Risk Factors For post-ESD Bleeding Research Articles

Risk factors for post-colorectal endoscopic submucosal dissection bleeding and efficacy of carbazochrome sodium sulfonate: A multicenter retrospective cohort study.

Carbazochrome sodium sulfonate (CSS) is a hemostatic agent that reduces capillary permeability and enhances capillary resistance. However, its specific effects on colorectal endoscopic submucosal dissection (ESD) outcomes remain uncertain. This study aimed to assess the risk factors for post-ESD bleeding and the effect of CSS on colorectal ESD outcomes. First, we retrospectively analyzed the risk factors for post-ESD bleeding using data from 1,315 lesions in 1,223 patients who underwent ESD for superficial colorectal neoplasms at eight institutions. Second, patients were divided into CSS and non-CSS groups using propensity score matching, and their outcomes from colorectal ESD were analyzed. The risk factors for post-colorectal ESD bleeding were identified as age of ≥70 years, tumor located in the rectum, tumor size of ≥40 mm, and post-ESD defect unclosure in both univariate and multivariate analyses. The CSS and non-CSS groups each consisted of 423 lesions after propensity score matching. The post-colorectal ESD bleeding rate was 3.5% (15/423) and 3.3% (14/423) in the CSS and non-CSS groups, respectively, indicating no significant differences. Among patients with the high-risk factors for post-ESD bleeding, the administration of CSS also did not demonstrate a significant reduction in the post-ESD bleeding rate compared to the non-CSS group. CSS administration is ineffective in preventing post-colorectal ESD bleeding in both the general population and individuals at a high risk for such bleeding. Our results indicate the necessity to reconsider the application of CSS for preventing post-colorectal ESD bleeding.

Risk factors for postgastric endoscopic submucosal dissection bleeding in direct oral anticoagulant users.

Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post-ESD bleeding and drug differences in patients taking DOACs. We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri-cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post-ESD bleeding. The incidence of post-ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post-ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post-ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran. The administration of DOACs was shown to be a possible factor involved in post-ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD.

Association of direct oral anticoagulant and delayed bleeding with pharmacokinetics after endoscopic submucosal dissection

Pharmacokinetic parameters, such as drug plasma level at trough, time to maximum plasma concentration (Tmax), and coagulation factor Xa (FXa) activity generally predict factors for the anticoagulant effects of direct oral anticoagulants (DOACs). Although GI bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about the association between post-ESD bleeding in patients taking DOACs and the pharmacologic parameters. This study aimed to evaluate pharmacologic risk factors for post-ESD bleeding in patients taking DOACs. We prospectively evaluated the incidence of post-ESD bleeding in patients taking DOACs between April 2018 and May 2022 at 21 Japanese institutions and investigated the association with post-ESD bleeding and pharmacologic factors, including plasma concentration and FXa activity at trough and Tmax. The incidence of post-ESD bleeding was 12.8% (14 of 109; 95% confidence interval [CI], 7.2-20.6). Although plasma DOAC concentration and plasma level/dose ratio at trough and Tmax varied widely among individuals, a significant correlation with plasma concentration and FXa activity was observed (apixaban: correlation coefficient, -0.893; P< .001). On multivariate analysis, risk factors for post-ESD bleeding in patients taking DOACs were higher age (odds ratio [OR], 1.192; 95% CI, 1.020-1.392; P= .027) and high anticoagulant ability analyzed by FXa activity at trough and Tmax (OR, 6.056; 95% CI, 1.094-33.529; P= .039). The incidence of post-ESD bleeding in patients taking DOACs was high, especially in older patients and with high anticoagulant effects of DOACs. Measurement of pharmacokinetic parameters of DOACs may be useful in identifying patients at higher risk of post-ESD bleeding.

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants.

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors. The rate of post-ESD bleeding for gastric cancer is higher (around 5%-8%) than that for esophagus, duodenum and colon cancer (around 2%-4%). Although investigations into the risk factors for post-ESD bleeding have identified several procedure-, lesion-, physician- and patient-related factors, use of antithrombotic drugs, especially anticoagulants [direct oral anticoagulants (DOACs) and warfarin], is thought to be the biggest risk factor for post-ESD bleeding. In fact, the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%, which is higher than that in patients not receiving anticoagulants. However, because clinical guidelines for management of ESD in patients receiving DOACs differ among countries, it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice. Given that the pharmacokinetics (e.g., plasma DOAC level at both trough and Tmax) and pharmacodynamics (e.g., anti-factor Xa activity) of DOACs are related to risk of major bleeding, plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

Modified BEST-J Score Model Predicts Bleeding after Endoscopic Submucosal Dissection with Fewer Factors.

