Advances in endoscopic closure techniques for endoscopic full-thickness resection

Abstract

Recently, the continuous advancement of endoscopic technology has led to the widespread application of endoscopic full-thickness resection (EFTR) in clinical practice. The crucial aspect of EFTR is the successful closure of the wound. Initially, endoscopic clip and nylon thread suturing was employed; subsequently, a variety of innovative suturing techniques based on that have been developed, driving ongoing technological innovation in this field. Given the unique characteristics of EFTR, an increasing number of specialized endoscopic suturing devices are being explored. This article aims to systematically evaluate the efficacy, limitations, and clinical applicability of current endoscopic closure techniques for EFTR-induced defects.

Key Words: Endoscopic full-thickness resection; Endoscopy closure; Endoloop; Endoscopic clip closure technique; Closing devices

Core Tip: Endoscopic full-thickness resection (EFTR) has emerged as a valuable technique for treating subepithelial lesions. Successful closure of EFTR-induced defects is crucial for minimizing complications. Endoscopic clip suturing has evolved into advanced methods such as over-the-scope clips, endoloop-assisted techniques, and novel suturing devices like OverStitch, Full-Thickness Resection Device (FTRD), OverStitch, etc. This review highlights the latest advancements in EFTR closure techniques, emphasizing their efficacy, limitations, and clinical applications to guide optimal treatment selection.

INTRODUCTION

Subepithelial lesions (SELs) are elevated lesions originating from the muscularis mucosa, submucosa, or muscularis propria, and even also include extraluminal lesions[1]. The most common type of SEL is gastrointestinal stromal tumor[2,3], accounting for approximately 60% of cases[4]. These lesions exhibit a malignant potential[5], and guidelines recommend[4-6] resection for lesions with a diameter ≥ 2 cm. Other lesions, such as lipomas or leiomyomas, should also be treated if they cause symptoms such as obstruction or bleeding, or the patient strongly desires treatment.

Previous treatments for SELs typically involved local surgical resection, which is expensive and associated with slow recovery[7]. Endoscopic techniques offer a more minimally invasive and effective alternative. The safety and efficacy of submucosal tunnel endoscopic resection, as well as endoscopic submucosal dissection (ESD) and endoscopic submucosal excavation, have been reported[8,9]. However, as SELs often originate in the muscularis propria, achieving complete resection remains challenging. Endoscopic full-thickness resection (EFTR), an extension of ESD, could resect the lesion along with the involved gastrointestinal wall. This technique improves the rate of complete lesion resection, gradually becoming a treatment option for refractory mucosal and submucosal lesions[10]. Nonetheless, EFTR causes "iatrogenic perforation", making successfully closing the wound be a critical aspect of this technique. As EFTR gains wider clinical adoption, the need for effective and reliable suturing techniques has become more apparent. Various suturing methods have been proposed and developed to address this challenge, each with its own advantages and limitations. This article aims to provide a comprehensive review of the current suturing techniques employed in EFTR, focusing on their efficacy, safety profiles, and clinical applicability.

ENDOSCOPIC CLIP CLOSURE TECHNIQUE

Metallic clip closure

Metallic clip suturing is currently the foremost used method for closing gastrointestinal wall defects in clinical practice, characterized by its ease of operation and relatively low cost[11-13]. If the defect diameter is smaller than the opening size of the metallic clip, direct closure can be achieved by approximating the wound edges from the proximal or distal side toward the center. In cases where the defect diameter slightly exceeds the clip opening, suction can be applied to reduce the wound size before closure[14]. For larger defects, omental fat around the wound could be secured to the edges of the defect, then the metallic clips were used to close the defect[14,15]. Studies have demonstrated that the wound < 2 cm can be successfully closed with metallic clips; however, their effectiveness diminishes as the defect area increases[16].

To further enhance the closure efficacy of metallic clips, the "interrupted suturing" technique has been introduced recently. This approach involves making a full-thickness incision around the lesion and immediate suturing of the wound with metallic clips, followed by alternating lesion dissection and wound closure. The “interrupted suturing” has successfully closed EFTR wounds with a maximum diameter of approximately 3.0 cm, which not only reduces operative time compared to traditional suturing techniques but also lowers the incidence of postoperative complications.

