Publications by authors named "Yosuke Tsuji"

78 Publications

Nonsteroidal anti-inflammatory drugs prevent gastric cancer associated with the use of proton pump inhibitors after eradication.

JGH Open 2021 Jul 5;5(7):770-777. Epub 2021 Jun 5.

Department of Gastroenterology, Graduate School of Medicine The University of Tokyo Bunkyo City Tokyo Japan.

Background And Aim: Proton pump inhibitors (PPIs) are a potential cause of gastric carcinogenesis after eradication. Thus, appropriate management including chemoprevention is required. The aim of this study was to evaluate the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the incidence of post-eradication gastric cancer in PPI users.

Methods: A multicenter retrospective cohort study was conducted. Patients who used a PPI (≥30 days) after eradication between 2014 and 2019 were analyzed in nine hospital databases. Gastric cancer incidence was a primary outcome, and their association with NSAIDs use and clinical factors was evaluated. Hazard ratios were adjusted by age, sex, smoking, and Charlson Comorbidity Index.

Results: During the mean follow-up period of 2.38 years, 1.13% (31/2431) of all patients developed gastric cancer. The cumulative incidence of gastric cancer in PPI users was 0.25% at 1 year, 0.51% at 3 years, and 1.09% at 5 years in the NSAID users and 0.89% at 1 year, 2.32% at 3 years, and 3.61% at 5 years in nonusers. NSAIDs were associated with a lower gastric cancer risk (adjusted hazard ratio = 0.28,  = 0.005). No gastric cancer was observed in the cyclooxygenase-2 inhibitor users ( = 256). NSAID use with high dose and long duration was significantly associated with a lower incidence of gastric cancer.

Conclusion: NSAIDs were associated with a 60% decrease in the gastric cancer incidence in -eradicated PPI users, with dose and duration response effects. NSAIDs may be effective for chemoprevention against PPI-related gastric cancer.
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http://dx.doi.org/10.1002/jgh3.12583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264245PMC
July 2021

Clustering Esports Gameplay Consumers Game Experiences.

Front Sports Act Living 2021 17;3:669999. Epub 2021 Jun 17.

Rikkyo University, Tokyo, Japan.

This study focuses on "game experiences" in the context of esports gameplay consumption and aims to identify adequate consumer groups based on their esports experience including perceptions of gameplay, watching, and purchasing hardware. The purpose of this study is to identify adequate consumer groups through consumer segmentation. Based on the literature review, a matrix of esports gameplay was proposed based on high/low esports gameplay, viewing esports, and hardware enthusiasm. Four esports gameplay consumer groups are proposed (all-around gamer, conventional player, observer, recreational gamer) based on their prior esports experiences (esports gameplay, viewing esports content via media, and hardware enthusiasm). A total of 699 usable observations were initially collected by the online survey. Eventually, 508 observations were retained (127 for each group) for multivariate analysis of variance and subsequent univariate tests. The findings indicated the four esports gameplay consumer groups were empirically supported. Furthermore, this study found similarities and differences for each group based on the six antecedents of esports gameplay intention. The findings indicated hedonic motivation and price value might be considered general factors that may be applied to all esports consumers. Contrarily, the findings indicated that social influence, habit, effort expectancy, and flow might be suitable for tailored marketing strategies targeting esports consumer groups. Theoretically, the suggested esports experience will contribute to the growing body of knowledge aimed at understanding esports consumers' behavior through the consistent clustering of behavioral prior experience. Practically, the proposed esports consumers' clustering will contribute to more efficient marketing, with spending on more targeted marketing leading to effectively reaching the right people.
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http://dx.doi.org/10.3389/fspor.2021.669999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245691PMC
June 2021

Simple feedback of colonoscopy performance improved the number of adenomas per colonoscopy and serrated polyp detection rate.

Endosc Int Open 2021 Jul 17;9(7):E1032-E1038. Epub 2021 Jun 17.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

 High-quality endoscopy requires improvement of not only the adenoma detection rate (ADR) but also the serrated polyp (SP) detection rate and the mean number of adenomas per positive procedure (MAP +). We evaluated whether a simple feedback of colonoscopy performance improves those quality indicators using propensity-score matching.  Eleven endoscopists were evaluated regarding colonoscopy performance including ADRs, SP detection rates, mean numbers of adenomas per procedure (MAPs), and MAPs + with their ranking in the clinic. Endoscopic performance was compared before and after the feedback.  Colonoscopies were performed for 874 patients before the feedback and 1,272 patients after the feedback. Using propensity-score matching, 803 patients before the feedback and 803 patients after the feedback were matched. ADR after the feedback was significantly higher than that before the feedback (50.8 % and 40.8 %, respectively). MAP after feedback was significantly larger than that before the feedback (0.92 and 0.69, respectively), as well as MAP + (1.96 and 1.69, respectively). Clinically significant SP detection rate was also improved from 10.0 % to 14.9 %.  Feedback including ADR, MAP, MAP +, and clinically significant SR detection rate could improve on those quality indicators. Further studies are needed to effectively prevent colorectal cancer in colonoscopy practice.
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http://dx.doi.org/10.1055/a-1393-5469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211485PMC
July 2021

Use of Antibiotics and Probiotics Reduces the Risk of Metachronous Gastric Cancer after Endoscopic Resection.

