Publications by authors named "Yasushi Yamasaki"

116 Publications

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Clin Gastroenterol Hepatol 2021 Sep 27. Epub 2021 Sep 27.

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

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http://dx.doi.org/10.1016/j.cgh.2021.09.031DOI Listing
September 2021

Outcomes of endoscopic resection for superficial duodenal tumors: 10 years' experience in 18 Japanese high-volume centers.

Endoscopy 2021 Sep 8. Epub 2021 Sep 8.

Cancer Center, School of Medicine, Keio University, Tokyo, Japan.

Background And Study Aim: There is no enough data for endoscopic resection (ER) of superficial duodenal epithelial tumors (SDETs) due to its rarity. There are two main kinds of ER techniques for SDETs: EMR and ESD. In addition, modified EMR techniques, underwater EMR (UEMR) and cold polypectomy (CP), are getting popular. We conducted a large-scale retrospective multicenter study to clarify detailed outcomes of duodenal ER.

Patients And Methods: Patients with SDETs who underwent ER at 18 institutions from January 2008 to December 2018 were included. The rates of en bloc resection and delayed adverse events (AEs) (defined as delayed bleeding or perforation) were analyzed. Local recurrence was analyzed using Kaplan-Meier method.

Results: In total, 3107 patients (including 1017 receiving ESD) were included. En bloc resection rates were 79.1%, 78.6%, 86.8%, and 94.8%, and delayed AE rates were 0.5%, 2.2%, 2.8%, and 7.3% for CP, UEMR, EMR and ESD, respectively. The delayed AE rate was significantly higher for ESD group than non-ESD group among lesions less than 19 mm (7.4% vs 1.9%, p<0.0001), but not among lesions larger than 20 mm (6.1% vs 7.1%, p=0.6432). The local recurrence rate was significantly lower in ESD group than non-ESD group (p<0.001). Furthermore, for lesions larger than 30 mm, the cumulative local recurrence rate at 2 years was 22.6% in non-ESD group compared to only 1.6% in ESD group (p<0.0001).

Conclusions: ER outcomes for SDETs were generally acceptable. ESD by highly experienced endoscopists might be an option for very large SDETs.
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http://dx.doi.org/10.1055/a-1640-3236DOI Listing
September 2021

Nonrecurrence Rate of Underwater EMR for ≤20-mm Nonampullary Duodenal Adenomas: A Multicenter Prospective Study (D-UEMR Study).

Clin Gastroenterol Hepatol 2021 Jul 2. Epub 2021 Jul 2.

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

Background And Aims: Endoscopic resection of nonampullary duodenal adenoma is often challenging, and its technique has not yet been standardized. To overcome the practical difficulty of conventional endoscopic mucosal resection, underwater endoscopic mucosal resection (UEMR) was recently developed; therefore, we investigated the effectiveness and safety of UEMR for nonampullary duodenal adenoma.

Methods: A multicenter, prospective cohort study was conducted at 21 institutions in Japan. We enrolled patients with no more than 2 nonampullary duodenal adenomas ≤20 mm in size, who were scheduled to undergo UEMR. After UEMR, follow-up endoscopies were scheduled at 2 and 12 months after the procedure, and biopsy specimens were taken from the post-UEMR scars. The primary endpoint was the proportion of patients with histologically proven nonrecurrence at follow-up endoscopy and biopsy.

Results: A total of 155 patients with 166 lesions underwent UEMR. One patient with a non-neoplastic lesion in the resected specimen and 10 patients with 10 lesions who were lost to follow-up were excluded. Finally, 144 patients with 155 lesions who received all follow-up endoscopies were analyzed for the primary endpoint. The proportion of patients with proven nonrecurrence was 97.2% (n = 140 of 144; 95% confidence interval, 92.8%-99.1%) which exceeded the predefined threshold value (92%). Two cases of delayed bleeding (1.2%) occurred and they were successfully managed by clips. All recurrences were successfully treated by additional endoscopic treatment.

Conclusions: This multicenter, prospective cohort study demonstrated effectiveness and safety of UEMR for nonampullary duodenal adenomas ≤20 mm in size. (University Hospital Medical Network Clinical Trials Registry, Number: UMIN000030414).
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http://dx.doi.org/10.1016/j.cgh.2021.06.043DOI Listing
July 2021

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease.