This study constructed a simplified post-endoscopic submucosal dissection (ESD) prediction model with a prognostic nutritional index (PNI). A total of 449 patients who underwent gastric ESD was included, divided with a ratio of 2:1, and assigned to the model or validation cohort. A prediction model of post-ESD (modified BEST-J score) was constructed using the model cohort. The modified BEST-J score was evaluated by comparing its accuracy to the BEST-J score in the validation cohort. Within 4 weeks of ESD, melena, hematemesis, or a 2 g/dL or greater decrease in hemoglobin level that required esophagogastroduodenoscopy was defined as post-ESD bleeding. In the model cohort, 299 patients were enrolled and 25 (8.4%) had post-ESD bleeding. Independent risk factors for post-ESD bleeding were use of P2Y12RA, tumor size &gt; 30 mm, location of lesion at lower one-third of the stomach, and PNI ≤ 47.9. Constructing the modified BEST-J score based on these variables, the sensitivity, specificity, and positive likelihood ratio were 73.9%, 78.1%, and 3.37. When comparing the modified BEST-J score to the BEST-J score in the validation cohort, no significant difference was observed by ROC-AUC (0.77 vs. 0.75, p = 0.81). Modified BEST-J score can predict post-ESD bleeding more simply, with the same accuracy as the BEST-J score.

Postoperative Bleeding Risk after Gastric Endoscopic Submucosal Dissection in Patients Receiving a P2Y12 Receptor Antagonist.

The safety of gastric endoscopic submucosal dissection (ESD) in users of a P2Y12 receptor antagonist (P2Y12RA) under current guidelines has not been verified. Patients treated by gastric ESD at Okayama University Hospital between January 2013 and December 2020 were registered. The postoperative bleeding rates of patients (group A) who did not receive any antithrombotic drugs; patients (group B) receiving aspirin or cilostazol monotherapy; and P2Y12RA users (group C) those on including monotherapy or dual antiplatelet therapy were compared. The risk factors for post-ESD bleeding were examined in a multivariate analysis of patient background, tumor factors, and antithrombotic drug management. Ultimately, 1,036 lesions (847 patients) were enrolled. The bleeding rates of group B and C were significantly higher than that of group A (p=0.012 and p<0.001, respectively), but there was no significant difference between group B and C (p=0.11). The postoperative bleeding rate was significantly higher in dual antiplatelet therapy than in P2Y12RA monotherapy (p=0.014). In multivariate analysis, tumor diameter ≥12 mm (odds ratio [OR], 4.30; 95% confidence interval [CI], 1.99 to 9.31), anticoagulant use (OR, 4.03; 95% CI, 1.64 to 9.86), and P2Y12RA use (OR, 3.40; 95% CI, 1.07 to 10.70) were significant risk factors for postoperative bleeding. P2Y12RA use is a risk factor for postoperative bleeding in patients who undergo ESD even if receiving drug management according to guidelines. Dual antiplatelet therapy carries a higher risk of bleeding than monotherapy.

Complete omission of second-look endoscopy after gastric endoscopic submucosal dissection in real-world practice.

Gastric endoscopic submucosal dissection (ESD) is increasingly performed in patients receiving antithrombotic therapy. Second-look endoscopy (SLE) has been performed empirically in several clinical settings. We investigated whether SLE omission was associated with an increased risk of postESD bleeding in all patients, including those administered antithrombotic agents. Between July 2016 and June 2018, 229 patients were treated with a clinical pathway for gastric ESD that involved SLE on the day after ESD (SLE group). Between September 2018 and May 2020, 215 patients were treated using a clinical pathway that did not include SLE (nonSLE group). We retrospectively compared the incidence of postESD bleeding among the propensity score-matched cohorts and determined the risk factors for postESD bleeding using multivariate analysis. The propensity score-matched cohorts showed no significant differences in the incidence of postESD bleeding between the SLE (3.2%) and nonSLE (5.1%) groups. Multivariate analysis revealed that the presence of lesions in the lower gastric body (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.06-4.35, P.03) was a significant risk factor for postESD bleeding during admission, whereas resected specimen size ≥ 40 mm (adjusted OR 3.21, 95% CI 1.19-8.19, P.02) and antiplatelet therapy (adjusted OR 4.16, 95% CI 1.47-11.80, P.007) were significant risk factors after discharge. Complete omission of SLE after gastric ESD does not increase postESD bleeding in clinical practice.