Additionally, there is an “internal traction-assisted suspended closure” technique that has also demonstrated promising outcomes. After full-thickness resection, a rubber band is used to apply internal traction from the proximal or distal end of the wound to the gastric wall, shaping the defect into a linear configuration, and metallic clips are then applied for closure. This technique has successfully sutured defects averaging 3.25 cm in length (ranging from 2.5 to 9.0 cm) and 2.8 cm in width (ranging from 1.8 to 6.0 cm)[17], with no adverse events reported postoperatively.

In conclusion, metallic clips can effectively suture the EFTR defect. When the defect diameter is less than 2 cm, simple metallic clips can be used for suture directly; when the wound is larger, omental patching, interrupted suturing, and internal traction-assisted suspended closure can be used.

It is important to note that metallic clips were initially designed for hemostasis during endoscopic procedures, providing effective closure for the mucosal and submucosal layers; however, the superficial bite limits the application in the muscularis propriae and serosa[18], thereby increasing the risk of delayed complications when used alone[19].

Over-the-scope clip closure system

Over-the-scope clip (OTSC) is an externally mounted metallic clip affixed to the distal end of the endoscope. During closure, surrounding tissue is captured into the transparent cap using twin graspers or an endoscopic anchor, then the OTSC is released to close the wound. It is currently believed that a single OTSC can effectively close defects smaller than 2 cm[20-22], with a maximum capability of 3 cm[23]. The OTSC can firmly grasp the entire gastrointestinal wall[24], offering distinct advantages over conventional metallic clips, particularly in full-thickness closure. Previous studies have confirmed the safety and efficacy of OTSC in EFTR wound closure[25,26]. Although OTSC has unique advantages in EFTR, it still has certain limitations: (1) OTSC is mostly used for the closure of wounds with a diameter of less than 3 cm, and it is still challenging for the closure of wounds with larger or irregular defects; (2) Precise placement of the OTSC requires a high technical level, and the improper application may lead to postoperative complications[27,28]; (3) Placement of the OTSC within the narrow lumen of the gastrointestinal tract may result in obstruction; and (4) The OTSC cannot be moved.

Novel endoscopic anastomosis clip

The novel endoscopic anastomosis clip is a detachable device based on the OTSC, which can be removed via a tying wire and a pulling ring. Its removable feature allows for timely adjustments if the placement is unsatisfactory. Animal experiments[29] and early clinical trials[30] have initially proved that it is safe and effective to suture full-thickness wounds with the novel endoscopic anastomosis clip, but there is a lack of further verification.

ENDOLOOP CLOSURE TECHNIQUE

Grasp-and-loop closure

The grasp-and-loop closure method utilizes only an endoloop and a pair of foreign body forceps. After full-thickness resection of the lesion, the foreign body forceps and endoloop are inserted into a double-channel endoscope. The forceps are threaded through the center of the endoloop, allowing the edges of the gastric wall defect to be grasped and lifted. The endoloop is then pushed down to the base of the defect and tightened, effectively suturing the wound[31].

Studies have revealed that the grasp-and-loop closure method is feasible and effective for closing full-thickness defects, with an average suturing time of 9.4 minutes[32], and no serious postoperative complications are reported. Several advantages of this technique have been highlighted: (1) Pushing or pulling the forceps during closure can provide a good surgical field of view; (2) Retracting the everted gastric wall back into the cavity minimizes damage to adjacent extramural structures during closure; and (3) Since the ligation occurs at the base of the gastric wall defect, it should be firmer without any gap compared with other techniques using clips.

Metallic clip-assisted endoloop suture

Kissing suture: After full-thickness resection, a metallic clip carrying an endoloop is placed at the edge of the wound defect, while another metallic clip is positioned on the opposite side to anchor the endoloop. By tightening the endoloop, the margins are brought together, effectively converting a larger defect into two narrower linear defects. Previous studies have proved the safety and effectiveness of this method[33,34]. Notably, some wounds exceeded 5 cm, with the largest measuring approximately 7 cm. Thus, the kissing suturing technique offers specific advantages for closing larger defects.

