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Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video)
Journal Pre-proof Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video) Pichamol Jirapinyo, MD, MPH, Diogo T.H. de Moura, MD, PhD, Christopher C. Thompson, MD, MSc PII:
S0016-5107(20)30094-8
DOI:
https://doi.org/10.1016/j.gie.2020.01.036
Reference:
YMGE 11952
To appear in:
Gastrointestinal Endoscopy
Received Date: 2 November 2019 Accepted Date: 16 January 2020
Please cite this article as: Jirapinyo P, de Moura DTH, Thompson CC, Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video), Gastrointestinal Endoscopy (2020), doi: https://doi.org/10.1016/j.gie.2020.01.036. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020 by the American Society for Gastrointestinal Endoscopy
Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video)
Authors: Pichamol Jirapinyo, MD, MPH1,2, Diogo T.H. de Moura, MD, PhD1,2,3, Christopher C. Thompson, MD, MSc1,2
1. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA 2. Harvard Medical School, Boston, MA, USA 3. Gastroenterology Department, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
Author Contributions: P.J.: Study design and concept, data collection, statistical analysis, manuscript preparation D.D.: Data collection C.C.T.: Study design and concept, critically reviewing the manuscript
Conflict of Interests: P.J. has received research support from Apollo Endosurgery, Fractyl and GI Dynamics, and has served as a consultant to Endogastric Solutions and GI Dynamics. D.D. has no conflict of interest. C.C.T. has served as a consultant for Boston Scientific and Apollo Endosurgery, has served as an advisory boards member for USGI Medical, has received research grant and support from USGI Medical, Apollo Endosurgery and GI Dynamics, and holds stock and royalties for GI Windows.
Corresponding Author: Christopher C. Thompson, MD, MSc Corresponding Author’s Institution: Brigham and Women’s Hospital Corresponding Author’s Address: Brigham and Women’s Hospital, Division of Gastroenterology, 75 Francis Street, Boston, MA 02115, USA Corresponding Author’s Telephone: +1-617-525-8266 Corresponding Author’s Fax Number: +1-617-264-6342 Corresponding Author’s E-mail: [email protected] Reprint Requests: Christopher C. Thompson, MD, MSc (Corresponding Author)
Funding: No financial or material support was received for this research project
Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video) ABSTRACT Background and Aims: Although traditional transoral outlet reduction (TORe) involves argon plasma coagulation (APC) before endoscopic suturing, modified endoscopic submucosal dissection (ESD) has also been used. This study aims to evaluate the safety and efficacy of modified ESD-TORe in comparison with traditional APC-TORe. Methods: This was a retrospective study of prospectively collected data of patients who underwent modified ESD-TORe and APC-TORe for weight regain after Roux-en-Y gastric bypass (RYGB). Our outcomes were (1) technical success, adverse events as categorized by the ASGE lexicon, and percent total weight loss (TWL) at 6 and 12 months, and (2) patients who underwent ESD-TORe were matched 1:3 based on gastrojejunal anastomosis (GJA) and pouch sizes to those who underwent APC-TORe. TWLs were compared. A linear regression was performed to control for any confounders. Results: Nineteen RYGB patients underwent ESD-TORe. Technical success rate was 100%. There were no severe adverse events. At 6 and 12 months, patients experienced 13.4±6.6 % and 12.1±9.3% TWL, respectively (p<0.05 for both). Nineteen ESD-TORe patients were also matched to 57 APC-TORe patients based on GJA and pouch sizes. At 12 months, the ESDTORe group experienced greater weight loss compared with the APC-TORe group (12.1±9.3% TWL versus 7.5±3.3 TWL (p=0.036)). On regression analysis, ESD remained a significant
predictor of %TWL at 12 months after controlling for age, sex, BMI, weight regain and years from RYGB (β=5.99, p=0.02). Conclusion: Combining endoscopic tissue dissection with suturing providers greater and more durable weight loss for patients with weight regain after RYGB.
INTRODUCTION Weight regain is a common adverse event of Roux-en-Y gastric bypass (RYGB). Despite its efficacy at inducing weight loss and improving obesity-related comorbidities, RYGB is associated with weight regain with the majority of patients gaining approximately 20% to 30% of the maximal weight they initially lost at 10 years.1,2 Additionally, it has been demonstrated that approximately one-third of RYGB patients gain almost all of their lost weight back.1 Etiologies of weight regain are multifactorial with possible causes including anatomical, medical, behavioral, and psychological factors. From an anatomical standpoint, it has been demonstrated that a dilated gastrojejunal anastomosis (GJA) and the presence of gastrogastric fistula (GGF) are associated with weight regain.3–6 Therefore, several endoscopic and surgical procedures targeting these anatomical factors have been developed for the treatment of this condition. Transoral outlet reduction (TORe) is an endoscopic approach for the treatment of weight regain. In 2013, a prospective, multicenter, randomized, blinded, sham-controlled trial (RESTORe trial) demonstrated that patients who underwent TORe experienced greater weight loss compared with those who underwent a sham procedure. This study therefore established level I evidence for TORe for the treatment of weight regain.7 In this trial, a superficial partial-
thickness endoscopic suturing device was used to reduce the GJA size. Since then, a newer fullthickness suturing device has become available and has been demonstrated to be superior at performing TORe compared with the older partial-thickness device.8 Additionally, during this period, technical details of the procedure, such as suture pattern and stitch location, have been further refined in order to optimize the outcome.9 With the current technique, argon plasma coagulation (APC) is performed circumferentially around the GJA before pursestring suturing.10 This ablation step is thought to be important as it ablates the mucosal layer in order to allow for submucosal to submucosal tissue apposition during the suturing step. Additionally, this initial step may also help minimize bleeding and enhance visualization during suturing. A previous meta-analysis demonstrated that the TORe technique that combines APC with suturing resulted in greater weight loss compared with that with suturing alone.11 In 2018, our group first described an adaptation of the current TORe technique. Specifically, instead of performing APC, modified endoscopic submucosal dissection (ESD) is performed circumferentially around the GJA to expose the submucosal and muscular layers before pursestring suturing.12 Although our prior report demonstrated that this novel TORe technique is technically feasible, its safety and efficacy profiles remain unknown. This study aims to assess the technical feasibility, safety and efficacy of the novel modified ESD-TORe procedure. Additionally, these outcomes in comparison to traditional APC-TORe are evaluated.
