A narrative review of postoperative bleeding in patients with gastric cancer treated with endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is now considered a standard treatment for selected patients with early gastric cancer. Compared with endoscopic mucosal resection (EMR), ESD provides a higher complete resection rate (R0), and therefore, a lower local recurrence rate. However, ESD is a more time-consuming procedure, creating a wider and deeper ulcer floor which may cause complications. Post-ESD bleeding is one of them. Although most post-ESD bleedings can be controlled by endoscopic hemostasis at the time of operation, some bleeding after ESD may result in serious conditions such as hemorrhagic shock. Even with preventive methods such as ulcer closure, the application of fibrin glue and polyglycolic acid shielding, acid secretion inhibitors and hemostasis on second-look endoscopy, our experiences told us that post-ESD bleeding cannot be entirely avoidable, especially for patients with big size ulcer bed, anticoagulants/antithrombosis and chronic kidney diseases. The present review first defined post-ESD bleeding, then the incidence, the risk factors, such as the location of operative lesion, the size and depth, chronic kidney diseases, the impacts of anticoagulant and antithrombotic agents. We finally reviewed the managements of post-ESD bleeding, including approaches of coagulating potential bleeding spots during the procedure, lesion closure, lesion shielding and the application of gastric acid secretion inhibitors.

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

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Endoloop closure following gastric endoscopic submucosal dissection to prevent delayed bleeding in patients receiving antithrombotic therapy.

OBJECTIVES: Given the high risk of bleeding in post-endoscopic submucosal dissection (ESD) patients receiving antithrombotic therapy, a new effective method is needed to prevent delayed bleeding among such patients. The aim of this study was to assess the efficacy of endoloop closure, using an endoloop and clips, after gastric ESD to prevent bleeding among patients receiving antithrombotic therapy. METHODS: This retrospective study enrolled patients taking antithrombotic agents who underwent ESD for early gastric cancer between March 2016 and January 2019. Patients were classified into two groups: the endoloop closure group and the control group (no prophylactic treatment). We compared the rates of post-endoscopic submucosal dissection bleeding between the two groups. RESULTS: Overall, 178 patients were included, with 37 patients in the endoloop closure group and 141 patients in the control group. The rate of post-endoscopic submucosal dissection bleeding was in general lower in the endoloop closure group than in the control group; however, the difference was not statistically significant (8% vs. 23%, p = 0.06). Among patients with a resected specimen size <40 mm and those using multiple antithrombotic agents, the endoloop closure group showed a lower rate of post-endoscopic submucosal dissection bleeding (0% vs. 16%, p = 0.03 and 10% vs. 70%, p = 0.02, respectively). CONCLUSIONS: Closure using an endoloop and endoclips after gastric ESD might prevent post-procedure bleeding in patients receiving antithrombotic therapy, particularly in those patients with a resected specimen <40 mm and those receiving multiple antithrombotic agents.

Low-dose PPI to prevent bleeding after ESD: A multicenter randomized controlled study.

BACKGROUND: Although proton pump inhibitors (PPIs) are widely used in the prevention of gastric bleeding caused by endoscopic submucosal dissection (ESD), there is no consensus on the optimal regimen for these patients. Therefore, we aim to investigate whether intermittent use of low-dose PPI is sufficient to prevent post-ESD bleeding. METHODS: This multicenter, non-inferiority, randomized controlled trial was conducted at 9 hospitals in China. Consecutive eligible patients with a diagnosis of gastric mucosal lesions after ESD treatment were randomly assigned (1:1) to receive either intermittent low-dose or continuous high-dose PPIs treatment. After three days, all patients administered orally esomeprazole 40 mg once a day for 8 weeks. The primary endpoint was post-ESD bleeding within 7 days. Analysis was done according to the intention-to-treat principle with the non-inferiority margin (Δ) of 5%. RESULTS: 526 consecutive patients were assessed for eligibility from 30 September 2017 to 30 July 2019, of whom 414 were randomly assigned to low-dose (n = 209) or high-dose (n = 205) esomeprazole treatment group without dropouts within7 days. The total post-ESD bleeding is occurred in 13 (6.2 %, 95 % CI 3.3-9.6) of 209 within 7 days in the intermittent low-dose group, and 12 (5.9 %, 95 % CI 2.9-9.3) of 205 in the continuous high-dose group. The absolute risk reduction (ARR) was 0.4 % (-4.2, 4.9). One month after ESD, There are 44 patients (21.1 %, 95 % CI 15.8, 26.8) and 39 patients (19.0 % 95 % CI 13.7, 24.4) in scar stage respectively in low-dose group and high-dose group (P = 0.875).The hospital costs in the low-dose PPI group was lower than high -dose group (P = 0.005). CONCLUSION: The intermittent use of low-dose PPIs is sufficient to prevent post-ESD bleeding. It might be applied in clinical practice to prevent post-ESD bleeding and reduce the costs related to PPIs.

Polyglycolic acid sheets decrease post-endoscopic submucosal dissection bleeding in early gastric cancer: A systematic review and meta-analysis.

