Eiji Umegaki

Randomised clinical trial: vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis

Vonoprazan is a novel potassium‐competitive acid blocker which may provide clinical benefit in acid‐related disorders.

Randomised clinical trial: a dose‐ranging study of vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis

The potassium‐competitive acid blocker vonoprazan (VPZ) has potent acid‐inhibitory effects and may offer clinical advantages over conventional therapy for acid‐related disorders.

Endoscopic submucosal dissection of cecal lesions in proximity to the appendiceal orifice

BACKGROUND AND STUDY AIMS Endoscopic submucosal dissection (ESD) is performed for treatment of various gastrointestinal lesions; however, the cecum in proximity to the appendiceal orifice remains a challenging area. We reviewed our experience with cecal ESD near the appendiceal orifice in order to clarify whether this procedure is a safe and effective therapeutic option. PATIENTS AND METHODS We retrospectively reviewed ESD for lesions within approximately 12 mm of the appendiceal orifice at Kobe University Hospital and an affiliated hospital between January 2003 and December 2014. Lesions were classified as: Type 0, proximity to the appendiceal orifice but does not reach it; Type 1, reaches border of the appendix, but does not enter orifice; Type 2, enters orifice, and transition to normal appendiceal mucosa is discernible on inspection of the appendiceal lumen; and Type 3, enters orifice deeply and tumor edge cannot be observed. ESD was not performed for Type 3 lesions unless appendectomy was performed prior to ESD. RESULTS A total of 76 lesions satisfied the inclusion criteria (47 Type 0 lesions, 20 Type 1, 6 Type 2, and 3 Type 3). En bloc resection was achieved in 72 lesions (94.7 %). Median specimen size was 49 mm (range 15 - 114 mm), and median tumor size was 35.5 mm (10 - 110 mm). One patient experienced postoperative bleeding, which was treated by endoscopic hemostasis. Another patient who experienced intraoperative perforation and was treated by clip closure later developed appendicitis; he underwent emergency ileocecal surgical resection. Another patient experienced postoperative appendicitis and recovered with antibiotic treatment. CONCLUSIONS ESD in close proximity to the appendiceal orifice seems safe and effective.

Risk of stricture after endoscopic submucosal dissection for large rectal neoplasms.

BACKGROUND AND STUDY AIMS Improvements in the endoscopic submucosal dissection (ESD) technique have made circumferential ESD in the rectum possible. However, little is known about the clinical course after extensive ESD in the rectum. The aim of this study was to determine the stricture risk in the rectum after total or subtotal circumferential ESD. PATIENTS AND METHODS A total of 69 patients with 69 rectal tumors that required ≥ 75 % circumferential resection were identified at Kobe University Hospital and an affiliated hospital between April 2005 and May 2014. Among the patients, 61 were available for evaluation of stricture development, either by follow-up colonoscopy or by surgical specimens. The rate and possible risk factors of post-ESD strictures were investigated. RESULTS Post-ESD rectal strictures developed in 12 patients (19.7 %). Patients who underwent total circumferential ESD developed a stricture (5/7, 71.4 %) more frequently than those with subtotal (≥ 90 %) ESD (7/16, 43.8 %). Patients undergoing an ESD procedure that involved < 90 % of the circumference did not develop strictures. The strictures were membranous or < 10 mm long in all cases. Of the patients with stricture, 11 received endoscopic balloon dilation and one received bougie with short-caliber-tip transparent hood; all strictures improved following dilation therapy. Statistical analysis revealed that ≥ 90 % circumferential resection was an independent risk factor for stricture, whereas morphology and size were not. CONCLUSIONS Patients who underwent total or subtotal circumferential ESD of a rectal tumor had a high risk of stricture formation. Dilation helped to alleviate the stenosis.Study registered at University Hospital Medical Information Network (UMIN 000016559).

