林 芳和

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is recognized as a challenging procedure. Previously, we reported that a new ESD strategy using the pocket-creation method (PCM) is useful for colorectal ESD, but no prospective randomized study has evaluated the efficacy of the PCM. The aim of this study was to evaluate the efficacy and safety of PCM for colorectal ESD compared with the conventional method (CM). METHODS: This was a prospective randomized controlled trial at 3 institutions in Japan. Patients with superficial colorectal neoplastic lesions >20 mm predicted to be intramucosal were randomly assigned to undergo ESD using the PCM or CM. Primary outcome was the ESD completion rate defined as completion of colorectal ESD with an en bloc resection using the assigned ESD method without changing to other methods or assisted by other devices. RESULTS: We analyzed 59 patients with 59 colorectal tumors in the PCM group and 55 in the CM group. The ESD completion rate was significantly higher in the PCM group compared with the CM group (93% [55/59] vs 73% [40/55]; P  = .01). En bloc resection rates, R0 resection rates, procedure time, and dissection speed were not significantly different between the 2 groups. The incidence of adverse events was similar in the 2 groups. CONCLUSIONS: Use of the PCM allows the endoscopist to complete the procedure with the intended method more often than the CM with similar clinical outcomes. (Clinical trial registration number: UMIN 000024394.).

Background and study aims  Resecting large colorectal sessile tumors using endoscopic submucosal dissection (ESD) is challenging because of severe submucosal fibrosis. Previously, we reported that ESD strategy using the pocket-creation method (PCM) is useful for large colorectal sessile tumors, but there are no large studies reporting the effectiveness and safety of the PCM for resection of large colorectal sessile tumors. Patients and methods  This was a retrospective review of 90 large colorectal sessile tumors in 89 patients who underwent ESD in our institution. Large colorectal sessile tumors were defined as polypoid lesions 20 mm or more in diameter. We divided them into PCM (n = 40) and conventional method (CM) groups (n = 50). The primary outcome measure was en bloc resection. The inverse-probability-treatment weighting (IPTW) approach was used to adjust for selection bias. Results  Both PCM and CM achieved high en bloc resection (100 % vs. 94 %, non-adjusted P  = 0.25, IPTW-adjusted P  = 0.19) and R0 resection rates (88 % vs. 78 %, non-adjusted P  = 0.28, IPTW-adjusted P  = 0.27). When PCM was used, the rate of pathologically negative vertical margins was significantly greater than with the CM (IPTW-adjusted P  = 0.045). The dissection time was significantly shorter (IPTW-adjusted P  = 0.025) and dissection speed faster (IPTW-adjusted P  = 0.013) using the PCM than when the CM was used. There was no significant difference in the incidence of adverse events (intraprocedural perforation and delayed bleeding, IPTW-adjusted P  = 0.68). Conclusion  Although en bloc resection and R0 resection rates were similar, PCM significantly increased the rate of negative vertical margins with rapid dissection for treatment of large colorectal sessile tumors.

BACKGROUND: A novel potassium-competitive acid blocker, vonoprazan (VPZ), improves first-line Helicobacter pylori eradication success. The aim of this systematic review is to clarify the effectiveness and safety of second-line H. pylori eradication therapy comparing VPZ and proton pump inhibitor (PPI)-based regimens. METHODS: Medline (PubMed), EMBASE, Web of Science, Cochrane Library, and the Japan Medical Abstract Society Database were searched. RESULTS: We selected 16 studies for quantitative review. Forest plot analysis showed significant superiority of VPZ over PPI-based regimens in overall second-line H. pylori eradication success (OR 1.51, 95% CI 1.27-1.81, p < 0.001). Forest plots from 2 studies with propensity score matched analysis showed significant superiority of VPZ over PPI-based regimens (OR 3.09, 95% CI 1.71-5.58, p < 0.001). The remaining 14 studies with per-protocol analysis and the full analysis set also showed significant superiority (OR 1.40, 95% CI 1.16-1.69, p < 0.001). Regarding adverse events, Forest plot analysis did not show a significant difference between the 2 regimens (OR 0.88, 95% CI 0.58-1.32, p = 0.53). CONCLUSIONS: A VPZ-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. A VPZ-based second-line H. pylori eradication regimen can be the first choice.

BACKGROUND/AIMS: The long-term outcomes of patients after cessation of acotiamide therapy in patients with functional dyspepsia remains unclear. The aim of this study is to investigate the timing and predictors of recurrence of dyspepsia symptoms after cessation of acotiamide therapy for functional dyspepsia. METHODS: Seventy patients treated with acotiamide for functional dyspepsia who then ceased treatment were enrolled. Changes in dyspepsia symptoms were evaluated using the Izumo scale, a self-reporting questionnaire of abdominal symptom-related quality of life. Patients were subclassified into epigastric pain, postprandial distress, and overlapped types. RESULTS: The mean follow-up after cessation of acotiamide was 1.9 years. After cessation of acotiamide, 39 patients (56%) had recurrence. Kaplan-Meier analysis revealed a recurrence-free rate of 51% at 1 year. Predictors of recurrence evaluated with a Cox proportional hazards model showed that overlapped-type dyspepsia and consultation with the treating physician before cessation were identified as significant positive and negative predictors, respectively (p < 0.05). The resumption of acotiamide significantly decreased the score for dyspepsia symptoms at 1 month. CONCLUSIONS: Dyspepsia symptoms recur about one year after cessation of acotiamide therapy. Patients with overlapped-type dyspepsia should be carefully followed after cessation. Patients should consult their treating physician before stopping acotiamide.

