The effect of anticoagulants on delayed bleeding after colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: The withdrawal of antithrombotic therapy from patients at high risk of thromboembolism is controversial. Previously, treatment with anticoagulants, such as warfarin and dabigatran, was recommended for heparin bridge therapy (HBT) during endoscopic submucosal dissection (ESD). However, HBT is associated with a high risk of bleeding during and after ESD. This study aimed to investigate the clinical outcomes of colorectal ESD in patients treated with warfarin and direct oral anticoagulants (DOAC). METHODS: This study included 412 patients with superficial colorectal neoplasms that were resected by ESD between June 2010 and June 2018. The patients were classified into two groups: without antithrombotics (n = 286) and with anticoagulants (n = 51). The anticoagulants group was further divided into two groups: warfarin (n = 26) and DOAC (n = 25). RESULTS: Among all patients, delayed bleeding occurred in 35 (8.5% [35/412]) patients. The bleeding rate in the anticoagulants group (11.8% [6/51]) was higher than that in the group without antithrombotics (6.6% [19/286]), but the difference was not statistically significant (P = 0.240). The bleeding rate in the DOAC group (16.0% [4/25]) was higher than that in the warfarin group (7.7% [2/26]), but the difference was not statistically significant (P = 0.419). All delayed bleeding was successfully managed with endoscopic hemostasis. Thromboembolic events were not observed in any patients. CONCLUSIONS: The bleeding rate with anticoagulants was relatively high. However, all bleeding events with anticoagulants were minor and clinically controllable. Colorectal ESD with DOAC and warfarin may be feasible and acceptable.

Endoscopic Resection of Ampullary Neuroendocrine Tumor.

We report the case of a 57-year-old man with a 1.0-cm grade 1 neuroendocrine tumor (G1 NET) of the ampulla of Vater (ampullary NET) who underwent endoscopic snare papillectomy. Pancreatitis occurred after endoscopic resection but was cured with conservative therapy. In two years of follow-up, no local recurrence or metastasis occurred. Endoscopic snare papillectomy for small G1 NET of the ampulla of Vater is relatively safe and less invasive than surgical treatment and should be considered as treatment option.

Endoscopic submucosal dissection for small submucosal tumors of the rectum compared with endoscopic submucosal resection with a ligation device.

AIM: To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for small rectal submucosal tumors (SMTs). METHODS: Between August 2008 and March 2016, 39 patients were treated with endoscopic submucosal resection with a ligation device (ESMR-L) (n = 21) or ESD (n = 18) for small rectal SMTs in this study. Twenty-five lesions were confirmed by histological evaluation of endoscopic biopsy prior to the procedure, and 14 lesions were not evaluated by endoscopic biopsy. The results for the ESMR-L group and the ESD group were retrospectively compared, including baseline characteristics and therapeutic outcomes. RESULTS: The rate of en bloc resection was 100% in both groups. Although the rate of complete endoscopic resection was higher in the ESD group than in the ESMR-L group (100% vs 95.2%), there were no significant differences between the two groups (P = 0.462). In one patient in the ESMR-L group with a previously biopsied tumor, histological complete resection with a vertical margin involvement of carcinoid tumor could not be achieved, whereas there was no incomplete resection in the ESD group. The mean length of the procedure was significantly greater in the ESD group than in the ESMR-L group (14.7 ± 6.4 min vs 5.4 ± 1.7 min, P < 0.05). The mean period of the hospitalization was also significantly longer in the ESD group than in the ESMR-L group (3.7 ± 0.9 d vs 2.8 ± 1.5 d, P < 0.05). Postoperative bleeding was occurred in one patient in the ESMR-L group. CONCLUSION: Both ESMR-L and ESD were effective for treatment of small rectal SMTs. ESMR-L was simpler to perform than ESD and took less time.

Continuous use of low-dose warfarin for gastric endoscopic submucosal dissection: a prospective study.

