Chapter 25

Prevention and Management of Bleeding

Dushant S. Uppal, MD, MS and Andrew Y. Wang, MD, AGAF, FACG, FASGE

Introduction

Skill and experience with endoscopic hemostasis is a requirement before embarking on any type of advanced endoscopic resection in the luminal gastrointestinal (GI) tract. As with most aspects of interventional endoscopy, being prepared and anticipating problems before they occur are central to performing safe and effective procedures. This same strategy applies to preventing and managing endoscopic bleeding. Bleeding associated with endoscopic resection can occur immediately during a procedure or it can occur in a delayed fashion, sometimes up to 2 or 3 weeks after a large resection. Following a widefield piecemeal endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), delayed bleeding is a serious risk, and patients and physicians should be prepared should such an adverse event occur.

Rates of Bleeding From Endoscopic Resection

The frequency of bleeding following routine colonoscopic polypectomy is typically < 1%.¹ However, when EMR is performed, much higher bleeding rates have been reported in the esophagus (4% to 20% for EMR of squamous cell lesions and 0% to 33% for EMR of Barrett’s lesions), stomach (1% to 22%), and colon (0% to 45%).² With newer-generation adaptive electrosurgical generators that modulate the amount of energy required and use proprietary settings that deliver cycles of cutting and coagulating current, bleeding rates following EMR are typically in the lower end of the ranges provided above. However, it has been demonstrated that EMR of larger lesions is associated with greater bleeding risk, with > 32% of bleeding for lesions > 3 cm in one series.³

A French study of 188 ESDs from throughout the GI tract (though predominantly in the stomach and rectum), conducted at multiple centers largely in the developmental phase of offering ESD, reported clinically significant ESD-related bleeding in 11.2% of cases, with 19% of those cases requiring transfusion but no surgical intervention.4

Preprocedural Lab Testing

For most endoscopic procedures, routine preprocedural lab testing (including platelet count, prothrombin time, and partial thromboplastin time) is not required or recommended because of the low likelihood that testing will influence perioperative management.⁵ The exception would be for patients with a history of easy bleeding, bruising, bleeding diatheses, or suspected thrombocytopenia. However, treatment including preprocedural testing must be individualized to the patient and to local or regional norms, which requires taking into account anesthesia protocols. Preprocedural lab testing in patients who might undergo a large piecemeal EMR or en bloc ESD, particularly if general anesthesia is to be performed for an upper GI tract lesion, is not unreasonable.

Antiplatelet and Antithrombotic Agents

The field of antiplatelet and antithrombotic agents is continually changing, and physicians should consult the most updated guidelines and resources in terms of managing these medications prior to any significant endoscopic resection. Polypectomy, EMR, and ESD were all categorized as high-risk procedures in a 2016 American Society for Gastrointestinal Endoscopy guideline.⁶ In general, use of aspirin in patients undergoing any form of endoscopic resection (including ESD) is acceptable if there is a good indication for this medication.⁷ When possible, it is advisable to discontinue thienopyridines (eg, clopidogrel) at least 5 to 7 days before endoscopic resection and/or switch to aspirin monotherapy until the thienopyridine can be safely resumed.⁶ Anticoagulation medications (ie, warfarin; the direct thrombin inhibitor dabigatran; and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban) should be discontinued for an appropriate drug-specific interval in the periendoscopic period. In situations of elevated thromboembolic risk, bridge therapy with shorter-acting unfractionated heparin and low molecular weight heparin (enoxaparin) may be required.

Endoscopic Techniques to Limit and Control Bleeding

It is strongly advised to use newer-generation endoscopes that offer high-definition imaging and have a dedicated water-jet feature when attempting a large endoscopic resection. High-quality imaging is critical to identification of bleeding vessels, and the ability to irrigate water during active bleeding affords a clean endoscopic field for treatment and also reduces blood clotting, which can make identification of the bleeding vessel impossible.

When performing submucosal-lifting to assist in endoscopic resection, one consideration is to use very dilute epinephrine (1:100,000 to 1:200,000) in the lifting solution to provide hemostasis of small vessels. While systemic effects such as severe hypertension, ventricular tachycardia, and intestinal ischemia have been reported, injection of very dilute epinephrine is generally a safe practice. However, the resultant mucosal blanching due to epinephrine can sometimes make delineation of the borders of a lesion difficult if they were not marked beforehand.⁸

In situations where bleeding occurs after hot-snare resection, the tip of the snare can be used to efficiently and safely coagulate the bleeding vessel using a soft coagulation mode at 50 W to 80 W.9 When there is a brisk hemorrhage, injection of 1:10,000 epinephrine solution into the submucosa can slow the bleeding to allow identification of the bleeding site for therapy. Submucosal epinephrine injection should not be used as monotherapy.¹⁰ A variety of monopolar (snare-tip, closed hot-biopsy forceps), bipolar/multipolar, and other (heater probe) devices can be used to provide coagulation. In situations in which the vessel is large, 1 to 2 mm in size or greater, atraumatic hemostatic forceps (Coagrasper, Olympus) are often required. A general rule is if the vessel in question is larger than the width of the blade of the ESD knife that one is using, hemostatic forceps are advisable. In bleeding situations where the endoscopic resection has already been completed, placement of endoclips is another option. When using hemostatic forceps or endoclips, we recommend closing the device around the bleeding site and watching for bleeding cessation due to mechanical force (before applying electrosurgical energy or firing the clip), which signifies that the device has been closed over the appropriate area. It should be recognized that bleeding vessels ≥ 2 to 3 mm in size might not respond effectively to endoscopic hemostasis techniques and the resultant blood loss can be severe and rapid. During situations of difficult-to-control hemorrhaging, while the endoscopist is attempting to stop the bleeding using a large hemostatic forceps or an endoclip, the interventional radiology team and surgical team should also be notified, and preparations for emergency red-blood-cell transfusion should be made.