Evaluation of the Efficacy and Safety of Vonoprazan in Patients with Nonerosive Gastroesophageal Reflux Disease: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

Background For many patients, current treatments do not adequately resolve heartburn in nonerosive reflux disease (NERD). Objective To compare vonoprazan and placebo with respect to the frequency and severity of heartburn in patients with NERD. Methods This Phase III, double-blind, placebo-controlled, parallel-group, multicenter study included patients in Japan aged ≥20 years with Grade N or M NERD and recurrent acid reflux symptoms. Patients were blinded and randomized 1:1:1 to receive placebo or vonoprazan 10 mg or 20 mg. The primary efficacy outcome was the proportion of days without heartburn measured by patient scores during the 4-week treatment period. Results Eight hundred twenty-seven patients were randomized (placebo: n = 278, vonoprazan 10 mg: n = 278, and vonoprazan 20 mg: n = 271). Median proportion of days without heartburn was 7.4% (placebo), 10.3% (vonoprazan 10 mg), and 12.0% (vonoprazan 20 mg). Proportion of days without heartburn was not statistically significant between the vonoprazan and placebo groups (P = 0.2310 [10 mg] and P = 0.0504 [20 mg]). Mean severity of heartburn was significantly higher with placebo (median score = 1.070) than with vonoprazan 10 mg (median score = 0.990; P = 0.0440) and 20 mg (median score = 0.960; P = 0.0139). Patients whose symptoms improved at Week 2 experienced significantly increased proportion of days without heartburn and reduced mean severity of heartburn at Week 4 with vonoprazan compared with placebo (proportion of days without heartburn: P = 0.0004 [10 mg] and P = 0.0001 [20 mg] and mean severity: P < 0.0001 [10 mg] and P < 0.0001 [20 mg]). A significant difference in median proportion of days without heartburn was observed for vonoprazan 20 mg compared with placebo in patients with Grade M NERD. Incidence of treatment-emergent adverse events was 32.7% (placebo), 27.7% (vonoprazan 10 mg), and 28.0% (vonoprazan 20 mg). Conclusions Vonoprazan at doses of 10 mg and 20 mg are not superior to placebo with respect to proportion of days without heartburn, whereas the mean severity of heartburn is lower with vonoprazan compared with placebo in patients with NERD. ClinicalTrials.gov identifier: NCT01474369.

Feasibility and safety of endoscopic submucosal dissection for lesions involving the ileocecal valve

BACKGROUND AND STUDY AIM Endoscopic submucosal dissection (ESD) has been applied to treat early colorectal cancers. The aim of this study was to clarify the clinical course of ESD for lesions involving the ileocecal valve (ICV) by evaluating the successful resection rates, and the risk and frequency of adverse events. PATIENTS AND METHODS The outcome of ESD on 38 ICV lesions was compared with the outcome of 132 cecal lesions that did not involve the ICV or appendiceal orifice during the same study period. The factors related to longer procedure time, postoperative stricture development, and tumor recurrence were investigated for ESD of ICV lesions. RESULTS There was no significant difference between the ICV and non-ICV groups in the en block resection rates. The median procedure time was significantly longer in the ICV group than in the non-ICV group, with a point estimate of the difference of 37 minutes (95 % confidence interval [CI] 20.00 to 56.00; P  < 0.01). None of the patients developed symptomatic post-ESD stricture or tumor recurrence. ESD procedure duration was ≥ 120 minutes in 16 lesions and < 120 minutes in 22 lesions of the ICV group. A specimen diameter of ≥ 40 mm and tumor extension into terminal ileum were factors related to a longer procedure time (odds ratio [OR] 8.40, 95 %CI 1.53 to 46.10, P = 0.01; OR 10.60, 95 %CI 2.17 to 51.40, P  < 0.01, respectively). CONCLUSIONS ICV lesions can be resected by ESD without major adverse events or causing symptomatic stricture development. However, ESD for ICV lesions should be performed only by expert endoscopists, as the procedure requires accomplished endoscopic skill and experience.

Efficacy of a new hemostatic forceps during gastric endoscopic submucosal dissection: A prospective randomized controlled trial

Currently, endoscopic submucosal dissection (ESD) is a widely accepted standard treatment for early gastric cancer, but one challenging aspect of ESD is hemostasis.

