Colonoscope insertion through a narrowed, angulated, and fixated sigmoid colon (a) resulting in a large perforation with visualization of intra-abdominal organs (b)
As described below, several endoscopic devices are currently available that can be used either alone or in combination for closure of defects and perforations. These devices include through-the-scope (TTS) (Fig. 19.2) and over-the-scope (OTS) clips (Fig. 19.3), endoscopic suturing (Fig. 19.4), and covered stents (Fig. 19.5) [29–32]. Some of these devices are a result of technical innovations in the field of natural orifice transluminal endoscopic surgery (NOTES). A working knowledge and appropriate use of these instruments, based in part on lesion location and features, are critical for the successful application of these devices. In some cases, needle decompression of tension pneumoperitoneum must be performed before endoscopic closure .
Through-the-scope clips. (a) QuickClip2. (b) QuickClip Pro. (c) Resolution clip. (d) Instinct clip
Over-the-scope clipping devices. (a) Over-the-scope clip (OTSC™) system with a through-the-scope twin grasper device for lesion retraction (picture courtesy of Ovesco Endoscopy AG, Tubingen, Germany). (b) Padlock clip
OverStitch™ endoscopic suturing system (picture courtesy of Apollo Endosurgery, Austin, TX, USA)
(a) Covered self-expandable plastic stent. (b) Covered self-expandable metal stents
In addition to endoscopic repair, supportive measures, including nothing by mouth, intravenous fluids, tube feeding/parenteral nutrition, intravenous antibiotics, and continuous monitoring of the patient’s status to determine the need for operative intervention, are essential.
Devices and Technical Considerations
Several endoscopic devices are available for the management of procedure-related bleeding and perforation. A good working knowledge of these devices is important for their safe and effective use.
Procedure-related bleeding that may require intervention more commonly follows endoscopic resection techniques, such as EMR and ESD. Biopsy and cold snare resection of small mucosal lesions is rarely associated with persistent intra-procedural (Fig. 19.6) or delayed bleeding that requires endoscopic therapy. An endoscope that is equipped with water-jet irrigation is very helpful for precise identification and therapy of the bleeding point.
(a) Intra-procedural persistent post-biopsy bleeding . (b) Hemostasis achieved with clip placement
Intra-procedural bleeding as a result of EMR or ESD can be managed by a variety of hemostatic techniques. Epinephrine injection in 1:10,000 dilution (or higher) can be injected in 1–2 ml aliquots to stop active bleeding, although it does not prevent delayed hemorrhage. If active bleeding occurs immediately after completion of lesion resection, placement of clips targeting the bleeding point is preferable to contact thermal coagulation (e.g., bipolar coagulation) since the former does not extend tissue injury. However, clip placement should be avoided if the EMR, for example, is not complete since the clips may interfere with subsequent resection of residual lesion and serve as a current conductor to deeper tissue layers during inadvertent snare wire contact with the clips. The selection of a particular TTS clip for hemostasis is primarily dependent upon device availability and operator preference since there are no prospective comparative trials demonstrating the superiority of one clip over another in the setting of intra-procedural iatrogenic bleeding. The use of a dedicated hemostatic forceps (Coagrasper, Olympus Corp., Tokyo, Japan) is ideal for hemorrhage that occurs in the midst of an EMR or ESD procedure. The technique involves grasping, tenting, and applying coagulation current for sealing of the vessel (Fig. 19.7). The suggested settings for the Coagrasper are a power of 50 W and 1–2 s pulse duration using a soft coagulation mode (Video 19.1).
(a) Active arterial bleeding during endoscopic resection of a large rectal lesion. (b) Visible vessel targeted using the monopolar coagulation grasping forceps (Coagrasper, Olympus Corp., Tokyo, Japan). (c) Hemostasis secured within the resection bed
Snare resection of a pedunculated polyp with a thick stalk can result in active bleeding, which can immediately be controlled by recapturing and constricting the stump with the snare for several minutes. If bleeding resumes upon loosening the snare, epinephrine can be injected within the stump to slow or stop bleeding, followed by definitive therapy. If feasible, mechanical hemostasis is preferable to avoid extending thermal injury. Clips can be used to close the end of the stump. A detachable snare is also an option if the length and location of the residual stump is suitable for loop placement. Occasionally, access to the stump is difficult for either clip or loop placement, and a contact thermal probe is used with light–moderate contact pressure of 3–5 s to achieve hemostasis, with suggested settings of 15 J for the heater probe and 12–15 W for the bipolar probe.