The degree of mucosal atrophy is associated with post-endoscopic submucosal dissection bleeding in early gastric cancer.

Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H.pylori infection status. We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding. There were 3935 H.pylori-positive patients and 4235 H.pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H.pylori-negative patients (odds ratio: 1.51, P=0.007), but not in H.pylori-positive patients (odds ratio: 0.91, P=0.600). Further, in H.pylori-negative, but not H.pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H.pylori-negative patients but not in H.pylori-positive patients.

Validation of the BEST-J score, a prediction model for bleeding after endoscopic submucosal dissection for early gastric cancer: a multicenter retrospective observational study.

A new scoring system, the BEST-J score, using ten risk factors to assign cases to different post-endoscopic submucosal dissection (ESD) risk groups for bleeding, has been shown to be accurate for risk stratification. We first aimed to validate the BEST-J score at four hospitals not specialized in performing ESD and then aimed to identify other risk factors for post-ESD bleeding. We evaluated the incidence of post-ESD bleeding in 791 cases of early gastric cancer (EGC) between October 2013 and December 2020 as a retrospective, multi-center observational study conducted at four hospitals. Multivariate logistic regression models to examine the effect of independent variables on post-ESD bleeding firstly included ten possible factors raised by the BEST-J score and secondly included statistically significant (p &lt; 0.01) in univariate analysis. The prediction accuracy of the model was evaluated by receiver-operating characteristic analysis and the areas under the curve (AUC). The incidence of post-ESD bleeding was 4.8% (38/791, 95% confidence interval [CI] 3.4-6.5%). On multivariate analysis, the risk factors were P2Y12 receptor antagonist (odds ratio [OR]: 5.870, 95% CI 1.624-21.219), warfarin (8.382, 1.658-42.322), direct oral anticoagulant (DOAC) (8.980, 1.603-50.322), and tumor location in lower third of stomach (2.151, 1.012-4.571), respectively. When we categorized cases into low-risk by BEST-J score, intermediate-risk, high-risk, and very high-risk groups, the bleeding rates were 2.8%, 7.3%, 12.8%, and 19.0%, respectively. The AUC for our cohort was 0.713 (95% CI 0.625-0.802) for the BEST-J score. In the multivariate analysis in our cohort, the risks were age, body mass index, P2Y12 receptor antagonist, warfarin, DOAC, respectively. The BEST-J score is equally accurate in risk stratification of patients with EGC for post-ESD bleeding at non-specialized facilities for ESD as in specialized hospitals. BMI and age may be helpful additional risk factors at hospitals not specialized.

Feasibility of gastric endoscopic submucosal dissection in elderly patients aged ≥ 80 years.

