Frequency

Fortunately, the perforation rate for simple screening or diagnostic colonoscopy is low. Perforation tends to complicate 0.03% to 0.9% of all colonoscopies, although rates as low as 0.01% have been reported. A 2016 meta-analysis of 21 studies, encompassing almost 2 million colonoscopies showed a pooled perforation rate of 0.5/1000 (0.05%) procedures for screening or diagnostic colonoscopy. The risk of perforation during colonoscopy increases with any therapeutic intervention. ^, Even a procedure as simple as a diagnostic biopsy has been shown to increase the risk of perforation, although the risk with biopsy remains quite low. The risk for perforation from diagnostic lower GI endoscopy in patients with underlying bowel diseases (such as ulcerative colitis [UC], Crohn’s disease [CD], and radiation colitis) increases.

Therapeutic intervention during lower GI endoscopy also increases the risk of perforation. While only one study failed to demonstrate an increased risk of perforation with polypectomy, multiple prospective and retrospective studies as well as meta-analyses have reported an increase in perforation rates with standard polypectomy of 0.08% to 1.1%. ^{, ,} EBD, increasingly performed for patients with both primary and anastomotic IBD-associated strictures, carries a risk of perforation of 2.5% to 4%. The perforation rates for therapeutic colonoscopy, including EMR and ESD have been demonstrated in prospective, retrospective, and systematic reviews to be between 0.08% and 4%, varying widely by resection technique. ^{, , , , , ,} EMR-associated perforations occur in anywhere from 0.1% to 2.6% of procedures. ^{, , , ,} In a prospective study of 1214 patients undergoing EMR for 1255 neoplastic lesions ≥20 mm in size, the incidence of perforation was 1.4%. A recent review by the American Society for Gastrointestinal Endoscopy (ASGE) showed a pooled perforation rate of 1.1% (95% confidence [CI]: 0.9–1.5%) associated with EMR. ^, ESD, which involves the injection of a submucosal lifting agent, followed by needle-knife dissection of advanced polyps or early malignancies, is being increasingly incorporated and allows for the achievement of R0 resections and often obviates the need for surgery. This procedure carries a substantially higher risk of perforation cited to be between 1.4% and 10%. ^, A meta-analysis of 13,833 colorectal neoplasms treated with ESD showed a 4.2% rate of immediate and 0.22% rate of delayed perforation although a more recent meta-analysis suggests the risk of perforation may be over 7%. Endoscopists should be aware that the overall risk of mortality from colorectal perforations can be as high as 5% to 7%. ^,

Although the risk of perforation is low for screening and diagnostic colonoscopies, the implementation of therapeutic interventions including polypectomy, EBD, EMR, and ESD can substantially increase the risk of perforation.

While one recent meta-analysis suggests that the incidence of perforation over time has remained stable, other studies have shown a decrease in the perforation rates associated with both diagnostic and therapeutic colonoscopy. This has been attributed to improvements in endoscopic technique despite a significant increase in the number of colonoscopies performed annually, as more countries have encouraged and implemented national screening programs for CRC.

Mechanisms

The etiological mechanisms of perforation differ between diagnostic and therapeutic colonoscopies. Perforations that occur during screening or diagnostic colonoscopy are often secondary to blunt injury, excessive looping, use of torque force, or barotrauma (excessive colonic insufflation). Blunt injury may occur from the direct or lateral force on the colonic wall, retroflexion in the rectum, or passage of the colonoscope across or into pathological areas in the colon such as benign or malignant strictures, radiation colitis, or diverticula. ^{, ,} Perforations that arise during diagnostic colonoscopy tend to be significantly larger than those resulting from therapeutic interventions. ^{, , ,}

Therapeutic endoscopy-associated perforations are often caused by over-aggressive electroincision or resection of normal colonic tissue during polypectomy, thermal injury from cautery or argon-plasma coagulation, or dilation of malignant strictures, CD-associated strictures, or benign anastomotic strictures. ^{, , , ,} A review of 180 colon perforations complicating both diagnostic and therapeutic colonoscopy demonstrated that 55% were caused by blunt or torque injury, 27% resulted from polypectomy, and 18% stemmed from thermal injury.

Risk Factors

A number of risk factors for perforation have been described in both retrospective and prospective studies. These characteristics can be specific to patients, the endoscopist, the nature of the procedure itself, or characteristics of polyps when polypectomy is performed. Patient-related factors include older age, female sex, low body-mass index, the presence of multiple medical comorbidities, prior diverticular disease, bowel obstruction, and prior history of abdominopelvic surgery. ^{, , , , , , ,} Colonoscopies performed by gastroenterologists with higher procedure volumes have been shown to have a lower risk of perforation than the control group. ^, In contrast, those performed by nongastroenterologist endoscopists have nearly twice the odds of perforation. Some studies suggest that anesthesia assistance and intravenous propofol administration increase the perforation risk. This is hypothesized to be a consequence of the decreased ability to respond to stretch during loop formation or increased likelihood of endoscopists to push through loops in deeply sedated patients. ^, Disease activity and concurrent use of systemic corticosteroids were found to be associated with colonoscopy-associated perforation in patients IBD. ^,

When polypectomy is performed, increasing polyp size and polyp location in the right colon (especially in the thin-walled cecum) are well-established risk factors for perforation. ^{, , , , ,} Nonpolypoid or laterally spreading lesions, especially those >20 mm in size may be associated with a higher risk of perforation as well. ^, In one series, a nonpedunculated cecal polyp had a comparative odds ratio (OR) of 12.2 for perforation.

In EBD of CD-associated strictures, the risk of perforation is increased in patients with angulated strictures, patients requiring multiple dilations, and those with active inflammation adjacent to a stricture. These findings are limited by the small sample size and require further study. In the authors’ experience, EBD of extrinsic, constrictive strictures carries a higher risk for procedure-associated perforation than intramural, hypertrophic strictures. For the treatment of IBD-associated stricture, endoscopic electroincision with stricturotomy or strictureplasty has a lower risk for perforation than EBD.

Certainly, EMR or ESD alone increases the risk of perforation given the invasive nature of these procedures. In a prospective, multicenter study of over 1000 EMRs, en bloc resection as compared to piecemeal polypectomy and Vienna classification 4 or 5 (corresponding to high-grade neoplasia or submucosal invasive carcinoma) were independently associated with an increased risk of perforation. When ESD is employed, right-sided colon lesions, the use of a nonhyaluronic-acid-based lifting agent, failure to lift after submucosal injection, larger polyps, and flat polyps all are associated with an increased risk of perforation. ^, Risk factors for endoscopy-associated complications are also discussed in Chapter 3 .

