Endoscopic Therapies for the Dilated Gastrojejunostomy and Gastric Pouch: How to Achieve Weight Loss After the “Honeymoon” Is Over

by Daniel M. Herron, MD and Adheesh Sabnis, MD

Column Editor: Marc Bessler, MD

The following is the first column in a series that will appear quarterly in Bariatric Times. This column will investigate current research in the surgical and clinical aspects of obesity treatment, and will educate bariatric care professionals on the most up-to-date, concrete information in the field of obesity treatment.

The leadoff article in this series is written by Dr. Daniel M. Herron and Dr. Adheesh Sabnis, from the Section of Bariatric Surgery at the Mount Sinai Medical Center in New York City.

Dr. Marc Bessler, a leading authority in the surgical treatment of obesity, is the Column Editor of this series, and Surgical Director, New York-Presbyterian Hospital Center for Obesity Surgery, and Assistant Professor of Surgery, Department of Surgery, Director of Laparoscopic Surgery, Columbia University College of Physicians and Surgeons, New York, New York. He has spoken at numerous forums and has published on a variety of topics pertaining to surgical management of obesity.

Introduction
The first year after gastric bypass surgery is often considered to be the “honeymoon” period of near-effortless weight loss. Patients report a remarkable decrease in appetite, resulting in rapid weight loss without much need for strict dietary regulation. During the first postoperative month, it is not uncommon to measure weight loss of one pound per day or more. This rapid weight loss is temporary, however; by 8 to 12 months after surgery, the honeymoon is over and weight tends to stabilize.

The precise mechanism for this effect is unknown and is likely multifactorial, but many bariatric surgeons feel that it is a result of gradual tissue remodeling and dilatation of the gastrojejunostomy (stoma) or stomach pouch. As the pouch dilates, the gastric bypass patient will tend to increase the quantity of food eaten; as the anastomosis expands, the pouch will empty more quickly. While these processes typically lead to weight stabilization,hey may also result in the regain of a substantial portion of the initial excess weight loss.

Generally, the diagnostic workup for weight regain after gastric bypass is straightforward. An upper GI series and upper endoscopy will identify whether the surgical anatomy is intact. If a gross anatomic defect, such as a gastro-gastric fistula, is identified, the appropriate surgical intervention usually involves restoration of the original anatomy. The bariatric surgeon is presented with a conundrum, however, when the anatomy is found to be essentially normal except for a dilated gastrojejunostomy or slightly enlarged pouch.

Surgical revision is certainly effective in restoring the original dimensions of the pouch or anastomosis. Either via an open or laparoscopic approach, the pouch can be restapled, the original gastrojejunostomy excised, and a new anastomosis fashioned using stapled or handsewn technique. Such an approach can present considerable technical challenges, however, due to scarring and adhesion formation between the anastomosis, liver, stomach, and surrounding omentum. Additionally, a fresh staple line or anastomosis presents the possibility of a number of major, potentially life-threatening complications, including anastomotic leak and staple-line bleed.

These concerns have stimulated the investigation of endoscopic-based therapies for the treatment of the dilated pouch and gastrojejunostomy. By approaching this anatomy transorally, the morbidity and mortality associated with the intra-abdominal dissection can be eliminated. Several different endoscopic pouch and stoma revision therapies have been investigated to date.

Endoscopic Sclerotherapy
The first endoscopic therapy aimed at reduction of stoma diameter utilized endoscopic injection of a sclerotherapy agent into the area of the stoma. In 2003, Spaulding reported on her experience using multiple endoscopic injections of 1mL sodium morrhuate five percent to induce scarring and thereby reduce stomal diameter.1 Serial injections were performed around the circumference of the stoma until its diameter was reduced to approximately 10mm. If this reduction could not be attained with a single endoscopy, then the procedure was repeated up to two additional times.

In this initial report, Spaulding treated 20 patients. An average of 1.3 treatments per patient was required. The procedure was found to be safe overall with no major complications, such as bleeding, perforation, or stenosis. Minor complications included immediate epigastric pain that occurred in one-third of patients and resolved within four hours. Occasional vomiting was noted in two patients during the first two weeks postoperatively.

In 15 of the 20 patients (75%), the endoscopic treatment was considered to be successful, resulting in a mean weight loss of 5.8kg at two months post-procedure and 6.8kg at six months. Interestingly, the five patients who did not lose weight after the procedure had stomas that were identical in size to those who did (10.0 mm vs. 9.8). All patients noted an increase in satiety after eating during the first two weeks after therapy. In this initial study, however, no long-term data beyond six months were reported.

In October, 2007, Spaulding published a follow-up study looking at all patients treated with the technique from 1999 to 2006.2 One-year follow-up data were available for 32 of these patients. More than half of those treated (56%) lost weight during the 12-month follow-up period. In one-third (34%) of patients, weight stabilized, while nine percent continued to gain weight.