Biology (Basel) 2021 May 22;10(6). Epub 2021 May 22.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Metachronous gastric cancer often occurs after endoscopic resection. Appropriate management, including chemoprevention, is required after the procedure. This study was performed to evaluate the association between medication use and the incidence of metachronous gastric cancer after endoscopic resection. This multicenter retrospective cohort study was conducted with data from nine hospital databases on patients who underwent endoscopic resection for gastric cancer between 2014 and 2019. The primary outcome was the incidence of metachronous gastric cancer. We evaluated the associations of metachronous gastric cancer occurrence with medication use and clinical factors. Hazard ratios were adjusted by age and Charlson comorbidity index scores, with and without consideration of sex, smoking status, and receipt of eradication therapy during the study period. During a mean follow-up period of 2.55 years, 10.39% (140/1347) of all patients developed metachronous gastric cancer. The use of antibiotics other than those used for eradication was associated with a lower incidence of metachronous gastric cancer than was non-use (adjusted hazard ratio (aHR) 0.56, 95% confidence interval (CI) 0.38-0.85, = 0.006). Probiotic drug use was also associated with a lower incidence of metachronous gastric cancer compared with non-use (aHR 0.29, 95% CI 0.091-0.91, = 0.034). In conclusion, the use of antibiotics and probiotic drugs was associated with a decreased risk of metachronous gastric cancer. These findings suggest that the gut microbiome is associated with metachronous gastric cancer development.
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http://dx.doi.org/10.3390/biology10060455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224738PMC
May 2021

Comparison of endoscopic gastritis based on Kyoto classification between diffuse and intestinal gastric cancer.

World J Gastrointest Endosc 2021 May;13(5):125-136

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Background: Gastric cancers can be categorized into diffuse- and intestinal-type cancers based on the Lauren histopathological classification. These two subtypes show distinct differences in metastasis frequency, treatment application, and prognosis. Therefore, accurately assessing the Lauren classification before treatment is crucial. However, studies on the gastritis endoscopy-based Kyoto classification have recently shown that endoscopic diagnosis has improved.

Aim: To investigate patient characteristics including endoscopic gastritis associated with diffuse- and intestinal-type gastric cancers in ()-infected patients.

Methods: Patients who underwent esophagogastroduodenoscopy at the Toyoshima Endoscopy Clinic were enrolled. The Kyoto classification included atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. The effects of age, sex, and Kyoto classification score on gastric cancer according to the Lauren classification were analyzed. We developed the Lauren predictive background score based on the coefficients of a logistic regression model using variables independently associated with the Lauren classification. Area under the receiver operative characteristic curve and diagnostic accuracy of this score were examined.

Results: A total of 499 -infected patients (49.6% males; average age: 54.9 years) were enrolled; 132 patients with gastric cancer (39 diffuse- and 93 intestinal-type cancers) and 367 cancer-free controls were eligible. Gastric cancer was independently associated with age ≥ 65 years, high atrophy score, high intestinal metaplasia score, and low nodularity score when compared to the control. Factors independently associated with intestinal-type cancer were age ≥ 65 years (coefficient: 1.98), male sex (coefficient: 1.02), high intestinal metaplasia score (coefficient: 0.68), and low enlarged folds score (coefficient: -1.31) when compared to diffuse-type cancer. The Lauren predictive background score was defined as the sum of +2 (age ≥ 65 years), +1 (male sex), +1 (endoscopic intestinal metaplasia), and -1 (endoscopic enlarged folds) points. Area under the receiver operative characteristic curve of the Lauren predictive background score was 0.828 for predicting intestinal-type cancer. With a cut-off value of +2, the sensitivity, specificity, and accuracy of the Lauren predictive background score were 81.7%, 71.8%, and 78.8%, respectively.

Conclusion: Patient backgrounds, such as age, sex, endoscopic intestinal metaplasia, and endoscopic enlarged folds are useful for predicting the Lauren type of gastric cancer.
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http://dx.doi.org/10.4253/wjge.v13.i5.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134854PMC
May 2021

Clinicopathological features and prognosis of developed gastric cancer based on the diagnosis of mucosal atrophy and enlarged folds of stomach by double-contrast upper gastrointestinal barium X-ray radiography.

Clin J Gastroenterol 2021 Aug 20;14(4):947-954. Epub 2021 May 20.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Mucosal atrophy and enlarged folds of stomach by double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) are two major features of Helicobacter pylori-induced chronic gastritis. These were previously shown to be risk indicators of gastric cancer, but their predictability for clinicopathological characters of developed gastric cancer is unelucidated. In addition, evidence for decreasing the mortality of gastric cancer by appropriate follow-up of UGI screening is needed.

Methods: The 5134 generally healthy UGI-XR examinees, who underwent follow-up UGI-XR or upper gastrointestinal endoscopy (UGI-ES) more than once, were prospectively observed for 10 years.