MATERIALS AND METHODS Study Design
This study was a retrospective study of prospectively collected data. The study was conducted at a single quaternary referral center with the bariatric center of excellence. Part I was an observational cohort study of all RYGB patients who underwent modified ESD-TORe for weight regain. The procedures were performed by a single attending endoscopist with fellow participation. Part II was a matched cohort study with one modified ESD-TORe patient being matched to 3 consecutive APC-TORe patients based on the pretreatment pouch and GJA sizes (Figure 1). In order to further control for potential unmatched confounders, a linear regression analysis was conducted to assess for significant predictors of %TWL at 12 months. Potential predictors were deemed a priori and included age, sex, body mass index (BMI), amount of weight regain, duration from RYGB and TORe technique (modified ESD-TORe versus APCTORe). Because the pretreatment pouch and GJA sizes were matched parameters, they were not included in the regression model. Collected data included age, sex, pre-RYGB weight, nadir weight, pre-TORe weight, height, procedural details, adverse events (AEs), and follow-up weights at 6 and 12 months. Procedures During modified ESD-TORe, a solution of normal saline solution or hetastarch mixed with methylene blue and epinephrine is first injected into the submucosal layer around the GJA. A mucosal incision is made circumferentially around the GJA. The submucosal space is then trimmed to widely expose the muscular layer circumferentially around the GJA. Any exposed staples or sutures are removed. This exposed muscular layer is approximately 1 cm wide extending from the GJA rim. After this step, APC is performed at the inner and outer margins of the trimmed mucosa. Subsequently, an endoscopic suturing device is used to place stitches through the exposed muscle around the GJA in a pursestring suture pattern before cinching over
a CRE balloon (Figure 1, Video 1). Details regarding the devices used for each step are reported in the results section. During APC-TORe, the margin of the GJA is first ablated using APC (forced APC, flow of 0.8 L/min and power of 30-70 watts). On average, the GJA rim is ablated until it is approximately 1 to 2 cm wide. After this step, an endoscopic suturing device is used to place stitches into the ablated area around the GJA in a pursestring suture pattern before cinching over a CRE balloon (Figure 1). Outcomes In part I, the primary outcome was the technical success rate of modified ESD-TORe, defined as successful circumferential mucosal incision and trimming to widely expose the submucosal layer before endoscopic suturing. A secondary outcome was the AE rate categorized as mild, moderate, severe, and fatal as per the American Society for Gastrointestinal Endoscopy (ASGE) lexicon. The AEs were considered mild when the procedure was aborted due to the event or when there was an unplanned admission of 3 nights or less. Moderate AEs referred to when there was an unplanned admission of 4 to 10 nights, intensive care unit (ICU) admission for 1 night, or when transfusion, repeat endoscopy, or interventional radiology procedure was required. Severe AEs were when there was an unplanned admission of greater than 10 nights, ICU admission for greater than 1 night and when a surgery was required to address the AE. Fatal AEs referred to when death occurred due to the event13. Another secondary outcome was weight loss efficacy of ESD-TORe at 6 and 12 months. This was reported using absolute weight loss (AWL), percent total weight loss (%TWL), change in body mass index (BMI), and a proportion of patients who achieved clinically significant weight loss, defined as %TWL of at least 5%.
In part II, the primary outcome was the amount of weight loss of modified ESD-TORe in comparison to the matched APC-TORe. Secondary outcomes included the AE rates of the modified ESD-TORe in comparison with the APC-TORe as well as the follow-up GJA size at 12 months. Of note, only patients with symptoms underwent a repeat endoscopy. In this subgroup of patients, the indication and endoscopic finding on follow-up endoscopy, including the GJA size, were recorded. Statistical Analysis Continuous variables were expressed as mean ± standard deviation (SD) unless otherwise specified. Categorical variables were expressed as proportions (%). The Student t-test and chisquared test were used to compare continuous and categorical variables, respectively. Univariable and multivariable linear regression analyses were used to determine predictors of %TWL at 12 months after TORe. Standardized β coefficients with standard errors (SE) were reported. A significant 2-sided P value was set at 0.05 or less. All statistical modeling was performed using SAS version 9.4 software (Cary, NC, USA). The study was approved by the Institutional Review Board.
RESULTS Part I: Modified ESD-TORe Nineteen consecutive patients who underwent ESD-TORe for weight regain were included. Baseline characteristics are shown in Table 1. Technical success rate was 100%. All cases were performed with the patient under general anesthesia (100%). Fellows participated in 15 out of 19 cases (78.9%). Average time
for the entire procedure was 104±26 minutes. Before suturing, modified ESD was performed circumferentially around the GJA using a combination of a needle knife and insulated tip knife (57.9%), a combination of a dual-J and insulated tip knife (36.8%) and mutiband mucosectomy (5.3%). After modified ESD, the mucosal rim around the dissected area was treated with APC in 16 out of 19 cases (84.2%). Subsequently, endoscopic suturing of the GJA was performed using a pursestring suture pattern (100%) with an average of 12 ± 4 bites per GJA and the final GJA size of 8.6 ± 0.9 mm. After GJA suturing, reinforcement stitches were placed in the pouch in 11 out of 19 cases (57.9%). After the procedure, 18 out of 19 cases (94.7%) were admitted for observation per our institution’s protocol. All patients (100%) were then prescribed open proton pump inhibitor, liquid sucralfate and liquid diet for 45 days. Adverse events occurred in 4 out of 19 cases (21.1%). Of these, 3 were mild AEs— esophageal erosions found at the end of the procedure, which required no intervention. The other one was moderate AE including severe abdominal pain, with follow-up endoscopy revealing erosions around the GJA. None of the AEs were classified as severe per the ASGE lexicon. Out of 19 patients, 3 were lost to follow-up. This represented a follow-up rate of 84.2%. At 6 and 12 months, patients lost 12.2 ± 6.2 kg (p<0.0001) and 11.8 ± 9.4 kg (p=0.02), respectively. This corresponded to 13.4 ± 6.6 % and 12.1 ±9.3% TWL at 6 and 12 months, respectively. The changes in BMI were -3.9 ± 2.6 kg/m2 and -3.9 ± 3.8 kg/m2 at 6 and 12 months, respectively. Proportions of patients who experienced at least 5% TWL at 6 and 12 months were 80% and 83.3%, respectively.