BACKGROUND AND AIM: Linked color imaging (LCI) is a novel image-enhancing technology which enhances color differences between a colorectal lesion and surrounding mucosa with enough brightness to illuminate the wide colorectal lumen. The aim of this study is to compare colorectal polyp detection using LCI with that using white light imaging (WLI). METHODS: Randomized controlled trials and prospective studies comparing LCI with WLI for colorectal polyp detection were selected. Outcomes included overall polyp/adenoma detection and additional polyp detection at a second observation. Outcomes were documented by pooled risk ratios (RR) with 95% confidence interval (CI) using the Mantel-Haenszel random effect model. RESULTS: Seven studies were included. LCI showed significant superiority for polyp and adenoma detection compared with WLI (RR 1.16, 95% CI 1.09-1.25, P < 0.001 for polyp detection; RR 1.26, 95% CI 1.14-1.39 P < 0.001 for adenoma detection). LCI significantly increased the number of polyps detected per patient compared with WLI (mean difference 0.27, 95% CI 0.01-0.53, P = 0.040). LCI significantly increased the number of adenomas detected per patient compared with WLI (mean difference 0.22, 95% CI 0.08-0.36, P = 0.002). LCI significantly increased the number of flat polyps detected per patient compared with WLI (mean difference 0.14, 95% CI 0.01-0.27, P = 0.040). LCI had a significantly higher rate of additional polyp detection compared with WLI in the right colon (RR 2.68, 95% CI 1.71-4.19, P < 0.001). CONCLUSIONS: Linked color imaging has significantly greater polyp and adenoma detection rates and detection rate of previously missed polyps compared with WLI. We recommend the initial use of LCI for routine colonoscopy.

A 67-year-old woman presented with symptoms of bowel obstruction. Radiographic and ultrasonographic findings suggested colo-colonic intussusception caused by a colonic lipoma. Colonoscopy with an endoscope tip balloon was performed for reduction. The intussusception was partially reduced by injecting dilute contrast media with a wedged inflated balloon at the endoscope tip. For definitive treatment of the polyp, ischemia was induced using a detachable snare. The abdominal pain well improved after endoscopic treatment. However, ultrasonography suggested a residual lesion. Another detachable snare was applied to the stalk on day 6. A large amount of dark-red necrotic tissue was passed per anus the following day. One month later, complete scarring of the site was confirmed colonoscopically. This is the first report of curative endoscopic treatment of an intussusception due to a giant colonic lipoma with detachable snares after the reduction with a wedged balloon of colonoscope tip.

BACKGROUND AND AIMS: Small-bowel varices (SBVs) are an uncommon consequence of portal hypertension. Radiologic intervention is usually considered for first-line management. When radiologic intervention is not possible, management options become very limited. The aim of this study was to evaluate the usefulness of double-balloon enteroscopy (DBE)-facilitated cyanoacrylate-injection endotherapy of SBVs. METHODS: This was a retrospective review of DBE-facilitated cyanoacrylate-injection endotherapy of SBVs (December 2015 to October 2016). RESULTS: Ten DBEs were performed in 6 patients (4 women; median age, 68.5 years). No radiologic or surgical options were deemed feasible. Thirteen nests of SBVs were identified and injected with cyanoacrylate glue without hemorrhagic or embolic adverse events. At the 30-day follow-up after therapy, only 1 patient had experienced a mild recurrence of mid-gut bleeding; this was managed conservatively. One patient presented with acute GI bleeding 7 months later, and a repeat DBE with cyanoacrylate-injection endotherapy was successfully performed. One patient succumbed to his underlying advanced cholangiocarcinoma after 2 months. The remaining patients had a median follow-up of 12 months without any recurrent GI bleeding. CONCLUSIONS: DBE-facilitated cyanoacrylate-injection endotherapy of SBVs appears to be a safe and effective option when other first-line options are not feasible.

BACKGROUND AND AIMS: Colonic endoscopic submucosal dissection (ESD) is more difficult than rectal ESD because of poor maneuverability of the endoscope due to physiologic flexion, peristalsis, and respiratory movements. The aim of this study was to assess the usefulness of the pocket-creation method (PCM) for colonic ESD compared with the conventional method (CM) regardless of lesion shape or location. METHODS: A total of 887 colorectal lesions were treated by ESD. Of 887 lesions, 271 rectal lesions, 72 lesions smaller than 20 mm in diameter, and 1 non-neoplastic lesion were excluded. This is a retrospective chart review of the remaining 543 colon lesions in 512 patients. We divided them into the PCM group (n = 280) and the CM group (n = 263). The primary outcome was the en bloc resection rate. Secondary outcomes were R0 resection (en bloc resection with negative margin), adverse events, dissection time (in minutes), and dissection speed (in mm2/min). RESULTS: The PCM group achieved a significantly higher en bloc resection rate (PCM, 100% [280/280], vs CM, 96% [253/263]; P < .001) and R0 resection rate (91% [255/280] vs 85% [224/263], respectively; P = .033) than the CM group. Dissection time was similar (69.5 ± 44.4 vs 78.7 ± 62.6 minutes, P = .676). Dissection speed was significantly faster with the PCM than with the CM (23.5 ± 11.6 vs 20.9 ± 13.6 mm2/min, P < .001). The incidence of adverse events was similar (perforation, 2% vs 4% [P = .152], and delayed bleeding, 2% vs 1% [P = .361]). CONCLUSIONS: Colonic ESD using the PCM significantly improves the rates of en bloc resection and R0 resection and facilitates rapid dissection.

Early detection and resection of neoplastic lesions are key objectives to diminish colorectal cancer mortality. Resection of superficial colorectal neoplasms, cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection have all been developed and used worldwide. The pocket-creation method facilitates the resection of tumors in difficult and routine locations. Early detection is the most important first step to maximize the benefits of recent advancements in endoscopic techniques. However, the detection of small, flat-shaped, or faded color lesions remains difficult. Linked color imaging, a novel multi-light technology, facilitates the recognition of minor differences in tissue by enhancing the color contrast between early colorectal neoplasms and surrounding normal mucosa in a bright field of view. The most striking feature of linked color imaging is its ability to display the color of early neoplastic lesions as distinct from inflammatory changes, both of which have similar "redness" when viewed using white light imaging. To increase the detection rate of neoplasms, linked color imaging should be used from the outset for endoscopic observation. Early detection of superficial colorectal tumors can result in decreased mortality from colorectal cancer and maintain a good quality of life for patients.