Diagnosis and Timing of Diagnosis

The diagnosis of perforation can be made intra- or immediate post (commonly defined as a diagnosis within 24 hours), or delayed post (diagnosis after 24 hours) procedure. Immediate recognition and diagnosis during the index procedure is critical as early recognition helps facilitate rescue endoscopic intervention ( Fig. 11.1 .) Perforations occurring as a result of diagnostic colonoscopy are more likely to arise from blunt or torque injury and tend to be larger, and therefore, more clinically evident, whereas those caused by therapeutic maneuvers, such as electrocautery may be smaller and present later. ^{, , ,} A diagnosis of perforation during colonoscopy can be made by visualization of an obvious tear after blunt injury, sudden loss of luminal distension, observation of intraperitoneal organs, fat tissue, or shiny serosal surfaces, or by appreciating full-thickness mucosal defects after polypectomy whether advanced resection techniques are employed or not. ^{, , , ,} A mere one-fourth to one-third of perforations are diagnosed intraprocedurally, ^{, ,} 68% to 75% are diagnosed within 1 day and virtually all clinically significant perforations are recognized within 96 hours. ^, In rare instances, perforations have not been diagnosed until two weeks after the date of occurrence. In a review of 35 perforations, those that resulted from diagnostic colonoscopy were diagnosed in a more timely manner (0.36 days) than those resulting from therapeutic interventions (1.5 days). Multiple retrospective studies evaluated delays in diagnosis and have almost uniformly identified poorer outcomes and an increased need for surgery when the diagnosis is delayed. ^{, ,} In a retrospective review of 165 iatrogenic colon perforations managed operatively, Iqbal et al. showed that patients presenting within 24 hours were less likely to have peritoneal contamination and were more likely to be able to undergo primary repair or resection with anastomosis, whereas those presenting after 24 hours were more likely to have feculent peritonitis and require an ostomy. The importance of early diagnoses was well demonstrated in a review of 38 perforations by Yang et al. Of the 28 patients with endoscopically evident or suspected perforations, 22 patients underwent clipping, with only a single patient requiring surgery. Of the 10 patients with delayed perforations detected radiographically, the seven patients whose perforations were diagnosed within 24 hours, all were managed nonoperatively, whereas, of those diagnosed after 24 hours, two-thirds required emergency surgical interventions. When polypectomy or EMR is employed, identification of a target sign (a white or gray central disc surrounded by a web of blue-stained submucosa encircled by white cauterized mucosa) on either the portion of resected mucosa or the polyp specimen itself is suggestive of partial or full-thickness injury and can prompt further management intraprocedurally ^, ( Fig. 11.2 ). This highlights the importance of careful evaluation of both the polypectomy specimen and the resection bed. Classification schemes to grade the integrity of the muscularis propria after EMR have been proposed and may assist with predicting perforation and informing endoscopic management. Signs and symptoms suggestive of delayed perforation must be thoroughly evaluated after colonoscopy, especially when advanced resection techniques are implemented. Computed tomography (CT) scan has a high sensitivity for detecting free air and can assist with localizing the site of perforation in up to 86% of patients. ^, However, as not all radiographically diagnosed perforations are visualized endoscopically, the need for abdominal imaging is imperative if perforation is suspected.

The prompt diagnosis of perforation is critical to enable possible endoscopic therapy.

(From: Raju GS, Saito Y, Matsuda T, Kaltenbach T, Soetikno R. Endoscopic management of colonoscopic perforations (with videos). Gastrointest Endosc . 2011;74(6):1380–1388. https://doi.org/10.1016/j.gie.2011.08.007 .) (From: Raju GS, Saito Y, Matsuda T, Kaltenbach T, Soetikno R. Endoscopic management of colonoscopic perforations (with videos). Gastrointest Endosc . 2011;74(6):1380–1388. https://doi.org/10.1016/j.gie.2011.08.007 .)

An example of a target sign is in the resection bed (panels A, B) and the polyp specimen (panel C).

(Taken from: Swan MP, Bourke MJ, Moss A, Williams SJ, Hopper A, Metz A. The target sign: an endoscopic marker for the resection of the muscularis propria and potential perforation during colonic endoscopic mucosal resection. Gastrointest Endosc . 2011;73(1):79–85. https://doi.org/10.1016/j.gie.2010.07.003 .) (Taken from: Swan MP, Bourke MJ, Moss A, Williams SJ, Hopper A, Metz A. The target sign: an endoscopic marker for the resection of the muscularis propria and potential perforation during colonic endoscopic mucosal resection. Gastrointest Endosc . 2011;73(1):79–85. https://doi.org/10.1016/j.gie.2010.07.003 .)

Abdominal pain is the most prevalent symptom in patients with iatrogenic perforation. Signs of peritoneal irritation including rebound tenderness and guarding should further increase the suspicion. Abdominal distension is also commonly identified early in the course. Unusual abdominal pain or abdominal distention, sudden wake-up from sedation, or monitored anesthesia care during the procedure should alert the endoscopist for possible perforation. As fluid and fecal content pass into the peritoneal cavity, symptoms may progress to those of clinical peritonitis and include fever, nausea, vomiting, respiratory distress, and sepsis. ^{, , ,} Air may also cross fascial planes, tracking into the soft tissues of the abdomen, chest, scrotum, or neck. ^, Rarely patients with large perforations will develop signs and symptoms of pneumoperitoneum intraprocedurally, which will manifest as hypotension and bradycardia, and may progress to cardiopulmonary arrest if not appropriately treated. ^{, ,} Clinical signs and symptoms of perforation may be immediately clinically evident or may manifest after the initial procedure. Regardless, early diagnosis is critical for the appropriate management and may facilitate endoscopic management and obviate the need for surgical intervention.