Endoscopic purse-string suture: Endoscopic purse-string suture (EPSS) involves inserting an endoloop onto the margin of the full-thickness defect with multiple metallic clips. The closure is achieved by tightening the endoloop, while ensuring that the metal clips span the full thickness of the gastrointestinal wall and maintain roughly equal spacing between them. EPSS has become the preferred method for closing larger EFTR wounds in clinical practice[35-38].

Building on this technique, Wu et al[38] introduced the prepurse-EPSS (P-EPSS). In this method, after precutting the mucosal and submucosal layers, the metallic clips and endoloop are immediately anchored to the normal mucosa near the resection margin; once the lesion is completely excised, the nylon loop is tightened right away[39]. Compared to EPSS, P-EPSS offers the advantages of reducing both the perforation duration and the incidence of postoperative complications[40]. Although no postoperative adverse events have been observed, the risk of early detachment exists due to the fixation of the metallic clips and endoloop to the mucosal layer in the prepurse-string technique.

Reinforced endoloop suture

To prevent metallic clip detachment and ensure robust wound closure following EFTR, Ye et al[40] proposed placing an additional endoloop at the base of the wound and tightening it to reinforce the initial closure[41]. Similarly, Liu et al[41] introduced a technique known as "double purse-string suture": After traditional purse-string suture, an additional endoloop is placed approximately 5-10 mm outside the original wound, and a second purse-string suture is applied to reinforce the closure.

Although this approach slightly increases the average suturing time compared to the standard technique, it offers significant benefits for large or high-tension defects. Traditional purse-string suturing may struggle to provide adequate closure strength for larger defects, potentially increasing the risk of wound reopening postoperatively. In contrast, the reinforced endoloop suture significantly reduces local tension on the wound, leading to more secure and durable closure outcomes after EFTR.

CLOSING DEVICES

Full-thickness resection device

The full-thickness resection device (FTRD) was initially designed for colonic full-thickness resection. It integrates a heat snare outside the OTSC, housed within a plastic-covered transparent cap. During the procedure, the lesion and surrounding mucosa are grasped with forceps and retracted into the cap, and the OTSC is deployed at the lesion base. The snare is then activated to perform full-thickness resection.

Successful FTRD application depends on lesion size and mobility. The thinner colonic wall (compared to the stomach wall) facilitates lesion containment, supporting its primary use in the lower gastrointestinal tract. However, a study of 1178 colorectal patients reported an 88.2% technical success rate, with 2% experiencing severe complications requiring surgical intervention[42,43]. Additional complications, including delayed bleeding and perforation, have also been documented[44-46].

Recently, the FTRD has gradually begun to be applied in the upper gastrointestinal tract. However, the reported R0 resection rates range from 63.2% to 68%, with complication rates ranging from 15.8% to 19.6%[47,48]. Therefore, despite its procedural simplicity, there are still limitations: (1) Strict limitations on lesion size; (2) High rate of postoperative adverse events; and (3) Low R0 resection rate. Thus, FTRD use requires careful consideration in established EFTR workflows.

OverStitch suturing device

The Eagle Claw device, a precursor to OverStitch, demonstrated perforation closure efficacy in animal studies but was hindered by technical complexity[49]. OverStitch, a Food and Drug Administration-approved endoscopic suturing system, enables continuous or interrupted sutures only via double-channel endoscopes without external suture reinsertion. The device is composed of a needle driver and an anchor exchange catheter[50].

During the procedure, the suture—mounted on the anchor exchange catheter—is passed through the endoscope channel. The wound is grasped with a tissue grasper, the anchor is transferred to the needle drive, and the suture is performed by transferring the anchor back and forward between the needle drive and the anchor exchange catheter. After completion of the suture, the anchor is released via the release button on the anchor exchange catheter, and the suture is threaded onto the cinch device and then cut.