Sci Rep 2021 05 27;11(1):11086. Epub 2021 May 27.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.
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http://dx.doi.org/10.1038/s41598-021-90441-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160157PMC
May 2021

Propensity score-matched analysis of endoscopic resection for recurrent colorectal neoplasms: A pilot study.

J Gastroenterol Hepatol 2021 Sep 5;36(9):2568-2574. Epub 2021 May 5.

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

Background And Aim: Local residual/recurrent colorectal lesions after endoscopic resection (ER) are difficult to treat with conventional ER. Underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) are reportedly effective. We investigated the appropriate indications of ESD and UEMR for recurrent colorectal lesions.

Methods: This single-center, retrospective, observational study was conducted at a tertiary cancer institute. Patients who underwent UEMR or ESD for residual/recurrent colorectal lesions after ER from October 2013 to February 2019 were enrolled. Propensity score matching was performed between the UEMR and ESD groups to compare the clinical characteristics, treatment, and outcomes.

Results: In total, 30 UEMRs and 21 ESDs were performed. Median (range) diameter of the lesions was 8 mm (2-22 mm) in UEMR and 15 mm (2-58 mm) in ESD. Median procedure time in UEMR was significantly shorter than that of ESD (4 min [2-15 min] vs 70 min [17-193 min], P < 0.001). En bloc and complete resection rates of ESD were significantly higher than that of UEMR (73% vs 100%, 41% vs 81%, respectively). No adverse events occurred with UEMR, but there were two cases (10%) of delayed perforation with ESD. Neither group reported recurrence after treatment. Propensity score-matched cases showed significantly shorter procedure time and hospitalization period in UEMR than in ESD.

Conclusions: The outcomes of UEMR and ESD were comparable. UEMR could be a useful salvage therapy for small local residual/recurrent colorectal lesions after ER with shorter procedure time and hospitalization period.
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http://dx.doi.org/10.1111/jgh.15519DOI Listing
September 2021

Underwater endoscopic mucosal resection versus endoscopic submucosal dissection for 20-30 mm colorectal polyps.

J Gastroenterol Hepatol 2021 Sep 29;36(9):2549-2557. Epub 2021 Mar 29.

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

Background And Aim: Endoscopic submucosal dissection (ESD) for large polyps provides a high en bloc resection rate, accurate pathological diagnosis, and low recurrence rate. However, ESD requires advanced techniques, and underwater endoscopic mucosal resection (UEMR) is an alternative. We investigated the efficacy and safety of UEMR for 20-30 mm colorectal lesions compared with ESD.

Methods: We retrospectively evaluated systematically collected data of patients who underwent UEMR or ESD for 20-30 mm sessile colorectal lesions. Outcome measures were the incidence of local recurrence, procedure time, en bloc resection rate, and incidence of adverse events. We performed propensity score matching and inverse probability weighting adjustment to control for possible confounders.

Results: We evaluated 125 patients undergoing UEMR and 306 patients undergoing ESD. Using propensity score matching, we analyzed 74 lesions in each group. UEMR had a shorter procedure time than ESD [6.7 min (95% confidence interval (CI), 5.3-8.1 min) vs 64.8 min (95% CI, 57.4-72.2 min), respectively]. Although the en bloc resection rate with UEMR was inferior to ESD [61% (95% CI, 49-72%) vs 99% (95% CI, 93-100%), respectively], there was no significant difference in the local recurrence rate between the procedures [0% (95% CI, 0-4.0%) in each group]. Inverse probability weighting adjustment revealed that neither ESD nor UEMR had a significant association with local recurrence.

Conclusions: Underwater endoscopic mucosal resection for 20-30  mm colorectal lesions was comparable with ESD regarding long-term outcomes, with a shorter procedure time, despite the lower en bloc resection rate.
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http://dx.doi.org/10.1111/jgh.15494DOI Listing
September 2021

Stop taking routine biopsy specimens for the diagnose of a duodenal adenoma!

Endosc Int Open 2021 Mar 19;9(3):E470-E471. Epub 2021 Feb 19.

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

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http://dx.doi.org/10.1055/a-1339-1089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895647PMC
March 2021

Strategy for Removing an Impacted Enterolith using Double-Balloon Enteroscopy in Crohn's Disease.

Eur J Case Rep Intern Med 2021 28;8(1):002266. Epub 2021 Jan 28.