Prevention

While not all perforations can be prevented, the risk can be mitigated by employing good clinical practices. Endoscopists’ awareness of risk factors for perforation including older age, female sex, multiple comorbidities, and IBD is critical, as is avoiding unnecessary procedures by strictly adhering to society-driven screening and surveillance guidelines. For patients undergoing therapeutic lower GI endoscopy, such as EBD of CD strictures, preprocedural cross-sectional imaging can provide detailed information on targeted lesions, including number, location, length, and severity of strictures and associated fistula or abscess. Adequate bowel preparation is important to avoid contamination of the peritoneal cavity in case of bowel perforation. The use of systemic corticosteroids should be minimized or avoided. Insufflation of CO ₂ or water instead of air should be used for colon insufflation and abdominal distension should be monitored routinely. Excessive torque and looping should be avoided, and intravenous sedation should be kept to the minimum necessary dose to enable patients to respond to pain. When polypectomy is required, endoscopists should avoid unnecessary thermal injury by using cold forceps for polyps less than 5 mm and cold snare techniques for polyps 5-10 mm in size. ^, When electrocautery is required, typically for polyps 10-20 mm in size, the polyp should be lifted off the mucosa using the endoscope prior to cutting, which may reduce cautery-associated injury. Lastly, for polyps larger than 20 mm in size, consideration should be made for piecemeal resection and using a submucosal injection to lift the polyp off of the muscle layer.

When considering EBD for IBD-associated strictures, perforation can be avoided by carefully selecting appropriate patients, avoiding dilations in those with angulated strictures, and adjacent active inflammation, and maintaining a balloon diameter of less than 18 mm. Endoscopic stricturotomy or endoscopic strictureplasty with the endoscopist’s full control of the depth and location of electroincision of the stricture may reduce the risk for perforation.

When EMR is performed, standard techniques for safe polypectomy described above should be employed. The question of whether or not endoscopic closure of mucosal defects improves the risk of delayed perforation after EMR colorectal lesions remains under debate. This question was evaluated in a randomized controlled trial, of patients with colorectal polyps 10-40 mm in size. While a decrease in all adverse events was noted, there was no difference in perforation rates between patients who were randomly assigned to clip closure versus those who were not. There is evidence, however, that defect closure when deep mural injury or a target sign is noted is beneficial. ^, Due to the rare nature of this outcome during EMR, the question of whether prophylactic clip closure reduced perforation has not been answered in a randomized controlled fashion.

Despite the paucity of data, ESD-associated bleeding, large mucosal defects, or perforations are often closed by a variety of modalities. For the mucosal or transmural defect, endoscopic closure is used to ensure mechanical apposition of the defect edges as these resection defects contribute to complications. ^, In a study of 68 patients undergoing colorectal ESD, 27 underwent clip closure using standard through-the-scope (TTSC) or over-the-scope (OTSC) clips. Clipping was successful in 96% of patients with a median procedure time of 16.6 minutes. No patients experienced perforation. While this was not a statistically significant difference from the nonclosure group, differences were noted in postprocedure abdominal pain, white blood cell counts, and C-reactive protein levels. Aside from standard clips, a number of additional techniques have been reported to successfully close post-ESD mucosal defects, although data are limited. Using the Overstitch® endoscopic suturing system (Apollo Endosurgery, Austin, TX.), Kantsevoy and colleagues reported successful closure of colonic ESD defects in 8 patients. No patient experienced perforation after closure. Han and colleagues subsequently reported the successful suturing of post-ESD defects in the rectum in 4 patients without any evidence of delayed perforation or bleeding. More recently Abe, et al reported success of 11 colorectal ESD defects that were closed using endoscopic hand suturing, a technique that showed success in 8/11 (73%) patients and sustained closure in 7/11 (64.9%), although the long procedure time (median 56 minutes) was a noted limitation. The technique was not attempted in 2 patients who developed frank perforation during the procedure. Other treatment modalities include the use of a “figure-8”-shaped metallic device that is clipped to one edge of the defect, after which another clip is used to secure the other ring is used to the opposite edge of the defect thereby mechanically opposing the two borders. Despite the inventive ways in which mucosal closure has been approached, prospective data are lacking to support a reduction in delayed perforation, in part, due to the rare nature of this event. It should be pointed out that extraluminal air leaks without obvious or clinically meaningful perforation may occur in endoscopic electroincision, such as endoscopic stricturotomy, myotomy, and third space endoscopy such as ESD.

Unfortunately, perforation cannot always be avoided, but choos­ing the right patient population, avoiding excessive looping and torque, implementing CO ₂ or water insufflation (as compared to air), and implementing appropriate resection techniques can reduce its occurrence. The decision to close postpolypectomy, post-EMR, or post-ESD defects, while widely practiced, remains understudied with no retrospective evidence suggesting a benefit in preventing perforation.

Management: General

The general management of iatrogenic perforations depends on a number of factors that affect the patient’s prognosis, including the size and location of the perforation, the promptness of diagnosis, patients’ clinical stability and comorbidities, the degree of bowel cleansing, the observation of gross fecal contamination of the peritoneum and the time since perforation. ^{, , , , ,} Patients with acutely identified iatrogenic perforations should be managed endoscopically if feasible and within the expertise of the endoscopist. The World Society of Emergency Surgery (WSES) recommends endoscopic management of acute perforations in their 2017 guidelines if the perforation has occurred within four hours. Tension pneumoperitoneum, a condition that develops in the setting of air leakage into the peritoneum and compression of vascular structures, is a medical emergency that can progress to hypotension, cardiovascular collapse, and death if not managed rapidly. Needle decompression should be employed by the insertion of a hollow, large-bore needle into the peritoneal cavity. ^, All patients should be made nil-per-os until abdominal pain and anorexia improve. Broad-spectrum antibiotics including coverage of gram-negative bacteria and anaerobes should be administered intravenously and can safely be converted to oral at the time of diet resumption. ^, Surgical consultation is imperative as, despite the recent advances in endoscopic management, a proportion of patients will require surgical intervention. In cases of unrepaired or suspected perforation, abdominal imaging should be obtained with either an X-ray or CT. Further management depends on clinical stability, perforation size, and underlying comorbidities. Some patients can be monitored clinically with antibiotics and bowel rest alone, without the need for surgical intervention provided no significant underlying pathology such as malignancy is present. ^{, ,}

Management: Through-the-Scope Clipping

Over the last two decades, an important paradigm shift has occurred, where many iatrogenic colorectal perforations can now be managed endoscopically. In patients with iatrogenic perforations diagnosed immediately, clip application has also been shown to reduce or even obviate the need for surgical intervention ^{, , , ,} and may lessen hospital length of stay, fasting periods, and intravenous antibiotic requirement. ^, The advantages of using through-the-scope clips (TTSC) for the closure of perforation include wide availability, prompt closure, and avoidance of peritoneal contamination without having to withdraw and reinsert the colonoscope, as may be necessary with other modalities ( Fig. 11.3 ). The efficacy of hemoclip closure has also been demonstrated in controlled studies of porcine models in which 1.5 to 2 cm perforations were created and successfully closed using TTSC. ^, In human retrospective human studies, the reported success rate for TTSC treatment of iatrogenic perforation ranged from 80% to 90% ; however, this is highly dependent on the size and location of the perforation and the experience of the endoscopist.