In patients who require endoscopic intervention for delayed post-polypectomy bleeding, assessment of the post-polypectomy ulcer site partly dictates the need for therapy, although the significance and rebleeding rates of stigmata of recent hemorrhage (SRH) within post-resection ulcers are not as well studied as SRH associated with bleeding peptic ulcers. Post-polypectomy ulcers with clean bases or flat pigmented spots are not generally treated, whereas endoscopic therapy is performed for post-polypectomy ulcers with non-bleeding visible vessels (Fig. 19.8), adherent clots, or active bleeding. Clip placement and contact (coaptive) coagulation, with or without epinephrine injection, are commonly used modalities for delayed post-polypectomy hemorrhage. However, TTS clips may be ineffective if the ulcer base is quite indurated due to insufficient clip closure force. Also, a bleeding vessel entrenched in a fibrotic ulcer base may not be amenable to Coagrasper coagulation. The indurated base, however, provides a safety cushion for the use of coaptive coagulation, such as a bipolar probe, which may be more suitable in this setting (Fig. 19.9). The over-the-scope clip (OTSC® , Ovesco Endoscopy AG, Tübingen, Germany) provides greater compression force and tissue capture than TTS clips (Video 19.2), although the use of this device requires endoscope removal to fit the OTSC, which may not be practical in some actively bleeding cases. The use of a hemostatic spray (Hemospray, Cook Medical Inc., Bloomington, Indiana, US) requires active bleeding, and its role in the management of delayed post-polypectomy bleeding is currently being defined.
(a) Delayed bleeding from post-polypectomy ulcer with visible vessel. (b) Hemostasis secured with clip placement
(a) Delayed bleeding from post-polypectomy cecal ulcer with visible vessel (arrow) next to appendiceal orifice (asterisk). (b) Bipolar coagulation of visible vessel following failed attempt at clip placement (asterisk) due to indurated ulcer base. (c) Obliteration of visible vessel following bipolar coagulation (arrow)
A key determinant for a successful endoscopic outcome is intra-procedural recognition and attempted closure of the perforation, if technically feasible. If the perforation site is quite small and passes unrecognized, continuation of the procedure with liberal air insufflation may result in air under tension (e.g., tension pneumoperitoneum) requiring percutaneous needle decompression to relieve cardiorespiratory compromise. Once a perforation is recognized, CO2 insufflation should be employed instead of air and its use should be minimized to curtail egress of gas and enteric contents outside the gut lumen.
After dye-assisted EMR, the target sign should be sought, which is characterized by concentric rings with an outer white ring (cauterization), a blue-stained submucosal connective tissue ring (due to submucosal injection of methylene blue or indigo carmine), and a central white-gray circular disk, which corresponds to injury to the muscularis propria and potential perforation (Fig. 19.10). A mirror target sign can also be seen on the cut surface of the resected specimen. The target sign should be closed with placement of clips.
(a) Target sign following endoscopic mucosal resection (EMR) . (b) Clip closure of) EMR defect
For obvious colonic perforations due to EMR or ESD, the decision between endoscopic versus operative repair is influenced by several factors, including size and location of the perforation, status of colon prep, the presence or absence of extraluminal egress of colonic contents, unresected pathology (i.e., incomplete EMR/ESD), clinical stability of the patient, available devices, and operator expertise. Surgical intervention is indicated in the setting of a large perforation, gross extraluminal spillage, residual lesion, and clinical deterioration on conservative management. Endoscopic closure can be considered for readily accessible perforations <1–2 cm in size.
TTS clips are the most commonly used devices for closure of EMR and ESD perforations and are generally successful at closing linear perforations <2 cm in size (Fig. 19.11). The clips are placed in a zipper fashion and controlled suction helps in capturing the margins of the perforation between the opened prongs of the clip prior to closure and deployment. Successful TTS clip application requires familiarity with the chosen device and coordination between the endoscopist and assistant handling the clip. In some cases where the perforation is large, the omental patch method may be effective, if technically feasible. This involves pulling omental fat through the defect into the lumen, followed by clip anchoring of the fat pad to the mucosa.
