Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study).

BACKGROUND: Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding. METHODS: We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events. DISCUSSION: The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy. TRIAL REGISTRATION: UMIN-CTR UMIN000023720 . Registered on 22 August 2016.

Successful treatment of giant rectal varices by modified percutaneous transhepatic obliteration with sclerosant: Report of a case.

We present a female patient with continuous melena, diagnosed with rectal variceal bleeding. She had a history of esophageal varices, which were treated with endoscopic therapy. Five years after the treatment of esophageal varices, continuous melena occurred. Since colonoscopy showed that the melena was caused by giant rectal varices, we thought that they were not suitable to receive endoscopic treatment. We chose the modified percutaneous transhepatic obliteration with sclerosant, which is one of the interventional radiology techniques but a new clinical procedure for rectal varices. After the patient received this therapy, her condition of rectal varices was markedly improved.

Risk factors for bleeding after endoscopic mucosal resection.

AIM: To clarify the risk factors for bleeding after endoscopic mucosal resection (EMR). METHODS: A total of 297 consecutive patients who underwent EMR were enrolled. Some of the patients had multiple lesions. Bleeding requiring endoscopic treatment was defined as bleeding after EMR. Odds ratios (OR) with 95% confidence intervals (CI), calculated by logistic regression with multivariate adjustments for covariates, were the measures of association. RESULTS: Of the 297 patients, 57 (19.2%) patients with bleeding after EMR were confirmed. With multivariate adjustment, the cutting method of EMR, diameter, and endoscopic pattern of the tumor were associated with the risk of bleeding after EMR. The multivariate-adjusted OR for bleeding after EMR using endoscopic aspiration mucosectomy was 3.07 (95%CI, 1.59-5.92) compared with strip biopsy. The multiple-adjusted OR for bleeding after EMR for the highest quartile (16-50 mm) of tumor diameter was 5.63 (95%CI, 1.84-17.23) compared with that for the lowest (4-7 mm). The multiple-adjusted OR for bleeding after EMR for depressed type of tumor was 4.21 (95%CI, 1.75-10.10) compared with elevated type. CONCLUSION: It is important to take tumor characteristics (tumor size and endoscopic pattern) and cutting method of EMR into consideration in predicting bleeding after EMR.

[Pathogenesis and treatment of refractory gastroesophageal reflux disease in Japanese patients].

Prevalence of refractory gastroesophageal reflux disease (GERD) defined as a patient who have persistent GERD symptoms during treatment with proton pump inhibitor (PPI) is rare in Japanese patinets. Pathogenesis of refractory GERD is associated with several factors including dysfunction of esophageal motility, presence of severe hiatal hernia, complication such as stricture and short esophagus, extensive metabolizer of CYP2C19 genotype, nocturnal gastric acid breakthrough, absence of H. pylori infection, or bile reflux. Examination by 24 hr pH monitoring is necessary to assess refractory GERD and if acid suppression is insufficient, treatment with double doses of PPIs or combination of PPI and H2 blocker is effective. However, most cases of refractory GERD are required surgical treatment. Endoscopic therapy might be useful for refractory GERD in future.

A multicenter study on the prevalence of eosinophilic esophagitis and PPI-responsive esophageal eosinophilic infiltration.

OBJECTIVE: Eosinophilic esophagitis (EoE) is diagnosed by the presence of dysphagia and intraepithelial eosinophilic infiltration of ≥15 per high-power field (HPF). EoE should be distinguished from proton pump inhibitor-responsive esophageal eosinophilic infiltration (PPI-R EEI) in patients that are responsive to PPI treatment. The aim of this study was to determine the prevalence of EoE and PPI-R EEI in Japanese patients in a multicenter study. METHODS: Ten hospitals participated in this study. Esophageal biopsy was performed when the patients had typical EoE symptoms or when endoscopic findings revealed a typical EoE appearance. EEI was defined as the intraepithelial eosinophilic infiltration of ≥15 per HPF. Patients with EEI received rabeprazole for 8 weeks to distinguish EoE from PPI-R EEI. RESULTS: A total of 13,634 subjects that underwent upper gastrointestinal endoscopy because of further examination or as a routine checkup were enrolled. Seventy-one (0.5%) patients suspected with EoE were examined by biopsy. A histological examination of 7 (9.9%) cases revealed EEI. Two of these 7 patients showed no symptoms and the other 5 were treated with PPI. Two (0.01%) patients were diagnosed with EoE and 3 (0.02%) with PPI-R EEI. CONCLUSION: EoE and PPI-R EEI were rare in Japanese patients that underwent upper gastrointestinal endoscopy.