OBJECTIVE: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer (EGC). However, post-ESD bleeding remains a serious issue, particularly in patients treated with an antithrombotic agent or those have had a large mucosal resection (≥4 cm). Whether covering the ulcer bed induced by ESD with polyglycolic acid (PGA) sheets can prevent post-ESD bleeding remains to be questioned. Therefore, we performed a systematic review and meta-analysis to evaluate the effectiveness of PGA sheets on preventing post-ESD bleeding in patients with early gastric cancer (EGC) at a high risk of post-ESD bleeding. METHODS: PubMed, Cochrane Library and EMBASE databases were searched for studies on the effect of PGA sheets shielding on inpatients with EGC and at a high risk of bleeding using post-ESD bleeding rate as the primary outcome. RESULTS: Among the four included studies (212 lesions in the PGA sheet group and 208 in the control group), post-ESD bleeding rate was significantly lower in the PGA sheet group than in the control group (4.9% vs 13.7%, risk ratio [RR] 0.33, 95% confidence interval [CI] 0.18-0.72, P = 0.004). A subgroup analysis showed that the application of PGA sheets effectively reduced the post-ESD bleeding rate in patients receiving antithrombotic agents (5.5% vs 15.2%; RR 0.37, 95% CI 0.17-0.79, P = 0.01). Although the application of PGA sheets tended to decrease the post-ESD bleeding rate in patients who had undergone large mucosal resections, the difference was not significant (4.5% vs 9.6%; RR 0.52, 95% CI 0.15-1.78, P = 0.29). CONCLUSIONS: PGA sheets can effectively prevent post-ESD bleeding in patients receiving antithrombotic agents. Further studies are needed to confirm whether PGA sheets can decrease post-ESD bleeding in patients underwent large mucosal resection.

Endoscopic submucosal dissection for early gastric cancer on the lesser curvature in upper third of the stomach is a risk factor for postoperative delayed gastric emptying.

BACKGROUND: Advances in Endoscopic submucosal dissection (ESD) technology have established ESD for early gastric cancer as a safe and stable technique. However, ESD may induce delayed gastric emptying and the cause of food residue retention in the stomach after ESD is not clear. This study aimed to clarify risk factors for delayed gastric emptying with food retention after gastric ESD. METHODS: We retrospectively examined for food residue in the stomach 1 week after ESD was performed for early gastric carcinoma at Osaka Saiseikai Nakatsu Hospital from February 2008 to November 2016. RESULTS: Food residue was observed in 68 (6.1%) of 1114 patients who underwent gastric ESD. The percentage of lesions located on the lesser curvature of the upper third of the stomach was 45.6% (31/68) in the food residue group and 3.5% (37/1046) in the non-food residue group, which was significantly different (P < 0.01). Multivariate logistic regression analysis revealed that lesions on the lesser curvature of the upper third of the stomach (Odds ratio [OR] 23.31, 95% confidence interval [CI] 12.60-43.61, P < 0.01), post-ESD bleeding (OR 4.25, 95%CI 1.67-9.80, P < 0.01), submucosal invasion (OR 2.80, 95%CI 1.34-5.63, P < 0.01), and age over 80 years (OR 2.34, 95%CI 1.28-4.22, P < 0.01) were independent risk factors for food retention after gastric ESD. Of the 68 patients, 3 had food residue in the stomach on endoscopic examination for follow-up observation after the ESD ulcer had healed. CONCLUSIONS: Delayed gastric emptying with food retention after gastric ESD was associated with lesions located in the lesser curvature of the upper stomach, submucosal invasion of the lesion, age older than 80 years, and post-ESD bleeding, though it was temporary in most cases.

Efficacy of hemostatic powder in preventing bleeding after gastric endoscopic submucosal dissection in high-risk patients.

BACKGROUND AND AIM: The prevention of post-endoscopic submucosal dissection (ESD) bleeding in high-risk patients is an important problem. This study evaluated the efficacy of polysaccharide hemostatic powder in preventing post-ESD bleeding in high-risk patients. METHODS: Patients at high risk for post-ESD bleeding were prospectively enrolled between December 2015 and July 2016. A high risk of post-ESD bleeding was considered if the patients were taking antithrombotic agents or had undergone a large resection (specimen size ≥ 40 mm). The endpoints were Forrest classification of the post-ESD ulcer on second-look endoscopy 2 days after the procedure and bleeding rates within 48 h and at 4 weeks. RESULTS: Forty-four patients underwent gastric ESD and treatment with hemostatic powder. Among them, 33 patients (70.5%) underwent large resection (≥ 40 mm) without antithrombotic therapy, and 13 patients (29.5%) received antithrombotic therapy. The mean resected specimen size was 55.3 ± 13.9 mm. The proportion of high-risk delayed bleeding lesions (Forrest IIa) at second-look endoscopy was 4.5% (2/44). The overall bleeding rate was 9.1% (4/44). There was no early bleeding event. The median (interquartile range) timing of bleeding after the procedure was 12.5 (interquartile range 10.3-15.5) days. The bleeding rate in the large resection (≥ 40 mm) group without antithrombotic therapy and the antithrombotic therapy group was 3.2% (1/33) and 23.1% (3/13), respectively. CONCLUSIONS: Hemostatic powder may be a promising new simple and effective method to prevent early post-ESD bleeding in high-risk patients, especially for those with larger resection. (Clinical trial registration number: NCT02625792).