Endoscopic Submucosal Dissection–Associated Bleeding

While bleeding is a significant concern following snare polypectomy and EMR, the ability to prevent and manage bleeding during ESD can mean the difference between success and failure. Bleeding is a major obstacle when performing ESD and can lead to inability to visualize the dissection plane, which can result in perforation during the act of bleeding control or subsequent submucosal dissection.

ESD-related bleeding has been separated into intraprocedural, postprocedural (typically within 48 hours of the procedure), and delayed (> 48 hours).¹¹ While 50% to 70% of postprocedural bleeding occurs within 2 days of ESD, bleeding may be delayed and can occur up to 2 weeks later.^12,13 Early bleeding rates with ESD in Japan were reported to be 7% for immediate bleeding and 6% to 8% for delayed bleeding.^14,15 Bleeding rates from ESD have been reported anywhere from 0% to 15.6%¹⁶ with immediate bleeding being the most frequently recognized occurrence. Organ-specific rates of delayed bleeding can range from 0% to 5% in the esophagus, 0% to 16% in the stomach, and 0% to 3% in the colorectum.¹⁷ Although immediate bleeding is generally felt to be easily managed, delayed bleeding is often more dangerous because of potential cardiovascular compromise—particularly in a patient who is at home—and the difficulty of arranging urgent endoscopic intervention, which typically necessitates an inpatient admission. Thus, strategies to mitigate intraprocedural bleeding and limit delayed bleeding are imperative for successful ESD.

Risk Factors for Bleeding From Endoscopic Submucosal Dissection

Various studies and expert reviews have discussed certain risk factors for ESD-related bleeding including use of antithrombotic agents,^15,18–40 specimen and resection-site size,^{15,19,28,37,41–46} and the anatomic location of ESD.^{15,27,28,37,44,47–53} While discordant results have been reported among some studies, the data overall appear to support the notion that the risk of ESD bleeding is greater in patients on anticoagulation therapy, those undergoing larger resections, and for ESD procedures being performed in the stomach and duodenum.

A recent large systematic review and meta-analysis found that the following risk factors were associated with postprocedural bleeding following gastric ESD: male sex (odds ratio [OR], 1.25), cardiomyopathy (OR, 1.54), antithrombotic drugs (OR, 1.63), cirrhosis (OR, 1.76), chronic kidney disease (OR, 3.38), tumor size > 20 mm (OR, 2.70), resected specimen size > 30 mm (OR, 2.85), localization in the lesser curvature (OR, 1.74), flat/depressed morphology (OR, 1.43), carcinoma histology (OR, 1.46), and ulceration (OR, 1.64). Procedure duration > 60 minutes (OR, 2.05) and the use of H2-receptor antagonists instead of proton pump inhibitors (PPIs) (OR, 2.13) were the procedural factors associated with post-ESD bleeding. Age, hypertension, submucosal invasion, and fibrosis were not risk factors for postprocedural bleeding.28

Resection Size

Expanding indications for ESD throughout the GI tract have led to the resection of large superficial dysplastic lesions. In contrast to data that showed increasing lesion size for EMR correlates with higher rates of bleeding, the data concerning ESD specimen size and delayed bleeding are somewhat inconclusive. Takizawa et al¹⁵ found no significant increased risk of delayed bleeding based on specimen resection size for gastric ESD. The lack of association between specimen size and bleeding has also been supported by studies of colorectal ESD.^44,45 However, as mentioned previously, other studies have demonstrated increased delayed bleeding risk with larger resected specimen sizes (> 30 mm) attributed to larger ulcer beds and the propensity for more exposed vessels.^{19,28,37,41,42,46,54} Lesion morphology may also be an important factor as Bae and colleagues⁴³ described increased intraprocedural and postprocedural bleeding in patients undergoing ESD for protruding lesions vs laterally spreading tumors (with respective intraprocedural bleeding rates of 22.4% vs 2.6%, P < .001, and postprocedural bleeding rates of 6.0% vs 0.7%, P = .031).

Organ-Specific Bleeding Concerns

Differences in bleeding from ESD have also been described based on location within the GI tract. Traditionally, locations such as the gastric fundus, the duodenum, and the cecum have been considered areas at increased risk for bleeding given increased vascularity. Generally speaking, intraprocedural bleeding is more common for gastric ESD in the proximal stomach, whereas delayed bleeding tends to occur more frequently following resection of distal gastric lesions.^14,17 Some authors have suggested that, although the antrum has little fibrotic tissue and a low density of perforating vessels,⁵⁵ antral contractility and bile exposure may lead to poor healing and subsequent bleeding.^15,56

Regarding colorectal ESD and bleeding, 2 studies reported a greater risk of bleeding for ESD performed within the rectum.^44,53 Coskun et al⁴⁸ commented that this increased bleeding risk may be related to copious vascularization within the rectum from the inferior mesenteric artery, internal iliac arteries, and the middle sacral artery. Additionally, Suzuki et al⁴⁹ described an increased risk of post-ESD bleeding in patients undergoing therapy for cecal lesions.