Electrolyte depletion syndrome (McKittrick–Wheelock syndrome) successfully treated by endoscopic submucosal dissection

A 66-year-old woman presented to us with malaise, anorexia and rectal mucous discharge, and her laboratory data showed severe hyponatremia, hypokalemia, hypochloremia and renal failure. Computed tomography revealed massive occupation of the rectum by a large tumor. Colonoscopy revealed a mucus-rich villous tumor in the rectum. As there were no other factors that could cause an electrolyte disorder, she was diagnosed with McKittrick–Wheelock syndrome (MWS). The current standard treatment for MWS is partial surgical colectomy. However, surgeries are invasive and postoperative complications sometimes become an issue. After confirming no signs of submucosal invasion of the tumor by magnifying chromoendoscopic examination, endoscopic submucosal dissection (ESD) was indicated. The tumor was completely removed en bloc without adverse events. The histology showed a mucosal adenocarcinoma containing a villous component, 24.5 x 17.0 cm in size. This removal dramatically improved the patient’s symptoms and the electrolyte abnormalities without medication. Although several sessions of endoscopic balloon dilation were required to treat postoperative stricture, she has been symptom-free and had no recurrence for 4 years after treatment. We experienced a case of MWS treated by ESD instead of surgery. ESD should be feasible and beneficial for the treatment of MWS.

Gastric plexiform fibromyxoma resected by endoscopic submucosal dissection after observation of chronological changes: A case report

A 66-year-old man was diagnosed with a gastric submucosal tumor. Endoscopic ultrasound (EUS) revealed an iso/hypoechoic mass in the third layer. No malignant cells were detected in a histological examination. Yearly follow-up endoscopy and EUS showed the slow growth of the tumor. Endoscopic submucosal dissection (ESD) was performed and a glistening tumor was resected. The lesion showed a multinodular plexiform growth pattern consisting of spindle cells with an abundant fibromyxoid stroma that was rich in small vessels. The tumor was diagnosed as plexiform fibromyxoma (PF) by immunohistochemistry. Although difficulties are associated with reaching a diagnosis preoperatively, chronological changes on EUS may contribute to the diagnosis of PF. ESD may also be useful in the diagnosis and treatment of PF.

Usefulness of a novel slim type FlushKnife-BT over conventional FlushKnife-BT in esophageal endoscopic submucosal dissection

AIM To investigated the usefulness of a novel slim type ball-tipped FlushKnife (FlushKnife-BTS) over ball-tipped FlushKnife (FlushKnife-BT) in functional experiments and clinical practice. METHODS In order to evaluate the functionality of FlushKnife-BTS, water aspiration speed, resistance to knife insertion through the scope, and waterjet flushing speed were compared between FlushKnife-BTS and BT. In clinical practice, esophageal endoscopic submucosal dissection (ESD) performed using FlushKnife-BTS or BT by an experienced endoscopist between October 2015 and January 2016 were retrospectively reviewed. The treatment speed and frequency of removing and reinserting the knife to aspirate fluid and air during ESD sessions were analyzed. RESULTS Functional experiments revealed that water aspiration speed by the endoscope equipped with a 2.8-mm working channel with FlushKnife-BTS was 7.7-fold faster than that with conventional FlushKnife-BT. Resistance to knife insertion inside the scope with a 2.8-mm working channel was reduced by 40% with FlushKnife-BTS. The waterjet flushing speed was faster with the use of FlushKnife-BT. In clinical practice, a comparison of 6 and 7 ESD using FlushKnife-BT and BTS, respectively, revealed that the median treatment speed was 25.5 mm2/min (range 19.6-30.3) in the BT group and 44.2 mm2/min (range 15.5-55.4) in the BTS group (P = 0.0633). However, the median treatment speed was significantly faster with FlushKnife-BTS when the resection size was larger than 1000 m2 (n = 4, median 24.2 mm2/min, range 19.6-27.7 vs n = 4, median 47.4 mm2/min, range 44.2-55.4, P = 0.0209). The frequency of knife replacement was less in the BTS group (median 1.76 times in one hour, range 0-5.45) than in the BT group (7.02 times in one hour, range 4.23-15) (P = 0.0065). CONCLUSION Our results indicate that FlushKnife-BTS enhances the performance of ESD, particularly for large lesions, by improving air and fluid aspiration and knife insertion during ESD and reducing the frequency of knife removal and reinsertion.