BACKGROUND: Gastric acid secretion is compromised in chronic Helicobacter pylori (H. pylori) infection allowing overgrowth of non-H. pylori gastric bacteria (NHGB) in the stomach. METHODS: NHGB were isolated from gastric mucosa in selective media and further characterized with biochemical methods and 16S rRNA gene sequencing. Human gastric tissues were studied with indirect immunofluorescence with antibodies against H. pylori and Neisseria subflava (N. subflava). Gastric epithelial cell lines were cocultured with bacteria or incubated with lipopolysaccharides isolated from NHGB, and interleukin-8 released in the media was measured by enzyme-linked immunosorbent assay. Expression of Toll-like receptor (TLR)2, TLR4, it's coreceptor myeloid differentiation factor 2 (MD2), and CD14 in gastric cells was investigated by immunofluorescence microscopy and reverse transcriptase-polymerase chain reaction. RESULTS: Haemophilus species, Neisseria species, Fusobacterium species, and Veillonella species were predominant Gram-negative bacteria coinfected with H. pylori. Lipopolysaccharides from N. subflava potently stimulated interleukin-8 secretion in MKN45 cells which was cancelled by preincubation with polymyxin B. TLR2, TLR4, CD14, and myeloid differentiation factor 2 were expressed in MKN45 cells, though their levels of expression were low. N. subflava adhered to MKN45 cells in vitro and colocalized with H. pylori in the human gastric mucosa. CONCLUSIONS: Our data suggest that N. subflava colonized in the gastric mucosa contribute to gastric inflammation during chronic H. pylori gastritis. TRANSLATIONAL IMPACT: NHGB may perpetuate gastric inflammation and accelerate neoplastic progression in the hypochlorhydric stomach.

The pocket-creation method (PCM) was introduced to overcome technical issues of endoscopic submucosal dissection (ESD) of large subpedunculated tumors. This innovative technique provides several advantages. PCM facilitates the dissection of a thick submucosal layer with minimal mucosal incision, preventing ‘diffuse lift', and provides effective traction and counter-traction as the tip of the ST hood elongates the submucosal tissue and assists dissection. This technique enhances recognition of the muscularis layer and thus a deep dissection is feasible, ensuring a high-quality pathological specimen with an adequate margin. In challenging lesions located on a vertical wall or over a fold, the approach of the knife converts from vertical to tangential by insertion of the tip of the endoscope into the pocket. In addition, having the tip of the endoscope in the pocket provides stability, counteracting any movement due to breathing or heartbeat. In our experience, ESD with PCM is a well-established, useful and safe technique that appears to be an effective alternative to standard ESD.

In routine upper and lower gastrointestinal endoscopy, overlooking neoplastic lesions is inevitable even for well-trained endoscopists. Various methods have been reported to improve the detection of gastrointestinal neoplasms including chromoendoscopy, special endoscopes, and processor and image enhanced technologies. Equipment-based image enhanced endoscopy (e-IEE) using narrow band imaging (NBI) and blue laser imaging (BLI) is useful to characterize known lesions with magnification at a close-up view. However, they are not useful for the early detection of superficial, pale neoplasms, or both because of the weak image at a distant view in a wide lumen such as the stomach or colon. Linked color imaging (LCI) is a novel pre- and post-processing technology developed by Fujifilm Corporation that has sufficient brightness to illuminate a wide lumen. LCI delineates early gastric cancers as orange-red and intestinal metaplasia as purple. LCI improves the adenoma detection rate in the colon and decreases the polyp miss rate. LCI contributes to the detection of superficial lesions throughout the gastrointestinal tract by enhancing the color contrast between the neoplasm and the surrounding mucosa. LCI can distinguish them by their specific color allocation based mainly on the distribution of capillaries. The authors believe that moving forward, LCI should be used in routine upper and lower gastrointestinal endoscopy.

BACKGROUND AND AIM: Safety and effectiveness of cold snare polypectomy (CSP) compared with hot snare polypectomy (HSP) has been reported. The aim of the present study is to carry out a meta-analysis of the efficacy and safety of HSP and CSP. METHODS: Randomized controlled trials were reviewed to compare HSP with CSP for resecting small colorectal polyps. Outcomes reviewed include complete resection rate, polyp retrieval, delayed bleeding, perforation and procedure time. Outcomes were documented by pooled risk ratios (RR) with 95% confidence intervals (CI) using the Mantel-Haenszel random effect model. RESULTS: Eight studies were reviewed in this meta-analysis, including 1665 patients with 3195 polyps. Complete resection rate using HSP was similar to CSP (RR: 1.02, 95% CI: 0.98-1.07, P = 0.31). Polyp retrieval after HSP was similar to CSP (RR: 1.00, 95% CI: 1.00-1.01, P = 0.60). Delayed bleeding rate after HSP was higher than after CSP, although not significantly (patient basis: RR: 7.53, 95% CI: 0.94-60.24, P = 0.06; polyp basis: RR: 7.35, 95% CI: 0.91-59.33, P = 0.06). Perforation was not reported in all eight studies. Total colonoscopy time for HSP was significantly longer than CSP (mean difference 7.13 min, 95% CI: 5.32-8.94, P < 0.001). Specific polypectomy time for HSP was significantly longer than CSP (mean difference 30.92 s, 95% CI: 9.15-52.68, P = 0.005). CONCLUSION: This meta-analysis shows significantly shorter procedure time using CSP compared with HSP. CSP tends toward less delayed bleeding compared with HSP. We recommend CSP as the standard treatment for resecting small benign colorectal polyps.