A small perforation resulting from a diagnostic colonoscopy (left panel). Through-the-scope clip placement with successful closure of the perforation (right panel).

(From: Jovanovic I, Zimmermann L, Fry LC, Mönkemüller K. Feasibility of endoscopic closure of an iatrogenic colon perforation occurring during colonoscopy. Gastrointest Endosc . 2011;73(3):550–555. https://doi.org/10.1016/j.gie.2010.12.026 .) (From: Jovanovic I, Zimmermann L, Fry LC, Mönkemüller K. Feasibility of endoscopic closure of an iatrogenic colon perforation occurring during colonoscopy. Gastrointest Endosc . 2011;73(3):550–555. https://doi.org/10.1016/j.gie.2010.12.026 .)

Mana and colleagues first reported successful closure of an iatrogenic perforation using TTSC during diagnostic colonoscopy in 2001. Since that time, additional case reports, case series, and retrospective studies have reported on the successful closure of perforations during screening and diagnostic colonoscopy. ^{, , , , ,} It is important to note, that the rate of successful TTSC closure of these perforations is significantly lower in diagnostic colonoscopy than perforations occurring during therapeutic interventions. In a retrospective series by Yang and colleagues, 38 perforations were reviewed, 13 of which occurred in a diagnostic setting. 6/13 (46%) perforations were successfully closed using clips, compared to 17/25 (68%) perforations arising from therapeutic interventions. Notably, the mean perforation size in the former group was 19.3 mm compared to 5.8 mm in the latter group, and 7/13 (54%) patients required emergent surgery compared to 2/25 (8%) in those with perforations resulting from polypectomy or EMR. Similarly, Cho and colleagues reviewed 29 perforations, 10 of which were attributed to diagnostic procedures. While the success rate for TTSC closure was 60% (6/10), only 2/10 patients had a favorable clinical course, with three patients developing intraabdominal abscesses despite attempted clip closure. The authors report an odds ratio (OR) of 9.25 for “unfavorable clinical course” in those large (defined as >10 mm) perforations or those arising during a diagnostic procedure. Some other investigators suggest that attempted closure of perforations greater than 10 mm is not feasible by TTSC alone and these individuals likely require surgery. ^, The above evidence suggests that TTSC closure may be appropriate for small perforations occurring during diagnostic colonoscopy.

There are limited reports of TTSC closure of perforations resulting from polypectomy, as perforations arising in this setting are uncommon. Dhalla reported the first case of polypectomy-associated perforation, which was successfully closed using a TTSC. In a meta-analysis of 24 cohort studies, Verlaan and colleagues reviewed 466 perforations, 38 of which occurred in the setting of simple polypectomy. The success of TTSC in 359 patients was 87.8%, although it was not specified how many of those were associated with polypectomy. For patients with stigmata of perforation or at risk of perforation, postpolypectomy placement of TTSC at the site is recommended.

No studies to date have examined TTSC closure of perforations developing in the setting of EBD of colonic or ileal strictures. Some experts suggest that if a small perforation can be immediately recognized following EBD of CD-associated strictures or small perforations from EBD of anastomotic strictures, TTSC can be attempted. However, the success rate for larger perforation has been low in our experience due to the nature of underlying diseases with inflammation in IBD or radiation.

The best evidence for TTSC closure is for perforations arising in the setting of other therapeutic colonic procedures. First described by Yoshikane and colleagues in 1997, several additional studies have supported the utility of TTSC placement for colonic perforations occurring during EMR ^{, , , , , ,} ( Fig. 11.4 ). Magdeburg and colleagues described 27 perforations occurring during 2176 therapeutic colonoscopies, of which 26 were the result of EMR. Of the 27 patients who developed perforation, 24 (89%) were treated successfully with the placement of TTSC. Similarly, TTSC is commonly used successfully during ESD. A case series of 200 ESD by Saito and colleagues showed the benefit of clipping iatrogenic perforations. Of the 10 perforations reviewed in the study, 9 were successfully treated intraprocedurally with TTSC with only one patient requiring surgery after clip failure. In another series by Fujishiro, 9/9 perforations from ESD were successfully treated with hemoclips alone. Other studies that have incorporated ESD-associated perforations have also demonstrated the benefit of TTSC placement. ^, Given the success of endoscopic clipping for iatrogenic colon perforation, a position statement from the European Society of Gastrointestinal Endoscopy (ESGE) and guidelines from the WSES recommended that one consider endoscopic clip placement, if within 4 hours of diagnosis, depending on the size and cause of the perforation, as well as endoscopist expertise. In our experience, for patients undergoing EMR or ESD at risk for perforation, or with large mucosal defects, prophylactic clipping is recommended as the thermal injury associated with these procedures often results in a deeper injury than can be endoscopically visualized.

Clip closure of a perforation resulting from colonic EMR. (A, B) EMR of a flat dysplastic lesion led to a large linear perforation (C). The perforation was closed with clips (D, E).

(From: Raju GS, Saito Y, Matsuda T, Kaltenbach T, Soetikno R. Endoscopic management of colonoscopic perforations (with videos). Gastrointest Endosc . 2011;74(6):1380-1388. https://doi.org/10.1016/j.gie.2011.08.007 .) (From: Raju GS, Saito Y, Matsuda T, Kaltenbach T, Soetikno R. Endoscopic management of colonoscopic perforations (with videos). Gastrointest Endosc . 2011;74(6):1380-1388. https://doi.org/10.1016/j.gie.2011.08.007 .)

