Endoscopic clips are instruments designed to approximate tissues during gastrointestinal endoscopy. Metallic clips were first introduced with the primary objective of achieving hemostasis for gastrointestinal bleeding. Because of their ease of application and limited potential complications, endoscopists have proceeded to use them in a number of other interventions. The current use of these devices has expanded to nonhemostasis applications, including securing catheters to the gastrointestinal wall (feeding tubes, manometry probes, esophageal stents); marking devices to direct endoscopic, surgical, and radiological therapy (fluoroscopic localization to guide endoscopic stent placement); and for closure of gastrointestinal mucosal defects in multiple situations (such as defects resulting from endoscopic mucosal resection, GI tract perforations and fistulae) [9].

There are numerous types of endoclips available in the market, but the most commonly used are the QuickClip2™ (Olympus America Inc.—Center Valley, PA), the TriClip™ (Wilson-Cook Medical Inc.—Winston-Salem, NC), and the Resolution™ Clip (Microvasive Endoscopy—Boston Scientific Corp., Natick, MA) [10].

The experience with endoscopic clipping as a tool to treat postsurgical leaks and fistulae comes from several reports of clip application for closure of perforations of the esophagus, stomach, duodenum, and colon as a component of nonoperative management [7, 11–15]. In most of these case reports and series, the patients were treated with a combination of endoscopic clip placements, bowel rest, and antibiotics.

Endoscopically placed clips can be used to mechanically appose mucosal defects in the GI tract. Ideal endoclip characteristics would allow for good tissue apposition or ability to grasp with an ability to rotate as well as open and close several times. The goal of using this modality is to approximate two edges of a defect and to seal the defect with the clip. In order to achieve this, the clips must be placed exactly across the defect, holding the mucosa a few millimeters away from the edge. Whenever there is a small perforation or leak, the clips may be applied across the entire defect. When larger perforations are encountered, sequential clipping, starting from the edges toward the center, is recommended in order to successfully close the entire gap. Attempting to place the first clips in the center of larger defects may not successfully re-approximate the defect, since the mucosal edges may be further apart than the opening of the endoclips. See Fig. 9.1.

The literature defining the efficacy of clip application for postoperative leaks and fistulae is limited to case reports and small series. Rodella et al. reported in a series of seven patients with postoperative anastomotic leakages after gastric surgery that the endoscopic closure of leaks with clips was successful in 100% of the patients, with a median time of leakage closure after endoscopic clipping of 2.3 days with 71% of the patients (five out of seven) requiring only a single session of endoscopic clipping [16]. Although this study shows promising results, expert discussions as well as other small series have demonstrated poor results with endoclips as the sole therapy for leak or fistulae.

Another recommended technique is mucosal ablation of the edges of the defect prior to closure with endoclips. This ablation can be achieved with mechanical scrapping of the tissue or thermal ablation. The addition of this technique prior to mucosal apposition has been demonstrated to have a more durable closure in animal studies [17]. Other combined techniques have also been documented: Luigiano et al. described with successful results a combination technique using multiple endoclips tightened around the head with an endoloop to close a large defect [18].

Successful placement of clips across the defect is highly dependent on the endoscopist’s skills and the technique used. Raju et al. recommended several technical aspects to follow for clip closure of perforations and leaks. They recommended that the clip is maintained close to the tip of the endoscope and fired at 90° across the defect. In order to obtain the most tissue opposition, they recommend suctioning the excess insufflation as the clips are being applied. Lastly, confirmation of both mucosal edges engaged in the clip after closure but before deploying must be done to prevent difficulties of applying subsequent clips. Subsequent clips should be placed in an up-to-down or left-to-right fashion with decompression of lumen at the end of the procedure [19].

Closure of fistulae or leaks with endoclips may be difficult in the presence of severe edema or ulceration of the mucosa and underlying active inflammation with abscess formation. In these situations, clip closure should be considered after adequate drainage of any adjacent collection has been achieved.

A variety of adhesive substances can be applied locally during surgery or endoscopy for hemostasis, wound closure, or fistula repair. The main classes of tissue adhesives are cyanoacrylates (synthetic glues) and fibrin sealant (fibrin glue and thrombin) [20]. Several plug materials will also be discussed in this section.

Cyanoacrylate glues are widely used in GI endoscopy outside of the United States for control of bleeding and for closure of fistulae and anastomotic leaks. Several published case series have described the use of cyanoacrylate glues for closure of intractable enterocutaneous fistulae: Lee et al. reported a case series of three patients with successful obliterations of gastropleural, esophagopleural, and enterocutaneous fistulae obtained by endoscopic injection of Histoacryl^® without significant complications, suggesting that endoscopic Histoacryl^® injection is a good therapeutic alternative to surgical management for fistulae arising from the gastrointestinal tract [21].

Fibrin sealant is a two-component topical hemostat, sealant, and tissue adhesive consisting of fibrinogen and thrombin. Fibrinogen and thrombin have been used extensively in all surgical disciplines for tissue adhesion, suture support, hemostasis, wound care, and the sealing of body cavities [22].

Fibrin sealants (Tisseel, Evicel) are the only materials available in the United States today that have been approved by the Food and Drug Administration (FDA). On-label indications include hemostasis, colonic sealing and skin-graft attachment, and off-label indications include tissue or mesh adherence, lymphatic sealing, and fistula closure.