Results: At the beginning of follow-up, 1515 (29.5%) had mucosal atrophy and 990 (19.5%) had enlarged folds. For the serum anti-H. pylori IgG, 1301 (25.3%) were positive, 177 (3.4%) were possibly positive, and 3656 (71.2%) were negative. During the 10-year observation period, gastric cancer developed in 15 subjects, among which 13 had mucosal atrophy and 10 had enlarged folds. These two features were expectedly useful indicators for gastric cancer incidence, but they showed no significant association with tumor stage or histological type of developed cancer. Only one of the 5134 subjects died of gastric cancer during 10 years, which was significantly lower than the predicted number of gastric cancer death (6.78 for 10 years) according to the mortality rate in Japan.

Conclusions: Neither mucosal atrophy nor enlarged folds of stomach showed a significant association with clinicopathological features of developed gastric tumors. Appropriate follow-up of cancer screening by UGI-XR or UGI-ES can reduce the risk of gastric cancer-related death.
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http://dx.doi.org/10.1007/s12328-021-01445-zDOI Listing
August 2021

Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan.

J Gastroenterol Hepatol 2021 May 7. Epub 2021 May 7.

Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.

Background And Aim: This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).

Methods: We retrospectively reviewed  10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated.

Results: Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1).

Conclusion: We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.
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http://dx.doi.org/10.1111/jgh.15536DOI Listing
May 2021

International Observational Survey of the Effectiveness of Personal Protective Equipment during Endoscopic Procedures Performed in Patients with COVID-19.

Digestion 2021 Feb 16:1-9. Epub 2021 Feb 16.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Introduction And Aims: This international survey was performed to evaluate the cumulative incidence of nosocomial novel coronavirus disease 2019 (COVID-19) among healthcare professionals during endoscopic procedures.

Methods: We performed an international web-based self-reported questionnaire survey. Participants completed the questionnaires every week for 12 weeks. The questionnaire elicited responses regarding the development of COVID-19 and details of the personal protective equipment (PPE) used.

Results: All 483 participants were included in the analysis. Participants had a mean age of 42.3 years and comprised 68.3% males. The geographic distribution of the study population was Asia (89.2%), Europe (2.9%), North and South America (4.8%), Oceania (0.6%), and Africa (1.5%). The most common endoscopy-related role of the participants was endoscopist (78.7%), and 74.5% had >10 years of experience. Fourteen participants had performed 83 endoscopic procedures in patients positive for COVID-19. During the mean follow-up period of 4.95 weeks, there were no cases of COVID-19 when treating COVID-19 positive patients. The most common PPE used by participants treating patients with COVID-19 was a surgical mask plus N95 mask plus face shield, goggles, cap, long-sleeved isolation gown, and single pair of gloves. The most common PPE used by participants treating patients without COVID-19 was a surgical mask, no face shield but goggles, cap, long-sleeved isolation gown, and single pair of gloves during all endoscopic procedures.

Conclusions: The risk of COVID-19 transmission during any endoscopic procedure was low in clinical practice.
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http://dx.doi.org/10.1159/000513714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018186PMC
February 2021

Palisade technique as an effective endoscopic submucosal dissection tool for large colorectal tumors.

Endosc Int Open 2021 Feb 3;9(2):E210-E215. Epub 2021 Feb 3.

Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan.

Endoscopic submucosal dissection (ESD) has become the standard treatment for colorectal ESD, but large colorectal tumors remain difficult to remove. We developed a new method, called the palisade technique, by modifying the multiple tunneling technique. In this method, a palisade of submucosal tissue is left beneath the tumor to anchor a dissected specimen, maintaining effective submucosal traction. The study included 11 patients with large colorectal tumors that were over half the circumference of the colorectal lumen which were treated using the palisade technique from August 2017 to October 2019. Overall resection outcomes were assessed. All 11 lesions were removed en bloc. The R0 resection rate was 45.6 % because of marginal burning of the specimen, but no local recurrence was found after a median observation period of 31 months. The median submucosal dissection time (SDT) and submucosal dissection speed (SDS) were 170 minutes and 23.1 mm /min, respectively. One case of post-ESD hemorrhage was successfully managed endoscopically, and two cases of post-colorectal ESD coagulation syndrome were managed conservatively. The palisade technique can be an effective and safe technique for treating large colorectal tumors that extend over half the luminal circumference.
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http://dx.doi.org/10.1055/a-1313-7026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857962PMC
February 2021

Rebleeding in patients with delayed bleeding after endoscopic submucosal dissection for early gastric cancer.

Dig Endosc 2021 Feb 4. Epub 2021 Feb 4.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Objectives: Delayed bleeding is a major adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Some patients may experience rebleeding after successful hemostasis for delayed bleeding, yet the details of rebleeding remain unclear. We aimed to clarify the frequency and risk factors of rebleeding.

Methods: Among 11,452 patients who underwent ESD for EGC at 33 institutions in Japan between 2013 and 2016, we analyzed 489 patients showing delayed bleeding. The rate of rebleeding was investigated. Subsequently, 15 candidate variables were evaluated for their influence on the risk of rebleeding via logistic regression analysis.