Vonoprazan-based regimens have improved the rate of successful Helicobacter pylori (H. pylori) eradication, but it has not reached 100%. The aim of this study is to clarify significant predictors of successful H. pylori eradication using a vonoprazan-based regimen. In this retrospective cohort study, 174 patients who underwent primary H. pylori eradication therapy were included. All patients underwent esophagogastroduodenoscopy before treatment. The vonoprazan-based regimen includes amoxicillin 750 mg, clarithromycin 200 mg and vonoprazan 20 mg twice daily for one week. Pre-treatment with a proton pump inhibitor (PPI) was defined as continued PPI use for more than four weeks prior to eradication therapy. The rates of successful eradication were 83% (145/174) in intention-to-treat analysis and 85% (145/171) in per-protocol analysis. Predictors of successful eradication among 171 patients were evaluated in per-protocol analysis. In univariate analysis, male gender was a significant positive predictor of successful eradication (odds ratio [OR] 3.813, 95% confidence interval [CI] 1.363-10.663, p = 0.010) and pre-treatment with PPIs was a negative predictor (OR 0.193, 95%CI 0.076-0.485, p < 0.001). In multivariate analysis, male gender remained a positive predictor (OR 3.826, 95%CI 1.317-11.116, p = 0.013), and pre-treatment with PPIs (OR 0.232, 95%CI 0.087-0.615, p = 0.003) remained a negative predictor. In conclusion, pre-treatment with PPIs before eradication therapy decreases the rate of successful eradication. Therefore, it may be desirable to discontinue pre-treatment with PPIs prior to eradication therapy, because of the potential to improve the rate of successful eradication.

OBJECTIVE: The novel potassium-competitive acid blocker, vonoprazan, provides rapid and effective acid suppression. The aim of this study is to evaluate the long-term outcomes of patients with symptomatic gastroesophageal reflux disease (GERD) treated with vonoprazan. METHODS: This retrospective cohort study included 55 patients with symptomatic GERD treated with vonoprazan who have been followed for more than one year. The effectiveness of vonoprazan on gastrointestinal symptoms was evaluated using the Izumo scale, a self-reported questionnaire reflecting quality of life related to various abdominal symptoms. RESULTS: These 55 patients with symptomatic GERD had non-erosive reflux disease (n = 30) or erosive esophagitis (n = 25). Vonoprazan (10 mg) for one month improved GERD symptoms in 89% (responders) and the improvement was maintained at one year in 82% without additional treatment. One-year maintenance therapy resulted in sustained resolution of GERD symptoms in 47%. Of the 49 responders, nine patients had relapse of GERD symptoms and dose escalation of vonoprazan improved the symptoms in six patients. Postprandial distress and the presence of erosive esophagitis before starting vonoprazan were identified as significant negative and positive predictors of sustained resolution of GERD symptoms for one year, respectively. Epigastric pain, postprandial distress, constipation and diarrhea were significantly improved at one-month and maintained at one year. After one-year of treatment, the endoscopic healing rate of erosive esophagitis was 95%. CONCLUSION: One-year treatment with vonoprazan significantly improves GERD symptoms and endoscopic healing of erosive esophagitis is satisfactory. The long-term use of vonoprazan is effective and useful to control GERD.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) can be technically difficult in some situations, such as paradoxical movement of the proximal colon. The double-balloon endoscope provides stable endoscopic maneuvering, even in the small intestine. The aim of this study was to assess the outcomes of balloon-assisted endoscopic submucosal dissection (BAESD) of colonoscopically difficult superficial proximal colon tumors. METHODS: We retrospectively reviewed the records of patients who underwent BAESD of superficial proximal colon tumors where colonoscopic difficulties were encountered, from January 2011 to September 2016. Difficulties were defined as a previous incomplete colonoscopy using a conventional colonoscope or unstable endoscopic maneuverability around the tumor with a conventional colonoscope. A propensity score model was used as a secondary analysis to compare outcomes of the BAESD group with those of a non-BAESD group.  RESULTS:  BAESD was performed on 63 tumors in 63 patients. En bloc resection was achieved for 62 tumors (98 %) and an R0 resection was achieved for 55 tumors (87 %). Propensity score matching analysis created 59 matched pairs from the BAESD and non-BAESD groups. There were no statistically significant differences between the two groups in en bloc resection (100 % vs. 100 %; P > 0.99), R0 resection (90 % vs. 93 %; P = 0.74), perforation (0 % vs. 2 %; P > 0.99) or postoperative bleeding (3 % vs. 0 %; P = 0.50). CONCLUSION: Balloon-assisted endoscopy achieved safe and reliable ESD of colonoscopically difficult superficial proximal colon tumors.

BACKGROUND/AIMS: A submucosal cushion of sodium hyaluronate facilitates gastric and colorectal endoscopic submucosal dissection (ESD). However, few studies have evaluated the utility of sodium hyaluronate for ESD of esophageal lesions. The aim of this study is to evaluate the utility and safety of sodium hyaluronate for ESD of superficial esophageal squamous cell neoplasms (ESCN). MATERIAL AND METHODS: We retrospectively reviewed 111 ESCN in 86 patients treated by ESD between September 2007 and April 2013. There were four double cancers, with 107 ESD procedures analyzed. RESULTS: The en bloc resection rate was 99% (106/107). The R0 resection rate was 93% (99/107). Of 106 specimens resected en bloc, four specimens had a positive horizontal margin, two specimens had non-assessable horizontal margins and one specimen had non-assessable horizontal and vertical margins. One patient with a non-assessable horizontal margin developed local recurrence seven months later, treated by repeat ESD. Delayed bleeding occurred in two procedures (2%), and intra-procedural perforation occurred in four (4%). None required operative repair. Endoscopy trainees performed 33 of 107 (31%) ESD procedures. Post-ESD stenosis requiring dilation occurred following five procedures (5%). CONCLUSIONS: Sodium hyaluronate for ESD of ESCN achieves a high R0 resection rate with a low rate of adverse events.