While the data are somewhat limited, the post-ESD bleeding risk in the esophagus appears to be low (< 1% to 6%),^17,47 whereas duodenal ESD likely carries the highest risk of post-ESD bleeding (8.4% to 18.4%).^50,52,57 Because of the increased rates of bleeding and perforation, duodenal ESD should be performed only by those endoscopist with extensive expertise in performing ESD in the upper and lower GI tracts.

Intraprocedural bleeding during ESD is common and may vary from small-volume, transient, venous bleeding, to more profuse arterial spurting, which may obscure the resection field thereby increasing the risk of perforation or a failed procedure. Therefore, meticulous dissection of the submucosal layer to enable visualization of vessels followed by preemptive coagulation is critical to performing successful ESD. Small vessels (≤ 1 mm) can often be simultaneously cut through and coagulated by using various types of blended current (in most instances of submucosal dissection we prefer SWIFT COAG 50 to 60 W (using a VIO300D electrosurgical unit, Erbe) and any type of ESD knife without slowing the dissection. Other possible settings for dividing and coagulating small vessels with an ESD knife, when using a VIO300D, include ENDO CUT, DRY CUT, SPRAY COAG, and FORCED COAG.58 Slow, deliberate movement of the knife through the vessel is important to maximize energy delivery and ensure hemostasis, particularly when using a primarily cutting current.

When larger veins (red cords, ≥ 2 mm) or perforating arterioles/arteries (white cords, due to a more muscular wall) are encountered, proactive coagulation using hemostatic forceps with SOFT COAG current (available on the VIO300D and also on electrosurgical units from other vendors) is advised prior to continuing dissection. This tends to occur more commonly in the proximal stomach, where perforating vessels are larger.⁵⁸ When larger vessels are identified, it is useful to skeletonize the vessel so that if it bleeds or retracts after application of electrosurgical energy further treatment is possible without additional dissection to expose the vessel. In instances where bleeding cannot be controlled with an ESD knife, hemostatic forceps can be used to grasp the bleeding vessel and apply coagulation current. Care should be taken to tent the vessel away from the underlying muscle to avoid deeper thermal injury, and generally, soft coagulation current is recommended to avoid deep muscle injury. Multipurpose grasping-type ESD scissors have been developed and described as an effective tool that enables incision, submucosal dissection, and hemostasis.^59,60

As discussed in prior chapters, ESD may be carried out using multiple different dissection devices (needle-type knives, insulated-type knives, scissors-type tools). In addition to specialized dissection devices and durable injection solutions, the modern adaptive electrosurgical unit has revolutionized the field of ESD enabling safer and more controlled cutting and dissection. While beyond the purview of this chapter, an understanding of the various settings on the electrosurgical unit used in your endoscopy lab is critical to performing safe and effective endoscopic resection.⁶¹ Rarely necessary, salvage therapy using Hemospray (Cook Medical) at the resection site or temporary mechanical tamponade using the endoscope (typically using the short distal attachment cap) of the actively bleeding vessel may be required to achieve hemostasis in instances of massive bleeding.^62,63

Proton Pump Inhibitor Therapy

Acid secretion inhibitors are commonly used to promote healing of ulcers that are created following ESD in the upper GI tract. A prospective study of patients undergoing gastric ESD demonstrated a significant reduction in delayed bleeding in those patients given the PPI pantoprazole (3.5%) vs patients given the H2-receptor antagonist famotidine (12.7%, P = .031).⁶⁴ A multivariate analysis by Uedo and colleagues⁶⁵ corroborated the superiority of PPI vs H2-receptor antagonists for reducing the likelihood of post-ESD bleeding in the stomach. In both studies, PPI was administered following the procedure. Additional studies suggest that 2 weeks,⁶⁶ or even as little as 1 week,⁶⁷ of PPI therapy might be as effective as longer durations in achieving post-ESD ulcer scar formation. Interestingly, a trial by Ono et al68 that randomized 81 patients to receive preoperative PPI before ESD vs 74 patients who received PPI only after ESD found no significant difference in delayed bleeding rates between the 2 groups (7.7% vs 7.4%). Overall, we recommend post-ESD PPI therapy for patients undergoing ESD in the esophagus, stomach, or duodenum to reduce acid exposure and the risk of delayed bleeding, and to promote ulcer healing.

Second-Look Endoscopy

A prior meta-analysis suggested that second-look endoscopy (SLE) following initial hemostasis of exposed vessels at the time of gastric ESD significantly reduced the risk of recurrent peptic ulcer bleeding.⁶⁹ More recently, however, a systematic review and meta-analysis of gastric ESD by Nishizawa et al⁷⁰ revealed no advantage of SLE for the prevention of post-ESD bleeding in patients without a high-risk of bleeding. Multiple other studies have also demonstrated no additional benefit in preventing delayed bleeding with SLE following gastric ESD.^28,71–77 In general, we no longer perform SLE following ESD.