BACKGROUNDEndoscopic resection, especially endoscopic submucosal dissection (ESD), is increasingly performed in elderly patients with early gastric cancer, and lesions beyond the expanded indications are also resected endoscopically in some patients. It is essential to assess whether gastric ESD is safe and suitable for elderly patients and investigate what type of lesions carry an increased risk of ESD-related complications.AIMTo assess the efficacy and feasibility of gastric ESD for elderly patients, and define high-risk lesions and prognostic indicators.METHODSAmong a total of 1169 sessions of gastric ESD performed in Kanagawa Cancer Center Hospital from 2006 to 2014, 179 sessions (15.3%) were performed in patients aged ≥ 80 years, and 172 of these sessions were done in patients with a final diagnosis of gastric cancer. These patients were studied retrospectively to evaluate short-term outcomes and survival. The short-term outcomes included the rates of en bloc resection and curative resection, complications, and procedure-related mortality. Curability was assessed according to the Japanese Gastric Cancer Treatment Guidelines 2010. Fisher’s exact test was used to statistically analyze risk factors. Clinical characteristics of each group were compared using Fisher’s exact test and Mann-Whitney U test. Survival rates at each time point were based on Kaplan-Meier estimation. Overall survival rates were compared between patients with gastric cancer in each group with use of the log-rank test. To identify prognostic factors that jointly predict the hazard of death while controlling for model overfitting, we used the least absolute shrinkage and selection operator (LASSO) Cox regression model including factors curative/ noncurative, age, gender, body mass index, prognostic nutritional index, Charlson comorbidity index (CCI), Glasgow prognostic score, neutrophil-to-lymphocyte ratio, and antithrombotic agent use. We selected the LASSO Cox regression model that resulted in minimal prediction error in 10-fold cross-validation. P < 0.05 was considered statistically significant.RESULTSThe en bloc dissection rate was 97.1%, indicating that a high quality of treatment was achieved even in elderly patients. As for complications, the rates of bleeding, perforation and aspiration pneumonitis were 3.4%, 1.1% and 0.6%, respectively. These complication rates indicated that ESD was not associated with a particularly higher risk in elderly patients than in nonelderly patients. A dissection incision > 40 mm, lesions associated with depressions, and lesions with ulcers were risk factors for post-ESD bleeding, and location of the lesion in the upper third of the stomach was a risk factor for perforation in elderly patients (P < 0.05). Location of the lesion in the lower third of the stomach tended to be associated with a higher risk of bleeding. The overall survival (OS) did not differ significantly between curative and noncurative ESD (P = 0.69). In patients without additional surgery, OS rate was significantly lower in patients with a high CCI (≥ 2) than in those with a low CCI (≤ 1) (P < 0.001).CONCLUSIONGastric ESD is feasible even in patients aged ≥ 80 years. Observation without additional surgery after noncurative ESD is reasonable, especially in elderly patients with CCI ≥ 2.

Strategies that Reduce Post-endoscopic Submucosal Dissection Bleeding

Bleeding after endoscopic submucosal dissection (ESD), one of the most common postprocedural adverse events, is the main cause of increased readmission rates and hospital costs. Generally, the incidence of post-ESD bleeding is estimated to be about 5%. However, the incidence of bleeding is particularly increased in high-risk patients. In particular, it has an incidence of over 50% in patients that use antithrombotic agents. The well-known risk factors for post-ESD bleeding include antithrombotic therapy, lesions in the proximal stomach, specimen size &gt;4 cm, and concomitant renal disease. Currently, the number of patients at a high risk of post-ESD bleeding has been increasing. This may be due to the aging society and the increase in the usage of antithrombotic agents. Therefore, several strategies have been employed to prevent post-ESD bleeding. These strategies include acid inhibition therapy, preventive hemostasis using Doppler endoscopic ultrasound and artery-selective clipping, second look endoscopy, the closings method, and the shield methods. However, these methods are technically demanding, which hinders their wide usage in clinical practice. Recently, several hemostatic powders have been developed and clinically used in the treatment of gastrointestinal bleeding. In this article, we review the risk factors for post-ESD bleeding and the recently introduced prevention methods. Moreover, we aimed to explore realistic and appropriate strategies for the prevention of post-ESD bleeding.

Prediction model for bleeding after endoscopic submucosal dissection of gastric neoplasms from a high-volume center.

Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model. We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated. Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49mm, and patient age <62years. The CART model accuracy was 94.9%, and the cross-validation accuracy was 94.8%. We developed a simple and easy-to-apply predictive tree model based on three risk factors that could help endoscopists identify patients at a high risk of bleeding. This model will enable clinicians to establish precise management strategies for patients at a high risk of bleeding and to prevent post-ESD bleeding.

Risk Factors for Post-gastric Endoscopic Submucosal Dissection Bleeding with a Special Emphasis on Anticoagulant Therapy.

Little is known about the risk factors for post endoscopic submucosal dissection (post-ESD) bleeding withanticoagulant therapy. We aimed to investigate the risk factors for post-ESD bleeding for early gastric cancer (EGC) with an emphasis on anticoagulant therapy. We retrospectively analyzed 2355 EGCs, including 137 lesions in patients treated under anticoagulants. Clinicopathological findings were evaluated between lesions in patients with and without anticoagulant therapy with propensity score matching analysis. The factors associated with post-ESD bleeding were analyzed with multivariate analysis with a logistic regression method. After propensity score matching, post-ESD bleeding was significantly more frequent in lesions of patients with than without anticoagulant therapy (11.7% vs 1.5%, respectively; P = 0.001). A univariate analysis revealed that anticoagulant therapy, heparin bridge therapy, undifferentiated type, deep submucosal invasion, and resected specimen size were associated with post-ESD bleeding. A multivariate analysis revealed anticoagulant therapy (OR 23.1, 95% CI 3.61-147.52) and resected specimen size (OR 1.03, 95% CI 1.00-1.06) to be independent factors associated with post-ESD bleeding. Anticoagulant therapy and resected specimen size were risk factors associated with post-ESD bleeding for EGC.

