of the explant, an endoscopic sleeve Gastroplasty(Apollo Endosurgery) was executed.Weight loss results; Body mass composition (Inbody 720), elastography (Fibroscan, Echosens), HOMA-IR, Glicated Haemoglobin, Triglyceride levels, 24-Hour Ambulatory Blood Pressure Monitoring (ABPM), Sleep Apnea Disorders (polysommnography) were analysed by the student t test and the Wilcoxon test.
Results: 68 patients (55 females) completed the two consecutive procedures(3 early balloon removals; 2 not eligible for ESG at the time proposed and 3 opted for bariatric surgery )The average total body weight loss at IGB removal/ESG procedure was 19.74%(±4.67).ESG was accomplished with sucess on all, using an average of 5.6 sutures (4-7) with 15-22 bites per suture. One patient required hospitalization due to difficulty in extubation (2-day admission). No serious adverse event was reported. At 12 months, TBWL % was 32.57%.(+-9.79). 58 patients(75%), presented type 2 diabetes, and 88.2% had their medications decreased, with an average decrease in Hb1ac of 1.65%(+-1.22). Steatosis was present in 82% of patients (S2 score predominant;) and fibrosis in 21% of the group (F3 predominant).Improvements in 69.64 and 50 percent respectively(p<0.001) Sleep apnea in 69.11% with a betterment in 82.97%(p<0.001)ABPM melioration in all HBP bearers(p<0.001).
Conclusion: Although 18 Months were necessary to achieve those results, WL and betterment in comorbidities were similar to those reported after a surgical technique. The role of Endobariatrics broadens to other classes of patients rather than the predetermined originally to fill the gap between clinical and surgical approaches, targeting patients with a BMI of 30-40) and provides safe, effective and life-changing modifications.Therefore,could be offered as an alternative to those who can not or don not wish to undergo surgery.

Background and Aim: Current endoscopic bariatric therapies fail to achieve the same degree of weight loss and improvement in metabolic profile similar to laparoscopic sleeve gastrectomy (LSG) because they merely mimic its restrictive/anatomic aspects. Four essential requirements should be met to achieve the same anatomical and physiological benefits of surgery: (a) reducing gastric volume, (b) decreasing gastric compliance, (c) increasing gastric emptying, and (d) eradicating the hormonally active gastric mucosa. We aim to replicate the efficacy of LSG through a safe, simple, and effective endoscopic approach. We hypothesized that an endoscopic submucosal injection of a sclerosant agent can induce gastric remodeling that will mimic the effects of LSG.
Methods: To better simulate human physiology, we designed a 3D organ-on-a-chip (OoC) intestinal culture model to control cell
microenvironments and maintain tissue-specific functions. The OoC was constructed using co-culture of human intestinal epithelial cells (InEpC), human intestinal myofibroblasts (InMyoFib), and colon carcinoma cell line (Caco-2). The OoC was then treated with bleomycin (1, 1.5, and 2 ug/ml); minocycline (5,10, and 20 mg/ml); recombinant TGF-beta1 (10, 20, and 40 ng/ml), and negative control (Sodium Tetradecyl Sulfate;1000 uM). After initial cell viability testing, we performed immunostaining to detect the expression of fibrosis biomarkers: alpha-smooth muscle actin (alpha-SMA), and collagen-1 (Col-1). The examination was performed using high-resolution confocal microscopy
seven days after incubation.
Results: Bioprinted acellular tubes were constructed and cocultured with the selected cells successfully. The initial viability tests showed that most cells in the OoC culture survived the range of doses of the three candidate agents. However, there was a dose-dependent increase in the cell death ratio (Figure 1). Immunostaining showed that the three candidate agents induced a dose-dependent increase in the fibrotic reaction as evidenced by alpha-SMA actin and Col-1 expression compared to the control. The drug doses that produced the best outcome balance for cell death to the fibrotic reaction were 1.5 ug/ml for bleomycin, 10 mg/ml for minocycline, and 40 ng/ml for TGF-beta1 (Figure 2).
Conclusion: We successfully designed a 3D organ-on-a-chip intestinal culture model and induced an intense fibrotic reaction with bleomycin, minocycline, and recombinant TGF-beta1. This culture model represents a platform for future gastrointestinal research applications. We are currently leveraging our experience on this model to rodent and porcine animal models. The ultimate goal is to develop a single outpatient endoscopic procedure to treat obesity that does not require advanced endoscopic techniques and can be easily disseminated.