Catalano, et al., also reviewed their experience with this technique over a three-year period and published their results in 2007.3 Twenty-eight patients underwent a mean of 2.3 treatment sessions. Successful endotherapy was obtained in 18 patients. In the successful group, stoma diameter was reduced from a mean of 16.1mm pre-procedure to 10.4mm afterward, a decrease of 5.7mm diameter. In the unsuccessful group, the mean pre-procedure diameter was larger (18.7mm) and the therapeutic change smaller (1.9mm decrease). Overall, patients in the “success” group lost a mean of 26kg after endoscopic therapy while those in the unsuccessful group lost 8.8kg.

As in the earlier studies, complications were relatively minor. Three-quarters of patients noted post-injection pain during the first post-procedure day, and 10 patients were found to have shallow circumferential ulcers at the treatment site during follow-up endoscopy. Interestingly, one patient developed enough scarring from therapy to form a stomal stricture and required endoscopic dilatation to treat recurrent nausea and vomiting.

Endoscopic Suture Placement
Although endoscopic sclerotherapy is technically straightforward to perform, it relies on a relatively unpredictable process—namely the formation of scar tissue at the gastrojejunostomy—to generate its results. The endoscopic placement of traditional sutures within the pouch or at the gastrojejunostomy offers the theoretical appeal of greater diameter reduction and more predictable results.

An early investigation into this technique was reported by Schweitzer in 2004.4 He utilized the Wilson-Cook Endoscopic Suture Device (ESD®, Wilson-Cook, Winston-Salem, North Carolina) to plicate the stoma in four gastric bypass patients. Although the procedure was successfully completed in all four patients, the results did not appear to be durable: One of the patients ruptured the suture by overeating at Thanksgiving dinner. No weight loss outcomes data were reported in this study.

The first report of endoscopic suture reduction of dilated gastric bypass gastrojejunostomy with weight loss follow-up was published by Thompson, et al., in 2006.5 In the study, the investigators used the Bard EndoCinch™ device (CR Bard, Inc., Murray Hill, New Jersey) to reduce the gastrojejunostomy of eight gastric bypass patients with a measured stomal diameter greater than 20mm.

The EndoCinch device was originally created to enable the endoluminal gastroplication procedure for the treatment of reflux. In this study, the device was not placed at the esophagogastric junction—where it would be utilized to create an anti-reflux valve—but rather at the gastrojejunostomy. Tissue at the stoma was aspirated into the device and the first portion of the stitch was placed. The device was then removed and reloaded, then reinserted so that the second bite could be taken. The procedure was repeated as needed until a total of 1 to 3 such suture appositions were formed perorally. Upon completion of the procedure, the anastomoses were measured. After recovering from the general anesthetic, patients were discharged home the same day.

Using this approach, Thompson’s group was able to reduce stomas from a mean diameter of 25mm pre-procedure to 10mm afterwards. The mean duration of the procedures was 98 minutes. During the follow-up period that averaged four months, 6 of the 8 patients lost weight. Four patients reported a durable improvement in satiety afterward. Three patients who felt a temporary improvement underwent a second treatment.

As with endoscopic sclerotherapy, patients had minimal side effects. Three patients noted nausea and emesis during the first few days after the procedure. Remarkably, only four complained of a sore throat afterwards.

The Bard device is currently being evaluated in the RESTORe study (Randomized Evaluation of Endoscopic Suturing Transorally for anastomotic Outlet Reduction), a randomized, double-blinded, controlled efficacy trial for patients with inadequate weight loss following Roux-en-Y gastric bypass surgery.6 The study includes subjects with a BMI between 30 and 50 who are six or more months post-gastric bypass with inadequate weight loss or weight regain and a dilated gastrojejunostomy. The study, which commenced in November, 2006, is expected to enroll 230 patients and conclude in 2008.

Other endoscopic suturing devices are currently under development. “Spiderman” is an endoscopic suturing device developed by Ethicon Endosurgery that uses a curved needle that rides along a semicircular track.7 Using a ratchet mechanism, the needle is advanced beyond the track through tissue. After the bite is taken, the needle re-enters the distal side of the track. By repositioning the device and repeating the process, running sutures can be placed. The device has potential for use as an endoscopic bariatric revisional device or for performing a primary endoscopic bariatric procedure. A PubMed search using the term endoscopic suturing in November, 2007, did not reveal any instances of the device being used clinically.

Endoscopic T-Fastener Placement
Similar to endoscopic sutures, endoscopic T-fasteners can also be used to reduce a dilated gastric stoma after gastric bypass. T-fasteners, similar in function to those used in the garment industry, offer the potential advantage of being quicker and simpler to deploy than other fasteners. EndoGastric Solutions currently markets a device under the trade name StomaphyX® (Figure 1), which can deploy polypropylene T-fasteners endoscopically (EndoGastric Solutions, Redmond, Washington).