Bleeding in patients who underwent scheduled second-look endoscopy 5\xa0days after endoscopic submucosal dissection for gastric lesions

BackgroundBleeding after endoscopic submucosal dissection (ESD) in antithrombotic drug users is still one of the important issues to be solved. We performed scheduled second-look endoscopy (SLE) 5 days after ESD, when the resumption of antithrombotic agents is assumed to have achieved a steady state, rather than on the day after ESD. We investigated bleeding incidence and the status of ulcers.MethodsA total of 299 lesions in 299 patients subjected to ESD for gastric neoplasms were enrolled. A double dose of proton pump inhibitors was administered after ESD. SLE was planned 5 days after ESD. Post-ESD bleeding occurring before SLE was defined as early phase post-ESD bleeding, whereas bleeding after SLE was defined as later phase post-ESD bleeding. Forrest IIa and IIb ulcers are defined as high-risk ulcers requiring prophylactic hemostasis. We investigated risk factors for post-ESD bleeding, particularly focusing on the use of antithrombotic agents and the presence of high-risk ulcers requiring prophylactic hemostasis during SLE.ResultsUnder a double dose of proton pump inhibitors, early phase post-ESD bleeding occurred in 2.3% of non-users (5/218) and 6.2% of users of antithrombotic agents (5/81). High-risk ulcers were found in 19.0% of the cases during scheduled SLE (55/289). Later phase bleeding occurred in 5.5% of cases [2.8% of non-users (6/213) and 13.2% of users of antithrombotic agents (10/76)]. Cox regression analysis revealed that the risk factor for post-ESD bleeding was antithrombotic treatment (HR: 3.56; 95% CI: 1.63–8.02, p = 0.002) alone. Among patients with high-risk ulcers, a statistically significant increase in bleeding was observed in the later phase in patients under antithrombotic therapy, compared to those not receiving any antithrombotic agents (p = 0.001).ConclusionsAntithrombotic treatment is a risk factor for post-ESD bleeding despite SLE being scheduled 5 days after ESD. Later phase post-ESD bleeding was observed in 13.2% of the patients under antithrombotic treatment even after prophylactic hemostasis for high-risk ulcers.Trial registrationThis study was registered in the UMIN Clinical Trials Registry System (000023306). Retrospectively registered on 23rd July 2016.

Postoperative bleeding risk after gastric endoscopic submucosal dissection during antithrombotic drug therapy.

The safety of gastric endoscopic submucosal dissection (ESD) in the antithrombotic drug users remains controversial. Patients who underwent gastric ESD at Okayama University Hospital between March 2006 and February 2016 were enrolled. This study investigated the risk of post-ESD bleeding according to the management of the antithrombotic drugs. One thousand twenty lesions (872 patients) were enrolled. In a multivariate analysis, heparin replacement (odds ratio [OR] 5.0, 95% confidence interval [CI] 1.8-14), multiple antithrombotic drug use (OR 2.9, 95% CI 1.1-6.9), a resected specimen of ≥33mm in diameter (OR 2.7, 95% CI 1.5-5.4), Helicobacter pylori negativity (OR 2.2, 95% CI 1.3-3.7), and tumors located in the lower third of the stomach (OR 1.7, 95% CI 1.0-2.9) were significant risk factors for post-ESD bleeding, while the continuation of aspirin or cilostazol was not (OR 2.6, 95% CI 0.72-7.8). The bleeding rate of the continuation group was comparable with that of the all cessation group among single antithrombotic drug users (4.5% vs 4.4%, P=1.0); however, the rate of the continuation group was significantly higher than that of the all cessation group among multiple antithrombotic drug users (67% vs 15%, P=0.020). The risk of post-ESD bleeding differed according to the management of the antithrombotic drugs. The gastric ESD under the cessation or continuation of aspirin or cilostazol monotherapy was acceptable. However, multiple antithrombotic drug use or heparin replacement was associated with a higher risk of post-ESD bleeding.