Results: Rebleeding occurred in 11.2% (55/489) of the enrolled patients. Multivariate analysis revealed that warfarin [odds ratio (OR), 2.71; 95% confidence interval (CI), 1.26-5.84] and a resection size >40 mm (OR, 1.99; 95% CI, 1.08-3.67) were independent risk factors for rebleeding. In the analysis of the management of warfarin after index bleeding, only warfarin discontinuation (OR, 3.66; 95% CI, 1.37-9.78) was significantly associated with rebleeding in comparison with no use of warfarin. However, many rebleeding events (75.0%) occurred following the resumption of warfarin. The rebleeding rate during discontinuation status and that in taking warfarin (continuation or resumption) were 6.1% and 20.0%, respectively.

Conclusions: Rebleeding was not a rare event in patients experiencing delayed bleeding after ESD for EGC. In addition to having a resection size >40 mm, warfarin usage placed patients at high risk for rebleeding, especially at the timing of its resumption following discontinuation as well as its continuation.
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http://dx.doi.org/10.1111/den.13943DOI Listing
February 2021

The simplified Kyoto classification score is consistent with the ABC method of classification as a grading system for endoscopic gastritis.

J Clin Biochem Nutr 2021 Jan 16;68(1):101-104. Epub 2020 Jul 16.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

The ABC method combined with antibody and serum pepsinogen is a useful predictive method for stomach cancer. Kyoto classification is a new grading system for endoscopic gastritis. However, the consistency of the Kyoto score with the ABC method remains unclear. The Kyoto classification score, which ranges from 0 to 8, is based on the following findings: atrophy, intestinal metaplasia, diffuse redness, nodularity, and enlarged folds. Furthermore, we defined a simplified Kyoto classification score as the sum of scores of just atrophy and intestinal metaplasia. The association between the Kyoto classification score and the ABC method was analyzed using the Kruskal-Wallis and Steel-Dwass tests. A total of 307 subjects were enrolled. Kyoto classification scores were similar in groups B, C, and D, while scores in group A were significantly lower than those of the other groups. The simplified Kyoto classification score showed the same stepwise increase as the classification of the ABC method. In conclusion, unlike the Kyoto classification score, the simplified Kyoto score showed the same significant stepwise increase as the classification of the ABC method.
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http://dx.doi.org/10.3164/jcbn.20-41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844658PMC
January 2021

Risk for lymph node metastasis in Epstein-Barr virus-associated gastric carcinoma with submucosal invasion.

Dig Endosc 2021 May 19;33(4):592-597. Epub 2020 Oct 19.

Departments of, Department of, Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Objectives: Epstein-Barr virus-associated gastric cancer (EBVGC) has been reported to be associated with a low risk for lymph node metastasis (LNM). However, the curative criteria for endoscopic submucosal dissection (ESD) for submucosal EBVGC (pT1b-EBVGC) remain unclear. Our study aimed to investigate the risk factors for LNM in pT1b-EBVGC.

Methods: This was a retrospective multicenter study at five institutes in Japan. We reviewed medical records and extracted all pT1b-EBVGC cases that met the following criteria: (i) histologically proven submucosal gastric cancer; (ii) surgical or endoscopic resection between January 2000 and December 2016; and (iii) presence of Epstein-Barr virus (EBV) in tumor cells verified by EBV-encoded small RNA in situ hybridization (EBER-ISH). The association between clinicopathological factors and LNM were assessed using multivariable logistic regression analysis.

Results: A total of 185 pT1b-EBVGC cases were included in the analysis. LNM was found in nine cases (4.9%). Multivariable logistic regression analysis demonstrated that lymphatic invasion (OR 9.1; 95% CI 2.1-46.1) and submucosal invasion ≥4000 μm (OR 9.2; 95% CI 1.3-110.3) were significant risk factors for LNM. When we focused on pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 μm, the rate of LNM was 0% (0/96, 95% CI 0-3.8%).

Conclusions: Our findings indicated that lymphatic invasion and submucosal invasion ≥4000 μm were significant risk factors for LNM. ESD could be an appropriate option for pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 μm.
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http://dx.doi.org/10.1111/den.13823DOI Listing
May 2021

A Novel Technique of Endoscopic Papillectomy with Hybrid Endoscopic Submucosal Dissection for Ampullary Tumors: A Proof-of-Concept Study (with Video).

J Clin Med 2020 Aug 18;9(8). Epub 2020 Aug 18.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Background: Endoscopic papillectomy (EP) carries a potential risk of procedure-related adverse events and incomplete resection. Since hybrid endoscopic submucosal dissection (ESD) had been established as an alternative option for relatively large and difficult gastrointestinal tumors, we evaluated a novel EP with hybrid ESD (hybrid ESD-EP) for curative safe margin in this proof-of-concept study.

Methods: A total of eight cases who underwent hybrid ESD-EP between 2018 and 2020 were identified from our prospectively maintained database. Hybrid ESD-EP involved a (sub)circumferential incision with partial submucosal dissection, and subsequent snare resection of ampullary tumors, which was performed by two endoscopists with expertise in ESD or endoscopic retrograde cholangiopancreatography. Demographic data and clinicopathological outcomes were retrospectively evaluated.

Results: En bloc resection was achieved by hybrid ESD-EP in all eight cases, with the median procedure time of 112 (range: 65-170) minutes. The median diameters of the resected specimens and tumors were 18 and 12 mm, respectively. All lateral margins were clear, whereas vertical margin was uncertain in three (38%), resulting in the complete resection rate of 63%. Postoperative bleeding and pancreatitis developed in each one (13%). No tumor recurrence was observed even in those cases with uncertain vertical margin, after a median follow-up of 244 (range, 97-678) days.