Background and study aims Patients who receive warfarin usually require heparin bridge therapy (HBT) to prevent thromboembolic events during endoscopic submucosal dissection (ESD); however, clinical evidence demonstrating the safety and efficacy of HBT during gastric ESD is limited. Conversely, warfarin can be continuously used as a substitute for HBT to endoscopic procedures which have a low risk of bleeding. This study aimed to clarify the safety and efficacy of continuous low-dose warfarin (LDW) for gastric ESD. Patients and methods This was a prospective observational study at a single institution. A total of 22 patients who received warfarin between December 2014 and January 2016 were enrolled. The patients were treated with gastric ESD with a low dose of warfarin ( ≤ 4 mg) at approximately 1.6 - 2.6 of the international normalized ratio (INR) levels. Furthermore, we analyzed a total of 23 patients with HBT who underwent gastric ESD between January 2011 and November 2014. Results The average of warfarin dose and the INR level on the day of gastric ESD in the continuous LDW group were 2.3 mg/day (range 0.5 - 4.0) and 1.87 (range 1.41 - 2.75), respectively. Two of the 22 patients (9.1 %) in the continuous LDW group and 5 of the 23 patients (21.7 %) in the HBT group had postoperative bleeding after gastric ESD. Although the postoperative bleeding rate in the continuous LDW group was lower than that in the HBT group, no significant difference was observed between the 2 groups (P = 0.414). Conclusions Gastric ESD with continuous LDW as a substitute for HBT was feasible and may be acceptable.

Clinical impact of prophylactic clip closure of mucosal defects after colorectal endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is useful for en bloc resection of superficial colorectal neoplasms to ensure accurate histologic diagnoses. However, colorectal ESD is associated with a high frequency of adverse events (AEs). We aimed to investigate the effectiveness of prophylactic clip closure (PCC) of mucosal defects for AEs after colorectal ESD. PATIENTS AND METHODS: This study included 197 patients with 211 lesions who underwent colorectal ESD between June 2010 and August 2016. Patients who had delayed perforation, delayed bleeding, abdominal pain, or fever were defined as AEs after colorectal ESD. Complete PCC was defined as completely sutured mucosal defect using endoclips following colorectal ESD, whereas incomplete PCC was defined as the mucosal defects that did not enable PCC or were partially sutured. Clinical records were retrospectively reviewed and clinical outcomes evaluated. RESULTS: AEs occurred in 29 lesions (13.7 %), including 12 with delayed bleeding, 12 with fever, 2 with abdominal pain, 2 with fever and abdominal pain, and 1 with delayed bleeding and fever. Delayed perforation was not observed in any patient. The frequency of AEs was significantly lower in the group with complete PCC than in the group with incomplete PCC (7.3 % [9/123] vs. 22.7 % [20/88]; P  < 0.001). Multivariate analysis revealed that AEs after colorectal ESD were significantly associated with tumor size and submucosal fibrosis. Subgroup analysis among the resected specimen size of < 40 mm revealed that there was no significant difference in AEs between the 2 groups (5.6 % [6/107] vs. 17.8 % [8/45]; P  = 0.069). However, the frequency of fever with complete PCC was significantly lower than that with incomplete PCC (2.8 % [3/107] vs. 13.3 % [6/45]; P  = 0.020). CONCLUSIONS: Tumor size and submucosal fibrosis were independent risk factors for AEs after colorectal ESD. PCC may be effective in minimizing AEs after colorectal ESD, especially the frequency of fever.

Continuous aspirin use does not increase post-endoscopic dissection bleeding risk for gastric neoplasms in patients on antiplatelet therapy.