Figure 1: a, b) brightfield microscopic images of co-cultured InMyoFibs+CaCO2 cells in the lumen of bioprinted tubes at day 4 after seeding CaCO2 cells; c) viability of co-cultured InMyoFibs+CaCO2 cells in the lumen of bioprinted tubes at Day 10 after seeding CaCO2 cells; d, e, f) microscopic images showing the viability of InMyoFibs+InEpCs +CaCO2 cells in the lumen bioprinted tubes at day 7 after addition of 1.5 ug/ml bleomycin, 10 mg/ml for minocycline and 40 ng/ml TGF-beta1, respectively (note that the green color represents live cells, and the red represents dead cells); g, h, i) microscopic images showing immunostained for Collagen-I at Day 7 of 1.5 ug/ml bleomycin, 10 mg/ml for minocycline and 40 ng/ml TGF-beta1, respectively.

Figure 1: a, b) brightfield microscopic images of co-cultured InMyoFibs+CaCO2 cells in the lumen of bioprinted tubes at day 4 after seeding CaCO2 cells; c) viability of co-cultured InMyoFibs+CaCO2 cells in the lumen of bioprinted tubes at Day 10 after seeding CaCO2 cells; d, e, f) microscopic images showing the viability of InMyoFibs+InEpCs +CaCO2 cells in the lumen bioprinted tubes at day 7 after addition of 1.5 ug/ml bleomycin, 10 mg/ml for minocycline and 40 ng/ml TGF-beta1, respectively (note that the green color represents live cells, and the red represents dead cells); g, h, i) microscopic images showing immunostained for Collagen-I at Day 7 of 1.5 ug/ml bleomycin, 10 mg/ml for minocycline and 40 ng/ml TGF-beta1, respectively.

Figure 2: Confocal images of the organ-on-a-chip culture showing immunostaining for α-SMA and Collagen-I (Col-I) at day 7 after the addition of 40 ng/ml recombinant TGFB1, and 1000 uM of Sodium Tetradecyl Sulfate (STS).

Figure 2: Confocal images of the organ-on-a-chip culture showing immunostaining for α-SMA and Collagen-I (Col-I) at day 7 after the addition of 40 ng/ml recombinant TGFB1, and 1000 uM of Sodium Tetradecyl Sulfate (STS).

