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.

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.

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 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.

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.

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.