The device has an internal channel that allows a flexible endoscope to pass through it. After the device is passed transorally, the endoscope is withdrawn into the device to view an internal chamber with a side opening. Suction is applied to the chamber, drawing the stomach wall inward through the opening. A T-fastener is then fired through the gastric wall to approximate the tissue (Figure 2). The device can be reloaded and refired multiple times with a single transoral insertion. By rotating and refiring the device, multiple tissue approximations can be created to potentially decrease gastric pouch or stoma size.

Although no data are yet available regarding the use of these T-fasteners for gastric bypass stoma or pouch revision, some data exist for a related device marketed by the same company. The EsophyX® uses tissue fasteners to create an endoluminal plication for the treatment of gastroesophageal reflux. Early data in this application suggest that the fasteners are both safe and effective in achieving gastric tissue apposition. Porcine studies demonstrate that smooth muscle hypertrophy persists after removal of mucosal sutures used in gastroplication at the gastroesophageal junction.8 A similar phenomenon might bolster the durability of this or any other endoscopic plication technique.

Although non-absorbable material is used for the T-fasteners, concern still exists regarding the permanence of the tissue apposition. Fasteners may potentially erode through the gastric wall or become dislodged. Torquati and Richards’s review of endoluminal gastroesophageal reflux disease (GERD) treatments found grade 1b and 2b evidence supporting the hypothesis that full-thickness plications are effective in decreasing acid exposure in the distal esophagus and GERD symptoms.9 Whether similarly supportive evidence will be found for stoma reduction with T-fasteners after gastric bypass remains to be determined.

Endoscopic Anchor Placement
A commonly voiced objection to the use of sutures or T-fasteners at the gastrojejunostomy site relates to the durability of the repair. Many investigators are concerned that simple sutures or T-fasteners do not have enough purchase on the gastric tissue to keep from pulling out when stressed. This concern is supported by the patient in Schweitzer’s study who ruptured the plication suture by overeating. The issue of tissue pull-through is addressed by devices that employ tissue anchors instead of simple sutures. Tissue anchors, analogous to pledgeted sutures, spread their holding strength over a substantially larger surface area and may thus be more resistant to pull-through.

This hypothesis is supported by a 2006 study by Seaman, et al., comparing the use of T-fasteners, rigid star-shaped anchors, and pliable basket anchors.10 The investigators placed the different types of fasteners across stomach folds in a live pig model. Follow-up endoscopy was performed at 2, 4, and 9 weeks, and the animals were ultimately sacrificed at 4 or 9 weeks. T-fasteners were noted to pull through the mucosa earliest, at two weeks. Basket anchors provided the most durable tissue apposition, with 78 percent in place after 4 or 9 weeks.

USGI Medical (San Clemente, California) has created a multi-tool system to allow placement of such basket-type anchors via a transoral endoscopic approach. Their Transport™ device is a multi-lumen endoscopic access device that facilitates gastric access (Figure 3). Appearing superficially like a flexible endoscope, the device can be placed through the mouth, steered with an endoscope-like control mechanism, and locked into position once the tip is located near the stoma. Four operating lumens range in size from 4 to 7mm in diameter (Figure 4). A 5mm flexible endoscope (GIF-N180, Olympus America, Inc., Center Valley, Pennsylvania) is inserted through the 6mm lumen to provide visualization.

The USGI g-Prox™ anchor placement device is a flexible endoscopic tool with large grasping jaws and a curvable anchor deployment tube that can be inserted through the main 7mm operating lumen of the Transport™ (Figure 5). After tissue is grasped in its toothed jaws, the needle-tipped deployment tube is penetrated through the tissue and a basket-type tissue anchor is deployed on one side of the tissue (Figure 6 and Figure 7). After the needle is withdrawn, a second anchor is deployed and the connecting suture tightened to achieve tissue plication.

With two flexible mesh baskets connected by a permanent braided suture, the tissue anchor functions like a pledgeted suture. By placing multiple tissue plications around the circumference of the stoma, its diameter is reduced. The steerable tip of the Transport™ device allows the anchors to be placed in a longitudinal or transverse orientation, which in turn allows plications to be created at the gastojejunostomy or in the gastric pouch wall to achieve a pouch volume reduction.

This author (Herron) presented the results of an animal study using the device at the SAGES 2007 meeting in Las Vegas.11 By placing 4 to 6 anchors around the stoma in an explanted stomach model, it was possible to reduce diameter by an average of 7.8mm. Placement of anchors throughout the stomach pouch wall resulted in a pouch volume reduction of almost 30 percent. Similar results were achieved in an in-vivo model as well.