The success of endoscopic clipping has marked a true shift in the management of iatrogenic colorectal perforation. While the overall success ranges from 80-90%, ^, it is important to note that the likelihood of uncomplicated closure is greater in the setting of small perforations, associated with therapeutic procedures and less so in the setting of large diagnostic perforations. ^{, , ,}

Management: Over-the-Scope Clipping

Endoscopic clipping has been a critical development in the management of colorectal perforations. However, as described above, TTSC may be inadequate when attempting to close large perforations. The over-the-scope clip (OTSC®, Ovesco Endoscopy GmbH, Tübingen, Germany) is comprised of a highly elastic nitinol alloy that is deployed using an applicator, in a similar fashion to a band ligator, and remains closed after placement due to its shape-memory effect. ^{, ,} These clips have the advantage of incorporating a greater thickness of the tissue and creating a better approximation than traditional TTSC. OTSCs were systematically studied in porcine models with artificially created perforations and reported to be effective and comparable in efficacy to surgical closure for perforations 10–35 mm in size. and have been studied in iatrogenic perforations associated with both diagnostic and therapeutic colonoscopy in humans. The success rate of endoscopic closure, when properly employed, is reported to be 90–100%, although the quality of data is limited to small case series and retrospective analyses, many of which incorporate perforations of the upper GI tract as well. ^{, , , ,}

As perforations resulting from diagnostic colonoscopy tend to be larger, it stands to reason that OTSCs would have more success in treating such lesions. In 2007, Kirschniak, et al first described the clinical success of OTSC in a case series of three patients, one of whom suffered a perforation during diagnostic colonoscopy ( Fig. 11.5 ). The success of these clips has been shown in several case reports, case series, and retrospectively analyzed data as well as in one prospective study. ^{, , , , ,} Voermans and colleagues prospectively performed OTSC closure in 13 colorectal perforations, 8 of which were a result of diagnostic colonoscopy. All 8 patients had clinically successful closure, confirmed radiographically.

Successful closure of an iatrogenic perforation in a patient with ulcerative colitis using an over-the-scope clip. (A) A full-thickness colonic perforation. (B) Deployment of an over-the-scope clip at the perforation site.

(From: Kirschniak A, Kratt T, Stüker D, Braun A, Schurr MO, Königsrainer A. A new endoscopic over-the-scope clip system for treatment of lesions and bleeding in the GI tract: first clinical experiences. Gastrointest Endosc . 2007;66(1):162–167. https://doi.org/10.1016/j.gie.2007.01.034 .) (From: Kirschniak A, Kratt T, Stüker D, Braun A, Schurr MO, Königsrainer A. A new endoscopic over-the-scope clip system for treatment of lesions and bleeding in the GI tract: first clinical experiences. Gastrointest Endosc . 2007;66(1):162–167. https://doi.org/10.1016/j.gie.2007.01.034 .)

OTSC placement has also been shown to be successful for perforations resulting from polypectomy, first described in the same series by Kirschniak and colleagues. ^{, , , ,} In a prospectively followed cohort, Gubler and colleagues analyzed 7 patients undergoing OTSC placement for polypectomy-associated perforation. Clip placement successfully closed the perforation in all 7 (100%) patients. One patient ultimately warranted surgical evaluation for pain and peritoneal signs, however, the clip was shown to be in situ and the perforation was noted to be appropriately sealed.

To date, there is no published evidence regarding the efficacy of OTSC use for perforations resulting from EBD of IBD-associated strictures. While OTSC closure has been reported to be successful in the setting of perforations after esophageal balloon dilation, ^, it stands to reason, that this may be a future application of OTSCs. The authors have successfully used OTSC to close perforations related to EBD for the treatment of an ileocolonic anastomotic stricture. However, the time required to load the clip and reintubate the colon to the location of perforation should be considered, and in this case, TTSC may have more utility as they can be quickly and easily passed through the scope for small perforations. The authors have successfully employed OTSC to close perforations.

The successful use of OTSCs has also been reported for closing perforations caused by EMR or ESD. ^{, , , ,} Mangiavillano and colleagues described 20 acute perforations, including 4 from EMR and 2 from ESD. The technical success was 20/20 and clinical success was 18/20 (90%). All patients with EMR- or ESD-associated perforations had clinically successful closure using OTSC. Despite the sparse data to date, OTSC placement will likely continue to be of benefit for the closure of acute perforations in the setting of EMR and ESD.

Given the widespread achievement of adequate closure of perforation with OTSCs, in a recent position statement, the ESGE recommended OTSCs for closing larger acute perforations. While there is a paucity of data, the available evidence suggests that OTSC placement will continue to play a role in the endoscopic management of such perforations well into the future.

Management: Suturing, Stenting, and Other Management Approaches of Iatrogenic Perforation

Both TTSC and OTSC may fail or not be technically feasible for the closure of iatrogenic perforations. Much of the literature on additional therapeutic modalities is limited to case reports or case series. Endoscopic suturing, stenting, and band ligation have all been reported to be successful in treating iatrogenic perforations. Endoscopic suturing requires specialized skill and equipment that may not be available in standard endoscopy suites and therefore, the generalizability of this technique may be limited. Suturing was first demonstrated to be successful for large, gaping perforations up to 4 cm in length in a porcine model and may overcome the limitations of clip application. Endoscopic suturing has been shown to assist with closure after full-thickness polypectomy in animal studies and Schulman and colleagues reported on the successful suturing of a gastric perforation arising from balloon dilation of a postsurgical structure. To date, endoscopic suturing has been reported to be successful in the closure of perforations occurring during diagnostic colonoscopy ^, ( Fig. 11.6 ). Kantsevoy and colleagues describe one patient with a perforation resulting from EBD of a transverse colon stricture who was treated successfully with endoscopic suturing. Endoscopic suturing has also been applied to the treatment of iatrogenic perforation in the setting of EMR and ESD, although the literature remains limited. In perhaps the most comprehensive series described above by Kantsevoy et al. 3 patients underwent successful suturing of EMR-associated perforations and 11 for ESD-associated perforations. One patient undergoing clip closure after an EMR-associated perforation developed abdominal pain upon awakening from the initial procedure and underwent an urgent repeat procedure with successful suturing. While two patients underwent laparoscopic evaluation for persistent abdominal pain, complete closure was confirmed at the time of laparoscopy and no adverse events were reported.

A colonic perforation (Panel A) during screening colonoscopy was successfully closed with an endoscopic suture (Panel B).

(From: Kantsevoy SV, Bitner M, Hajiyeva G, et al. Endoscopic management of colonic perforations: clips versus suturing closure (with videos). Gastrointest Endosc . 2016;84(3):487–493. https://doi.org/10.1016/j.gie.2015.08.074 .) (From: Kantsevoy SV, Bitner M, Hajiyeva G, et al. Endoscopic management of colonic perforations: clips versus suturing closure (with videos). Gastrointest Endosc . 2016;84(3):487–493. https://doi.org/10.1016/j.gie.2015.08.074 .)