大腸内視鏡挿入の基本テクニックを理解するためには単純化して考えることが重要である。物理的に内視鏡先端の動きが深部に進んでいくように操作をすればよく、その基本テクニックは、(1)内視鏡シャフトの操作を直線的に先端に伝える、(2)内視鏡シャフトのたわみが戻る性質をうまく利用して先端を進める、(3)内視鏡シャフトがカーブを描いた状態で、そのカーブに沿って力が伝わり内視鏡が進む、の3つのパターンに単純化することができる。また、初心者が意識するべき重要事項として「オリエンテーション」、「距離感」、「操作性」の3つがあげられる。操作性を保った苦痛を与えない挿入法として軸保持短縮法が基本ではあるが、ループを形成するときこそ愛護的な挿入を心がけ、無理のないループを効率よく活用することが重要である。最近の機器の進化に伴い、解剖学的に自然な形状をできるだけ崩さず利用するような無理のない挿入法が主体となってきている。(著者抄録)

BACKGROUND AND AIMS: Long-term outcomes in patients with functional dyspepsia remain elusive. Acotiamide, a prokinetic drug, has been available in Japan since 2013. The aim of this study was to assess long-term outcomes in patients with functional dyspepsia treated with acotiamide. METHODS: We retrospectively reviewed 79 consecutive patients with functional dyspepsia whose symptoms improved with acotiamide therapy and who were followed for more than one year. All patients underwent esophagogastroduodenoscopy prior to acotiamide therapy. The mean follow-up was 1.9 (range, 1.0-3.3) years. We assessed the patients' symptom severity using the Izumo scale, which reflects changes in various abdominal symptoms. RESULTS: At one year, dyspepsia symptoms recurred in 25% (20/79) of the patients. In multivariate analysis, severe dyspepsia was significantly associated with increased recurrence (odds ratio [OR] 15.04, 95% confidence interval [CI] 1.73-130.47, p=0.013). Continued use of acotiamide for one year diminished the recurrence of dyspepsia symptoms significantly (OR 0.16, 95%CI 0.04-0.61, p=0.006). The influence of these significant predictors on long-term outcomes was analyzed using the Kaplan-Meier method. Patients with severe dyspepsia before starting acotiamide had significantly more recurrences than those with mild symptoms (p=0.004, log-rank test). Patients who continued acotiamide therapy throughout the follow-up period had significantly fewer recurrences than those who stopped therapy (p<0.001). CONCLUSIONS: Over the long-term, patients with functional dyspepsia have a considerable rate of recurrence of dyspepsia. Severe dyspepsia before treatment increases the recurrence rates, while adherence to an acotiamide therapeutic regimen decreases recurrence rate.

The effects of vonoprazan, a new potassium-competitive acid blocker, on gastroesophageal reflux disease (GERD) symptom are not fully elucidated. The aim of this study is to determine the effect of vonoprazan on GERD and associated gastrointestinal symptoms. We retrospectively reviewed 88 Helicobacter pylori negative patients with GERD treated with vonoprazan 10 mg daily. Symptoms were evaluated using the Izumo scale, which reflects quality of life related to various abdominal symptoms. The rates of improvement and resolution of GERD symptoms were 86% (76/88) and 57% (50/88), respectively. Improvement and resolution in patients with erosive esophagitis was higher than in those with non-erosive reflux disease (91% vs 83%, p = 0.260 and 71% vs 47%, p = 0.025, respectively). We attempted to identify factors which predict the effects of vonoprazan. Multivariate analysis identified advanced age (≥60-year-old) (odds ratio [OR] 7.281, 95% confidence interval [CI] 2.056-25.776, p = 0.002), obesity (BMI ≥ 24) (OR 3.342, 95%CI 1.124-9.940, p = 0.030) and erosive esophagitis (OR 4.368, 95%CI 1.281-14.895, p = 0.018) as positive predictors of resolution of GERD symptoms. Alcohol use (OR 0.131, 95%CI 0.027-0.632, p = 0.011) and history of H. pylori eradication (OR 0.171, 95%CI 0.041-0.718, p = 0.015) were identified as negative predictors. Vonoprazan also improved epigastric pain (73%), postprandial distress (60%), constipation (58%) and diarrhea (52%) in patients with GERD. In conclusion, vonoprazan 10 mg daily is effective in improving GERD symptoms. Advanced age, obesity, erosive esophagitis, alcohol use and history of H. pylori eradication influence the resolution of GERD symptoms. Treatment with vonoprazan favorably affects gastrointestinal symptoms in patients with GERD.

Gastroesophageal reflux disease (GERD) is commonly treated by primary care physicians. Although proton pump inhibitors (PPI) have been the mainstay of GERD treatment for two decades, in some patients GERD is refractory to standard dose PPI for more than eight weeks and is referred to as PPI-resistant GERD. Vonoprazan, a novel competitive acid blocker, became available in Japan for the treatment of patients with GERD, and has greater acid inhibition than existing PPIs. The aim of the present study was to determine the effect of vonoprazan 10 mg daily on PPI-resistant GERD. We retrospectively reviewed 24 patients with PPI-resistant GERD treated with vonoprazan 10 mg daily. The Izumo scale was used to evaluate the effect of vonoprazan before and one month after treatment, which reflects quality of life related to gastrointestinal symptoms. The overall rates of improvement and resolution of GERD symptoms were 88% (21/24) and 42% (10/24), respectively, and the score was significantly decreased (before 5.8±1.7, at one month 1.9±1.9, P<0.001). To evaluate the influence of esophageal erosions despite prior PPI treatment, the patients were divided into erosive (n=6) and non-erosive groups (n=18). Vonoprazan achieved 100% (6/6) improvement in the erosive group and 83% (15/18) in the non-erosive group. Patients in the erosive group had a significantly higher rate of resolution than in the non-erosive group [83% (5/6) vs 28% (5/18), P=0.017]. No adverse events occurred. Other GI symptoms in patients with PPI-resistant GERD were evaluated. The scores for epigastric pain, postprandial distress, constipation and diarrhea were unchanged during the treatment period. In conclusion, vonoprazan 10 mg daily is effective for the treatment of patients with PPI-resistant GERD. Vonoprazan resolves GERD symptoms in patients with erosions more than in those without erosions. This is the first report on the effect of vonoprazan 10 mg on PPI-resistant GERD.