Postendoscopic Submucosal Dissection Coagulation

Post-ESD coagulation (PEC) of nonbleeding visible vessels has been advocated following ESD in the stomach and upper GI tract to reduce the risk of delayed bleeding. A retrospective review of 968 patients who underwent ESD for early gastric cancers found a delayed bleeding rate of 3.1% for patients undergoing PEC vs 7.1% in patients undergoing ESD without proactive coagulation of nonbleeding vessels (P < .01), leading the authors to surmise that delayed bleeding after ESD for early gastric cancers might be prevented by PEC.¹⁵

However, this technique may not be as effective when applied in the colorectum. Bahin and colleagues⁷⁸ conducted a prospective trial that randomized 347 patients with colorectal polyps larger than 2 cm to prophylactic endoscopic coagulation or to no additional therapy following widefield EMR. Clinically significant post-EMR bleeding occurred in 9 patients receiving prophylactic endoscopic coagulation (5.2%) and in 14 controls (8.0%, P = .30). These investigators concluded that prophylactic endoscopic coagulation does not significantly decrease the incidence of clinically significant bleeding following widefield colorectal EMR, which raises the question whether PEC is necessary or effective following colorectal ESD.

Endoscopic Closure

In an effort to prevent post-ESD bleeding, innovative methods of defect closure have been employed. Generally, larger ESD resections are associated with larger luminal ulcers, more numerous exposed visible vessels in the resection base, and the resultant potential for increased bleeding. While clip closure to prevent post-ESD bleeding may be optimal for smaller defects, large defect closure may be technically difficult and incomplete. Lee et al⁷⁹ reported on the successful use of a detachable soft loop-snare in conjunction with endoclips to achieve endoscopic closure of ESD defects. Otake and colleagues⁸⁰ used small mucosal incisions made around large colorectal ESD resection sites with a significant amount of exposed muscle to give clips a “hand-hold,” thereby enabling the efficient closure of large defects. A small but interesting study by Osada et al⁸¹ demonstrated, on relook colonoscopy 4 weeks after colorectal ESD, that the rate of ulcer reduction (P = .01) and the rate of complete healing (69.2% vs 7.7%, P = .005) was superior in the group that had clip closure (augmented by using a loop clip) of their post-ESD defects.

Kantsevoy et al82 retrospectively reported no delayed bleeding in 12 patients who underwent endoscopic suturing to close ESD resection sites. While endosuturing is not practical or possible in all locations of the luminal GI tract (it is difficult to perform in the duodenum and right colon), closure of large defects might obviate the need to admit patients after ESD for observation in case of post-ESD bleeding or perforation. While conceptually reasonable, more data are required regarding the costs and benefits of this practice.

Summary

Bleeding is the most common complication of endoscopic resection of luminal neoplasia, be it by polypectomy, EMR, or ESD. Although intraprocedural bleeding is relatively common and easily treated, it can lead to suboptimal outcomes due to poor resultant visualization, which is associated with an increased risk of perforation and incomplete resection, in particular when performing ESD. Delayed bleeding following endoscopic resection can lead to serious clinical consequences, given the potential for delayed resuscitation and hemostatic therapy, as this often occurs days after EMR or ESD when patients are at home.

When performing ESD, intraprocedural bleeding may be mitigated by meticulous submucosal dissection using the proper tools, good technique, and by proper use of modern electrosurgical units. The rate of post-ESD bleeding for upper GI tract lesions can be reduced by ensuring that the resection bed has been carefully inspected and appropriate PEC has been applied, particularly in the stomach. Endoscopic suturing is an innovative method of closing large defects following widefield piecemeal EMR or ESD, which might reduce the risk of delayed bleeding and obviate the need for inpatient observation. By understanding the factors that might contribute to bleeding during and after ESD, and with continued technical innovation and experience, clinically significant ESD-associated bleeding should be uncommon and manageable. Expertise in preventing and managing the bleeding that occurs with ESD is critical to successful outcomes and broader application of this innovative technique.

References

1.     ASGE Standards of Practice Committee, Fisher DA, Maple JT, et al. Complications of colonoscopy. Gastrointest Endosc. 2011;74(4):745-752. doi:10.1016/j.gie.2011.07.025.

2.     Conio M, Ponchon T, Blanchi S, Filiberti R. Endoscopic mucosal resection. Am J Gastroenterol. 2006;101(3):653-663. doi:10.1111/j.1572-0241.2006.00424.x.

3.     Ahmad NA, Kochman ML, Long WB, Furth EE, Ginsberg GG. Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases. Gastrointest Endosc. 2002;55(3):390-396. doi:10.1067/mge.2002.121881.

4.     Farhat S, Chaussade S, Ponchon T, et al. Endoscopic submucosal dissection in a European setting. A multi-institutional report of a technique in development. Endoscopy. 2011;43(8):664-670. doi:10.1055/s-0030-1256413.

5.     ASGE Standards of Practice Committee, Pasha SF, Acosta R, et al. Routine laboratory testing before endoscopic procedures. Gastrointest Endosc. 2014;80(1):28-33. doi:10.1016/j.gie.2014.01.019.