Stenting of esophageal perforations caused by EBD has been described. Colonic stenting is typically employed for the treatment of malignant colonic strictures, and in rare cases of benign primary or anastomotic CD-associated strictures Currently, there are no reported cases of endoluminal stenting in treating iatrogenic perforation from diagnostic colonoscopy. Kim, et al, however, reported the successful treatment of one EBD-associated perforation with a fully-covered self-expandable metal stent (SEMS). While stenting is described for the management of EMR and ESD-associated esophageal perforations, ^, limited information exists on its utility for colorectal perforations. The author (B.S.) has attempted to use SEMS to close EBD-associated perforation in a CD patient without success.

Band ligation and endoloop placement have been used in the treatment of iatrogenic colon perforation as well. Han and colleagues reported the successful closure of a perforation from a diagnostic colonoscopy with a band ligation device after the failure of endoclip closure with the resolution of peritoneal symptoms. In addition, Ryu and colleagues performed successful treatment of 6 patients with iatrogenic colorectal perforations during diagnostic colonoscopy using a dual-channel therapeutic endoscope. The endoscopists describe affixing an endoloop to the rim of the perforation using clips and subsequently pulling the endoloop to create a “purse-string” effect. Although these varying methods were successful in the literature reported, further study is needed before these methods can be formally recommended for attempted closure of diagnostic perforations.

Fortunately, perforation occurs uncommonly during lower GI endoscopies, especially those performed for screening or diagnostic purposes, as well as those in which biopsy, simple polypectomy, or EMR are performed. As the complexity of what can be accomplished endoscopically has grown to include en bloc resection of large polyps and early-stage cancers, the perforation risk will increase as well. Over the last 20 years, endoscopic management of iatrogenic colorectal perforations has replaced immediate surgical intervention, once the mainstay of management of this complication. Endoscopic techniques including TTSC and OTSC are generally successful with closure rates reported in the range of 80-100%. It is important to note that the evidence behind the additional modalities of treating perforation (stenting, suturing, band-ligation, and purse-string cinching) is limited to case reports and case series. The best evidence exists for endoscopic clip placement, either TTSC or OTSC, depending on the size of the perforation and the endoscopist’s comfort. It is also worth noting that in the evidence of large, gaping perforations, gross peritoneal contamination, or clinical instability, surgery remains the standard of care.

Therapeutic endoscopy-associated perforations in IBD patients have been difficult to manage endoscopically, presumable due to unhealthy tissue at the site with underlying bowel inflammation and fibrosis.

Management: Surgery

Surgical management has been the mainstay of therapy for iatrogenic colon perforation until recently. ^, As the implementation of endoscopic management has grown, avoiding surgery is becoming increasingly common. Large perforations, such as those resulting from a diagnostic or screening colonoscopy, especially those occurring in patients with inadequately cleansed colons, patients who develop frank peritonitis, severe abdominal pain, or clinical deterioration are all indications for operative management. ^{, , ,} Furthermore, surgery is indicated when an endoscopic modality such as clip placement fails. ^, The decision to perform laparoscopy versus open laparotomy generally depends on the clinical status of the patient, the size of the presumed perforation, and the surgical expertise available. Laparoscopic approaches are effective with a lower morbidity. ^{, ,} In a prospective evaluation of 18 patients with iatrogenic colon perforations, Bleier, et al reported similar operative times, shorter length of stay, decreased morbidity, and shorter incision length than open approaches. Laparoscopic approaches may be more cost-efficient than laparotomy when feasible. Although the evidence is graded as weak, the WSES strongly recommends diagnostic laparoscopy as a safe, first-line surgical approach, with conversion to open laparotomy as indicated. Surgical management for endoscopy-associated perforation caries a morbidity risk as high as 45% and mortality as high as 25%. ^, This highlights the need for the attempt of rescue endoscopic approaches first.

Etiologies

Despite the increasing implementation of advanced procedures such as EMR and ESD, the rate of postpolypectomy bleeding (PPB) seems to have decreased over time. ^, The overall risk of bleeding for any colonoscopy is generally well under 1% and ranges from as low as 0.001% to 0.7%. ^{, , , , ,}

Bleeding after colonoscopy is further categorized into immediate and delayed. While the definition of immediate bleeding differs between studies, most agree that immediate bleeding is defined as intraprocedural bleeding lasting greater than 60 seconds or requiring endoscopic hemostasis or clinically significant hematochezia within 24 hours, however, some argue that immediate bleeding is only that which occurs prior to completion of the procedure. Delayed bleeding occurs any time after immediate bleeding, most commonly defined to be within 14 days, although some studies consider delayed bleeding up to 30 days. ^,

The risk of bleeding parallels the invasiveness of the endoscopic procedure. Studies have shown that there is virtually no bleeding risk in diagnostic and screening colonoscopies in which biopsy or polypectomy are not performed. Biopsy alone has been shown to increase the risk for complications, including bleeding. ^, In a study of over 16,000 colonoscopies, of which 5235 patients had colonoscopy without biopsy or polypectomy, 0 patients experienced bleeding complications. Of the 11,083 patients who underwent a biopsy, 53 patients (0.5%) experienced a bleeding complication. When polypectomy is performed the overall clinically significant bleeding risk ranges from as low as 0.1% to over 1%, ^{, , , , ,} although this is highly dependent on a number of factors discussed below. A 2005 study analyzed almost 4000 snare polypectomies and found minor bleeding occurred in 7.0% of cases, although clinically significant bleeding, defined as bleeding resulting in hospitalization, blood transfusion, shock, surgery, or recurrent bleeding after endoscopic intervention occurred in 1.6%. In a study of 69,000 colonoscopies by Rutter and colleagues in which polypectomy was performed, the bleeding rate was 1.14% and polypectomy was found to increase the risk of bleeding over 11-fold. More recently, a meta-analysis of 21 studies, analyzing almost 2 million colonoscopies, showed the PPB rate to be just under 1%.

Three small studies have evaluated the bleeding rate associated with EBD in the terminal ileum and colon. While one small study showed no hemorrhagic complications, larger studies suggest a small but increased risk of bleeding associated with EBD. ^, In a study of 178 patients undergoing 776 dilations, the overall risk of major bleeding requiring transfusion was 1.0% and minor bleeding was 1.3%. A recent meta-analysis confirmed an overall low risk of hemorrhage with endoscopic balloon dilation. Endoscopic stricturotomy is more effective in the treatment of strictures in CD; however it is important to note that endoscopic stricturotomy carries a higher risk of bleeding.