What are the risk factors for aggravation of esophageal varices in patients with hepatocellular carcinoma?

BACKGROUND AND AIM: The risk factors for aggravation of esophageal varices (EV) in patients with hepatocellular carcinoma (HCC) are poorly understood. The aim of this study was to evaluate the effects of HCC on the appearance of the red color (RC) sign on EV and also investigate whether risk factors for the appearance of the RC sign differed between patients with and without HCC. METHODS: A total of 243 patients with cirrhosis (127 with HCC, 116 without HCC) without the RC sign, with no previous variceal hemorrhage, and not on prophylactic treatment for EV were enrolled. The endpoint was defined as being either when the RC sign was first noted, or when variceal bleeding occurred. In patients without HCC, follow-up was discontinued if HCC was discovered. The risk factors were analyzed by Cox proportional hazards regression. RESULTS: In patients with HCC, portal vein tumor thrombus was a statistically independent risk factor (risk ratio [RR] 4.58, 95% confidence interval [CI] 1.32-15.86), although the presence of HCC was not. A large HCC (> or =50 mm) tended to be a risk factor, but this was not statistically significant (RR 2.50, 95%CI 0.98-6.39). Child-Pugh classification and low platelet count were common risk factors regardless of whether HCC was present or not. CONCLUSIONS: Portal vein tumor thrombus, but not the presence of HCC, was a significant risk factor for aggravation of EV in patients with HCC. Cirrhotic patients with portal vein tumor thrombus should receive more aggressive management of portal hypertension to prevent aggravation of EV.

Regression of primary low-grade mucosa-associated lymphoid tissue lymphoma of duodenum after long-term treatment with clarithromycin.

A 74-year-old woman was referred to our department because of epigastralgia. Endoscopic findings revealed yellowish bumpy mucosa from the bulbus to the second portion of the duodenum. The patient was admitted to our hospital for further examinations and treatment for this lesion. Endoscopic mucosal resection (EMR) was performed on part of the lesion to obtain the final diagnosis, and then mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum was diagnosed using this procedure. In this case, no evidence of Helicobacter pylori infection in the patient's stomach was detected by any of the diagnostic examinations used, such as the urea breath test, histological study, culture, and serological antibody. For this reason, the patient's duodenal MALT lymphoma was treated solely with long-term clarithromycin, which had an inhibitory action on lymphocyte activation. The lesion showed slight improved during the first 12 days of treatment, and complete regression was reached after 6 months of treatment. It is suggested that the long-term use of clarithromycin may be effective for diseases of the gastrointestinal tract associated with the lymphocyte proliferation.

Differences in clinical characteristics between patients with endoscopy-negative reflux disease and erosive esophagitis in Japan.

OBJECTIVE: Helicobacter pylori infection and atrophic gastritis are inversely related to erosive esophagitis. Whether these factors affect the pathogenesis of endoscopy-negative reflux disease is not clear. We aimed to elucidate the differences in clinical characteristics between endoscopy-negative erosive disease and erosive esophagitis. METHODS: 253 subjects (89 with endoscopy-negative reflux disease and 164 with erosive esophagitis) were studied. Gastric atrophy was assessed by measurement of serum pepsinogen. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) of endoscopy-negative reflux disease compared with erosive esophagitis. RESULTS: Among GERD patients, female gender (OR = 2.27, 95% CI, 1.25-4.10), smoking (OR = 0.45, 95% CI, 0.22-0.91), and the presence of hiatal hernia (OR = 0.30, 95% CI, 0.17-0.56) were significantly associated with endoscopy-negative reflux disease compared with male gender, not smoking, and absence of hiatal hernia, respectively. Body mass index (BMI) was also significantly associated with a decreased OR for endoscopy-negative reflux disease. Although H. pylori infection and gastric atrophy were significantly more common in patients with endoscopy-negative reflux disease, these associations did not persist in a multiple-adjustment model. After adjustment for gender, BMI, smoking, and hiatal hernia, a decrease in serum pepsinogen I/II ratio was significantly associated with an increased OR for endoscopy-negative reflux disease (p for trend = 0.018). CONCLUSIONS: Female gender, low BMI, not smoking, absence of hiatal hernia, and severity of gastric atrophy were positively associated with endoscopy-negative reflux disease compared with erosive esophagitis among Japanese patients.