Part II: Comparison of Modified ESD-TORe with APC-TORe Matched Cohort Nineteen ESD-TORe patients were matched 1:3 to 57 APC-TORe patients based on pretreatment pouch and GJA sizes. Baseline characteristics of the 2 groups are shown in Table 2. Technical success rate was similar between the 2 techniques (100% vs 100%, p=1.00). Average time for the entire procedure was longer for ESD-TORe compared with APC-TORe (104 ± 26 minutes vs 71 ± 22 minutes, p=0.0005). Otherwise, other technical outcomes were similar between the 2 techniques (number of suture bites per GJA: 12 ± 4 bites vs 10 ± 4 bites [p=0.07]; final GJA size: 8.6 ± 0.9 mm vs 8.0 ± 1.2 mm [p=0.05]; and proportion of cases with pouch reinforcement stitches: 57.9% vs 43.9% [p=0.29] for ESD-TORe versus APC-TORe, respectively). At 6 and 12 months, patients who underwent modified ESD-TORe experienced greater weight loss compared with those who underwent APC-TORe. Specifically, at 6 months, the ESD-TORe and APC-TORe groups experienced 13.4 ± 6.6% TWL and 8.5 ± 3.4 % TWL (p=0.045), respectively. At 12 months, the ESD-TORe and APC-TORe groups experienced 12.1 ± 9.3% TWL and 7.5 ± 3.3% TWL (p=0.036), respectively (Figure 2). At 6 months, 80% and 66.7% of the ESD-TORe and APC-TORe patients experienced at least 5% TWL (p=0.33), respectively. At 12 months, 83.3% and 56.1% of the ESD-TORe and APC-TORe patients experienced at least 5% TWL (p=0.14), respectively. At 12 months, follow-up endoscopy was performed in 52.6% and 52.6% of the ESDTORe and APC-TORe groups, respectively (p=1.00). For the ESD-TORe group, the indications
for repeat endoscopy were abdominal pain/nausea/vomiting (60%) and inadequate weight loss (40%). For the APC-TORe group, the indications for repeat endoscopy were abdominal pain/nausea/vomiting (30%) and inadequate weight loss (70%). In the responder group, defined as those who underwent repeat endoscopy for abdominal pain/nausea/vomiting, the follow-up GJA size was 9.9 ± 3.7 mm and 15.8 ± 1.7 mm for the ESD-TORe and APC-TORe groups, respectively (p=0.02). In the nonresponder group, defined as those who underwent repeat endoscopy for inadequate weight loss, the follow-up GJA size was 14.0 ± 4.9 mm and 18.4 ± 5.1 mm for the ESD-TORe and APC-TORe groups, respectively (p=0.18). The adverse event rate was 21.1% for ESD-TORe and 8.77% for APC-TORe (p=0.15). The 4 AEs in the ESD-TORe group were esophageal erosions (x3; mild) and GJA erosions causing severe abdominal pain (x1, moderate) as mentioned above. The 5 AEs in the APCTORe group included intraprocedural bleeding treated with epinephrine injection (x1, mild), stuck needle due to surgical staple (x1, mild), esophageal tear treated with hemoclips (x1, mild), melena secondary to GJA ulcer (x1, moderate) and GJA stenosis treated with balloon dilation (x1, moderate). None of the AEs were graded as severe according to the ASGE lexicon. Regression Analysis On a univariable linear regression analysis, ESD-TORe (compared with APC-TORe), amount of weight regain and duration from RYGB were associated with greater %TWL at 12 months (Table 3). On a multivariable linear regression analysis, the ESD-TORe technique (compared with APC-TORe) remained a significant predictor of %TWL at 12 months after controlling for age, sex, BMI, amount of weight regain and duration from RYGB (β = 5.99, p = 0.02). Additionally,
BMI and the amount of weight regain at the time of TORe were significant predictors of %TWL at 12 months after controlling for the remaining confounders (β = -0.40, p = 0.01 and β = 0.12, p = 0.001, respectively) (Table 3).
DISCUSSION This study demonstrates that a modified ESD-TORe is technically feasible and appears safe and effective at treating weight regain after RYGB. Additionally, compared with traditional APC-TORe, this novel technique appears to be associated with greater weight loss and durability. In contrast to APC, ESD allows for a deeper level of tissue exposure. Traditionally invented for en bloc removal of gastrointestinal lesions that have not yet entered the muscular layer, ESD involves submucosal lifting before entrance into the submucosal layer in a controlled and well-visualized manner.14,15 In adapting this technique, we use an electrosurgical knife to dissect the submucosal layer around the GJA until the muscular layer is exposed. Doing so helps ensure that tissue apposition during the suturing step occurs at the muscular layer rather than the mucosal/submucosal layer. In contrast, APC applies a noncontact thermal method to ablate the mucosal tissue. Although the coagulation effect from APC likely reaches the upper portion of the submucosal layer, whether its effect is through the entire submucosal layer and reaches the muscular layer is unknown and is uncontrolled. Goulet et al16 previously demonstrated in an in vivo porcine colon model that muscularis propria injury occurs in 22% of lesions when 10 watts of APC is applied, which increases to 62% with 20 watts, 86% with 40 watts and 80% with 60 watts. Additionally, treatment duration also affects the depth of tissue injury with muscularis
propria injury occurring in 42% of lesions at 1 second, 66% at 3 seconds and 69% at 5 seconds per region of exposure.16 In our study, although the APC power setting remains constant (70-80 watts), treatment duration at each area varies. Furthermore, despite high wattage and long treatment duration, it is unlikely that the entire submucosal layer is affected unlike during the ESD technique. The concept of combining a mucosal denudation technique to endoscopic suturing to enhance weight loss was first introduced by our group in 2006. In this series, patients who underwent mucosal ablation before TORe experienced more weight loss than those that underwent endoscopic suturing alone.17 This is likely due to rapid healing of the epithelial cells within the mucosal layer in addition to little biochemical support from the epithelium itself. Wound healing within the GI tract may be divided into 3 phases—phase I: the lag phase (fibrin clot deposition), phase II: the proliferative phase (fibroblast proliferation to form immature collagen resulting in rapid gain in wound strength) and phase III: the maturation phase (collage reorganization and remodeling).18 Out of the 3 phases, phase I is considered the most critical period because this is when most wound dehiscence and leaks occur. This phase begins on day 1 and lasts for 3 to 4 days. It is characterized by contraction of blood vessels, platelet aggregation, and activation of the coagulation mechanism, which lead to fibrin clot deposition.19 Because fibrin clot and the epithelium itself provide little support for wound strength, the main wound support comes from functional sutures placed during the procedure.20 Therefore, without a denudation step, placement of stitches alone to appose the mucosa to the mucosa will likely result in rapid epithelial regeneration (which can take place in as little as 3 days) leading to suture loss.18 In contrast, when the deeper submucosal layer is injured/exposed, fibrous protein synthesis predominates and delayed mucosal healing occurs. This then allows the wound to heal