6.     ASGE Standards of Practice Committee, Acosta RD, Abraham NS, et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83(1):3-16. doi:10.1016/j.gie.2015.09.035.

7.     Wang AY, Emura F, Oda I, Cox DG, Kim HS, Yeaton P. Endoscopic submucosal dissection with electrosurgical knives in a patient on aspirin therapy (with video). Gastrointest Endosc. 2010;72(5):1066-1071. doi:10.1016/j. gie.2010.06.008.

8.     ASGE Technology Committee, Hwang JH, Konda V, et al. Endoscopic mucosal resection. Gastrointest Endosc. 2015;82(2):215-226. doi:10.1016/j.gie.2015.05.001.

9.     Fahrtash-Bahin F, Holt BA, Jayasekeran V, Williams SJ, Sonson R, Bourke MJ. Snare tip soft coagulation achieves effective and safe endoscopic hemostasis during wide-field endoscopic resection of large colonic lesions (with videos). Gastrointest Endosc. 2013;78(1):158-163.e1. doi:10.1016/j.gie.2013.02.030.

10.   Calvet X, Vergara M, Brullet E, Gisbert JP, Campo R. Addition of a second endoscopic treatment following epinephrine injection improves outcome in high-risk bleeding ulcers. Gastroenterology. 2004;126(2):441-450.

11.   Lim SM, Park JC, Lee H, Shin SK, Lee SK, Lee YC. Impact of cumulative time on the clinical outcomes of endoscopic submucosal dissection in gastric neoplasm. Surg Endosc. 2013;27(4):1397-1403. doi:10.1007/s00464-012-2643-3.

12.   Goto O, Fujishiro M, Kodashima S, et al. A second-look endoscopy after endoscopic submucosal dissection for gastric epithelial neoplasm may be unnecessary: a retrospective analysis of postendoscopic submucosal dissection bleeding. Gastrointest Endosc. 2010;71(2):241-248. doi:10.1016/j.gie.2009.08.030.

13.   Ryu HY, Kim JW, Kim HS, et al. Second-look endoscopy is not associated with better clinical outcomes after gastric endoscopic submucosal dissection: a prospective, randomized, clinical trial analyzed on an as-treated basis. Gastrointest Endosc. 2013;78(2):285-294. doi:10.1016/j.gie.2013.02.008.

14.   Oda I, Gotoda T, Hamanaka H, et al. Endoscopic submucosal dissection for early gastric cancer: technical feasibility, operation time and complications from a large consecutive serIES. Dig Endosc. 2005;17(1):54-58. doi:10.1111/j.1443-1661.2005.00459.x.

15.   Takizawa K, Oda I, Gotoda T, et al. Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection—an analysis of risk factors. Endoscopy. 2008;40(3):179-183. doi:10.1055/s-2007-995530.

16.   Oda I, Suzuki H, Nonaka S, Yoshinaga S. Complications of gastric endoscopic submucosal dissection. Dig Endosc. 2013;25(Suppl 1):71-78. doi:10.1111/j.1443-1661.2012.01376.x.

17.   Takizawa K. Prevention, identification, and treatment of hemorrhage. In: Fukami N, ed. Endoscopic Submucosal Dissection: Principles and Practice. New York, NY: Springer; 2015.

18.   Koh R, Hirasawa K, Yahara S, et al. Antithrombotic drugs are risk factors for delayed postoperative bleeding after endoscopic submucosal dissection for gastric neoplasms. Gastrointest Endosc. 2013;78(3):476-483. doi:10.1016/j. gie.2013.03.008.

19.   Matsumura T, Arai M, Maruoka D, et al. Risk factors for early and delayed post-operative bleeding after endoscopic submucosal dissection of gastric neoplasms, including patients with continued use of antithrombotic agents. BMC Gastroenterol. 2014;14:172. doi:10.1186/1471-230X-14-172.

20.   Takeuchi T, Ota K, Harada S, et al. The postoperative bleeding rate and its risk factors in patients on antithrombotic therapy who undergo gastric endoscopic submucosal dissection. BMC Gastroenterol. 2013;13:136. doi:10.1186/1471-230X-13-136.

21.   Dong J, Wei K, Deng J, et al. Effects of antithrombotic therapy on bleeding after endoscopic submucosal dissection: A systematic review and meta-analysis. Gastrointest Endosc. 2017;86(5):807-816. doi:10.1016/j.gie.2017.07.017.

22.   Furuhata T, Kaise M, Hoteya S, et al. Postoperative bleeding after gastric endoscopic submucosal dissection in patients receiving antithrombotic therapy. Gastric Cancer. 2017;20(1):207-214. doi:10.1007/s10120-015-0588-7.

23.   Gotoda T, Hori K, Iwamuro M, et al. Evaluation of the bleeding risk with various antithrombotic therapies after gastric endoscopic submucosal dissection. Endosc Int Open. 2017;5(7):E653-E662. doi:10.1055/s-0043-110050.

24.   Harada H, Suehiro S, Murakami D, et al. Continuous use of low-dose warfarin for gastric endoscopic submucosal dissection: a prospective study. Endosc Int Open. 2017;5(5):E348-E353. doi:10.1055/s-0043-105493.