BACKGROUND AND AIMS: Most studies have not reported an improvement in the detection of adenomas with the use of image-enhanced colonoscopy methods, possibly because of the darkness of the images. To overcome this limitation, a new-generation endoscopic system has been developed. This system has 2 blue-laser imaging (BLI) observation modes. The BLI observation was set to BLI-bright mode to detect lesions. We aimed to evaluate the efficacy of BLI in detecting lesions. METHODS: This study was designed as a randomized controlled trial with participants from 8 institutions. We enrolled patients aged ≥40 years. The participants were randomly assigned to 2 groups: observation by using white-light imaging (WLI) with a conventional xenon light source (WLI group) or observation by using BLI-bright mode with a laser light source (BLI group). All of the detected lesions were resected or had a biopsy taken for histopathologic analysis. The primary outcome was the mean number of adenomas per patient (MAP) that were detected per procedure. RESULTS: The WLI and BLI groups consisted of 474 and 489 patients, respectively. The MAP was significantly higher in the BLI group than in the WLI group (mean ± standard deviation [SD] WLI 1.01 ± 1.36, BLI 1.27 ± 1.73; P = .008). Adenoma detection rate in the BLI group was not significantly higher than in the WLI group. Observation times differed significantly, with BLI (9.48 minutes) being longer than WLI (8.42; P < .001). The mean (± SD) number of polyps per patient was significantly higher in the BLI group compared with the WLI group (WLI 1.43 ± 1.64, BLI 1.84 ± 2.09; P = .001). CONCLUSIONS: A newly developed system that uses BLI improves the detection of adenomatous lesions compared with WLI. (Clinical trial registration number: UMIN 000014555.).

BACKGROUND/AIM: Cecal intubation using conventional colonoscopy (CC) requires substantial training. We hypothesized that double-balloon colonoscopy (DBC) facilitates cecal intubation by endoscopy naïve operators. The aim of this study is to evaluate the cecal intubation rate and learning curve of DBC compared with CC. METHODS: Eighteen endoscopy naïve medical students were allocated to two groups and attempted cecal intubation within 20 min using a colon simulator. In group A, CC was performed ten times and then DBC ten times. In group B, the reverse was carried out. We evaluated the cecal intubation rate and learning curve. RESULTS: The overall success rate for cecal intubation using DBC was significantly superior to CC [132/180 (73%) vs. 12/180 (7%), p < 0.001]. To evaluate the success rate overtime, we divided the ten repetitions of the procedure into three time periods: first (1-3), second (4-6), and third (7-10). The success rate using CC is <20%, even during the third time period, in both groups, and one perforation occurred. The success rate using DBC is over 30% in the first period and increased to nearly 80% in the third period in both groups. Finally, we evaluated the time needed for cecal intubation using DBC. The mean cecal intubation time in the first period is 14 min and decreased to 11 min in the third period. CONCLUSIONS: DBC has a higher cecal intubation rate than CC performed by endoscopy naïve medical students using a colon simulator in this randomized-controlled, cross-over study.

Background and study aims The pocket-creation method (PCM) is a novel strategy for endoscopic submucosal dissection (ESD). The aim of this study is to determine the efficacy of the PCM for colorectal laterally spreading tumors, non-granular type (LST-NG). Patients and methods The records of 126 consecutive patients with colorectal LST-NG who underwent ESD between April 2012 and July 2015 were retrospectively reviewed. Patients were divided into PCM (n = 73) and conventional method (CM) (n = 53) groups. Results The en bloc resection rate in the PCM group was significantly higher than in the CM group (100 % [73/73] vs. 92 % [49/53], P = 0.03). The en bloc resection rate with severe fibrosis was higher in the PCM group than in the CM group (100 % [3/3] vs. 60 % [3/5]). The R0 resection rate for the two groups was not statistically significantly different (93 % [68/73] vs. 91 % [48/53], P = 0.74). The perforation rate in the PCM group was lower than in the CM group although not statistically significantly less (0 % 0/73 vs. 4 % 2/53, P = 0.18). For lesions resected en bloc, dissection speed for the PCM group was significantly faster than for the CM group (median [IQR], 19 [13 -24] vs. 14 [10 - 22] mm2/min, P = 0.03). Conclusion ESD using PCM achieves a reliable and safe resection of colorectal LST-NG.

Background and study aims Duodenal endoscopic submucosal dissection (ESD) requires sophisticated endoscopic techniques because of a high rate of perforation. We introduced the pocket-creation method (PCM) of duodenal ESD to overcome difficulties. The aim of this study was to evaluate the safety and usefulness of ESD using the PCM for superficial tumors of the duodenum. Patients and methods We performed ESD of 17 non-ampullary duodenal lesions using the conventional method and of 28 lesions using the PCM from 2006 to 2015 and retrospectively reviewed the results, comparing the PCM and the conventional method. The median follow-up period was 35 months (range 2 - 97). Results There were more lesions at the duodenal angles in the PCM group compared with the conventional method group (54 % [15/28] vs. 22 % [4/17]; P = 0.048), and the resected specimen diameter was larger in the PCM than the conventional method group (median 37 mm [range 25 - 101] vs. 25 mm [15 - 55]; P = 0.007). Dissection speed was faster in the PCM than the conventional method group (9.4 mm2/min [3.0 - 15.7] vs. 6.5 mm2/min [1.5 - 19.7]; P = 0.09). En bloc resection was more frequent in the PCM (100 % [28/28]) than the conventional method group (88 % [15/17]) (P = 0.07). Perforation was significantly less frequent in the PCM (7 % [2/28]) than the conventional method group (29 % [5/17]; P = 0.046). The one delayed perforation in the conventional method group required surgical repair, while other intraprocedural perforations were treated by clipping. There were no recurrences. Conclusions ESD of duodenal lesions can be safely performed using the PCM, which stabilizes the tip of the endoscope even in difficult locations.