Conclusions: Hybrid ESD-EP seems to be feasible and promising in ensuring the lateral resection margin. However, further investigations, especially to secure the vertical margin and to shorten the procedure time, should be required.
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http://dx.doi.org/10.3390/jcm9082671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466163PMC
August 2020

Influence of anticoagulants on the risk of delayed bleeding after gastric endoscopic submucosal dissection: a multicenter retrospective study.

Gastric Cancer 2021 Jan 18;24(1):179-189. Epub 2020 Jul 18.

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background And Aims: Delayed bleeding after gastric endoscopic submucosal dissection (ESD) in patients receiving anticoagulants remains an unpreventable adverse event. Although direct-acting oral anticoagulants (DOACs) have superior efficacy in preventing thromboembolism, their effects on the occurrence of delayed bleeding remain unclear. This study aimed to elucidate the clinical effect of DOACs on delayed bleeding after gastric ESD.

Patients And Methods: We retrospectively examined 728 patients who received anticoagulants and were treated for gastric neoplasms with ESD in 25 institutions across Japan. Overall, 261 patients received DOACs, including dabigatran (92), rivaroxaban (103), apixaban (45) and edoxaban (21), whereas 467 patients were treated with warfarin.

Results: Delayed bleeding occurred in 14% of patients taking DOACs, which was not considerably different in patients receiving warfarin (18%). Delayed bleeding rate was significantly lower in patients receiving dabigatran than in those receiving warfarin and lower than that observed for other DOACs. Multivariate analysis showed that age ≥ 65, receiving multiple antithrombotic agents, resection of multiple lesions and lesion size ≥ 30 mm were independent risk factors, and that discontinuation of anticoagulants was associated with a decreased risk of bleeding. In multivariate analysis among patients taking DOACs, dabigatran therapy was associated with a significantly lower risk of delayed bleeding.

Conclusions: The effects of DOACs on delayed bleeding varied between agents, but dabigatran therapy was associated with the lowest risk of delayed bleeding. Switching oral anticoagulants to dabigatran during the perioperative period could be a reasonable option to reduce the risk of delayed bleeding after gastric ESD.
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http://dx.doi.org/10.1007/s10120-020-01105-0DOI Listing
January 2021

Endoscopic submucosal dissection for colorectal neoplasms in proximity or extending to a diverticulum.

Surg Endosc 2021 Jul 15;35(7):3479-3487. Epub 2020 Jul 15.

Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan.

Background And Aims: At specialized facilities, endoscopic submucosal dissection (ESD) has currently been performed even for difficult cases such as tumors extending to a diverticulum that previously required surgery. This study aims to classify the type of lesion according to the degree of infiltration to a diverticulum and assessed the safety and efficacy of ESD for each type of lesion.

Methods: We retrospectively reviewed ESD for lesions at NTT Medical Center Tokyo between January 2014 and April 2019. Lesions were classified as follows: Type 1: lesions in contact with or within 3 mm of the edge of a diverticulum; Type 2: lesions that partially infiltrated into a diverticulum; and Type 3: lesions that infiltrated into and completely covered the diverticulum. Furthermore, ESD strategies were divided into A and B, which indicates that a lesion was resected separately from the diverticulum and along the entire diverticulum, respectively. The clinicopathological characteristics and clinical outcomes were analyzed according to the strategy.

Results: A total of 47 lesions satisfied inclusion criteria (19 Type 1, 12 Type 2, and 16 Type 3 lesions). 19 Type 1 and 8 Type 2 lesions were resected using Strategy A, while 4 Type 2 and 16 Type 3 lesions were resected using Strategy B. En bloc resection was achieved in all cases. In Strategy A, the R0 resection rate was 96.3% and the curative resection rate was 88.9%. On the contrary, in Strategy B, the R0 resection rate was 95.0% and the curative resection rate was 90.0%. In Strategy B, one of the patients developed post-operative bleeding that required endoscopic hemostasis; another patient developed delayed perforation that required emergency surgery.

Conclusions: ESD for colorectal neoplasms in proximity or extending to a diverticulum is challenging, but this procedure can be a safe and effective therapeutic option.
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http://dx.doi.org/10.1007/s00464-020-07795-yDOI Listing
July 2021

Highly accurate artificial intelligence systems to predict the invasion depth of gastric cancer: efficacy of conventional white-light imaging, nonmagnifying narrow-band imaging, and indigo-carmine dye contrast imaging.

Gastrointest Endosc 2020 Oct 25;92(4):866-873.e1. Epub 2020 Jun 25.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background And Aims: Diagnosing the invasion depth of gastric cancer (GC) is necessary to determine the optimal method of treatment. Although the efficacy of evaluating macroscopic features and EUS has been reported, there is a need for more accurate and objective methods. The primary aim of this study was to test the efficacy of novel artificial intelligence (AI) systems in predicting the invasion depth of GC.