The USGI device is currently being evaluated in humans in the Restorative Obesity Surgery Endoscopic (ROSE) trial.12 The feasibility study, formally titled, “Endoscopic stoma and pouch reduction in patients with weight regain following Roux-en-Y bypass surgery,” includes patients two or more years out from their operation who were initially successful in weight loss but have regained 15 percent or more of their lost weight. They must meet BMI criteria for bariatric surgery (BMI above 40 or above 35 with comorbidity) and have a pouch greater than 5cm in length and a gastrojejunostomy of more than 20mm diameter as measured endoscopically.

Under general anesthesia, the Transport and g-Prox devices are inserted into the stomach pouch and tissue plications created at the stoma and gastric pouch wall. After a brief observation period, patients are discharged and weight is carefully monitored. Although formal results have not yet been published, early data suggest that this technique is feasible and effective in achieving short-term weight loss loss. Longer-term investigation is underway.

Conclusion
In the past, there were only two therapeutic options available to treat the failed gastric bypass: Medical/dietary therapy or a revisional bariatric operation. While medical/dietary therapy is attractive because of its safety, the results are generally disappointing. Surgical intervention, while effective, presents substantial technical challenges owing to the adhesions that form between the gastrojejunostomy and surrounding tissue. Because of the difficult surgical dissection and the substantial morbidity and non-zero mortality of revisional surgery, many bariatric surgeons have been reluctant to perform such revisional interventions.

The endoscopic approach to stoma and pouch reduction may allow for a similar therapeutic result to be achieved without the need for a transabdominal procedure. By avoiding an intra-abdominal dissection, considerable morbidity may be prevented. Preliminary data from endoscopic therapy suggest that reasonable one-year results may be obtained in some patients.

Additionally, it has been shown that procedures can be repeated as needed if efficacy or durability is not achieved with the initial intervention. Although more technically demanding to perform than sclerotherapy, endoscopic suturing or tissue anchor procedures offer the potential for a more substantial stoma reduction and more durable results.

The technology to place endoscopic sutures and tissue anchors is advancing at a rapid pace. Despite the fact that endoscopic suturing is still in its infancy, the short-term data are encouraging, and it seems likely that such techniques will continue to evolve and increase in popularity. Continued research will be necessary to develop new endoscopic revision techniques, and to confirm efficacy and durability of endoscopic interventions beyond 6 to 12 months.

Disclosure
Dr. Herron has served as a scientific advisor to USGI Medical.

Author Note
Photos courtesy of USGI Medical and EndoGastric Solutions.

References
1. Spaulding L. Treatment of dilated gastrojejunostomy with sclerotherapy. Obes Surg 2003;13:254–7.
2. Spaulding L, Osler T, Patlak J. Long-term results of sclerotherapy for dilated gastrojejunostomy after gastric bypass. Surg Obes Relat Dis 2007 Oct 10 [Epub ahead of print].
3. Catalano MF, Rudic G, Anderson AJ, Chua TY. Weight gain after bariatric surgery as a result of a large gastric stoma: endotherapy with sodium morrhuate may prevent the need for surgical revision. Gastrointest Endoscop 2007;66(2):240–5.
4. Schweitzer M. Endoscopic intraluminal suture plication of the gastric pouch and stoma in postoperative Roux-en-Y gastric bypass patients. J Laparoendosc Adv Surg Tech 2004;14(4):223–6.
5. 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.
6. Website ClinicalTrials.gov, a service of the U.S. National Institutes of Health. www.clinicaltrials.gov/ct2/show/NCT00394212. Access date: December 7, 2007.
7. Swain P. Endoscopic suturing: now and incoming. Gastrointest Endoscopy Clin N Am 2007;17:505–20.
8. Cadière GB, Rajan A, Rqibate M, et al. Endoluminal fundoplication (ELF)—Evolution of Esophyx™, a new surgical device for transoral surgery. Minim Invasive Ther 2006;15(6):348–55.
9. Torquati A, Richards WO. Endoluminal GERD treatments: critical appraisal of current literature with evidence-based medicine instruments. Surg Endosc 2007;21(5):697–706. Epub 2007 Mar 31.
10. Seaman DL, Gostout CJ, de la Mora Levy JG, Knipschield MA. Tissue anchors for transmural gut-wall apposition. Gastrointest Endosc 2006;64(4):577–81.
11. Herron DM, Birkett DH, Thompson CC, et al. Gastric bypass pouch and stoma reduction using a transoral endoscopic anchor placement system: A feasibility study. Surg Endosc; Accepted for publication 29 August 2007, in press.
12. Website ClinicalTrials.gov, a service of the U.S. National Institutes of Health. www.clinicaltrials.gov/ct2/show/NCT0041148. Access date: December 7, 2007.

Category: Emerging Technologies, Past Articles