from the deeper submucosal layer, which is considered the strongest layer of the GI tract with the most significant suture-holding capabilities likely due to the vast connective tissue content. With modified ESD, a greater proportion of the submucosal tissue is exposed, stimulating more intense healing and tissue fusion. This likely leads to better suture retention, resulting in the GJA healing closer to the treated size (7-9 mm), a smaller follow-up GJA size at 1 year and greater weight loss. In this modified ESD technique, the circumferential incision is trimmed to widen the exposure to the muscular layer. This step not only allows the exposed area to serve as a suturing bed in a later step, but it also reveals any staples and/or foreign bodies. It has been demonstrated that foreign bodies impair wound healing and may serve as a source of wound infection. Therefore, one of the principles during surgical revision is to remove foreign bodies before wound closure. By applying this principle, the modified ESD technique is likely associated with better wound healing compared with the APC technique. This study has a few limitations. First, the study was conducted at a single bariatric center of excellence, which likely affects the generalizability of our findings. Additionally, the submucosal technique requires separate training than standard bariatric endoscopic work. Therefore, comfort and competence at performing the traditional APC-TORe technique, as well as experience in submucosal endoscopy, is recommended before advancing to this novel modified ESD-TORe technique. Another limitation includes the retrospective nature of the study. This study reports the use of a variety of devices as the procedure developed and new devices became available. The procedure is now typically performed with an injection needle, an electrosurgical knife, which allows for fluid injection, and an insulated tip knife. Additionally, our preferred injection solution is currently hetastarch mixed with methylene blue
and epinephrine. This is now fairly standardized but will likely continue to evolve. Additionally, some of the baseline characteristics of the 2 treatment groups differ, such as age and sex. Nevertheless, the 2 most important factors for weight regain, ie, the pouch and GJA sizes, were matched. Furthermore, a regression analysis was performed to control for any potential confounders of weight regain. With the regression analysis, the modified ESD-TORe technique remained a predictor of significant weight loss after the procedure. In conclusion, modified ESD-TORe is more effective than APC-TORe at treating weight regain after RYGB. Combining endoscopic tissue dissection with suturing may promote better wound healing leading to more effective and durable therapies beyond bariatric indications.
TABLES Table 1. Characteristics of RYGB patients who underwent ESD-TORe for weight regain. Characteristics Age (years) Sex (female, %) Pre-RYGB weight (kg) Nadir weight (kg) Weight at initial TORe (kg) BMI at initial TORe (kg/m2) Weight regain (% from maximal weight loss) Years from RYGB (years) Pre-TORe GJA diameter (mm) Pre-TORe pouch length (cm)
N = 19 45 ± 9 18 (95) 130.3 ± 30.3 70.6 ± 13.8 95.4 ± 20.0 36.5 ± 6.7 45.3 ± 18.9 11 ± 5 24.3 ± 7.3 4.3 ± 1.7
Table 2. Characteristics of RYGB patients who underwent modified ESD-TORe and APCTORe for weight regain. Characteristics Unmatched parameters
All (n = 76)
Modified ESD TORe (n = 19)
APC TORe (n = 57)
P value
Age (years) Sex (F, %) BMI (kg/m2) Weight regain (% of maximal weight loss) Years from RYGB (years) Matched parameters Pre-TORe GJA size (mm) Pre-TORe Pouch size (cm)
50 ± 12 66 (87) 37.5 ± 7.3 44.7 ± 30.6
45 ± 9 18 (95) 36.5 ± 6.7 45.3 ± 18.9
52 ± 12 38 (84) 37.9 ± 7.4 44.6 ± 33.7
0.01 0.02 0.46 0.93
9±4
11 ± 5
9±4
0.10
24.2 ± 7.0 4.1 ± 1.4
24.3 ± 7.3 4.3 ± 1.7
24.2 ± 7.0 4.0 ± 1.3
0.97 0.52
Table 3. Linear regression analyses of predictors of %TWL at 1 year after TORe. Univariable β Age -0.06 Male sex -5.95 BMI 0.002 Weight regain 0.08 Years from RYGB 0.52 ESD-TORe (vs APC-TORe) 6.66 Variables
S.E. 0.09 3.15 0.14 0.03 0.21 2.66
P value 0.50 0.07 0.99 0.02 0.02 0.02
Multivariable β Age -0.11 Male sex -0.54 BMI -0.40 Weight regain 0.12 Years from RYGB 0.37 ESD-TORe (vs APC-TORe) 5.99 Variables
S.E. 0.08 2.96 0.16 0.03 0.22 2.49
P value 0.16 0.86 0.01 0.001 0.10 0.02
FIGURE LEGENDS Figure 1. Transoral outlet reduction (TORe). A, Modified endoscopic submucosal dissection (ESD) before endoscopic suturing. B, Argon plasma coagulation (APC) before endoscopic suturing. Figure 2. Efficacy of modified ESD-TORe in comparison with APC-TORe at treating weight regain after RYGB. Patients were matched based on baseline GJA and pouch sizes. TWL: total weight loss. Video 1. Modified ESD-TORe for the treatment of weight regain after RYGB.
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13. Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71:446–54. 14. Hirao M, Masuda K, Asanuma T, Naka H, Noda K, Matsuura K, et al. Endoscopic resection of early gastric cancer and other tumors with local injection of hypertonic salineepinephrine. Gastrointest Endosc 1988;34:264–9. 15. ASGE Technology Committee, Maple JT, Abu Dayyeh BK, Chauhan SS, Hwang JH, Komanduri S, et al. Endoscopic submucosal dissection. Gastrointest Endosc 2015;81:1311– 25. 16. Goulet CJ, Disario JA, Emerson L, Hilden K, Holubkov R, Fang JC. In vivo evaluation of argon plasma coagulation in a porcine model. Gastrointest Endosc 2007;65:457–62. 17. Thompson CC, Slattery J, Bundga ME, Lautz DB. Peroral endoscopic reduction of dilated gastrojejunal anastomosis after Roux-en-Y gastric bypass: a possible new option for patients with weight regain. Surg Endosc 2006;20:1744–8. 18. Ellison GW. Wound healing in the gastrointestinal tract. Semin Vet Med Surg (Small Anim) 1989;4:287–93. 19. Peacock EE. Biology of wound repair. Life Sci 1973;13:I–IX. 20. Ravitch MM. Observations on the healing of wounds of the intestines. Surgery 1975;77:665–73.