(a) Iatrogenic linear esophageal perforation recognized intra-procedurally. (b) TTS clip closure of perforation in a zipper fashion
TTS clips may not provide secure sealing of large, gaping perforations, and in this regard the OTSC may be a better alternative as it is capable of grasping more tissue and applying greater compression force for full-thickness closure (Fig. 19.12). Furthermore, dedicated TTS grasping devices, such as the twin grasper, can be used to grasp and pull the opposite margins of the perforated defect into the OTSC cap prior to clip deployment (Video 19.3). Controlled suction during OTSC placement is advised to minimize the risk of extraluminal tissue or organ entrapment into the OTSC cap. Although the setup and deployment are similar to that of a variceal band ligator, limitations of the OTSC include the need to withdraw the endoscope for device loading, as well as the potential difficulty in maneuvering the device through a narrowed and angulated lumen (e.g., sigmoid colon), and failure to reidentify the perforation site. The latter can be avoided by placing a tattoo or TTS clip on the opposite wall of the perforation prior to scope withdrawal.
(a) Perforation following cap-assisted EMR in the rectum. (b) Over-the-scope clip closure of the perforated site
Endoscopic suturing of certain luminal perforations is feasible, with one endoscopic suturing device (OverStitch™, Apollo Endosurgery, Austin, Texas, USA) currently available on the market. This particular suturing system requires a specific double-channel upper endoscope (GIF 2 T160 or GIF2TH-180, Olympus Corp., Tokyo, Japan) and allows placement of interrupted or running stitches for full-thickness closure (Fig. 19.13). Device limitations include the inability to treat lesions beyond the reach of the upper endoscope and accessibility issues. Locations that are relatively accessible for endoscopic suturing include the esophagus, distal stomach, and rectum. Experience with regard to this system is accumulating.
(a) Esophageal stricture . (b) Dilation-induced perforation. (c) OverStitch™ suturing system in the esophagus for perforation closure. (d) Appearance following suture closure of perforation. (e) The absence of fluoroscopic contrast extravasation at the site of endoscopic repair of perforation
With regard to esophageal perforation, endoscopic management is limited when the perforation is situated in a hypopharyngeal or high cervical esophageal location. Conservative management in this setting is generally sufficient, though ongoing cervical leaks can be managed by neck incision and drainage, with primary surgical repair as appropriate. Thoracoabdominal esophageal perforations that are recognized intra-procedurally or within hours post-procedure may be amenable to endoscopic closure and/or diversion. Endoscopic clips can effectively close fresh esophageal perforations that are <2 cm in size, whereas larger perforations can be sealed by temporary placement of covered self-expandable plastic (SEPS) or metal stents (SEMS), with or without defect approximation with endoscopic suturing. Stents are also preferable for sealing iatrogenic perforations and palliation of dysphagia in patients with non-operable malignant esophageal obstruction. Stents are not appropriate for very large gaping perforations (>6 cm), for perforations in a high cervical esophageal location, and in the setting of near-complete anastomotic dehiscence or necrosis of the gastric conduit. Also, a dilated esophageal lumen (>3 cm luminal diameter), as can be seen in achalasia, for example, will not allow adequate sealing of the stent against the esophageal wall.
If stent placement is entertained, the selected stent should be of sufficient diameter and length to provide adequate sealing between the stent and esophageal wall and bridge the perforation for at least 2–3 cm above and below the site (Fig. 19.14 and Video 19.4). Smaller diameter stents are generally used for proximal esophageal perforations due to a narrower esophageal lumen and to minimize the risk of stent-induced tracheoesophageal fistula. Larger diameter stents are used in the mid and distal esophagus, especially if there is no shelf or stricture to anchor the stent. Although fully covered stents are preferred, stent migration is problematic when the device is placed across the gastroesophageal junction, though stent fixation techniques, such as endoscopic suturing, have reduced the risk of migration in this setting (Video 19.5). The alternative is to place a partially covered SEMS so that the uncovered flanges of the stent embed into tissue to minimize its migration. The partially covered SEMS can be removed using the stent-in-stent technique by placing a fully covered SEMS through the indwelling stent to cause pressure necrosis of tissue ingrowth at the uncovered flanges of the partially covered SEMS. This technique facilitates removal of both stents in one procedure 1–2 weeks later.
(a) Dilation of esophageal stricture resulting in perforation with fluoroscopic contrast extravasation. (b) Disrupted esophageal wall with visualization of perforation site. (c) Placement of a fully covered self-expandable metal stent. (d) Successful sealing of perforation site without contrast extravasation and nasogastric tube placement. (e) Stent removal at 4 weeks with healing of perforation site. (f) Contrast esophagram confirming healed perforation site
Once the stent is placed, the ideal dwell time is unknown and ranges from 4 to 12 weeks. Partially covered SEMS should be removed within 4–6 weeks and may necessitate the stent-in-stent technique, whereas plastic and fully covered stents can be left in place for a longer time period.