With regard to advanced endoscopic resection techniques, including EMR and ESD, the risk of bleeding is notably higher. During EMR the incidence of intraprocedural and immediate bleeding is significantly higher than delayed bleeding ; however significant differences in reporting immediate and delayed bleeding in the literature. In a 2016 meta-analysis of 6442 patients undergoing EMR, Hassan and colleagues reported a pooled bleeding rate of 6.5% However, in a more recent review, the pooled bleeding rate was shown to be only 4.0% (95% CI 3.5–4.5%). Immediate versus delayed bleeding was not specified in either of these studies. Eleven studies of bleeding rates in patients undergoing ESD were evaluated in the same series and the authors showed a pooled delayed procedural bleeding rate of 2.2% (95% CI 1.5–3.0%) and there was no significant difference between EMR and ESD. Similar results were noted in a meta-analysis of 104 studies including 13,833 tumors undergoing ESD, which showed a delayed bleeding rate of 2.1%. There are limited reports of immediate bleeding during ESD, as given the nature of the procedure, intraprocedural bleeding is quite common and not considered an adverse event. ^,

Risk Factors

An area of great research interest is the underlying risk factors of postpolypectomy and postcolonoscopy bleeding. Given the infrequency of bleeding from screening colonoscopy or colonoscopy with biopsy alone, specific risk factors for bleeding in these circumstances have not been studied, although it stands to reason that patients with any platelet dysfunction or coagulopathy (inherited, acquired, or iatrogenic) are at increased risk for bleeding. This is discussed in detail below. Expectedly, performing polypectomy alone increases the risk of postprocedural bleeding as much as 10-to-11-fold. ^{, ,} When polypectomy is performed, polyp size is one of the most important risk factors for both immediate and delayed bleeding. ^{, , , ,} In a case-control study of 39 cases of PPB compared with 117 controls, for every 1 mm increase in polyp diameter, a 13% increase in the risk of bleeding was noted. Other studies, however, have suggested a smaller magnitude increase in bleeding risk for each 1 mm increase in size. Polyp size greater than 10 mm itself is an independent risk factor for PPB. ^{, , ,} Additional polyp characteristics including pedunculated appearance, laterally spreading tumors, villous histology, and the presence of high-grade dysplasia have been associated with increased risk as well. ^, Inadvertent cutting of a polyp stalk prior to coagulation may also increase the risk of immediate bleeding due to the transection of vessels without adequate cautery. Polyp location in the right colon is also an important risk factor and has been shown to increase the risk as much as 4.7-fold. This is hypothesized to be a consequence of the thinner wall of the right colon, thereby apposing submucosal vessels more closely to the epithelium. Alternative hypotheses suggest that digestive enzymes and bile acids flowing from the ileum may dissolve hemostatic thrombi. ^{, , ,} Other purported risk factors for PPB include; male sex, older age, higher body-mass index, the presence of comorbidities (i.e., cardiac disease, renal disease or ASA [American Society of Anesthesiologists] class III or IV), and having the procedure performed by a nongastroenterologist. ^{, , , , , , ,} The use of systemic corticosteroids is an important risk factor for post-EBD bleeding in IBD patients. There are additional risk factors specifically associated with bleeding after EMR. These include the presence of malignancy and the presence of 3 or more blood vessels in the resection bed. ^{, ,} Albeniz and colleagues developed a scoring system to risk-stratify patients with regard to bleeding risk after EMR. The authors found six factors that correlated with post-EMR bleeding including age ≥75, ASA class III or IV, aspirin use, right-sided lesions, lesion size ≥40 mm, and mucosal gap not closed by hemoclips. The receiver operating characteristic curve of all 6 predictive factors was 0.77. Patients with risk scores of 8-10 had a bleeding risk as high as 40% when EMR was performed. With regard to ESD, much of the literature has focused on risk factors for gastric ESD as the application of ESD into colorectal lesions is relatively recent. Few studies have evaluated specific risk factors for bleeding in patients undergoing colorectal ESD, but have shown that males, failure to prophylactically place a clip, rectal or cecal location, the use of anticoagulants, and significant intraprocedural bleeding are all associated with an increased risk of postprocedural bleeding.

The use of anticoagulants or antiplatelets as a risk factor for endoscopy-associated bleeding warrants specific attention. The risk of bleeding with antiplatelet agents including acetylsalicylic acid (aspirin), nonsteroidal antiinflammatory drugs (NSAIDs), thienopyridines (clopidogrel, prasugrel, ticagrelor), and anticoagulants including intravenous (unfractionated) heparin, subcutaneous (low-molecular-weight) heparin (enoxaparin), or oral anticoagulants (primarily warfarin) has been broadly studied. No studies have evaluated the risk of bleeding in colonoscopy without biopsy or polypectomy as this is an exceedingly rare complication and diagnostic colonoscopy (even with biopsy) and is considered a low-risk procedure by The ASGE Standards of Practice Committee with no recommendation for cessation of antiplatelet agents. Studies have shown no increased risk of bleeding with mucosal biopsy in patients on antiplatelet agents. Much of the focus of the literature is with regard to bleeding risk after polypectomy. Results have been mixed with regards to bleeding risk in patients taking aspirin or NSAIDs and notably, much of the evidence comes from retrospective studies. While some findings suggest an increased risk of bleeding in patients taking aspirin, but not NSAIDs, ^, others have shown no increased risk with these agents. ^, A meta-analysis of 9 studies by Shalman and colleagues, confirmed no increased risk of PPB attributable to aspirin or NSAID use. However, a more recent systematic review and meta-analysis by Pigo and colleagues, which included prospective studies, found a small but significant increased risk of delayed, but not immediate PPB in patients on uninterrupted aspirin or NSAID therapy with an odds ratio of 1.7 (95% CI 1.7-2.2). The ASGE Standards of Practice Committee guidelines consider polypectomy to be a low-risk procedure with regards to hemorrhage in patients on uninterrupted aspirin or NSAIDs. These authors and others recommended that aspirin be continued in patients undergoing polypectomy if there is a reasonable indication for its use. ^,