The over-the-scope clip (OTSC) system is a new technology that enables closure of fistulae which cannot be closed with a conventional clip. A 57-year-old woman had long-term hypoalbuminemia, edema and general malaise. Peroral double-balloon endoscopy (DBE) showed a jejuno-sigmoid fistula and blind loop syndrome of the jejunum and ileum, because ingested food bypassed the ileum through the fistula. She was advised to undergo surgical closure of the fistula, but she refused the procedure. For 7 years following DBE, repeat courses of antibiotics were required to treat bacterial overgrowth due to blind loop syndrome. The fistula was successfully closed using the OTSC system from the sigmoid colon side. The patient's symptoms and quality of life improved. Two years after closure, hypoalbuminemia, edema and general malaise developed again due to dislocation of the OTSC. She then accepted surgical closure of the fistula, because she had experienced improvement after closure using the OTSC. Her quality of life improved again following surgery. OTSC application can demonstrate the improvement expected after surgical closure of a fistula, and may convince a patient of the benefits of surgical closure.

Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium-competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid-suppressing drug [lansoprazole 30 mg (LAC), rabeprazole 10 mg (RAC), esomeprazole 20 mg (EAC), or vonoprazan 20 mg (VAC)] twice daily for 1 week. Eradication was successful in 73% (419/573) of patients using intention-to-treat (ITT) analysis and 76% (419/549) of patients in per-protocol (PP) analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p < 0.01) and PP analysis (VAC 85%, LAC 69% and RAC 70%, p < 0.01), and had a similarly high eradication rate to the EAC group (83% in ITT and 87% in PP). Although the eradication rate in the VAC and EAC groups was not significantly higher than in the LAC and RAC groups in patients with mild gastric atrophy with both ITT and PP analyses, it was significantly higher in patients with severe gastric atrophy (p < 0.01). The VAC group had a significantly higher H. pylori eradication rate than the LAC and RAC groups, and a > 80% eradication rate regardless of the degree of atrophy.

A 48-year-old man underwent laparoscopic sigmoid colon resection for cancer and surveillance colonoscopy was performed annually thereafter. Five years after the resection, a submucosal mass was found at the anastomotic staple line, 15 cm from the anal verge. Computed tomography scan and endoscopic ultrasound were not consistent with tumor recurrence. Endoscopic mucosa biopsy was performed to obtain a definitive diagnosis. Mucosal incision over the lesion with the cutting needle knife technique revealed a creamy white material, which was completely removed. Histologic examination showed fibrotic tissue without caseous necrosis or tumor cells. No bacteria, including mycobacterium, were found on culture. The patient remains free of recurrence at five years since the resection. Endoscopic biopsy with a cutting mucosal incision is an important technique for evaluation of submucosal lesions after rectal resection.

Development and improvement of endoscopic techniques and devices have changed the treatment of colorectal tumors over the last decade. For the treatment of diminutive polyps, the cold snare technique of the West is becoming a promising treatment in the East because of its short procedure time and low rate of delayed bleeding by eliminating the delayed effect of electrocautery. Rather than using piecemeal endoscopic mucosal resection or surgical resection for the treatment of large superficial tumors, the technique of the East of endoscopic submucosal dissection (ESD) achieves a high success rate of en bloc R0 resection, enabling detailed pathological evaluation with less invasive treatment. This procedure should also be useful in the West where large colorectal tumors are more frequent than in the East. Regarding outcomes, however, in the literature, the definition of 'curative resection' remains somewhat inconsistent and long-term outcomes of patients with deep submucosal and/or lymphovascular invasion in the en bloc specimen have not yet been determined. Large prospective, as well as retrospective, studies of these patients are warranted. When colorectal ESD is difficult because of size or location, the pocket-creation method and/or double-balloon-assisted technique may be useful. In the East, high-quality magnified chromoendoscopy is widely available, and endoscopists try to identify focal submucosal invasion. In the West, a systematic evaluation of surveillance for the prevention of colorectal cancer has been done and is highly refined. The East and West have much to learn from each other.

BACKGROUND AND AIMS: The feasibility of endoscopic submucosal dissection (ESD) for large superficial colorectal tumors is undefined. The aim of this study was to assess the outcomes for patients undergoing ESD of superficial colorectal tumors larger than 50 mm. METHODS: A total of 472 patients who underwent ESD for superficial colorectal tumors from 2010 to 2014 were enrolled. We retrospectively reviewed their records. RESULTS: We compared patients with 20-mm to 50-mm lesions and those with lesions >50 mm regarding demographics, the ESD procedure, and histopathology. Among patients with lesions >50 mm, laterally spreading tumors nongranular and protruded types were uncommon. Histopathologically, deeply invasive (≥1000 μm) submucosal carcinomas were more frequent in lesions >50 mm (14% [10/70] vs 5% [20/402], P < .01). Technically, en bloc resection was successfully accomplished in 99% of patients (69/70). Although the total dissection time for lesions >50 mm was significantly longer than for lesions 20 mm to 50 mm (mean ± SD, 157 ± 114 minutes vs 68 ± 50 min; P < .01), dissection speed for lesions >50 mm was significantly faster than for lesions 20 mm to 50 mm (P < .01). There were no significant differences in en bloc R0 resection rate comparing both groups (>50 mm, 83% vs 20 mm to 50 mm, 87%; P = .31). No perforations or postoperative bleeding occurred in patients with lesions >50 mm. Post-ESD colorectal strictures requiring intervention did not develop in any patient. CONCLUSIONS: ESD for superficial colorectal tumors >50 mm is feasible. ESD of these lesions had a high R0 resection rate and a low adverse event rate. En bloc resection by ESD provides adequate pathological specimens and may limit the need for surgical intervention.