Site-Specific Adverse Events and Outcomes
Esophageal perforation is associated with significant morbidity and mortality, especially when management is delayed for >24 h [34, 35]. In one systematic review, esophageal perforation occurred in 56/3071 (1.8 %) patients with achalasia who underwent pneumatic balloon dilation, with an incidence rate ranging from 0 % to 5.4 % . Recent data suggest that dilation is effective and relatively safe for the treatment of strictures associated with eosinophilic esophagitis. A meta-analysis involving 525 patients and a total of 992 dilations showed that perforation occurred in 3 patients only (0.3 %; 95 % CI: 0–0.9 %) .
Endoscopic clips are generally successful at closing esophageal perforations , particularly when the perforation size is <1 cm . Unlike chronic fistulas, acute esophageal perforations generally heal with clip closure alone within 1 week. For larger perforations, SEMS is a potential option. In general, larger diameter (23–28 mm) covered SEMS are employed particularly when there is not a stricture of shelf to anchor the stent . As previously mentioned, achalasia patients with a dilated esophagus (diameter >3 cm) may not benefit from stent placement due to the lack of adequate sealing between the stent and the esophageal wall . In one retrospective study, esophageal leaks and perforations were closed in 77.6 % of cases using SEMS . A partially covered SEMS may be placed to seal an esophageal perforation, especially when the stent crosses the gastroesophageal junction, to minimize the risk of stent migration. However, utilization of a partially covered SEMS may be hampered by tissue ingrowth and embedment at the uncovered flanges of the stent, requiring the stent-in-stent technique for its eventual removal . As discussed above, a more attractive alternative is to place a fully covered SEMS with endoscopic suture fixation of the stent to the esophageal wall to prevent its migration (Fig. 19.15). One prospective study of 33 patients with esophageal perforation, including 19 iatrogenic perforations, found that temporary placement of SEMS of different types was successful in as many as 97 % of cases . Of note, stent extraction was uneventful in all cases when performed within 6 weeks of insertion, whereas stent extraction was complicated in 50 % of cases when it was performed after 6 weeks . It is suggested, therefore, that the stent dwell time should be less than 6 weeks. Stent migration ranges from 11.1 % to 33 % among various studies and, therefore, ongoing patient monitoring is required for signs of stent migration following placement [39–42].
(a) Dilation-induced esophageal perforation . (b) Fully covered self-expandable stent placement. (c) Stent fixation using the OverStitch™ suturing system. (d) Anchored stent to the esophageal wall
In addition to EMR or ESD, endoscopic submucosal tunnel dissection (ESTD) has been pioneered for en bloc excision of larger lesions (>5 cm) [4, 43]. These advanced resection techniques may result in esophageal perforation, although such a complication can be managed successfully in the hands of a skilled endoscopist without resorting to surgery. It has been suggested that perforation is to be expected (or even sometimes intended) with these enhanced resection techniques, and it should not simply be considered as an adverse event in a controlled setting . In one study of 306 ESD and 171 EMR performed to remove esophageal neoplasms in 368 patients, esophageal perforations occurred in 7 (1.9 %) cases. All perforated patients were male and had undergone ESD, while no perforation occurred in the EMR group . Perforations occurred intra-procedurally in 3 cases, after stricture dilatation in another 3, and due to food bolus impaction in the remaining patient . In another study, perforations occurred in 4/58 (6.9 %) patients during ESD and was successfully managed conservatively following perforation closure with endoscopic clips [38, 45].
The incidence of perforation was higher following ESD for Barrett’s-associated adenocarcinoma (20 %; n = 25) compared to either esophagogastric junction (2.9 %; n = 103) or non-junction squamous cancers (2.7 %; n = 1335) . In contrast, two studies found no perforations following EMR performed in 102 patients  and following 2513 EMR procedures in 681 patients with neoplastic appearing lesions in Barrett’s esophagus . In another study, perforations occurred in only 3/185 (1.6 %) patients, which were successfully managed with clips .
Pneumomediastinum without overt perforation may occur after esophageal EMR and ESD, with an incidence of 6 % and 10 %, respectively [47, 49]. In a study where systematic radiographic imaging was performed in 58 patients who underwent esophageal ESD, mediastinal emphysema was detected in 18 (31 %) patients by chest CT as opposed to only 1 (1.7 %) patient by chest x-ray. The ESD-induced exposure of the muscularis propria (n = 32) was the only significant risk factor . In all the reported cases, pneumomediastinum promptly regressed with conservative treatment alone [47, 49, 50].