Abbreviations TORe: transoral outlet reduction APC: argon plasma coagulation ESD: endoscopic submucosal dissection RYGB: roux-en-y gastric bypass ASGE: American Society for Gastrointestinal Endoscopy TWL: total weight loss GJA: gastrojejunal anastomosis BMI: body mass index GGF: gastrogastric fistula AE: adverse event ICU: intensive care unit AWL: absolute weight loss SD: standard deviation SE: standard error
S0016-5107(20)30094-8
DOI:
https://doi.org/10.1016/j.gie.2020.01.036
Reference:
YMGE 11952
To appear in:
Gastrointestinal Endoscopy
Received Date: 2 November 2019 Accepted Date: 16 January 2020
Please cite this article as: Jirapinyo P, de Moura DTH, Thompson CC, Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video), Gastrointestinal Endoscopy (2020), doi: https://doi.org/10.1016/j.gie.2020.01.036. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020 by the American Society for Gastrointestinal Endoscopy
Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video)
Authors: Pichamol Jirapinyo, MD, MPH1,2, Diogo T.H. de Moura, MD, PhD1,2,3, Christopher C. Thompson, MD, MSc1,2
1. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA 2. Harvard Medical School, Boston, MA, USA 3. Gastroenterology Department, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
Author Contributions: P.J.: Study design and concept, data collection, statistical analysis, manuscript preparation D.D.: Data collection C.C.T.: Study design and concept, critically reviewing the manuscript
Conflict of Interests: P.J. has received research support from Apollo Endosurgery, Fractyl and GI Dynamics, and has served as a consultant to Endogastric Solutions and GI Dynamics. D.D. has no conflict of interest. C.C.T. has served as a consultant for Boston Scientific and Apollo Endosurgery, has served as an advisory boards member for USGI Medical, has received research grant and support from USGI Medical, Apollo Endosurgery and GI Dynamics, and holds stock and royalties for GI Windows.
Corresponding Author: Christopher C. Thompson, MD, MSc Corresponding Author’s Institution: Brigham and Women’s Hospital Corresponding Author’s Address: Brigham and Women’s Hospital, Division of Gastroenterology, 75 Francis Street, Boston, MA 02115, USA Corresponding Author’s Telephone: +1-617-525-8266 Corresponding Author’s Fax Number: +1-617-264-6342 Corresponding Author’s E-mail: [email protected] Reprint Requests: Christopher C. Thompson, MD, MSc (Corresponding Author)
Funding: No financial or material support was received for this research project
Endoscopic submucosal dissection with suturing for the treatment of weight regain after gastric bypass: outcomes and comparison with traditional transoral outlet reduction (with video) ABSTRACT Background and Aims: Although traditional transoral outlet reduction (TORe) involves argon plasma coagulation (APC) before endoscopic suturing, modified endoscopic submucosal dissection (ESD) has also been used. This study aims to evaluate the safety and efficacy of modified ESD-TORe in comparison with traditional APC-TORe. Methods: This was a retrospective study of prospectively collected data of patients who underwent modified ESD-TORe and APC-TORe for weight regain after Roux-en-Y gastric bypass (RYGB). Our outcomes were (1) technical success, adverse events as categorized by the ASGE lexicon, and percent total weight loss (TWL) at 6 and 12 months, and (2) patients who underwent ESD-TORe were matched 1:3 based on gastrojejunal anastomosis (GJA) and pouch sizes to those who underwent APC-TORe. TWLs were compared. A linear regression was performed to control for any confounders. Results: Nineteen RYGB patients underwent ESD-TORe. Technical success rate was 100%. There were no severe adverse events. At 6 and 12 months, patients experienced 13.4±6.6 % and 12.1±9.3% TWL, respectively (p<0.05 for both). Nineteen ESD-TORe patients were also matched to 57 APC-TORe patients based on GJA and pouch sizes. At 12 months, the ESDTORe group experienced greater weight loss compared with the APC-TORe group (12.1±9.3% TWL versus 7.5±3.3 TWL (p=0.036)). On regression analysis, ESD remained a significant
predictor of %TWL at 12 months after controlling for age, sex, BMI, weight regain and years from RYGB (β=5.99, p=0.02). Conclusion: Combining endoscopic tissue dissection with suturing providers greater and more durable weight loss for patients with weight regain after RYGB.
INTRODUCTION Weight regain is a common adverse event of Roux-en-Y gastric bypass (RYGB). Despite its efficacy at inducing weight loss and improving obesity-related comorbidities, RYGB is associated with weight regain with the majority of patients gaining approximately 20% to 30% of the maximal weight they initially lost at 10 years.1,2 Additionally, it has been demonstrated that approximately one-third of RYGB patients gain almost all of their lost weight back.1 Etiologies of weight regain are multifactorial with possible causes including anatomical, medical, behavioral, and psychological factors. From an anatomical standpoint, it has been demonstrated that a dilated gastrojejunal anastomosis (GJA) and the presence of gastrogastric fistula (GGF) are associated with weight regain.3–6 Therefore, several endoscopic and surgical procedures targeting these anatomical factors have been developed for the treatment of this condition. Transoral outlet reduction (TORe) is an endoscopic approach for the treatment of weight regain. In 2013, a prospective, multicenter, randomized, blinded, sham-controlled trial (RESTORe trial) demonstrated that patients who underwent TORe experienced greater weight loss compared with those who underwent a sham procedure. This study therefore established level I evidence for TORe for the treatment of weight regain.7 In this trial, a superficial partial-
thickness endoscopic suturing device was used to reduce the GJA size. Since then, a newer fullthickness suturing device has become available and has been demonstrated to be superior at performing TORe compared with the older partial-thickness device.8 Additionally, during this period, technical details of the procedure, such as suture pattern and stitch location, have been further refined in order to optimize the outcome.9 With the current technique, argon plasma coagulation (APC) is performed circumferentially around the GJA before pursestring suturing.10 This ablation step is thought to be important as it ablates the mucosal layer in order to allow for submucosal to submucosal tissue apposition during the suturing step. Additionally, this initial step may also help minimize bleeding and enhance visualization during suturing. A previous meta-analysis demonstrated that the TORe technique that combines APC with suturing resulted in greater weight loss compared with that with suturing alone.11 In 2018, our group first described an adaptation of the current TORe technique. Specifically, instead of performing APC, modified endoscopic submucosal dissection (ESD) is performed circumferentially around the GJA to expose the submucosal and muscular layers before pursestring suturing.12 Although our prior report demonstrated that this novel TORe technique is technically feasible, its safety and efficacy profiles remain unknown. This study aims to assess the technical feasibility, safety and efficacy of the novel modified ESD-TORe procedure. Additionally, these outcomes in comparison to traditional APC-TORe are evaluated.
