Introduction

Reported rates of delayed bleeding (DB) after endoscopic resection with each direct oral anticoagulant (DOAC) are high and heterogeneous. This large-scale multicenter study analyzed lesions resected by colorectal endoscopic submucosal dissection (ESD) under DOACs to compare the DB of each DOAC with warfarin.

Aims & Methods

We retrospectively reviewed 1,019 lesions with DOAC and 459 lesions with warfarin among 34,455 cases of ESD in 47 Japanese institutions from 2012 to 2021. The rate of DB in each DOAC was compared with warfarin. Risk factors of DB for DOAC and warfarin were also investigated.

Results

In the DOAC and warfarin groups, the mean age was 75.1±13.7 and 73.6±10.4 years, and the male rate was 70.2% and 71.4%, respectively. The mean tumor sizes (mm) were 29.5±14.0 and 30.3±16. The en bloc resection rates were 97.5% and 96.5%, respectively. Among 31,968 ESD cases from 46 institutions, the rate of DB was significantly higher in cases with anticoagulation (10.08%, 149/1478) than in cases without anticoagulation (2.21%, 677/30526) (p<0.001). Among the total 34,455 ESD cases, the rates of DOAC and warfarin were 9.32% (95/1019) and 11.76% (54/459), respectively (p=0.149).
The rate of DB with dabigatran (18.26%, 21/115) was significantly higher than with apixaban (10.08%, 25/248, p=0.029), edoxaban (7.73%, 25/323, p=0.001), and rivaroxaban (7.21%, 24/333, p=0.001). The rate of dabigatran was slightly higher than that of warfarin (11.76%, 54/459, p=0.055) and only the rate of rivaroxaban was significantly lower than that of warfarin (p=0.033).
Multivariate analysis showed that the significant risk factors of DB for DOAC were heparin exchange (odds ratio (OR), 95% confidence interval (CI), 2.185, 1.277-3.739, p=0.005), rectal site (2.013, 1.282-3.161, p=0.002), and longer procedure time ≥55 min (2.434, 1.498-3.956, p<0.001). The significant risk factors of DB for warfarin were antiplatelet combination (2.286, 1.274-4.100, p=0.006), rectal location (2.261, 1.248-4.095, p=0.007), and tumor size ≥35mm (2.019, 1.163-3.652, p=0.008).
The number of significant risk factors and the risk of DB (OR, 95%CI) for DOAC were 2.136 (1.301-3.507) and 4.53 (2.525-8.155) for one and two risk factors, respectively. Those for warfarin were 1.646 (0.742-3.650), 3.624 (1.593-8.243), and 13.037 (3.929-43.266) for one, two, and three risk factors, respectively.

Conclusion

The DB rate of dabigatran was higher than that of other DOACs, and only rivaroxaban was significantly lower than that of warfarin. The risk factors for DB with DOACs have been elucidated.

Introduction

Delayed perforation (DP) is a serious complication after colorectal endoscopic submucosal dissection (CESD), often requiring emergent surgery. Traditionally, DP has been managed conservatively or surgically. Recently, successful endoscopic closures have been reported. Since 2021, we have attempted endoscopic closure in patients meeting the following: (1) localized symptoms with stable condition, (2) no or minimal oral intake, and (3) endoscopic accessibility and feasibility of closure.

Aims & Methods

To compare clinical outcomes before and after the introduction of endoscopic closure for DP and to examine closure techniques. Among Among 4,848 CESD procedures (April 2008–December 2024), 16 cases (0.3%) of DP were identified. In Analysis 1, patients were divided into Group A (before closure: 2008–2020) and Group B (after closure: 2021–). In Analysis 2, closure techniques were reviewed. DP was defined as a perforation undetected during ESD but confirmed postoperatively by imaging or endoscopy.