25.   Igarashi K, Takizawa K, Kakushima N, et al. Should antithrombotic therapy be stopped in patients undergoing gastric endoscopic submucosal dissection? Surg Endosc. 2017;31(4):1746-1753. doi:10.1007/s00464-016-5167-4.

26.   Kono Y, Obayashi Y, Baba Y, et al. Postoperative bleeding risk after gastric endoscopic submucosal dissection during antithrombotic drug therapy. J Gastroenterol Hepatol. 2018;33(2):453-460. doi:10.1111/jgh.13872.

27.   Lee JY, Kim CG, Cho SJ, Kim YI, Choi IJ. Is the reinitiation of antiplatelet agents safe at 1 week after gastric endoscopic submucosal dissection? Assessment of bleeding risk using the Forrest Classification. Gut Liver. 2017;11(4):489-496. doi:10.5009/gnl16232.

28.   Libânio D, Costa MN, Pimentel-Nunes P, Dinis-Ribeiro M. Risk factors for bleeding after gastric endoscopic submucosal dissection: a systematic review and meta-analysis. Gastrointest Endosc. 2016;84(4):572-586. doi:10.1016/j. gie.2016.06.033.

29.   Ninomiya Y, Oka S, Tanaka S, et al. Risk of bleeding after endoscopic submucosal dissection for colorectal tumors in patients with continued use of low-dose aspirin. J Gastroenterol. 2015;50(10):1041-1046. doi:10.1007/s00535-015-1053-4.

30.   Ogasawara N, Yoshimine T, Noda H, et al. Clinical risk factors for delayed bleeding after endoscopic submucosal dissection for colorectal tumors in Japanese patients. Eur J Gastroenterol Hepatol. 2016;28(12):1407-1414. doi:10.1097/MEG.0000000000000723.

31.   Ojima T, Takifuji K, Nakamura M, et al. Complications of endoscopic submucosal dissection for gastric noninvasive neoplasia: an analysis of 647 lesions. Surg Laparosc Endosc Percutan Techn. 2014;24(4):370-374. doi:10.1097/SLE.0b013e318290132e.

32.   Ono S, Fujishiro M, Niimi K, et al. Technical feasibility of endoscopic submucosal dissection for early gastric cancer in patients taking anti-coagulants or anti-platelet agents. Dig Liver Dis. 2009;41(10):725-728. doi:10.1016/j. dld.2009.01.007.

33.   Sanomura Y, Oka S, Tanaka S, et al. Continued use of low-dose aspirin does not increase the risk of bleeding during or after endoscopic submucosal dissection for early gastric cancer. Gastric Cancer. 2014;17(3):489-496. doi:10.1007/s10120-013-0305-3.

37.   Yano T, Tanabe S, Ishido K, et al. Different clinical characteristics associated with acute bleeding and delayed bleeding after endoscopic submucosal dissection in patients with early gastric cancer. Surg Endosc. 2017;31(11):4542-4550. doi:10.1007/s00464-017-5513-1.

38.   Yoshida N, Naito Y, Murakami T, et al. High incidence of postoperative hemorrhage in colorectal endoscopic submucosal dissection during anticoagulant therapy. Int J Colorectal Dis. 2016;31(8):1487-1488. doi:10.1007/s00384-016-2540-7.

39.   Yoshio T, Nishida T, Kawai N, et al. Gastric ESD under Heparin replacement at high-risk patients of thromboembolism is technically feasible but has a high risk of delayed bleeding: Osaka University ESD Study Group. Gastroenterol Res Pract. 2013;2013:365830. doi:10.1155/2013/365830.

40.   Yoshio T, Tomida H, Iwasaki R, et al. Effect of direct oral anticoagulants on the risk of delayed bleeding after gastric endoscopic submucosal dissection. Dig Endosc. 2017;29(6):686-694. doi:10.1111/den.12859.

41.   Chung IK, Lee JH, Lee SH, et al. Therapeutic outcomes in 1000 cases of endoscopic submucosal dissection for early gastric neoplasms: Korean ESD Study Group multicenter study. Gastrointest Endosc. 2009;69(7):1228-1235. doi:10.1016/j.gie.2008.09.027.

42.   Mannen K, Tsunada S, Hara M, et al. Risk factors for complications of endoscopic submucosal dissection in gastric tumors: analysis of 478 lesions. J Gastroenterology. 2010;45(1):30-36. doi:10.1007/s00535-009-0137-4.

43.   Bae JH, Yang DH, Lee JY, et al. Clinical outcomes of endoscopic submucosal dissection for large colorectal neoplasms: a comparison of protruding and laterally spreading tumors. Surg Endosc. 2016;30(4):1619-1628. doi:10.1007/s00464-015-4392-6.

44.   Terasaki M, Tanaka S, Shigita K, et al. Risk factors for delayed bleeding after endoscopic submucosal dissection for colorectal neoplasms. Int J Colorectal Dis. 2014;29(7):877-882. doi:10.1007/s00384-014-1901-3.

45.   45. Ohata K, Nonaka K, Minato Y, et al. Endoscopic submucosal dissection for large colorectal tumor in a Japanese general hospital. J Oncol. 2013;2013:218670. doi:10.1155/2013/218670.