OverStitch accommodates various suture patterns, including interrupted sutures, continuous sutures, and figure-of-eight sutures, and is suitable for a wide range of defect sizes[51-58], particularly for full-thickness resection. To further expand the application of OverStitch, the OverStitch Sx was developed, featuring similar operational methods and compatibility with single-channel endoscopes. Nonetheless, additional clinical data are necessary to fully establish its safety and efficacy[59].

Double-armed bar suturing system

The double-armed bar suturing system (DBSS) comprises a main body with two arms (equipped with absorbable sutures) and a rotating rod with a puncture needle. The DBSS is mounted externally on the endoscope, with a preloaded nylon loop on the rod. When suturing, the main body passes through the wall defect to the extraluminal side, and the rotating rod—positioned on one arm—sequentially lifts both suture ends. The absorbable sutures are then tightened using the nylon loop to complete the suture. Additional sutures are placed 3-4 mm apart until the defect is fully closed. Ex vivo animal EFTR trials demonstrated that the closure strength of the DBSS is comparable to that of manual suturing, and that the DBSS is suitable for closing larger defects at a relatively low cost[60]. However, the device is still primarily in the animal testing phase[61,62], necessitating further validation of its effectiveness.

T-tags suturing system

The T-tags system utilizes threaded metallic anchors, which are deployed through a needle tip into the opposing edges of the defect. The metal anchors are symmetrically deployed through the defect edges via the endoscope channel and secured with a locking mechanism. Animal studies and a limited number of clinical reports support its efficacy in closing full-thickness wounds[63-65]. However, the absence of external visualization during deployment increases the risk of injury to adjacent organs or blood vessels[66,67]. More importantly, in vitro studies revealed a risk of gas leakage after suturing with this device, raising concerns about the integrity of the suture seal[68].

X-Tack endoscopic spiral stapling system

The X-Tack system, approved by the Food and Drug Administration for gastrointestinal defect closure, is mounted on a single-channel endoscope. It consists of a push catheter preloaded with four helical coil tissue tacks, strung on a polypropylene suture. Each helix tack is positioned about 5-10 mm from the edge of the wound, and the suture is tightened to bring the wound together. If helix tack placement is unsatisfactory, the catheter handle can be rotated backward to remove the staple from the tissue. Research has demonstrated its superior closure efficacy over metallic clips[69], particularly for irregular defects > 3 cm or proximal colonic wounds[70]. Despite its promise, the X-Tack is primarily used for endoscopic resection wounds[71,72], with only one multicenter study confirming its effectiveness in suturing EFTR wounds[73].

"Figure-8" suturing

Inspired by surgical suturing techniques, the “figure-8” suturing method was developed. The procedure involves securing a surgical suture onto a metallic clip, placed on one edge of the defect, and the second metalliic clip is positioned across the surgical suture on the opposite edge of the defect. The process is repeated, an assistant gradually tightens the suture externally until the defect is completely closed, and a biological clip is used to secure the terminal knot before cutting the suture. Tang et al[72] conducted a retrospective analysis of 38 EFTR patients and reported a 100% closure success rate without severe postoperative complications. The average suturing time was 12.6 minutes, and the average defect diameter was 3.8 cm. The results showed that this suture method could successful close the wound more than 3 cm in diameter. Additionally, this method resembles surgical suturing, resulting in a linear scar that is more conducive to physiological healing.

Endoscopic hand suturing

Goto et al[73] developed endoscopic hand suturing (EHS) using a flexible needle with V-Loc absorbable sutures. Prior to suturing, a knot is tied at the end of the suture. The needle holder grasps the flexible needle, which is introduced to the edge of the defect via an outer sheath. Continuous suturing is initiated from one side of the defect until complete closure is achieved, and the remaining suture is cut with scissor forceps. The researchers demonstrated that EHS with V-Loc sutures can reliably close EFTR defects, offering a promising alternative to conventional closure methods[74-76].