Although post-procedural bleeding in the esophagus is mainly attributed to endoscopic resection of Barrett’s esophagus or squamous cell dysplasia/early carcinoma, the risk appears to be small without an overall significant impact on patient outcome or procedural safety [51–53]. In an early series of 216 EMR for dysplastic Barrett’s esophagus , the risk of post-EMR bleeding occurred in 1 % of patients, which was successfully managed endoscopically in all cases. In a larger series encompassing 1060 resections in Barrett’s patients, the overall risk of delayed bleeding was 2.1 %, which was also effectively managed endoscopically. The same risk has been observed during the learning curve of this procedure with less experienced endoscopists . EMR of squamous dysplasia or early carcinoma appears to carry a lesser risk of bleeding than Barrett’s lesions [55, 56]. ESD is extensively used for the treatment of squamous cell carcinoma, especially in Asia. ESD does not appear to result in a greater risk of post-procedural bleeding relative to EMR [49, 57–59]. The same appears to be true with regard to ESD for Barrett’s esophagus based on a small series .
Endoscopic TTS or OTS clip approximation and closure of small gastric perforations (<2 cm) secondary to EMR or ESD are generally effective. For large perforations, the omental patch method should be considered . Alternatively, endoscopic suturing may be an option if the device is available and the defect readily accessible.
In a large single-center Japanese series, perforation occurred in 121/2460 (4.9 %) cases who underwent gastric EMR . The first 4 patients were treated with emergent surgery and the subsequent 117 patients were treated with endoscopic clips. The latter treatment was successful in 115 (98.3 %) patients, and salvage surgery was required in 2 patients due to failed endoscopic closure . In another study , a gastric perforation was encountered in 7/789 (0.88 %) patients following EMR, with the defect diameter ranging from 4 to 25 mm. These cases were successfully managed with clips (range 3 to 11), with the addition of an omental patch in the patient with the largest perforation.
A systematic review encompassing12 studies and 3806 gastric lesions evaluated the safety of ESD compared with EMR for the resection of early gastric cancers . A significantly higher perforation rate occurred in the ESD group (4.54 %) compared with the EMR group (1.03 %), with an estimated increased risk of 3.58 (95 % CI: 1.95–6.55). The perforation rate did not significantly differ according to the type of ESD knife used. In those who perforated, surgical intervention was required more frequently in the ESD group (11.7 %) than in the EMR group (6.2 %), although the difference was not statistically significant .
Risk factors for ESD-related perforation were assessed in a large single-center study involving 1123 lesions . Perforation occurred during ESD of 27 (2.4 %) lesions, and resection of lesions in the proximal stomach was the only significant risk factor (OR 4.88, 95 % CI: 2.21–10.75) on multivariate analysis. Surgical intervention was needed in one patient 5 days after an ESD-associated perforation due to dehiscence of the defect despite initial successful closure with endoscopic clips .
Both EMR and ESD procedures have been found to be relatively safe even in cirrhotic and elderly patients [8, 9]. In one systematic study, perforation occurred in only 1 (1.6 %) of 68 cirrhotic patients with gastric neoplastic lesions removed by ESD, which was successfully treated with endoscopic clips . A comparative study found that post-ESD perforation rate was not increased in the elderly (14/372; 3.8 %) relative to non-elderly patients (4/143; 2.8 %) patients . However, in those who perforated, emergency surgery was required in 14.3 % of elderly patients as opposed to none in the non-elderly group.
Similar to the esophagus, EMR and ESD of gastric lesions are the most frequent causes of post-procedural bleeding. A systematic review of 12 studies involving 3806 early gastric cancers compared the efficacy and safety of ESD (n = 1734) to EMR (n = 2072) . The overall bleeding rate was 7 % for both procedures, though the rate of immediate bleeding was over twofold higher in the ESD group compared to the EMR group. On the other hand, the delayed bleeding risk was slightly lower in the ESD group, but the difference was not statistically significant. None of the patients in the ESD group underwent surgery due to delayed bleeding. A similar risk profile for post-procedural bleeding was noted in another meta-analysis study . In cirrhotic patients, post-ESD bleeding occurred in 8/61 (13.1 %) patients, with successful endoscopic treatment in all cases . This data support similar previous findings with regard to ESD for early gastric cancer in the setting of liver disease [66–68].