Different clinical characteristics associated with acute bleeding and delayed bleeding after endoscopic submucosal dissection in patients with early gastric cancer.

Few studies have classified risk factors according to the onset time of bleeding after endoscopic submucosal dissection (post-ESD bleeding). We studied 1767 consecutive lesions in patients who underwent ESD for early gastric cancer from December 2006 through June 2016. Patients who had a remnant stomach or who had undergone reconstruction with a gastric tube were excluded. Post-ESD bleeding was classified into acute bleeding (0-5 days after ESD) and delayed bleeding (6 or more days after ESD), and the risk factors for each type of bleeding were compared. Post-ESD bleeding occurred in 150 (8.5%) of 1767 lesions. Bleeding was acute in 129 lesions (7.3%) and delayed in 21 (1.2%). Acute post-ESD bleeding was frequently associated with lesions located in the distal stomach, expanded indications or non-indicated lesions, a specimen diameter of ≥40mm, and antithrombotic therapy. Delayed post-ESD bleeding was often associated with lesions located in the proximal stomach, hemodialysis, and antithrombotic therapy. Among 334 lesions in patients who received antithrombotic therapy, post-ESD bleeding occurred in 47 lesions (14.1%). Independent risk factors for post-ESD bleeding were a specimen diameter of ≥40mm and treatment with 2 or more antithrombotic agents. Acute post-ESD bleeding and delayed post-ESD bleeding were associated with different clinical characteristics. Antithrombotic therapy is a risk factor for post-ESD bleeding in both the acute and delayed phases.

Clinical risk factors for delayed bleeding after endoscopic submucosal dissection for colorectal tumors in Japanese patients.

Endoscopic submucosal dissection (ESD) is a curative, standard therapy for colorectal neoplasms. Some studies have investigated the risk factors for perforation during colorectal ESD. However, few studies have assessed the risk factors for delayed bleeding after colorectal ESD. We studied patients undergoing ESD for colorectal epithelial neoplasms to identify the risk factors for post-ESD bleeding. We studied 124 consecutive patients undergoing ESD for colorectal epithelial neoplasms. To identify risk factors for delayed bleeding post-ESD, recurrent bleeding post-ESD was compared with patient-related and tumor-related factors. Delayed bleeding after ESD occurred in 10 (8.1%) lesions of 124 colorectal tumors, and the median time from the end of ESD to the onset of bleeding was 18.5 h. Delayed bleeding was significantly higher in tumors located in rectums than in colons (P=0.021), and the number of occurrences of arterial bleeding during ESD was significantly higher in the delayed bleeding group than in the nondelayed bleeding group (P=0.002). The procedure time was significantly longer in the delayed bleeding group than in the nondelayed bleeding group (P=0.012). On multivariate logistic regression analysis, tumor location (odds ratio, 10.13; 95% confidence interval, 1.18-87.03; P=0.035) and three or more occurrences of arterial bleeding during ESD (odds ratio, 6.86; 95% confidence interval, 1.13-41.5; P=0.036) were significant independent risk factors for delayed bleeding. The presence of lesions in the rectum and three or more arterial bleeding occurrences during ESD were risk factors for post-ESD bleeding. Patients with these risk factors should be followed up carefully after ESD for colorectal epithelial neoplasms.

Postoperative bleeding after gastric endoscopic submucosal dissection in patients receiving antithrombotic therapy