Methods: A total of 16,557 images from 1084 cases of GC for which endoscopic resection or surgery was performed between January 2013 and June 2019 were extracted. Cases were randomly assigned to training and test datasets at a ratio of 4:1. Through transfer learning leveraging a convolutional neural network architecture, ResNet50, 3 independent AI systems were developed. Each system was trained to predict the invasion depth of GC using conventional white-light imaging (WLI), nonmagnifying narrow-band imaging (NBI), and indigo-carmine dye contrast imaging (Indigo).

Results: The area under the curve of the WLI AI system was .9590. The lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the WLI AI system were 84.4%, 99.4%, 94.5%, 98.5%, and 92.9%, respectively. The lesion-based accuracies of the WLI, NBI, and Indigo AI systems were 94.5%, 94.3%, and 95.5%, respectively, with no significant difference.

Conclusions: These new AI systems trained with multiple images from different angles and distances could predict the invasion depth of GC with high accuracy. The lesion-based accuracy of the WLI, NBI, and Indigo AI systems was not significantly different.
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http://dx.doi.org/10.1016/j.gie.2020.06.047DOI Listing
October 2020

Prediction model of bleeding after endoscopic submucosal dissection for early gastric cancer: BEST-J score.

Gut 2021 Mar 4;70(3):476-484. Epub 2020 Jun 4.

Division of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.

Objective: Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC.

Design: This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration.

Results: A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a -statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01).

Conclusions: In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.
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http://dx.doi.org/10.1136/gutjnl-2019-319926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873424PMC
March 2021

Expert endoscopists with high adenoma detection rates frequently detect diminutive adenomas in proximal colon.

Endosc Int Open 2020 Jun 25;8(6):E775-E782. Epub 2020 May 25.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokoyo, Japan.

Adenoma detection rate (ADR) is an important quality indicator in colonoscopy, and improved ADR decreases the incidence of colorectal cancer. We investigated differences in polyp detection according to the endoscopist's ADR. We performed a propensity-score matching study using baseline patient characteristics of age, sex, body mass index, family history of colorectal cancer, smoking, drinking, indication for colonoscopy, bowel preparation, and colonoscope type. We compared polyp detection and colonoscopy procedures between patients who underwent colonoscopy by high-ADR endoscopists (high ADR group) and by low-ADR endoscopists (low ADR group). We matched 334 patients in the high ADR group with 334 in the low ADR group. The ADR was 44.0 % and 26.9 % for the high-ADR and low-ADR endoscopists, respectively. Proximal, nonprotruding, and diminutive adenomas were more frequently detected by high-ADR endoscopists than by low-ADR endoscopists (all  < 0.001); similarly, more high-risk adenomas were detected by high-ADR endoscopists (  = 0.028). Furthermore, more sessile serrated polyps detected by high-ADR endoscopists (  = 0.041). High-ADR endoscopists more frequently performed pancolonic chromoendoscopy (  < 0.001). Expert detectors often found nonprotruding and diminutive adenomas in the proximal colon along with increased detection rate of high-risk adenomas. Low-ADR endoscopists need to recognize the features of missed adenomas to improve their ADRs.
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http://dx.doi.org/10.1055/a-1136-9971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247898PMC
June 2020

Steroid injection and polyglycolic acid shielding to prevent stricture after esophageal endoscopic submucosal dissection: a retrospective comparative analysis (with video).

Gastrointest Endosc 2020 12 4;92(6):1176-1186.e1. Epub 2020 May 4.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background And Aims: Postoperative stricture after expansive esophageal endoscopic submucosal dissection (ESD) is a severe adverse event. Previous single-arm reports have suggested that polyglycolic acid (PGA) shielding may prevent stricture. This study was performed to assess the efficacy of this method through a comparative analysis.

Methods: This is a retrospective analysis of 500 consecutive cases of esophageal ESD performed between 2002 and 2018 at the University of Tokyo Hospital. After 2013, patients with a diagnosis of superficial esophageal carcinoma covering more than half of the esophageal circumference underwent preventive treatment with either PGA shielding or steroid injection + PGA shielding after ESD. The efficacy of these methods for preventing post-ESD stricture was assessed through multivariable logistic regression analysis.

Results: The risk of postoperative stricture was especially high in the cervical esophagus (odds ratio [OR], 4.60; 95% confidence interval [CI], 0.65-61.09) and after total circumferential resection (OR, 3.58×10; lower bound of 95% CI, >185). Steroid injection + PGA shielding was the only method significantly effective in preventing stricture (OR, 0.30; 95% CI, 0.10-0.78; P = .009). In the relatively low-risk subgroup (excluding cervical esophageal cancer and complete circumferential resection), the postoperative stricture rates for steroid injection + PGA shielding versus PGA shielding versus control were 18.9% versus 41.4% versus 51.7%, respectively (P = .015). However, the efficacy of this was limited in extremely high-risk cases.

Conclusion: The combination of steroid injection and PGA shielding is effective for preventing post-ESD stricture. There is a need for even more effective methods for cervical esophageal cancer and complete circumferential resection.
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http://dx.doi.org/10.1016/j.gie.2020.04.070DOI Listing
December 2020

Inflammatory fibroid polyp mimicking an early gastric cancer.

Gastrointest Endosc 2020 07 13;92(1):217-218. Epub 2020 Feb 13.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.gie.2020.02.007DOI Listing
July 2020

Reply to Murakami et al.