MATERIALS AND METHODS Study Design
This study was a retrospective study of prospectively collected data. The study was conducted at a single quaternary referral center with the bariatric center of excellence. Part I was an observational cohort study of all RYGB patients who underwent modified ESD-TORe for weight regain. The procedures were performed by a single attending endoscopist with fellow participation. Part II was a matched cohort study with one modified ESD-TORe patient being matched to 3 consecutive APC-TORe patients based on the pretreatment pouch and GJA sizes (Figure 1). In order to further control for potential unmatched confounders, a linear regression analysis was conducted to assess for significant predictors of %TWL at 12 months. Potential predictors were deemed a priori and included age, sex, body mass index (BMI), amount of weight regain, duration from RYGB and TORe technique (modified ESD-TORe versus APCTORe). Because the pretreatment pouch and GJA sizes were matched parameters, they were not included in the regression model. Collected data included age, sex, pre-RYGB weight, nadir weight, pre-TORe weight, height, procedural details, adverse events (AEs), and follow-up weights at 6 and 12 months. Procedures During modified ESD-TORe, a solution of normal saline solution or hetastarch mixed with methylene blue and epinephrine is first injected into the submucosal layer around the GJA. A mucosal incision is made circumferentially around the GJA. The submucosal space is then trimmed to widely expose the muscular layer circumferentially around the GJA. Any exposed staples or sutures are removed. This exposed muscular layer is approximately 1 cm wide extending from the GJA rim. After this step, APC is performed at the inner and outer margins of the trimmed mucosa. Subsequently, an endoscopic suturing device is used to place stitches through the exposed muscle around the GJA in a pursestring suture pattern before cinching over
a CRE balloon (Figure 1, Video 1). Details regarding the devices used for each step are reported in the results section. During APC-TORe, the margin of the GJA is first ablated using APC (forced APC, flow of 0.8 L/min and power of 30-70 watts). On average, the GJA rim is ablated until it is approximately 1 to 2 cm wide. After this step, an endoscopic suturing device is used to place stitches into the ablated area around the GJA in a pursestring suture pattern before cinching over a CRE balloon (Figure 1). Outcomes In part I, the primary outcome was the technical success rate of modified ESD-TORe, defined as successful circumferential mucosal incision and trimming to widely expose the submucosal layer before endoscopic suturing. A secondary outcome was the AE rate categorized as mild, moderate, severe, and fatal as per the American Society for Gastrointestinal Endoscopy (ASGE) lexicon. The AEs were considered mild when the procedure was aborted due to the event or when there was an unplanned admission of 3 nights or less. Moderate AEs referred to when there was an unplanned admission of 4 to 10 nights, intensive care unit (ICU) admission for 1 night, or when transfusion, repeat endoscopy, or interventional radiology procedure was required. Severe AEs were when there was an unplanned admission of greater than 10 nights, ICU admission for greater than 1 night and when a surgery was required to address the AE. Fatal AEs referred to when death occurred due to the event13. Another secondary outcome was weight loss efficacy of ESD-TORe at 6 and 12 months. This was reported using absolute weight loss (AWL), percent total weight loss (%TWL), change in body mass index (BMI), and a proportion of patients who achieved clinically significant weight loss, defined as %TWL of at least 5%.
In part II, the primary outcome was the amount of weight loss of modified ESD-TORe in comparison to the matched APC-TORe. Secondary outcomes included the AE rates of the modified ESD-TORe in comparison with the APC-TORe as well as the follow-up GJA size at 12 months. Of note, only patients with symptoms underwent a repeat endoscopy. In this subgroup of patients, the indication and endoscopic finding on follow-up endoscopy, including the GJA size, were recorded. Statistical Analysis Continuous variables were expressed as mean ± standard deviation (SD) unless otherwise specified. Categorical variables were expressed as proportions (%). The Student t-test and chisquared test were used to compare continuous and categorical variables, respectively. Univariable and multivariable linear regression analyses were used to determine predictors of %TWL at 12 months after TORe. Standardized β coefficients with standard errors (SE) were reported. A significant 2-sided P value was set at 0.05 or less. All statistical modeling was performed using SAS version 9.4 software (Cary, NC, USA). The study was approved by the Institutional Review Board.
RESULTS Part I: Modified ESD-TORe Nineteen consecutive patients who underwent ESD-TORe for weight regain were included. Baseline characteristics are shown in Table 1. Technical success rate was 100%. All cases were performed with the patient under general anesthesia (100%). Fellows participated in 15 out of 19 cases (78.9%). Average time
for the entire procedure was 104±26 minutes. Before suturing, modified ESD was performed circumferentially around the GJA using a combination of a needle knife and insulated tip knife (57.9%), a combination of a dual-J and insulated tip knife (36.8%) and mutiband mucosectomy (5.3%). After modified ESD, the mucosal rim around the dissected area was treated with APC in 16 out of 19 cases (84.2%). Subsequently, endoscopic suturing of the GJA was performed using a pursestring suture pattern (100%) with an average of 12 ± 4 bites per GJA and the final GJA size of 8.6 ± 0.9 mm. After GJA suturing, reinforcement stitches were placed in the pouch in 11 out of 19 cases (57.9%). After the procedure, 18 out of 19 cases (94.7%) were admitted for observation per our institution’s protocol. All patients (100%) were then prescribed open proton pump inhibitor, liquid sucralfate and liquid diet for 45 days. Adverse events occurred in 4 out of 19 cases (21.1%). Of these, 3 were mild AEs— esophageal erosions found at the end of the procedure, which required no intervention. The other one was moderate AE including severe abdominal pain, with follow-up endoscopy revealing erosions around the GJA. None of the AEs were classified as severe per the ASGE lexicon. Out of 19 patients, 3 were lost to follow-up. This represented a follow-up rate of 84.2%. At 6 and 12 months, patients lost 12.2 ± 6.2 kg (p<0.0001) and 11.8 ± 9.4 kg (p=0.02), respectively. This corresponded to 13.4 ± 6.6 % and 12.1 ±9.3% TWL at 6 and 12 months, respectively. The changes in BMI were -3.9 ± 2.6 kg/m2 and -3.9 ± 3.8 kg/m2 at 6 and 12 months, respectively. Proportions of patients who experienced at least 5% TWL at 6 and 12 months were 80% and 83.3%, respectively.
