The risks and characteristics of the delayed bleeding after endoscopic submucosal dissection for early gastric carcinoma in cases with anticoagulants.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric carcinoma. Vitamin K antagonists and direct oral anticoagulants (DOAC) were reported to increase the risk of delayed bleeding after ESD. However, the evaluation of ESD cases taking anticoagulants is scarce. We analyzed the risk and characteristics of delayed bleeding after gastric ESD in patients on anticoagulants. METHODS: We performed a retrospective observational study at a single center. Consecutive patients who underwent ESD for early gastric carcinoma and took anticoagulants, including warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban, between January 2012 and December 2018, were analyzed. We also calculated delayed bleeding rates for those without anticoagulants. RESULTS: Of 1855 eligible patients who underwent gastric ESDs, 143 took anticoagulants. Delayed bleeding occurred in 30 (21.0%) cases taking anticoagulants, with 15 (19.5%) cases in the DOAC group [rivaroxaban, seven cases (21.2%); dabigatran, four cases (20.0%); apixaban, four cases (23.5%); and edoxaban, zero cases (0%)] and 15 cases (22.7%) in the warfarin group. Furthermore, 43/344 (12.5%) patients taking antiplatelets and 76/1368 (5.6%) patients without antithrombic drugs experienced delayed bleeding. Multivariable logistic analysis revealed post-heart valve replacement (OR, 6.56; 95% CI, 1.75-24.7; p < .05) as a risk for delayed bleeding in warfarin-taking patients, while no statistically significant factor was found in DOAC-taking patients. CONCLUSIONS: Anticoagulants were associated with a high incidence of severe delayed bleeding. Careful attention should be paid to patients on anticoagulants after gastric ESD, especially those on warfarin after heart valve replacement.

The sub-classification of type B2 vessels according to the magnifying endoscopic classification of the Japan Esophageal Society.

OBJECTIVES: Guidelines for magnified endoscopic diagnosis of esophageal squamous cell carcinoma (SCC) have been proposed by the Japan Esophageal Society. Type B1, B2, and B3 reflect increasing tumor invasion depths (within mucosal epithelium or into lamina propria mucosa [T1a-EP/LPM], into muscularis mucosa or superficial invasion into submucosa [T1a-MM/T1b-SM1], and into submucosa [T1b-SM2], respectively). The diagnostic accuracy of type B1 and B3 is high, but accuracy of type B2 is low. We aimed to improve the diagnostic accuracy of type B2. METHODS: We retrospectively reviewed 248 SCC lesions treated with endoscopic submucosal dissection between January 2012 and July 2018 and identified the B2 lesions. The maximum diameter of the area presenting B2 was measured and evaluated in relation to tumor invasion, for which receiver-operating characteristic (ROC) curves were generated. The optimal area size for distinguishing T1a-EP/LPM from T1a-MM or deeper invasion was determined. RESULTS: There were 78 lesions with B2, of which 26 (33%) were T1a-MM or T1b-SM1 SCCs. ROC curve analysis indicated that the optimal cut-off for the target area showing B2 was 4 mm. The invasion depth (EP/LPM: MM/SM1: SM2) of B2 observed in an area with a diameter <4 mm (B2-Narrow) and those with diameter ≥4 mm (B2-Broad) was 46:11:1 and 1:15:4, respectively. To predict T1a-MM or deeper invasion, B2-Broad had a sensitivity, specificity, positive predictive value, and negative predictive value of 61%, 98%, 95%, and 79%, respectively. CONCLUSION: The diagnostic accuracy of type B2 was improved by evaluating the area of type B2.