Results

Analysis 1: Group A: 9 patients; Group B: 7. Median age: 72 vs. 70 years; male/female: 5/4 vs. 4/3. Lesion locations (cecum/ascending/transverse/sigmoid/rectum): Group A, 3/2/1/1/2; Group B, 1/3/2/1/0. Median specimen size: 48 mm vs. 46 mm.
Ulcer base closure (complete/partial/none): Group A, 2/2/5; Group B, 2/4/1. Histology (adenoma/serrated lesion/carcinoma in situ/adenocarcinoma/others): Group A, 3/4/1/1; Group B, 4/1/1/1. Median time to DP diagnosis: 63 vs. 55 hours.
Treatment in Group A was determined case-by-case; Group B applied defined criteria. Initial treatments (conservative/surgical/endoscopic): Group A, 5/4/0; Group B, 1/0/6. One case in each group initially managed conservatively required surgery later. Of 7 surgical cases, all underwent partial colectomy or drainage without stoma creation. All 6 endoscopic closure cases avoided surgery. Surgical avoidance rate: 33% vs. 86% (p=0.06).
Median time to oral intake: 8 vs. 7 days (p=0.67). Median hospitalization: 16 vs. 11 days (p<0.05).
Analysis2: All 6 closures were performed without bowel preparation. Two patients had resumed oral intake, but endoscopy was performed early.
Perforation diameter: median 10 mm (5–15). Closure methods: over-the-scope clip (OTSC; n=1), hemostatic clips (n=4), clips with polyglycolic acid (PGA) sheet (n=1).

Conclusion

Endoscopic closure for DP was associated with higher surgical avoidance and shorter hospitalization, without worsening outcomes. It may offer an effective treatment option for selected patients.​

Introduction

Endoscopic submucosal dissection (ESD) is emerging as the standard treatment for suspected superficial submucosal invasion lesions. Considering the global population ageing, understating the feasibility of this approach in elderly patients is of the utmost importance. Studies in this field have shown a tendency towards reduced resection rates and higher rates of complications.

Aims & Methods

We sought to assess the effectiveness and safety of colorectal ESD for patients aged ≥ 80 yo compared to 65-79 yo patients. We prospectively enrolled consecutive patients aged >64 years undergoing colorectal ESD between January 2019 and December 2023 from ten Italian Tertiary Referral Centres. Patients were classified as Elderly Group (E-Group, age >80 yo) and non-elderly group (NE-Group, 65-79 yo). Procedure outcomes and adverse events were compared between E-Group and NE-Group and between patients with comorbidities and healthy (1-CM-Group and H-Group).

Results

A total of 980 patients were included [269 (27.5%) in the E-Group and 711 (72.5%) in the NE-Group]. Table 1 summarises the principal data and outcomes.

En-bloc resection and R0 rate did not statistically differ (p=0.30; p=0.05) between E and NE-Groups. Oncological curative resection was achieved in the two groups without significant differences (p=0.41). Histological outcomes were comparable between the two groups, except for lymphovascular invasion [E:14 (5.2%) vs NE:14 (2.0%); p=0.007 – OR:2.9 (CI:1.3-6-6)]. Regarding clinical course, intraprocedural and 14 days-adverse events (AEs), no statistically significant differences were found between the two groups, except for a higher rate of post-procedure delirium in the E-Group [6 (2.2%) vs 1 (0.1%); p=0.001–OR:16.2 (CI:1.9-135.2)]. 1-CM-Group showed a higher rate of intraprocedural bleeding (p=0.001), fever onset (p<0.001), C-reactive protein (p=0.006) and procalcitonin increase (p=0.02), delayed perforation (p=0.03) and systemic infections (p=0.02) compared to the H-Group. The presence of one or more comorbidity, but not the age, was associated with a poorer clinical course [p<0.001; OR:2.3 (CI:1.5-3.6)] and poor overall course (poor clinical course combined with 14 days AEs) [p=<0.001; OR:2.1 (CI:1.4-3.0)]. ASA classification (OR: 1.36; CI:1.01-1.83), the presence of one comorbidity (OR: 1.73; CI:1.14-2.63), and procedure time (OR: 1.01; CI:1.00-1.01) were poor outcome predictors. After excluding patients with at least one comorbidity, still no differences in terms of poor overall course (p=0.21) were registered between E and NE-Group.

Conclusion

Colorectal ESD is an effective and safe procedure in elderly patients. Physicians should ackowledge delirium as a possible AE in patients aged over 80. The presence of comorbidities should drive the execution of a comprehensive pre-procedural assessment and post-procedural care, to optimize outcomes and minimize complications.

Introduction

Clinically significant delayed bleeding (CSDB) is the most frequent complication after colorectal endoscopic submucosal dissection (ESD). The Limoges Bleeding Score was recently developed to identify patients at risk of CSDB after colorectal ESD. The efficacy of prophylactic clipping to prevent bleeding has been a topic of ongoing debate.