46.   Ono S, Ono M, Nakagawa M, Shimizu Y, Kato M, Sakamoto N. Delayed bleeding and hemorrhage of mucosal defects after gastric endoscopic submucosal dissection on second-look endoscopy. Gastric Cancer. 2016;19(2):561-567. doi:10.1007/s10120-015-0507-y.

47.   Chiba H, Ashikari K, Takahashi A, et al. A case of delayed bleeding after endoscopic submucosal dissection for completely circumferential esophageal cancer. Endoscopy. 2015;47(Suppl 1 UCTN):E385-E386. doi:10.1055/s-0034-1392429.

48.   Coskun AK, Ozer MT, Demirbas S. Risk factors for delayed bleeding after endoscopic submucosal dissection. Int J Colorectal Dis. 2014;29(12):1575. doi:10.1007/s00384-014-1925-8.

49.   Suzuki S, Chino A, Kishihara T, et al. Risk factors for bleeding after endoscopic submucosal dissection of colorectal neoplasms. World J Gastroenterol. 2014;20(7):1839-1845. doi:10.3748/wjg.v20.i7.1839.

50.   Hoteya S, Yahagi N, Iizuka T, et al. Endoscopic submucosal dissection for nonampullary large superficial adenocarcinoma/adenoma of the duodenum: feasibility and long-term outcomes. Endosc Int Open. 2013;1(1):2-7. doi:10.1055/s-0033-1359232.

51.   Jeon SW, Jung MK, Cho CM, et al. Predictors of immediate bleeding during endoscopic submucosal dissection in gastric lesions. Surg Endosc. 2009;23(9):1974-1979. doi:10.1007/s00464-008-9988-7.

52.   Kakushima N. Hurdles of duodenal endoscopic submucosal dissection, delayed bleeding and perforation. Dig Endosc. 2015;27(3):298-299. doi:10.1111/den.12397.

53.   Takeuchi Y, Iishi H, Tanaka S, et al. Factors associated with technical difficulties and adverse events of colorectal endoscopic submucosal dissection: retrospective exploratory factor analysis of a multicenter prospective cohort. Int J Colorectal Dis. 2014;29(10):1275-1284. doi:10.1007/s00384-014-1947-2.

54.   Miyahara K, Iwakiri R, Shimoda R, et al. Perforation and postoperative bleeding of endoscopic submucosal dissection in gastric tumors: analysis of 1190 lesions in low- and high-volume centers in Saga, Japan. Digestion. 2012;86(3):273-280. doi:10.1159/000341422.

55.   Park CH, Lee SK. Preventing and controlling bleeding in gastric endoscopic submucosal dissection. Clin Endosc. 2013;46(5):456-462. doi:10.5946/ce.2013.46.5.456.

56.   Tsuji Y, Ohata K, Ito T, et al. Risk factors for bleeding after endoscopic submucosal dissection for gastric lesions. World J Gastroenterol. 2010;16(23):2913-2917.

57.   Hoteya S, Kaise M, Iizuka T, et al. Delayed bleeding after endoscopic submucosal dissection for non-ampullary superficial duodenal neoplasias might be prevented by prophylactic endoscopic closure: analysis of risk factors. Dig Endosc. 2015;27(3):323-330. doi:10.1111/den.12377.

58.   Toyonaga T, Nishino E, Hirooka T, Ueda C, Noda K. Intraoperative bleeding in endoscopic submucosal dissection in the stomach and strategy for prevention and treatment. Dig Endosc. 2006;18:S123-S127. doi:10.1111/j.1443-1661.2006.00645.x.

59.   Akahoshi K, Honda K, Akahane H, et al. Endoscopic submucosal dissection by using a grasping-type scissors forceps: a preliminary clinical study (with video). Gastrointest Endosc. 2008;67(7):1128-1133. doi:10.1016/j. gie.2007.12.007.

60.   Akahoshi K, Kubokawa M, Gibo J, et al. Endoscopic submucosal dissection of gastric adenomas using the clutch cutter. World J Gastrointest Endosc. 2017;9(7):334-340. doi:10.4253/wjge.v9.i7.334.

61.   ASGE Technology Committee, Tokar JL, Barth BA, et al. Electrosurgical generators. Gastrointest Endosc. 2013;78(2):197-208. doi:10.1016/j.gie.2013.04.164.

62.   Curcio G, Granata A, Traina M. Hemospray for multifocal bleeding following ultra-low rectal endoscopic submucosal dissection. Dig Endosc. 2014;26(4):606-607. doi:10.1111/den.12301.

63.   Jacques J, Legros R, Carrier P, et al. Salvage hemostasis by scope compression during rectal endoscopic submucosal dissection. Endoscopy. 2015;47(Suppl 1 UCTN):E22-E23. doi:10.1055/s-0034-1390724.

64.   Jeong HK, Park CH, Jun CH, et al. A prospective randomized trial of either famotidine or pantoprazole for the prevention of bleeding after endoscopic submucosal dissection. J Korean Med Sci. 2007;22(6):1055-1059. doi:10.3346/jkms.2007.22.6.1055.

65.   Uedo N, Takeuchi Y, Yamada T, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol. 2007;102(8):1610-1616. doi:10.1111/j.1572-0241.2007.01197.x.