Usefulness of the S-O clip for gastric endoscopic submucosal dissection (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is technically one of the most complicated endoscopic procedures. Traction methods have been reported to be effective for ESD. A recent study revealed that the S-O clip allowed faster and safer colonic ESD. We assessed the efficacy and safety of gastric ESD with the S-O clip for gastric epithelial neoplasm. METHODS: We performed a retrospective cohort study of patients treated for gastric ESD using the S-O clip between September and November 2016 (SO group, n = 48). The subjects were matched with patients treated with conventional gastric ESD from September 2015 to August 2016 (control group, n = 258) at Sendai Kousei Hospital, a tertiary endoscopic center. The primary outcome was procedure time. Multivariate logistic regression and propensity score matching analyses were performed to reduce the effects of selection bias for potential confounding factors differences like age, sex, lesion location, lesion position, presence of ulcer scarring, resected specimen size, and operator experiences. RESULTS: Forty-eight pairs were created after propensity score matching. The mean procedure time (including the S-O clip attachment time) was significantly shorter in the SO group (47.2 ± 24.6 vs. 69.2 ± 67.1 min, p = 0.035). The mean clip attachment time was 4.4 (range 2-15) min. There were no significant differences in other treatment outcomes (en-bloc resection rate: 100 vs. 100%, p = 1.000; perforation rate: 0 vs. 2.1%, p = 0.315; delayed bleeding rate: 2.1 vs. 4.3%, p = 0.558). CONCLUSIONS: The S-O clip improved the speed of gastric ESD by approximately 25%, without increasing adverse events.

Preoperative endoscopic ultrasonography-guided tattooing of the pancreas with a minuscule amount of marking solution using a newly designed injector.

BACKGROUND AND AIM: Recent studies have reported the usefulness of preoperative endoscopic ultrasonography-guided fiducial tattooing (EUS-tattooing) of the pancreas. However, problems of proper procedure, including markers and amounts, have not been resolved. The aim of the present study was to evaluate the feasibility of EUS-tattooing with a minuscule amount of marking solution using a new injector. METHODS: Six consecutive patients who underwent EUS-tattooing between June 2013 and April 2015 at our center were retrospectively analyzed (mean age, 60.7 years; males, 4). A 25-gauge needle was inserted into the surface of the pancreas near the tumor with EUS guidance. Then, 0.02 mL marking solution was injected three to five times (maximal total amount was defined as 0.1 mL). The marking solution used in this study was a compound of aqueous solution of sodium hyaluronate and India ink with proportions of 4 to 1. The newly developed injector for precise injection of minuscule amount of solution was used. RESULTS: All six patients were successfully injected with the intended amount of marking solution. The tattoo mark was easily detected during surgery and localized in a small area in five patients. In one patient, however, the tattoo mark was not detected during surgery. There were no adverse events, including bleeding, perforation, and acute pancreatitis, by EUS-tattooing. CONCLUSIONS: EUS-tattooing with a minuscule amount of marking solution using the newly developed injector was feasible and seemed useful and relatively safe. Further studies are warranted to confirm the safety and efficacy of EUS-tattooing.

A case of a glomus tumor of the stomach resected by laparoscopy endoscopy cooperative surgery.

A 56-year-old woman who was found to have a submucosal tumor (SMT) of the stomach in a medical check-up was admitted to our hospital for a detailed investigation of the SMT. Upper gastrointestinal endoscopy revealed an SMT of 20mm at the anterior wall of the antrum of the stomach. Endoscopic ultrasonography showed a hyperechoic tumor in the fourth layer of the stomach wall. CT examination showed a strongly enhancing tumor on arterial phase images and persistent enhancement on portal venous phase images. Laparoscopy endoscopy cooperative surgery was performed with a diagnosis of SMT of the stomach highly suspicious of a glomus tumor. Immunohistochemistry revealed expression of α-SMA but no expression of desmin, c-kit, CD34, or S-100. The tumor was finally diagnosed as a glomus tumor of the stomach.

Usefulness of dilated blood vessels in the tumor periphery for assessing the invasion depth of small-sized depressed colorectal cancer.