BACKGROUND AND STUDY AIMS: Discontinuation of all antiplatelet agents before endoscopic procedures may cause serious complications in some patients. The aim of this study was to evaluate the hemorrhagic risk of post-endoscopic submucosal dissection (ESD) in patients on antiplatelet therapy (APT). PATIENTS AND METHODS: The subjects were 350 patients (377 lesions) who underwent gastric ESD between January 2007 and July 2013. The patients were categorized based on antiplatelet therapies. The primary outcome was post-ESD bleeding. Multivariate analysis was performed to identify independent risk factors for post-ESD bleeding. RESULTS: The patients were categorized into three groups: (1) no APT, 261 patients with 281 lesions; (2) single APT, 58 patients with 63 lesions (53 patients with low dose aspirin [LDA] and 5 patients with a thienopyridine); and (3) dual APT (DAPT), 31 patients with 33 lesions (DAPT with LDA and a thienopyridine). Post-ESD bleeding occurred in 16 of 261 patients in the no APT group (6.1 %), 9 of 58 patients in the single APT group (15.5 %), and 11 of 31 patients in the DAPT group (35.5 %). In multivariate analysis with a Cox proportional hazards model in the no APT and single APT groups, APT (HR 2.7, 95 %CI 1.1 - 6.6, P = 0.03) and diameter of the resected specimen of 40 mm or greater (HR 2.7, 95 %CI 1.2 - 5.9, P = 0.01) were significant risk factors for post-ESD bleeding. In multivariate analysis in the no APT and DAPT groups, DAPT was the only significant risk factor for post-ESD bleeding (HR 16.3, 95 %CI 3.4 - 78.2, P < 0.01). Continuous LDA was not a significant risk factor for post-ESD bleeding in both analyses (HR 0.8, 95 %CI 0.2 - 3.6, P = 0.72 in the no APT and single APT groups; HR 1.0, 95 %CI 0.2 - 5.1, P = 0.95 in the no APT and DAPT groups). CONCLUSIONS: APT increased the risk for post-ESD bleeding, and DAPT markedly increased the risk for bleeding. Continuous LDA did not produce an additional hemorrhagic risk in all patients treated with APT. Thus, patients treated with APT should be careful monitored for post-ESD bleeding, and LDA should not be interrupted in patients with a high thromboembolic risk.

Endoscopic submucosal dissection for early gastric cancer without interruption of warfarin and aspirin.

Many guidelines for the management of antithrombotic therapy in endoscopic procedures state that warfarin should be replaced by heparin in high risk endoscopic procedures. However, heparin bridging therapy is costly, requires a long hospital stay, and is indicated as a risk factor for bleeding after endoscopic submucosal dissection (ESD). It is not yet clear whether it is better to perform gastric ESD on continuous warfarin therapy or heparin bridging therapy. We report the case of a 65-year-old Japanese man who had been diagnosed with early gastric cancer. He had a past medical history of metallic valve replacement for mitral valve regurgitation, coronary artery disease with bare metal stent, and coronary artery bypass graft. Warfarin and low dose aspirin had been used to prevent thromboembolic events in the metallic mitral valve and coronary artery stent. We performed gastric ESD safely on continuous warfarin and low dose aspirin without any complications.

Efficacy of a glycyrrhizin suppository for the treatment of chronic hepatitis C: a pilot study.

Intravenous administration of glycyrrhizin has potential efficacy on decreasing serum aminotransferase levels in patients with chronic hepatitis. However, patients receiving this treatment are recommended to attend hospital regularly for several years. To improve the quality of life for these patients, we developed a glycyrrhizin suppository. In this pilot study, we examined the most effective and safe material contents of the suppository and revealed clinical efficacy for patients with biopsy-proven chronic hepatitis C comparing intravenous administration of glycyrrhizin. As content combinations of the suppository, a mixture of 300 mg of glycyrrhizinic ammonium salt and 60 &mgr;g of sodium capric acid, with pH neutralization, was confirmed to be most effective and safe condition, based on analysis of serum glycyrrhizin levels and the grade of rectal irritations in tested patients. The efficacy on decreasing serum alanine aminotransferase levels for 12-week administration of the suppository in 13 patients with chronic hepatitis C was similar to that in another 13 patients intravenously administered glycyrrhizin. Moreover, no serious side effects were observed. In conclusion, the usage of the newly developed suppository of glycyrrhizin can improve the quality of life for chronic hepatitis C patients, especially those who do not respond with viral clearance to interferon therapy. Using this suppository, larger and longer-term studies are needed.