BACKGROUND: Crohn's disease (CD) strictures of the small intestine are a feared complication and difficult to treat because of difficulty gaining access to the stricture site. The development of double-balloon endoscopy (DBE) enabled access to the entire small intestine with interventional capabilities. The aim of this study was to assess the long-term outcomes in patients with small intestinal strictures secondary to CD after DBE-assisted endoscopic balloon dilation (EBD). METHODS: In this retrospective cohort study, DBE-assisted EBD was performed in 85 consecutive patients with CD strictures of the small intestine from 2002 to 2014. Follow-up data were available for 85 patients for a mean of 41.9 months (range, 0-141), and clinical outcomes were assessed. RESULTS: Overall, 321 DBE-assisted EBD sessions (473 procedures) were performed in 85 patients during the study period. Most CD strictures were de novo (97%). The surgery-free rate after initial DBE-assisted EBD was 87.3% at 1 year and 78.1% at 3 years. The presence of a fistula was significantly associated with the need for surgical intervention (hazard ratio = 5.50, 95% confidence interval: 2.16-14.0, P < 0.01). The surgery-free interval in patients with a fistula was significantly shorter than in patients without a fistula (P < 0.01, log-rank test). CONCLUSIONS: DBE-assisted EBD provides a favorable long-term outcome in patients with small intestinal CD-associated strictures. DBE-assisted EBD for CD strictures is a safe and effective treatment to avoid or postpone surgery over the long-term.

The effect of acotiamide on gastrointestinal symptoms is undefined. The aim of this study is to evaluate the effect of acotiamide on abdominal symptoms in patients with functional dyspepsia. We retrospectively reviewed 51 patients treated with acotiamide. We evaluated patient quality of life using the Izumo scale that detects changes in quality of life caused by abdominal symptoms. Acotiamide ameliorated the symptoms of functional dyspepsia at one and three months (improved: 61% vs 80%, p=0.029 and resolved: 17% vs 33%, p=0.069). We then evaluated the effect of acotiamide on epigastric pain syndrome (EPS) (n=33) and postprandial distress syndrome (PDS) (n=41). Acotiamide treatment showed an early effect on rates of improvement (63%) and resolution (42%) of EPS symptoms at one month, maintained up to three months (69% and 39%, respectively). Both rates of improvement and resolution of PDS symptoms showed a significant increase from one month to three months (56% vs 78%, p=0.021 and 17% vs 46%, p=0.004, respectively). The severity of functional dyspepsia symptoms before treatment was significantly associated with failed resolution of functional dyspepsia symptoms (p=0.013). Acotiamide improves and resolves EPS symptoms as well as PDS symptoms. PDS symptoms take longer to resolve than EPS symptoms. J. Med. Invest. 63: 230-235, August, 2016.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has been developed to facilitate en bloc resection of large lesions. However, it is laborious to retrieve the large colorectal specimens. We propose a novel retrieval technique using a Valsalva maneuver, known as Tumor Extraction by Defecation (TED). CASE SERIES: A total of nine lesions (median size 88 mm, maximum 225 mm; proximal colon three, rectum six) that could not be easily retrieved using net forceps were subsequently removed by TED. The rectum was filled with water through the colonoscope. The patient then strained to evacuate the specimen, facilitated by an almost straight anorectal angle. All specimens were retrieved without fragmentation, within minutes. Histology was assessed appropriately, including an adenoma in two and mucosal cancer in seven. All cut margins were verified to be negative. No adverse events occurred. CONCLUSIONS: TED is a promising technique for retrieving large colorectal specimens after ESD.

Conventional endoscopy can miss flat early gastric cancers (0-IIb) because they may not be visible. We treated a patient with synchronous flat early gastric cancers missed by conventional white-light endoscopy (WLE). A 74-year-old Japanese male was referred for endoscopic submucosal dissection (ESD) of a depressed-type early gastric cancer (0-IIc) on the posterior wall of the antrum. Linked color imaging (LCI) detected two flat reddish lesions (0-IIb) measuring 30 mm and 10 mm in diameter in the distal body and prepyloric area, respectively, which had not been detected by conventional WLE. LCI clearly demonstrated the line of demarcation between the malignant lesion and the surrounding mucosa without magnification. Flat early gastric cancers were suspected because both lesions had irregular surface patterns using magnifying blue laser imaging (BLI). An additional depressed lesion (0-IIc) was detected by laser WLE along the greater curvature in the antrum. Magnifying BLI suggested a malignant lesion. Histological examination of biopsy specimens revealed atypical glands in all four lesions. ESD of these lesions was performed. Pathological examination of the resected specimens confirmed well-differentiated adenocarcinoma localized to the mucosa in all four lesions. Flat early gastric cancers became clearly visible using new endoscopic technology.

BACKGROUND: The long-term outcomes of patients after negative double-balloon endoscopy (DBE) for obscure gastrointestinal (GI) bleeding remain unclear. AIM: The aim of this study was to assess the long-term outcomes of patients with negative DBE and clarify the effect of repeat endoscopic work-up. METHODS: A total of 42 patients with a negative DBE for overt obscure GI bleeding were enrolled, and their clinical data were retrospectively reviewed. The mean (± standard deviation) follow-up period is 5.4 (± 2.8) years. The outcome measurement was overt rebleeding witnessed by the patient after negative DBE. At the time of rebleeding, further endoscopic work-up and specific treatment were performed. RESULTS: Rebleeding occurred in 16 of 42 patients (38%). At the time of rebleeding, further investigations were made in 14 of 16 patients (88%), and the bleeding source was identified in 10 of 14 patients (71%). These 10 patients received specific treatment (endoscopic in five, surgical in two, medical in two, and angiographic in one). The bleeding source was in the small intestine in seven of 10 patients (70%). Blood transfusion before DBE and multiple bleeding episodes before DBE were significant predictive factors for rebleeding (odds ratio 5.056, 95% confidence interval 1.158-22.059, p = 0.031 and odds ratio 8.167, 95% confidence interval 1.537-43.392, p = 0.014, respectively). CONCLUSIONS: The rebleeding rate after a negative DBE is considerable. Careful long-term follow-up and repeat endoscopic work-up at the time of overt rebleeding are important.