The relationship between dilated blood vessels in the tumor periphery and the tumor invasion depth is unclear. Therefore, the present study aimed to clarify the relationship between dilated blood vessels and the invasion depth of small-sized (<30 mm) colorectal cancer (CRC), and its implications on endoscopic treatment.We performed a single-arm observational study of the diagnostic accuracy of the existence of dilated vessels in the tumor periphery of CRC lesions as an indicator of submucosal deep (SM-d, ≥1000 µm) carcinomas. Lesions were classified into two groups based on the existence of dilated vessels by two experienced endoscopists. The clinicopathological features, invasion depth, and lymphovascular invasion/poorly differentiated clusters were analyzed in all resected specimens.Four hundred and two consecutive small-sized CRC lesions were included. The dilated vessels were observed in 96/402 (24%) lesions, and most of them (93/96) were found in depressed lesions. In depressed lesions, the histopathological diagnosis of the dilated vessels group showed SM-d or deeper invasion in 84/93 (90%) cases, whereas 3/20 (15%) had SM-d invasion in the nondilated vessels group (P < 0.001). When the dilated vessels were used as an indicator of SM-d or deeper invasion in depressed lesions, the sensitivity was 95.6%, specificity was 66.7%, and accuracy was 90.2%. No correlation was observed between the existence of dilated vessels and the lesion site, lesion diameter, and lymphovascular invasion/poorly differentiated cluster.The existence of dilated blood vessels in the tumor periphery suggests SM-d or deeper invasion in depressed lesions.

Sequence-dependence of cisplatin and 5-fluorouracil in advanced and recurrent gastric cancer.

This randomized controlled clinical trial was designed to compare the safety and effectiveness of different sequences of treatment with cisplatin (CDDP) and 5-fluorouracil (5-FU) in patients with unresectable advanced and post-operative recurrent gastric cancer. Patients with unresectable advanced or post-operative recurrent gastric cancer were randomly assigned by a registration center to group A or B. Group A received CDDP (80 mg/m(2)) as a continuous 2-h intravenous infusion on day 1 and 5-FU (700 mg/m(2)) as a continuous intravenous infusion on days 2-5. Group B was given 5-FU (700 mg/m(2)) as a continuous intravenous infusion on days 1-4, followed by CDDP (80 mg/m(2)) as a continuous 2-h intravenous infusion on day 5. Each course of chemotherapy was repeated every 28 days. A total of 74 patients were enrolled. One patient died accidentally, and 5 could not be evaluated. Response was assessable in 68 patients. The response rate was 31.3% (10/32) in group A as compared with 13.9% (5/36) in group B. Although the response rate was higher in Group A, the difference was not significant (p=0.085). The response rate in patients with diffuse type tumors was significantly lower in group B. There was no difference between the groups in response among patients with intestinal type tumors. The median overall survival was 239 and 174 days and time to progression was 175 and 140 days in group A and group B, respectively. Although there were trends toward longer survival and time to progression in group A, the differences between the groups were not statistically significant. There was also no difference in the type or incidence of adverse reactions. The results of this controlled study indicate that the overall response rate was slightly but not significantly higher in patients who received CDDP before 5-FU. Among patients with diffuse type tumors, the response rate was significantly lower when 5-FU was administered before CDDP. Our results suggest that CDDP should be given before 5-FU in patients with gastric cancer when treated with a combination of CDDP and 5-FU.

Iron-deficiency anemia caused by a proton pump inhibitor.

A 59-year-old man was orally administered rabeprazole, a proton pump inhibitor (PPI), for gastroesophageal reflux disease, after which he gradually developed iron-deficiency anemia. The anemia did not improve following the administration of ferrous fumarate, and endoscopic screening of the entire gastrointestinal tract, including the small intestine, did not reveal any findings indicating the cause of the anemia. The patient was then switched from rabeprazole to famotidine and the anemia was cured within three months. There is much debate as to whether the long-term use of PPIs causes iron-deficiency. However, this case strongly suggests that PPIs can induce iron-deficiency anemia.