Advancements in endoscopic therapy for colonic diverticular bleeding and tips from public health viewpoints

Abstract

Kobayashi et al. conducted a retrospective evaluation of the effectiveness and adverse events associated with endoscopic detachable snare ligation (EDSL) for colonic diverticular bleeding (CDB) and identified risk factors for recurrent bleeding following EDSL.¹ Rebleeding events were analyzed as time-to-event data and compared between the complete and incomplete ligation groups.¹ The study discusses advancements in endoscopic therapies for CDB.

Endoscopic therapy has emerged as a widely employed approach in treating CDB, as highlighted by Jensen et al.² Among 17 CDB cases exhibiting stigmata of recent hemorrhage (SRH) such as active bleeding, nonbleeding visible vessels, and adherent clots treated with medical intervention, nine experienced additional bleeding postcolonoscopy and six required hemicolectomy. Conversely, of the 10 CDB patients with SRH treated endoscopically using epinephrine injection and bipolar coagulation, none experienced recurrent bleeding or required surgery. Endoscopic therapies demonstrated superiority over medical treatments in preventing recurrent bleeding and consequent colectomy in a historical cohort.² Hence, SRH management in CDB warrants an endoscopic approach.

However, due to the absence of muscular layers in most colonic diverticula and the presence of approximately half of the bleeding vessels at the diverticular dome in CDB,³ coagulation therapy poses a risk of perforation when applied to diverticular vessels. Clipping presents immediate mechanical hemostasis and theoretically inflicts lesser damage to colonic tissues compared to coagulation therapy, rendering it the preferred initial endoscopic therapy. Nonetheless, deploying hemoclips on vessels at the dome and treating CDB cases with a small orifice pose challenges. Hence, indirect clipping in a zipper fashion is selected for such cases. However, this technique may not adequately occlude the underlying artery, particularly in the ascending location.⁴ Thus, more effective endoscopic treatments are imperative for managing CDB.

Endoscopic band ligation (EBL) was pioneered by Witte in 2000.⁵ However, the O-band is involved in deeper portions of the colonic wall, which could lead to perforation. Akimaru et al. applied band ligation to the colon of pigs.⁶ Perforation did not occur for 2 weeks after ligation, and histopathological examination revealed interruption of the mucosal layer and replacement of the muscularis propria with granulation tissue at the ligated sites. Complications such as perforation or penetration did not occur in a case series of EBL, which was considered safe for the management of CDB.⁷ EBL can achieve successful immediate hemostasis, even at the dome location or for massive bleeding in the ascending location.⁷ In addition, scar formation occurred at the banded sites, and the banded colonic diverticula resolved after EBL. The risk of recurrent bleeding from the same diverticulum is thus expected to decrease. However, removal of the colonoscope and reinsertion after attaching the band-ligator device to the tip of the colonoscope were required to complete the EBL. Although the targeted diverticula with SRH could be easily detected during the second pass by prior marking with clips, the procedure took longer compared to through-the-scope treatment methods such as clipping.

Endoscopic detachable snare ligation exerts a hemostatic effect by ligating the diverticula with SRH using a detachable snare, which is commonly used for polypectomy; the hemostatic mechanism of EDSL is similar to that of EBL.¹ Initial hemostasis, 30 day rebleeding, long-term rebleeding, interventional radiology or surgery requirements, 30 day mortality, amount of packed red blood cells transfused, and length of stay did not differ significantly between the EBL and EDSL groups in a multicenter cohort study,⁸ and the effectiveness and safety were likely similar. However, reinsertion of the colonoscope for ligation is not required in EDSL treatment. The extent of the ligation force depends on the contractility of the O-band and the grasping force of the endoscopist's assistant in EBL and EDSL, respectively.^{1, 8} Therefore, assistants should be familiar with the use of a detachable snare, which may be an obstacle to the widespread introduction of EDSL.

No randomized controlled trials have compared the efficacy of endoscopic treatments for CDB. Only reports of observational studies, wherein selection bias by indication remained between comparative groups, exist. Therefore, a systematic review and meta-analysis of observational studies is required. In a systematic review and a meta-analysis of observational studies, pooled estimates of the requirement for interventional radiology or surgery included: coagulation, 0.18 (95% confidence interval [CI] 0.00–0.61; I² = 68.9%); clipping, 0.08 (95% CI 0.03–0.16; I² = 36.8%); and ligation including EBL and EDSL, 0.00 (95% CI 0.00–0.01; I² = 0.0%).⁹ The proportion of patients requiring interventional radiology or surgery in the ligation group was significantly lower than in the clipping group (P = 0.003) and marginally lower than in the coagulation group (P = 0.086). Ligation therapy is considered the most effective endoscopic method for managing CDB.

Sigmoid colon localization, a history of acute lower gastrointestinal bleeding, and ECOG performance status scores of 3 or 4 have been reported as risk factors for recurrent bleeding after ligation therapy with EBL and EDSL.⁸ Kobayashi et al. first reported that incomplete ligation was a risk factor for recurrent bleeding after EDSL and that complete ligation was desirable for reducing recurrent bleeding and obviating the need for interventional radiology and surgery.¹ The hemostatic mechanism of EBL is similar to that of EDSL, and complete ligation is vital in the former. From an epidemiological perspective, competing risks were not considered in the evaluation of risk factors using the Cox regression analysis. The deaths of CDB patients were considered competing events before recurrent bleeding, thus a competing-risk regression analysis might be required to manage competing risks and identify risk factors, especially for long-term recurrent bleeding.⁸

Recently, studies on the endoscopic treatment of CDB have been published. However, most studies had retrospective designs, and data management may be misclassified. Nondifferential misclassification can distort and underestimate the results toward null, while differential misclassification can distort data in any direction.¹⁰ Furthermore, the effectiveness of interventions, including endoscopic treatments, was compared using multivariate regression. In the multivariate regressions, the positivity assumption was not conserved, and the comparison of interventions was more biased and insufficient for causal inference. Therefore, prospective studies are required to reduce misclassification, and propensity score methods instead of multivariate regressions are desirable for the comparison of interventions.

Kobayashi et al. greatly contributed to advancements in endoscopic therapy for CDB, and we appreciate the excellent article by Kobayashi et al. in Digestive Endoscopy.

Authors declare no conflict of interest for this article.

None.