Endomaster suturing system

A team from Singapore developed the Master and Slave Trans Endoluminal Robot (MASTER) system, which consists of a master console, a working end, and a remote workstation. The operational section features two highly flexible micro-arms that can extend and retract freely, providing ample visibility and workspace[77]. Based on the MASTER system, the Endomaster EASE suturing system was introduced, which comprises a needle driver and a mechanical grasper. This system has shown effectiveness in suturing defects during animal experiments, and its flexible operation and broad visualization capabilities hold significant promise for suturing EFTR defects.

CONCLUSION

Currently, numerous methods are available for suturing EFTR defects, with simple metallic clip suturing and purse-string suturing being the most widely used in clinical practice. These techniques are favored for their ease of operation and cost-effectiveness. As endoscopic techniques continue to evolve, several derivative suturing methods based on these two approaches have proven effective in clinical studies. Recently, OTSC clips and FTRD suturing have become hotspots in EFTR-related research. These methods simplify the suturing process and significantly reduce suturing time; however, they have strict limitations regarding the size of the lesions and are relatively expensive, with higher rates of postoperative complications, which restricts their widespread clinical application. Additionally, several endoscopic suturing systems, such as OverStitch, DBSS, and EHS, have been developed. These systems can provide robust closure of the full thickness of the gastrointestinal wall, but are associated with high costs and complex procedures, and many are still in experimental phases, requiring extensive research to establish their safety and effectiveness (Table 1 provides a comparison of the techniques).

Table 1 Advantages and disadvantages of suture methods for endoscopic full-thickness resection.

Technique	Maximum defect size	Strengths	Weaknesses
Endoscopic clip closure technique
Simple metallic clips	2 cm	Low cost, ease of use	Limited for large/irregular defects
Modified simple metallic clips	9 cm	Adaptable to large defects	Risk of clip detachment
OTSC	3 cm	Full-thickness grasp	Technical difficulty, lumen obstruction, high cost
Endoloop closure technique
Grasp-and-loop closure	3.5 cm	Short operation time, no gap closure	Only for double-channel endoscope
Metallic clip-assisted endoloop suture	7 cm	Adaptable to large, irregular defects	Risk of clip detachment
Reinforced endoloop suture	5 cm	Robust closure	Long operation time
Closing devices
FTRD	3 cm	Short operation time, procedural simplicity	High complication rate, strict lesion criteria
OverStitch	> 5 cm	Robust closure, effective for irregular defects	High cost, steep learning curve
Endoscopic hand suturing, "Figure-8" suturing	> 3 cm	Robust closure	Long operation time, steep learning curve, limited EFTR data
X-Tack	> 3 cm	Effective for irregular defects	Limited EFTR data

OTSC: Over-the-scope clips; EFTR: Endoscopic full-thickness resection.

The exploration of EFTR wound closure holds substantial clinical significance. Effective closure is essential for minimizing complications and alleviating patient discomfort. Future approaches to gastrointestinal tract defect closure should emphasize safety, efficacy, simplicity, and cost-effectiveness. Moreover, with ongoing advancements in technology and materials, the use of bioabsorbable sutures and artificial intelligence-assisted suturing techniques may become feasible and transformative in clinical practice.

In clinical practice, the selection of an appropriate suturing technique for EFTR primarily depends on the location and size of the lesion. For gastric defects, smaller wounds are typically managed using simple metallic clips or OTSC, while larger or irregular lesions often require modified metallic clips or the endoloop closure technique. In the duodenum, simple metallic clips are generally sufficient for small defects, whereas larger wounds are more effectively addressed using the purse-string suture method. When lesions are located in the intestinal tract—most commonly in the rectum—the greater mobility of the intestinal wall often allows for suction-assisted reduction of wound size, thereby facilitating closure with metallic clips. If complete closure proves difficult, the purse-string suture method may be employed as an alternative. Although OTSC and FTRD techniques offer the advantage of simplified operation, their irreversibility after deployment and the potential risk of inducing luminal stenosis limit their use in the duodenum and intestinal tract. Regardless of the method of suturing, endoscopists should adopt a rigorous approach, leveraging their expertise and extensive clinical experience to adhere to principles of safety and efficiency, aiming for the best suturing outcomes.