It is controversial whether antithrombotic therapy increases the risk of bleeding after endoscopic submucosal dissection (ESD). The aim of this study was to evaluate the effects of antithrombotic therapy on gastric ESD. Patients who underwent gastric ESD at Toranomon Hospital between April 2005 and July 2014 were enrolled. The risk of post-ESD bleeding was evaluated by multivariate logistic regression analysis. Of 1781 patients enrolled, 253 were taking an antithrombotic; 186 discontinued taking a single antithrombotic (n=150) or multiple antithrombotics (n=36) before ESD, whereas 15 continued taking a single antiplatelet agent and another 52 switched to heparin alternative therapy during the peri-ESD period. Post-ESD bleeding occurred in 101 patients (5.7%): 68 patients (3.8%) who did not take an antithrombotic, 11 patients (7.3%) who discontinued taking a single antithrombotic, six patients (16.7%) who discontinued taking multiple antithrombotics, one patient (6.7%) who continued taking a single antiplatelet agent, and 15 patients (28.8%) who switched to heparin therapy. In multivariate analysis, heparin alternative therapy [odds ratio (OR) 10.04, 95% confidence interval (CI) 4.35-23.16], discontinuation of the use of multiple antithrombotics before ESD (OR 5.44, 95% CI 2.00-14.79), tumor location in the lower third of the stomach (OR 2.17, 95% CI: 1.32-3.58), and a long procedure time (100min or greater; OR 2.00, 95% CI 1.25-3.20) were independent risk factors for post-ESD bleeding. Among 52 subjects who switched to heparin therapy, one developed acute renal infarction and one developed cerebral bleeding. Because heparin alternative therapy significantly increases the risk of post-ESD bleeding and may not decrease the risk of thromboembolic events, other options should be considered for patients receiving anticoagulation therapy.

Risk factors for postoperative bleeding after gastric endoscopic submucosal dissection in patients under antithrombotics.

To evaluate the risk factors for postoperative bleeding after gastric endoscopic submucosal dissection (ESD) based on the latest guidelines. A total of 262 gastric neoplasms were treated by ESD at our center during a 2-year period from October 2012. We analyzed the data of these cases retrospectively to identify the risk factors for post-ESD bleeding. Of the 48 (18.3%) cases on antithrombotic treatment, 10 were still receiving antiplatelet drugs perioperatively, 13 were on heparin replacement after oral anticoagulant withdrawal, and the antithrombotic therapy was discontinued perioperatively in 25 cases. Postoperative bleeding occurred in 23 cases (8.8%). The postoperative bleeding rate in the heparin replacement group was 61.5%, significantly higher than that in the non-antithrombotic therapy group (6.1%). Univariate analysis identified history of antithrombotic drug use, heparin replacement, hemodialysis, cardiovascular disease, diabetes mellitus, elevated prothrombin time-international normalized ratio, and low hemoglobin level on admission as risk factors for post ESD bleeding. Multivariate analysis identified only heparin replacement (OR = 13.7, 95%CI: 1.2-151.3, P = 0.0329) as a significant risk factor for post-ESD bleeding. Continued administration of antiplatelet agents, based on the guidelines, was not a risk factor for postoperative bleeding after gastric ESD; however, heparin replacement, which is recommended after withdrawal of oral anticoagulants, was identified as a significant risk factor.

Risk factors for bleeding evaluated using the Forrest classification in Japanese patients after endoscopic submucosal dissection for early gastric neoplasm.

Bleeding remains a serious complication after endoscopic submucosal dissection (ESD). Second-look endoscopy for hemostasis helps prevent post-ESD bleeding. We investigated the relationships between patient characteristics, tumor characteristics, and the Forrest classification for exposed vessels on artificial ulcers after ESD and evaluated whether hemostasis during second-look endoscopy was useful for preventing post-ESD bleeding. We analyzed 250 patients (265 lesions) who underwent ESD for gastric neoplasms. Vessels classified by Forrest classifications during scheduled second-look endoscopy were analyzed for associations with patient characteristics, tumor characteristics, and recurrent bleeding. Two of 250 patients (0.8%) underwent emergency hemostatic endoscopy before scheduled second-look endoscopy. The remaining 248 patients (99.2%) underwent scheduled second-look endoscopy on the day after ESD. Patients with Forrest classification Ia, Ib, or IIa vessels had a significantly higher risk for recurrent bleeding after scheduled second-look endoscopy compared with patients with IIb or III vessels according to univariate analysis (P<0.05) and multivariate logistic regression analysis (odds ratio: 3.45; 95% confidence interval: 1.04-11.41; P=0.042). Univariate analysis indicated that hemodialysis correlated significantly with the presence of Ia, Ib, or IIa vessels compared with that of IIb or III vessels found during second-look endoscopy (P<0.05). Multivariate analysis indicated a significant relationship between hemodialysis and recurrent bleeding after second-look endoscopy (odds ratio: 10.05; 95% confidence interval: 1.97-51.26; P=0.006). Hemodialysis is a risk factor for post-ESD bleeding. Proper classification of exposed vessels within post-ESD ulcers according to the Forrest classification using second-look endoscopy might help predict or prevent recurrent bleeding.