Part II: Comparison of Modified ESD-TORe with APC-TORe Matched Cohort Nineteen ESD-TORe patients were matched 1:3 to 57 APC-TORe patients based on pretreatment pouch and GJA sizes. Baseline characteristics of the 2 groups are shown in Table 2. Technical success rate was similar between the 2 techniques (100% vs 100%, p=1.00). Average time for the entire procedure was longer for ESD-TORe compared with APC-TORe (104 ± 26 minutes vs 71 ± 22 minutes, p=0.0005). Otherwise, other technical outcomes were similar between the 2 techniques (number of suture bites per GJA: 12 ± 4 bites vs 10 ± 4 bites [p=0.07]; final GJA size: 8.6 ± 0.9 mm vs 8.0 ± 1.2 mm [p=0.05]; and proportion of cases with pouch reinforcement stitches: 57.9% vs 43.9% [p=0.29] for ESD-TORe versus APC-TORe, respectively). At 6 and 12 months, patients who underwent modified ESD-TORe experienced greater weight loss compared with those who underwent APC-TORe. Specifically, at 6 months, the ESD-TORe and APC-TORe groups experienced 13.4 ± 6.6% TWL and 8.5 ± 3.4 % TWL (p=0.045), respectively. At 12 months, the ESD-TORe and APC-TORe groups experienced 12.1 ± 9.3% TWL and 7.5 ± 3.3% TWL (p=0.036), respectively (Figure 2). At 6 months, 80% and 66.7% of the ESD-TORe and APC-TORe patients experienced at least 5% TWL (p=0.33), respectively. At 12 months, 83.3% and 56.1% of the ESD-TORe and APC-TORe patients experienced at least 5% TWL (p=0.14), respectively. At 12 months, follow-up endoscopy was performed in 52.6% and 52.6% of the ESDTORe and APC-TORe groups, respectively (p=1.00). For the ESD-TORe group, the indications
for repeat endoscopy were abdominal pain/nausea/vomiting (60%) and inadequate weight loss (40%). For the APC-TORe group, the indications for repeat endoscopy were abdominal pain/nausea/vomiting (30%) and inadequate weight loss (70%). In the responder group, defined as those who underwent repeat endoscopy for abdominal pain/nausea/vomiting, the follow-up GJA size was 9.9 ± 3.7 mm and 15.8 ± 1.7 mm for the ESD-TORe and APC-TORe groups, respectively (p=0.02). In the nonresponder group, defined as those who underwent repeat endoscopy for inadequate weight loss, the follow-up GJA size was 14.0 ± 4.9 mm and 18.4 ± 5.1 mm for the ESD-TORe and APC-TORe groups, respectively (p=0.18). The adverse event rate was 21.1% for ESD-TORe and 8.77% for APC-TORe (p=0.15). The 4 AEs in the ESD-TORe group were esophageal erosions (x3; mild) and GJA erosions causing severe abdominal pain (x1, moderate) as mentioned above. The 5 AEs in the APCTORe group included intraprocedural bleeding treated with epinephrine injection (x1, mild), stuck needle due to surgical staple (x1, mild), esophageal tear treated with hemoclips (x1, mild), melena secondary to GJA ulcer (x1, moderate) and GJA stenosis treated with balloon dilation (x1, moderate). None of the AEs were graded as severe according to the ASGE lexicon. Regression Analysis On a univariable linear regression analysis, ESD-TORe (compared with APC-TORe), amount of weight regain and duration from RYGB were associated with greater %TWL at 12 months (Table 3). On a multivariable linear regression analysis, the ESD-TORe technique (compared with APC-TORe) remained a significant predictor of %TWL at 12 months after controlling for age, sex, BMI, amount of weight regain and duration from RYGB (β = 5.99, p = 0.02). Additionally,
BMI and the amount of weight regain at the time of TORe were significant predictors of %TWL at 12 months after controlling for the remaining confounders (β = -0.40, p = 0.01 and β = 0.12, p = 0.001, respectively) (Table 3).
DISCUSSION This study demonstrates that a modified ESD-TORe is technically feasible and appears safe and effective at treating weight regain after RYGB. Additionally, compared with traditional APC-TORe, this novel technique appears to be associated with greater weight loss and durability. In contrast to APC, ESD allows for a deeper level of tissue exposure. Traditionally invented for en bloc removal of gastrointestinal lesions that have not yet entered the muscular layer, ESD involves submucosal lifting before entrance into the submucosal layer in a controlled and well-visualized manner.14,15 In adapting this technique, we use an electrosurgical knife to dissect the submucosal layer around the GJA until the muscular layer is exposed. Doing so helps ensure that tissue apposition during the suturing step occurs at the muscular layer rather than the mucosal/submucosal layer. In contrast, APC applies a noncontact thermal method to ablate the mucosal tissue. Although the coagulation effect from APC likely reaches the upper portion of the submucosal layer, whether its effect is through the entire submucosal layer and reaches the muscular layer is unknown and is uncontrolled. Goulet et al16 previously demonstrated in an in vivo porcine colon model that muscularis propria injury occurs in 22% of lesions when 10 watts of APC is applied, which increases to 62% with 20 watts, 86% with 40 watts and 80% with 60 watts. Additionally, treatment duration also affects the depth of tissue injury with muscularis
propria injury occurring in 42% of lesions at 1 second, 66% at 3 seconds and 69% at 5 seconds per region of exposure.16 In our study, although the APC power setting remains constant (70-80 watts), treatment duration at each area varies. Furthermore, despite high wattage and long treatment duration, it is unlikely that the entire submucosal layer is affected unlike during the ESD technique. The concept of combining a mucosal denudation technique to endoscopic suturing to enhance weight loss was first introduced by our group in 2006. In this series, patients who underwent mucosal ablation before TORe experienced more weight loss than those that underwent endoscopic suturing alone.17 This is likely due to rapid healing of the epithelial cells within the mucosal layer in addition to little biochemical support from the epithelium itself. Wound healing within the GI tract may be divided into 3 phases—phase I: the lag phase (fibrin clot deposition), phase II: the proliferative phase (fibroblast proliferation to form immature collagen resulting in rapid gain in wound strength) and phase III: the maturation phase (collage