Background: Analysis from the Centres for Disease Control and Preventions (CMS) suggests the prevalence of obesity in the U.S. was 41.9% in 2017, and is expected to increase to 50% by 2030. Obesity is a major risk factor for multiple chronic diseases (such as type II diabetes and cardiovascular disease) and can lead to reduced quality of life as well as increased risk of death. Lifestyle modification (LM) has traditionally been a first-line treatment for adults with obesity but recent guidelines recommend bariatric intervention. Endoscopic sleeve gastroplasty (ESG) is a reversible, endoluminal organsparing bariatric procedure that has demonstrated sustained weight loss in people with obesity. The MERIT randomized, controlled trial (RCT) recently showed that ESG with concomitant LM (‘ESG’) led to significant and durable additional excess weight loss versus LM alone (‘LM’) among adults with class I (BMI 30.0-34.9 kg/m2) and class II obesity (BMI 35.0-39.9 kg/m2) as well as improvements in obesity-related comorbidities including type 2 diabetes.
Aim: We aimed to provide the first US cost-utility analysis of ESG vs LM among people with class II obesity.
Methods: The model was built from the perspective of the commercial US payor and methods were aligned with ISPOR recommendations. We used a 6-state Markov model that included 5 BMI-based health states and an additional absorbing death state (Figure 1). Clinical parameters were informed the MERIT Trial. Six-month cycles were used in the first year to reflect the significant and rapid weight loss observed with ESG and annual cycles were used thereafter. Estimates of utility for each health state, disutilities for adverse events, and the incidence of obesity-related comorbidities were based on published literature. One-way sensitivity and probabilistic sensitivity analyses were undertaken.
Results: ESG is highly cost-effective compared to LM from the US perspective. The base-case incremental cost-effectiveness ratio (ICER) for ESG vs LM was $9,281/QALY. The estimated incidence of diabetes had the largest impact on the ICER in one-way sensitivity analyses, though ESG was consistently cost effective across all sensitivity and dominant (cost-saving and improving quality of life) in scenario analyses with no upper bound ICER estimate exceeding $23,000/QALY gained, at a willingness to pay ratio of $50,000/QALY.
Conclusion: Compared with LM alone, ESG is a highly cost-effective treatment option for adults and should be used in selected patients requiring bariatric intervention from the US commercial perspective. Further clinical studies are required the cost effectiveness of ESG with other bariatric obesity interventions including LSG and pharmacological agents.

Cost Utility Model Structure

Background: The UK has one of the highest obesity rates in Europe affecting more than one-quarter of adults in England. Obesity is a risk factor for many chronic diseases and is associated with reduced quality of life and premature mortality. Lifestyle modification (LM) is the first-line treatment for obesity, but bariatric intervention is recommended in contemporary international guidelines for adults with class II obesity (body mass index [BMI] 35.0-39.9 kg/m²). Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure with robust evidence demonstrating its effectiveness and safety. The MERIT randomized controlled trial (RCT) showed that ESG with concomitant LM (‘ESG’) led to significant and durable additional excess weight loss versus LM alone (‘LM’) in adults with class I obesity (BMI 30.0-34.9 kg/m²) and class II obesity, as well as improvements in obesity-related comorbidities. This is the first cost-utility analysis comparing ESG with LM for adults with class II obesity, incorporating evidence from the MERIT RCT.
Methods: A 6-state Markov model was developed comprising 5 BMI-based health states and an absorbing death state (Figure 1). A UK healthcare payer perspective was adopted and methods were aligned with NICE guidance. Baseline characteristics, utilities, and transition probabilities were informed by patient-level data from the subset of patients with class II obesity in MERIT. Adverse events (AEs) were based on the MERIT safety population. Mortality was estimated by applying BMI-specific hazard ratios from the literature to UK general population mortality rates. Utilities for the healthy weight and overweight states were informed from the literature; disutility associated with increasing BMI in obesity I-III states was estimated using MERIT utility data. Disutilities due to AEs and the prevalence of obesity-related comorbidities were based on the literature. Costs included intervention costs, AE costs, and comorbidity costs.
Results: ESG resulted in higher overall costs than LM, but led to an increase in life years and quality-adjusted life years (QALYs) (Table 1). The incremental cost-effectiveness ratio (ICER) for ESG vs LM was £1,887/QALY gained. One-way sensitivity analysis showed that results were most sensitive to utility estimates, though ESG was consistently cost effective across all sensitivity analyses with no ICER estimate exceeding £4,000/QALY gained. In the probabilistic sensitivity analysis, ESG remained cost effective in 98.6% of iterations at a willingness-to-pay threshold of £20,000/QALY gained.
Conclusion: Our analysis suggests that compared with LM alone, ESG is a highly cost-effective treatment option for adults with class II obesity in the UK. Further research is needed to validate findings of this study and to compare the clinical and cost effectiveness of ESG with other bariatric obesity interventions.

Cost Utility Model Structure

Base Case Results

Frank O'Neill

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