Data on other antiplatelet agents has shown similarly mixed results. A retrospective study of 142 patients undergoing 375 polypectomies maintained on thienopyridine therapy compared with 1,243 controls showed similar rates of immediate bleeding, although a higher risk of delayed bleeding, including bleeding requiring hospitalization, transfusion, and/or intervention. Two meta-analyses examined the same question and both studies found an increased risk of delayed PPB, ^, whereas only one showed an increased risk of immediate bleeding in patients on uninterrupted thienopyridine therapy. ASGE and the American College of Gastroenterology (ACG) regard polypectomy as a high-risk procedure in patients on uninterrupted thienopyridine therapy. ^, Joint guidelines by the American College of Cardiology and ACG recommend avoiding cessation of thienopyridines within 30 days after cardiac stent placement, deferring elective procedures up to 12 months if possible, and if thienopyridine therapy is held, performing the endoscopic procedure within 5-7 days. It is generally accepted that therapeutic anticoagulation with unfractionated heparin, low-molecular-weight heparin, and oral agents such as coumadin, or direct-acting oral anticoagulants increase the risk of bleeding with polypectomy, EMR, and ESD ^{, , , ,} with a risk as high as 13-fold. There is no evidence to suggest increased bleeding with mucosal biopsy in the patients on anticoagulant medication. A case-control study of 41 patients who developed PPB compared with 132 controls demonstrated that reinitiating therapeutic anticoagulation within one week of polypectomy increased the odds of PPB more than 5-fold. The decision on continued withholding of therapeutic anticoagulation depends on the degree of thrombotic risk. If the risk is felt to be high, patients may be bridged with either unfractionated or low-molecular-weight heparin in the week leading up to the procedure. Studies with heparin bridging have also shown mixed results with regard to PPB. In a retrospective uncontrolled study, Gerson and colleagues showed no increased risk of PPB in patients bridged with heparin. However, two more recent retrospective studies demonstrated in an increased risk of PPB with heparin bridging as high as 20%. ^, Furthermore, two meta-analyses suggested an increased risk of periprocedural bleeding. Siegel and all reviewed 34 studies including over 12,000 patients demonstrated that patients treated with heparin or low-molecular-weight heparin bridge therapy had an increased risk of overall bleeding (odds ratio [OR] 5.4) and major bleeding (OR 3.6) with no significant difference in thrombotic events (0.9% vs. 0.6%). These studies, however, were not specific to colonoscopy. Subsequently, Jaruvongvanich et al. reviewed five studies, including over 2600 patients undergoing heparin bridging specifically for polypectomy, and similarly found an increased risk of bleeding (pooled OR 8.29, 95% CI 4.96–13.87). Despite these findings, bridging therapy is still recommended for patients undergoing high-risk procedures (including polypectomy) for patients with atrial fibrillation and a history of cerebrovascular accident or a CHA ₂ DS ₂ -VASc score of ≥2 and or with mechanical valves and for patients without atrial fibrillation who have mechanical valves other than bi-leaflet mechanical aortic valves. Debate remains as to when to resume anticoagulants and antiplatelet therapy after colonoscopy, and generally antithrombotic or antiplatelet therapy should be resumed as soon as the risk of hemorrhage is felt to be sufficiently low.

Prevention

While endoscopic therapy is generally successful, given the possible requirement for hospitalization, transfusion, or repeat colonoscopy, much of the focus in the literature has been on the prevention of bleeding when polyps are removed. Aside from ensuring patients’ coagulation factors and platelets are in an appropriate range and anticoagulation has been held for an appropriate interval, there are additional mechanisms described that may reduce the risk of immediate and delayed bleeding after polypectomy.

The decision to use hot snare versus cold snare polypectomy may impact bleeding risk. Cold snare polypectomy is safe for polyps <10 mm. In a prospective study of 823 patients with polyps smaller than 10 mm, no cases of delayed bleeding were reported with cold snare polypectomy. Two meta-analyses have examined the safety of cold versus hot snare polypectomy for small polyps. One study showed a small increase in immediate bleeding with cold snare polypectomy, although bleeding ceased spontaneously in all cases and no patients required endoscopic therapy. Shinozaki et al. performed a subsequent meta-analysis of 8 studies of 1665 patients and showed a nonsignificant trend toward reduced PPB with cold snare polypectomy. In both analysis procedures, time was faster with cold snare polypectomy than with hot snare polypectomy. Furthermore, cold snare polypectomy was shown to be safer in patients on coumadin.

The benefit of using any form of bleeding prophylaxis was demonstrated in a meta-analysis of eight studies involving 2595 polyps. The investigators reported that prophylaxis was beneficial in reducing immediate bleeding (OR 0.34), but not delayed bleeding. Mechanisms to prevent immediate and delayed PPB include epinephrine injection, prophylactic hemoclipping, and the use of a detachable snare (endoloop) placed around the stalk of a polyp prior to polypectomy. In most studies, submucosal epinephrine injection has been shown to effectively reduce the rate of immediate but not delayed PPB. ^{, ,} This is accomplished by injecting dilute epinephrine (1:10,000) into the base or stalk of a polyp before resection. As such, many submucosal lifting agents used for polypectomy contain dilute epinephrine.

Endoscopic devices have also been used to prevent PPB. Prophylactic use of a detachable snare (endoloop), encircled around the base of the polyp stalk before resection, successfully reduces the risk of both immediate and delayed PPB. ^{, ,} In a three-arm randomized trial of 488 patients undergoing polypectomy of pedunculated polyps >10 mm, endoloop placement was directly compared with both conventional polypectomy and epinephrine injection. Rates of post polypectomy bleeding were similar between epinephrine injection and endoloop arms, although this risk was lower in both groups compared with conventional polypectomy. Additionally, Paspatis, et al, showed that the combination of epinephrine injection plus endoloop placement was superior to the injection of epinephrine alone in patients with polyps ≥20 mm in size, although this finding was primarily driven by a reduction in immediate bleeding. Perhaps the most studied prophylactic measure is TTSC placement ( Fig. 11.7 ). While clip placement is noninferior to endoloop placement for the prevention of PPB, the efficacy of prophylactic clipping remains under debate. Certain studies have shown clip placement to be beneficial in reducing immediate and delayed bleeding ^, including in patients on anticoagulation, however, the benefit may be limited to larger polyps. Zhang and colleagues prospectively randomized 348 patients with polyps 10–40 mm in size to clip closure versus no clip closure and showed a decreased risk of delayed PPB (1.1% vs. 6.9%, p = 0.01), as well as decreased length of hospital stay and greater patient satisfaction. Other studies, however, suggest that prophylactic clip placement does not reduce the risk of bleeding ^, and even has the potential to cause harm as an increased risk of perforation and mucosal burns have been reported. The addition of endoloops to prophylactic clipping has also been evaluated in a prospective randomized trial. This modality was compared to epinephrine injection alone and shown to be significantly more effective in patients with pedunculated polyps ≥20 mm. Given the cost of hemoclips and the mixed results in the literature, the cost-effectiveness of prophylactic clipping has come into question. Parikh and colleagues showed that prophylactic clip placement was cost-effective for patients who require anticoagulation, but otherwise was not.

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