Endoscopy 2020 01 18;52(1):77. Epub 2019 Dec 18.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1055/a-1026-6136DOI Listing
January 2020

Reply to Wang et al.

Endoscopy 2019 12 27;51(12):1184. Epub 2019 Nov 27.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1055/a-1013-4254DOI Listing
December 2019

Oxyntic gland neoplasm of the stomach: expanding the spectrum and proposal of terminology.

Mod Pathol 2020 02 2;33(2):206-216. Epub 2019 Aug 2.

Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Gastric neoplasms exhibiting oxyntic gland differentiation typically are composed of cells with mild cytonuclear atypia differentiating to chief cells and to a lesser extent, parietal cells. Such tumors with atypical features have been reported also and terminology for this entity remains a matter of considerable debate. We analyzed and classified 26 tumors as oxyntic gland neoplasms within mucosa (group A, eight tumors) and with submucosal invasion. The latter was divided further into those with typical histologic features (group B, 14 tumors) and atypical features, including high-grade nuclear or architectural abnormality and presence of atypical cellular differentiation (group C, four tumors). Groups A and B tumors shared similar histologic features displaying either a chief cell predominant pattern characterized by monotonous chief cell proliferation, or a well-differentiated mixed cell pattern showing admixture of chief and parietal cells resembling fundic gland. In addition, group C tumors displayed atypical cellular differentiation, including mucous neck cell and foveolar epithelium. Moderate or even marked cytological atypia was noted in group C, whereas it was usually mild in the other groups except for three group B tumors with focal moderate atypia. More than 1000 μm submucosal invasion and lymphovascular invasions were recognized only in group C. Mutation analyses identified KRAS mutation in one group C tumor as well as GNAS mutation in in one group A and group B tumors. Intramucosal tumors appear to behave biologically benign and should be classified as "oxyntic gland adenoma". Those with submucosal invasion also have low malignant potential; however, a subset will have atypical features associated with aggressive histologic features and should be designated as "adenocarcinoma of fundic gland type". Especially, we suggest "adenocarcinoma of fundic gland mucosa type" for tumors with submucosal invasion exhibiting atypical cellular differentiation, because the feature is likely to be a sign of aggressive phenotype.
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http://dx.doi.org/10.1038/s41379-019-0338-1DOI Listing
February 2020

New colorectal endoscopic submucosal dissection technique using a single tunnel: the "gateway" method.

Endoscopy 2019 12 1;51(12):E356-E357. Epub 2019 Jul 1.

Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1055/a-0917-6722DOI Listing
December 2019

Haemostasis treatment using dual red imaging during endoscopic submucosal dissection: a multicentre, open-label, randomised controlled trial.

BMJ Open Gastroenterol 2019 30;6(1):e000275. Epub 2019 Mar 30.

Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan.

Introduction: Patients scheduled to undergo oesophageal, gastric and colorectal endoscopic submucosal dissection (ESD) are to be investigated to verify the efficacy of dual red imaging (DRI) for establishing haemostasis during ESD.

Methods And Analysis: The trial is designed as a multicentre, open-label randomised, parallel-group, controlled intervention study. Registered patients will be randomly assigned to DRI and white light imaging (WLI) groups. In the DRI group, the mucosal incision and submucosal dissection will be performed by WLI, and haemostasis will be managed by DRI when bleeding occurs. In the WLI group, the mucosal incision and submucosal dissection are to be performed by WLI and the haemostasis management is to be performed by WLI. The primary endpoint is the time from the recognition of bleeding up to the achievement of complete haemostasis (haemostasis time). The secondary endpoints are the operation time, the proportion of cases in which perforation occurs, and the psychological stress experienced by the endoscopist during haemostasis treatment.

Ethics And Dissemination: This trial was approved by the Keio University Review Board for Clinical Trials (5 December 2016).

Discussion: This will be the first multicentre collaborative research using DRI for haemostasis treatment during ESD. When the safety and simplicity of DRI as a treatment for haemostasis during ESD can be proven, the ESD procedure can be simplified and disseminated more widely in clinical practice.

Trial Registration Number: UMIN000025134.
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http://dx.doi.org/10.1136/bmjgast-2019-000275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441255PMC
March 2019

Endoscopic shielding with polyglycolic acid sheets and fibrin glue for a large-sized ulcer after endoscopic submucosal dissection.

Dig Endosc 2019 Apr;31 Suppl 1:23-24

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1111/den.13318DOI Listing
April 2019

Management of adverse events related to endoscopic resection of upper gastrointestinal neoplasms: Review of the literature and recommendations from experts.

Dig Endosc 2019 Apr;31 Suppl 1:4-20

Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.