Aims & Methods

This study aimed to evaluate the real effectiveness of complete clip closure in preventing CSDB after colorectal ESD.
We performed a retrospective analysis of data prospectively collected from ten-centers between 2017 and 2023. Specifically, pre- and periprocedural data were collected prospectively, while post-procedural data, including the evaluation of CSDB, was retrospectively assessed. All epithelial colorectal lesions treated by ESD were included. The patients were allocated into the closure and non-closure groups which were compared before and after propensity-score matching based on risk factors of the Limoges Bleeding Score (age > 75 yrs, size > 50 mm, ASA III-IV, location in rectum and anticoagulant/antiplatelet). We further analyzed post-ESD CSDB in the subgroups of patients on anticoagulants and with high risk of bleeding (5 to 8 points according to Limoges score).

Results

A total of 3431 patients were included, 1236 in the closure group and 1985 in non-closure group. The propensity score matching based on risk factors of the Limoges Bleeding Score created 1064 matches pairs. The rate of CSDB was not significantly different between the two groups (closure group 7.04% vs non-closure group 6.8%; p = 0.85), nor after propensity score matching (closure group 7.47% vs non-closure group 6.11%; p = 0.38). The subgroup analysis including patients on anticoagulants (165 patients in closure group vs 251 in non-closure group) and those identified at high-risk by Limoges score (181 in each group), found no significant difference of CSDB between the groups (p= 0.31 and p =0.16, respectively).

Conclusion

In our population, prophylactic clipping after colorectal ESD did not significantly reduce the incidence of CSDB. These findings were confirmed even when the analysis was restricted to high-risk patients. Considering the technical challenges of complete clip closure, it could be reserved for selected clinical scenarios.

References

[1] Saito H, Igarashi K, Hirasawa D et al. The risks and characteristics of the delayed bleeding after endoscopic submucosal dissection for early gastric carcinoma in cases with anticoagulants. Scand J Gastroenterol 2020; 55: 1253–1260
[2] Boda K, Oka S, Tanaka S et al. Clinical outcomes of endoscopic submucosal dissection for colorectal tumors: a large multicenter retrospective study from the Hiroshima GI Endoscopy Research Group. Gastrointest Endosc 2018; 87: 714–722
[3] Bordillon P, Pioche M, Wallenhorst T et al. Double-clip traction for colonic endoscopic submucosal dissection: a multicenter study of 599 consecutive cases (with video). Gastrointest Endosc 2021; 94: 333–343
[4] Probst A, Ebigbo A, Märkl B et al. Endoscopic submucosal dissection for early rectal neoplasia: experience from a European center. Endoscopy 2017; 49: 222–232
[5] Albouys J, Montori Pina S, Boukechiche S et al. Risk of delayed bleeding after colorectal endoscopic submucosal dissection: the Limoges Bleeding Score. Endoscopy 2024; 56(2):110-118

Introduction

A positive resection margin after endoscopic submucosal dissection (ESD) of a colorectal neoplasm is associated with an increased risk of recurrence. However, it may be caused by cauterization or tangential specimen cutting. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD.

Aims & Methods

We reviewed 1010 patients who underwent colorectal ESD at two hospitals between 2015 and 2020. The inclusion criteria were that the patient 1) had an en bloc resection, 2) had at least one follow-up colonoscopy. The recurrence rates and presence of residual tumors in the surgical specimens were evaluated.

Results

A total of 632 patients were enrolled. Among them, 557 patients had complete resections, and 75 had incomplete resections with positive resection margins in vertical and/or horizontal margin. The rate of additional surgery after ESD and recurrence was significantly higher in patients with incomplete resection compared to patients with complete resection. However, in patients with non-invasive colorectal neoplasm, all 411 patients, including those with complete and incomplete resection, had no recurrence. Among 221 patients with invasive lesions, 39 underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with remnant tumors in the surgical specimen. Lymphovascular invasion was associated with lymph node metastasis. However, no remnant tumor nor lymph node metastases were found in patients with only one unfavorable histological factor, including 1) positive vertical margin, 2) a submucosal invasion depth > 1000 µm, 3) lymphovascular invasion, 4) poorly differentiated cancer, and 5) high tumor-budding grade.

Conclusion

A positive resection margin after en bloc colorectal ESD for noninvasive lesions was not associated with recurrence. In T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.