66.   Arai M, Matsumura T, Okimoto K, et al. Two-week treatment with proton pump inhibitor is sufficient for healing post endoscopic submucosal dissection ulcers. World J Gastroenterol. 2014;20(43):16318-16322. doi:10.3748/wjg.v20. i43.16318.

67.   Kajiura S, Hosokawa A, Ueda A, et al. Effective healing of endoscopic submucosal dissection-induced ulcers by a single week of proton pump inhibitor treatment: a retrospective study. BMC Res Notes. 2015;8:150. doi:10.1186/s13104-015-1111-2.

68.   Ono S, Kato M, Ono Y, et al. Effects of preoperative administration of omeprazole on bleeding after endoscopic submucosal dissection: a prospective randomized controlled trial. Endoscopy. 2009;41(4):299-303. doi:10.1055/s-0029-1214530.

69.   Marmo R, Rotondano G, Bianco MA, Piscopo R, Prisco A, Cipolletta L. Outcome of endoscopic treatment for peptic ulcer bleeding: Is a second look necessary? A meta-analysis. Gastrointest Endosc. 2003;57(1):62-67.

70.   Nishizawa T, Suzuki H, Kinoshita S, Goto O, Kanai T, Yahagi N. Second-look endoscopy after endoscopic submucosal dissection for gastric neoplasms. Dig Endosc. 2015;27(3):279-284. doi:10.1111/den.12410.

71.   Kim DS, Jung Y, Rhee HS, et al. Usefulness of the Forrest Classification to predict artificial ulcer rebleeding during second-look endoscopy after endoscopic submucosal dissection. Clin Endosc. 2016;49(3):273-281. doi:10.5946/ce.2015.086.

72.   Kim EH, Park SW, Nam E, Eun CS, Han DS, Park CH. Role of second-look endoscopy and prophylactic hemostasis after gastric endoscopic submucosal dissection: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2017;32(4):756-768. doi:10.1111/jgh.13623.

73.   Kim JS, Chung MW, Chung CY, et al. The need for second-look endoscopy to prevent delayed bleeding after endoscopic submucosal dissection for gastric neoplasms: a prospective randomized trial. Gut Liver. 2014;8(5):480-486. doi:10.5009/gnl13226.

74.   Mochizuki S, Uedo N, Oda I, et al. Scheduled second-look endoscopy is not recommended after endoscopic submucosal dissection for gastric neoplasms (the SAFE trial): a multicentre prospective randomised controlled noninferiority trial. Gut. 2015;64(3):397-405. doi:10.1136/gutjnl-2014-307552.

75.   Park CH, Park JC, Lee H, Shin SK, Lee SK, Lee YC. Second-look endoscopy after gastric endoscopic submucosal dissection for reducing delayed postoperative bleeding. Gut Liver. 2015;9(1):43-51. doi:10.5009/gnl13252.

76.   Takahashi F, Yoshitake N, Akima T, et al. A second-look endoscopy may not reduce the bleeding after endoscopic submucosal dissection for gastric epithelial neoplasm. BMC Gastroenterol. 2014;14:152. doi:10.1186/1471-230X-14-152.

77.   Na S, Ahn JY, Choi KD, et al. Delayed bleeding rate according to the Forrest Classification in second-look endoscopy after endoscopic submucosal dissection. Dig Dis Sci. 2015;60(10):3108-3117. doi:10.1007/s10620-015-3693-x.

78.   Bahin FF, Naidoo M, Williams SJ, et al. Prophylactic endoscopic coagulation to prevent bleeding after wide-field endoscopic mucosal resection of large sessile colon polyps. Clin Gastroenterol Hepatol. 2015;13(4):724-730. e721-e722. doi:10.1016/j.cgh.2014.07.063.

79.   Lee BI, Kim BW, Kim HK, et al. Routine mucosal closure with a detachable snare and clips after endoscopic submucosal dissection for gastric epithelial neoplasms: a randomized controlled trial. Gut Liver. 2011;5(4):454-459. doi:10.5009/gnl.2011.5.4.454.

80.   Otake Y, Saito Y, Sakamoto T, et al. New closure technique for large mucosal defects after endoscopic submucosal dissection of colorectal tumors (with video). Gastrointest Endosc. 2012;75(3):663-667. doi:10.1016/j.gie.2011.10.037.

81.   Osada T, Sakamoto N, Ritsuno H, et al. Closure with clips to accelerate healing of mucosal defects caused by colorectal endoscopic submucosal dissection. Surg Endosc. 2016;30(10):4438-4444. doi:10.1007/s00464-016-4763-7.

82.   Kantsevoy SV, Bitner M, Mitrakov AA, Thuluvath PJ. Endoscopic suturing closure of large mucosal defects after endoscopic submucosal dissection is technically feasible, fast, and eliminates the need for hospitalization (with videos). Gastrointest Endosc. 2014;79(3):503-507. doi:10.1016/j.gie.2013.10.051.

Related posts:

Introduction and History of Endoscopic Resection Techniques Per-Oral Endoscopic Myotomy Devices and Accessories for Endoscopic Submucosal Dissection Endoscopic Submucosal Dissection Technique in the Esophagus Full-Thickness Endoscopic and Combined Laparoscopic-Endoscopic Techniques Endoscopic Submucosal Dissection Technique to Conquer Difficult Cases

Stay updated, free articles. Join our Telegram channel

Join