Prevention therapy is recommended for lesions >1/2 of the esophageal circumference. Locoregional steroid injection is recommended for lesions >1/2-3/4 of the esophageal circumference and oral steroids are recommended for lesions >1/2 of the subtotal circumference. For lesions of the entire circumference, oral steroid combined with injection steroid is considered. Endoscopic balloon dilatation (EBD) is the first choice of treatment for stricture after esophageal endoscopic submucosal dissection (ESD). Radical incision and cutting or self-expandable metallic stent can be considered for refractory stricture after EBD. In case of intraoperative perforation during esophageal ESD, endoscopic clip closure should be initially attempted. Surgery is considered for treatment of delayed perforation. Current standard practice for prevention of delayed bleeding after gastric ESD includes prophylactic coagulation of vessels on post-ESD ulcers and giving proton pump inhibitors. Chronic kidney disease stage 4 or 5, multiple antithrombotic drug use, anticoagulant use, and heparin bridging therapy are high-risk factors for delayed bleeding after gastric ESD. Intraoperative perforation during gastric ESD is initially managed by endoscopic clip closure. If endoscopic clip closure is difficult, other methods such as over-the-scope clip (OTSC), polyglycolic acid (PGA) sheet shielding etc. are attempted. Delayed perforation usually requires surgical intervention, but endoscopic closure by OTSC or PGA sheet may be considered. Resection of three-quarters of the circumference is a risk factor for stenosis after gastric ESD. Giving prophylactic local steroid injection and/or oral steroid is reported, but effectiveness has not been fully verified as has been done for esophageal stricture. The main management method for gastric stenosis is EBD but it may cause perforation.
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http://dx.doi.org/10.1111/den.13388DOI Listing
April 2019

Red Fluorescence Probe Targeted to Dipeptidylpeptidase-IV for Highly Sensitive Detection of Esophageal Cancer.

Bioconjug Chem 2019 04 3;30(4):1055-1060. Epub 2019 Apr 3.

AMED-CREST, Japan Agency for Medical Research and Development , 1-7-1 Otemachi , Chiyoda-ku , Tokyo 100-0004 , Japan.

We have developed an activatable red fluorescence probe for dipeptidylpeptidase-IV (DPP-IV) by precisely controlling the photoinduced electron transfer (PeT) process of a red fluorescent scaffold, SiR600. The developed probe exhibited an extremely low background signal and showed significant fluorescence activation upon reaction with DPP-IV, enabling sensitive detection of esophageal cancer in clinical specimens from cancer patients.
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00198DOI Listing
April 2019

Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: a prospective multicenter randomized controlled trial.

Endoscopy 2019 07 12;51(7):619-627. Epub 2019 Mar 12.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Bleeding after endoscopic submucosal dissection (ESD) is a severe adverse event. Recent reports have described the efficacy of the endoscopic shielding method with polyglycolic acid (PGA) sheets and fibrin glue for the prevention of adverse events after ESD. The aim of the present study was to investigate whether the PGA shielding method provides additional benefit in preventing post-ESD bleeding compared with standard care.

Methods: This was a prospective, multicenter, randomized controlled trial. Patients at high risk of post-ESD bleeding were enrolled in the study. Before ESD, patients were randomized to either the PGA group or the control group. After completing ESD in the PGA group, PGA sheets were placed onto the ulcer floor and adhered with fibrin glue. The primary end point was the post-ESD bleeding rate.

Results: 140 eligible patients were enrolled from September 2014 to September 2016, and 137 were included in the intention-to-treat analysis (67 in the PGA group and 70 in the control group). Post-ESD bleeding occurred in three patients (4.5 %) in the PGA group and in four patients (5.7 %) in the control group; there was no significant difference between the two groups ( > 0.99). Post-ESD bleeding tended to occur later in the control group than in the PGA group (median 12.5 days [range 8 - 14] vs. 2 days [range 0 - 7], respectively).

Conclusion: The PGA shielding method did not demonstrate a significant effect on the prevention of post-ESD bleeding.
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http://dx.doi.org/10.1055/a-0860-5280DOI Listing
July 2019

Analysis of predictive factors for R0 resection and immediate bleeding of cold snare polypectomy in colonoscopy.

PLoS One 2019 1;14(3):e0213281. Epub 2019 Mar 1.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Factors associated with efficacy and safety of cold snare polypectomy (CSP) are not well established. The aim is to elucidate the predictors of R0 resection and immediate bleeding of CSP.

Methods: We retrospectively reviewed a database of patients who underwent CSP for subcentimetric polyps at the University of Tokyo Hospital in Japan. Using the data regarding the characteristics of patients and polyps, such as location, size, and macroscopic appearance; use of narrow band imaging with magnification (NBI-M); and endoscopists' experience, we revealed the predictive factors associated with R0 resection and immediate post-CSP bleeding by univariate and multivariate analyses.

Results: In total, 399 polyps, in 200 patients without antithrombotics, were removed. Failure of tissue retrieval was noted in 4% of resected lesions. There was no intramucosal carcinoma observed. The overall rate of R0 resection was 46%. Multivariate analysis elucidated that the observation of the polyp with NBI-M was an independent predictor associated with R0 resection (odds ratio [OR] 1.90; p = 0.024). Although immediate post-CSP bleeding occurred in 19 polyps (4.8%), no delayed bleeding or perforation was observed. Multivariate analysis revealed protruded lesion as an independent risk factor for immediate bleeding (OR 3.54; p = 0.018).

Conclusions: A higher rate of R0 resection with CSP can be achieved by performing colonoscopy with NBI-M, than with white-light imaging. Macroscopic protruding appearance of a polyp is a risk factor for immediate bleeding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213281PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396914PMC
December 2019
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