Fibrin glue is thought to close the fistula by using two major phases of physiologic coagulation. One phase is to act as a closing plug among tissues, resulting in quick adhesion. The other phase is to promote fibroblast cells into the fibrin glue and to grow granulation tissue, adsorbing various proteins such as fibronectin from surrounding tissue. Thus, the glue is absorbed within 4 weeks and replaced by connective scar tissue [20, 23].

Many studies have shown fibrin glue injections to be an effective treatment for gastrointestinal fistulae. Rabago et al. reported a series of 15 patients with postoperative digestive fistulae resistant to conservative treatment. In their series, after failure of conservative treatment, the fistulae were endoscopically located, and 2–4 mL of reconstituted fibrin glue was injected through a catheter. Complete sealing of fistulae was achieved in 86.6% of cases (87.5% of the low-output and internal fistulae and 55% of the high-output fistulae). The mean healing time was 16 days, and a mean of 2.5 sessions per patient were required. Follow-up, ranging between 2 months and 3 years, revealed only one of the sealed fistulae reopened. No complications were encountered. Overall mortality was 13.3% [24].

Kowalski et al. reported a retrospective review of 354 patients that underwent laparoscopic RYGB and identified eight patients who presented with a gastric leak (2.25%). Of these eight patients, three with unstable vital signs underwent exploratory laparotomy and drainage, and five clinically stable patients with a gastrointestinal leak were treated nonoperatively and subsequently underwent endoscopic injection of fibrin sealant into the leak. In the operative group, the mean duration of treatment between the identification of the gastric leak and closure was 24 days, with a mean length of stay of 66 days. Of the five patients in the endoscopic injection of fibrin sealant group, one required two injections within 11 days to achieve successful closure, and four underwent closure of the leak within 2 days after injection, with a mean length of stay of 13.5 days. No complications or recurrences developed in the group with endoscopic injection of fibrin sealant [25].

Only one single randomized trial has evaluated the use of fibrin glue for closure of enterocutaneous fistulae. Hwang et al. reported 13 patients with persistent low-output fistulae after 2–4 weeks of parenteral nutrition with conservative management. These patients were randomized into two groups: six patients were treated with endoscopic instillation of 15 mL of fibrin glue, and the fistulae closed within 4 days, while in the seven patients treated with continued conservative therapy, the fistulae closed after 13 days [23]. See Fig. 9.2.

Fibrin sealants have also been reported to be successful in filling residual cavities after leaks and to help close anastomotic dehiscence using intraluminal and submucosal instillation of the glue. In the case of a large defect, the use of a Vicryl plug or mesh for larger wounds followed by the application of fibrin glue may hasten the healing of anastomotic dehiscence [19].

Fistuloscopy is another helpful tool for the treatment of postsurgical chronic fistula. Fibrin glue has been used during fistuloscopy to treat these refractory fistulae and abscesses after upper gastrointestinal surgery. Wong et al. reported their experience with nine patients with postoperative fistulae and abscesses that were treated with therapeutic fistuloscopy. Three patients were suffering from duodenal stump fistula, three from gastrojejunostomy dehiscence after gastrectomy, two from gastro–pleuro–cutaneous fistula, and two from subphrenic abscesses. In their series, fistuloscopy was performed using a 5-mm choledochoscope under fluoroscopic guidance. Therapeutic procedures performed at the time of the fistuloscopy included mechanical debridement, irrigation, and sealing of fistula tract and abscess cavity with fibrin glue; all fistulae healed in an average of 18.7 days after the initial fistuloscopy. No complications related to this procedure occurred, and during a mean follow-up period of 12 months, no recurrent abscesses or fistulae developed [26].

Biomaterial plugs have also been used to treat gastrointestinal fistulae with a combination of endoscopy and percutaneous technique. Toussaint et al. described the management of enterocutaneous fistulae in patients in whom surgical or endoscopic treatments have failed, by insertion of Surgisis fistula plug in five patients with leaks after bariatric surgery. All patients had undergone previously failed surgical or endoscopic attempts to close the fistulae. The technique described by Toussaint entailed insertion of the fistula plug into the fistula tract by a “rendezvous” procedure, via both percutaneous and endoscopic routes. They observed that the leaks healed in four of the five patients (80%) [27].

Certain technical aspects must be taken into consideration when applying fibrin sealant for closure of perforations or leaks. The components of the fibrin glue—fibrinogen and thrombin—will quickly coagulate if a single lumen catheter is used for endoscopic applications. Dilution of the products or alternative injection has been attempted with limited effect. The use of a double lumen scope for dual catheter injection or use of a double lumen catheter—FibriJet (Micromedics—St Paul, Minnesota)—eliminates the premature coagulation of the components [28].

Endoscopic suturing has always been one of the significant limitations to the advancement of endoluminal surgery. Several suturing devices originally developed for endoscopic antireflux procedures have crossed over to be the first devices used in attempting to close fistulae and leaks. With the increasing interest in natural orifice transluminal endoscopic surgery (NOTES), multiple endoscopic closure and suturing devices have been developed by the endoscopic industry to facilitate closure of the portals of entry into body cavities. These devices have been investigated extensively in experimental animal models and have been shown to be successful in gastrostomy closure for NOTES [29, 30].

Currently, endoscopic clips are the only devices available on the market for closure of perforations, whereas suturing and stapling devices are not available for clinical use [19] (Table 9.2)

Most of the experience with the suturing devices comes from their previous use in humans for endoluminal gastroplication for the management of gastroesophageal reflux disease [31]. These devices have also been used with fairly good outcomes in patients after laparoscopic RYGB who required revisional procedures secondary to failure to lose weight due to dilation of the gastric pouch or gastrojejunal anastomosis [32, 33].