reorganization and remodeling).18 Out of the 3 phases, phase I is considered the most critical period because this is when most wound dehiscence and leaks occur. This phase begins on day 1 and lasts for 3 to 4 days. It is characterized by contraction of blood vessels, platelet aggregation, and activation of the coagulation mechanism, which lead to fibrin clot deposition.19 Because fibrin clot and the epithelium itself provide little support for wound strength, the main wound support comes from functional sutures placed during the procedure.20 Therefore, without a denudation step, placement of stitches alone to appose the mucosa to the mucosa will likely result in rapid epithelial regeneration (which can take place in as little as 3 days) leading to suture loss.18 In contrast, when the deeper submucosal layer is injured/exposed, fibrous protein synthesis predominates and delayed mucosal healing occurs. This then allows the wound to heal
from the deeper submucosal layer, which is considered the strongest layer of the GI tract with the most significant suture-holding capabilities likely due to the vast connective tissue content. With modified ESD, a greater proportion of the submucosal tissue is exposed, stimulating more intense healing and tissue fusion. This likely leads to better suture retention, resulting in the GJA healing closer to the treated size (7-9 mm), a smaller follow-up GJA size at 1 year and greater weight loss. In this modified ESD technique, the circumferential incision is trimmed to widen the exposure to the muscular layer. This step not only allows the exposed area to serve as a suturing bed in a later step, but it also reveals any staples and/or foreign bodies. It has been demonstrated that foreign bodies impair wound healing and may serve as a source of wound infection. Therefore, one of the principles during surgical revision is to remove foreign bodies before wound closure. By applying this principle, the modified ESD technique is likely associated with better wound healing compared with the APC technique. This study has a few limitations. First, the study was conducted at a single bariatric center of excellence, which likely affects the generalizability of our findings. Additionally, the submucosal technique requires separate training than standard bariatric endoscopic work. Therefore, comfort and competence at performing the traditional APC-TORe technique, as well as experience in submucosal endoscopy, is recommended before advancing to this novel modified ESD-TORe technique. Another limitation includes the retrospective nature of the study. This study reports the use of a variety of devices as the procedure developed and new devices became available. The procedure is now typically performed with an injection needle, an electrosurgical knife, which allows for fluid injection, and an insulated tip knife. Additionally, our preferred injection solution is currently hetastarch mixed with methylene blue
and epinephrine. This is now fairly standardized but will likely continue to evolve. Additionally, some of the baseline characteristics of the 2 treatment groups differ, such as age and sex. Nevertheless, the 2 most important factors for weight regain, ie, the pouch and GJA sizes, were matched. Furthermore, a regression analysis was performed to control for any potential confounders of weight regain. With the regression analysis, the modified ESD-TORe technique remained a predictor of significant weight loss after the procedure. In conclusion, modified ESD-TORe is more effective than APC-TORe at treating weight regain after RYGB. Combining endoscopic tissue dissection with suturing may promote better wound healing leading to more effective and durable therapies beyond bariatric indications.
TABLES Table 1. Characteristics of RYGB patients who underwent ESD-TORe for weight regain. Characteristics Age (years) Sex (female, %) Pre-RYGB weight (kg) Nadir weight (kg) Weight at initial TORe (kg) BMI at initial TORe (kg/m2) Weight regain (% from maximal weight loss) Years from RYGB (years) Pre-TORe GJA diameter (mm) Pre-TORe pouch length (cm)
N = 19 45 ± 9 18 (95) 130.3 ± 30.3 70.6 ± 13.8 95.4 ± 20.0 36.5 ± 6.7 45.3 ± 18.9 11 ± 5 24.3 ± 7.3 4.3 ± 1.7
Table 2. Characteristics of RYGB patients who underwent modified ESD-TORe and APCTORe for weight regain. Characteristics Unmatched parameters
All (n = 76)
Modified ESD TORe (n = 19)
APC TORe (n = 57)
P value
Age (years) Sex (F, %) BMI (kg/m2) Weight regain (% of maximal weight loss) Years from RYGB (years) Matched parameters Pre-TORe GJA size (mm) Pre-TORe Pouch size (cm)
50 ± 12 66 (87) 37.5 ± 7.3 44.7 ± 30.6
45 ± 9 18 (95) 36.5 ± 6.7 45.3 ± 18.9
52 ± 12 38 (84) 37.9 ± 7.4 44.6 ± 33.7
0.01 0.02 0.46 0.93
9±4
11 ± 5
9±4
0.10
24.2 ± 7.0 4.1 ± 1.4
24.3 ± 7.3 4.3 ± 1.7
24.2 ± 7.0 4.0 ± 1.3
0.97 0.52
Table 3. Linear regression analyses of predictors of %TWL at 1 year after TORe. Univariable β Age -0.06 Male sex -5.95 BMI 0.002 Weight regain 0.08 Years from RYGB 0.52 ESD-TORe (vs APC-TORe) 6.66 Variables
S.E. 0.09 3.15 0.14 0.03 0.21 2.66
P value 0.50 0.07 0.99 0.02 0.02 0.02
Multivariable β Age -0.11 Male sex -0.54 BMI -0.40 Weight regain 0.12 Years from RYGB 0.37 ESD-TORe (vs APC-TORe) 5.99 Variables
S.E. 0.08 2.96 0.16 0.03 0.22 2.49
P value 0.16 0.86 0.01 0.001 0.10 0.02
FIGURE LEGENDS Figure 1. Transoral outlet reduction (TORe). A, Modified endoscopic submucosal dissection (ESD) before endoscopic suturing. B, Argon plasma coagulation (APC) before endoscopic suturing. Figure 2. Efficacy of modified ESD-TORe in comparison with APC-TORe at treating weight regain after RYGB. Patients were matched based on baseline GJA and pouch sizes. TWL: total weight loss. Video 1. Modified ESD-TORe for the treatment of weight regain after RYGB.
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Abbreviations TORe: transoral outlet reduction APC: argon plasma coagulation ESD: endoscopic submucosal dissection RYGB: roux-en-y gastric bypass ASGE: American Society for Gastrointestinal Endoscopy TWL: total weight loss GJA: gastrojejunal anastomosis BMI: body mass index GGF: gastrogastric fistula AE: adverse event ICU: intensive care unit AWL: absolute weight loss SD: standard deviation SE: standard error