Department of Gastroenterology, Iwakuni Clinical Center, National Hospital Organization, Yamaguchi, Japan.

An enterolith in Crohn's disease is an uncommon but serious condition because it can cause intestinal obstruction. Endoscopic treatment to remove the enterolith is attempted first, but is sometimes difficult owing to poor accessibility of the endoscope. In such cases, surgical treatment is inevitable. We successfully overcame poor accessibility and removed an enterolith using double-balloon enteroscopy. We describe our method below and suggest several helpful techniques.

Learning Points: Patients with Crohn's disease sometimes have a history of intestinal stricture, which can cause intestinal obstruction by enterolith-related impaction.Endoscopic treatment is the first choice to remove an enterolith, but is sometimes difficult.We successfully removed an enterolith using double-balloon enteroscopy and employing several helpful techniques.
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http://dx.doi.org/10.12890/2021_002266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875588PMC
January 2021

Optimization of insufflation and pressure control in third-space endoscopy.

Surg Endosc 2021 Feb 1. Epub 2021 Feb 1.

Department of Next Generation Endoscopic Intervention (Project ENGINE), Osaka University Graduate School of Medicine, Osaka, Japan.

Background: Third-space endoscopy requires a delicate and accurate insufflation technique to secure the endoscopic visualization and maintain the working space. However, optimal third-space insufflation parameters have yet to be determined. The aim of this study was to assess: (1) the diversity of endoluminal third-space pressure by manual insufflation, and (2) the performance of the insufflation settings for third-space endoscopy.

Methods: A submucosal tunnel was created in the upper posterior wall of the porcine stomach. Using two-channel esophagogastroduodenoscopy, one channel was used for insufflation and the other was used for pressure measurement. Experiment 1 Endoluminal submucosal tunnel pressure was measured in a 10-cm submucosal tunnel of a single porcine. Six board-certified endoscopists in turn maintained what they considered sufficient exposure under manual insufflation. Experiment 2 Endoluminal submucosal tunnel pressure and number of insufflations were measured using the pressure-regulated insufflation device; the differences in the submucosal tunnel length (long: 10-cm, short: 4-cm) and the insufflation route diameter (large: 3.8-mm, small: 2.2-mm) were compared.

Results: Experiment 1 The endoluminal submucosal tunnel pressure profiles during third-space endoscopy varied between endoscopists. Experiment 2 Longer submucosal tunnels and larger insufflation route diameters lead to stable endoluminal submucosal tunnel pressure. The gap with the preset pressure of the insufflator and endoluminal pressure narrowed, and the required number of insufflations decreased with longer tunnel length and larger route diameter.

Conclusions: The pressure dynamics in third-space endoscopy differed among endoscopists. Longer submucosal tunnels and larger insufflation route diameters lead to stable endoluminal submucosal tunnel pressure.
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http://dx.doi.org/10.1007/s00464-021-08319-yDOI Listing
February 2021

Liquid biopsy for patients with IBD-associated neoplasia.

BMC Cancer 2020 Dec 3;20(1):1188. Epub 2020 Dec 3.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

Background: It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy.

Methods: Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR.

Results: Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%.

Conclusion: Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.
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http://dx.doi.org/10.1186/s12885-020-07699-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712625PMC
December 2020

Heterogeneous distribution of Fusobacterium nucleatum in the progression of colorectal cancer.

J Gastroenterol Hepatol 2021 Jul 14;36(7):1869-1876. Epub 2020 Dec 14.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Background And Aim: Fusobacterium nucleatum (Fn) is involved in colorectal cancer (CRC) growth and is a biomarker for patient prognosis and management. However, the ecology of Fn in CRC and the distribution of intratumoral Fn are unknown.

Methods: We evaluated Fn and the status of KRAS and BRAF in 200 colorectal neoplasms (118 adenomas and 82 cancers) and 149 matched adjacent normal mucosas. The differentiation status between "surface" and "deep" areas of cancer tissue and matched normal mucosa were analyzed in 46 surgical samples; the Ki-67 index was also evaluated in these samples.

Results: Fusobacterium nucleatum presence in the tumor increased according to pathological stage (5.9% [adenoma] to 81.8% [stage III/IV]), while Fn presence in normal mucosa also increased (7.6% [adenoma] to 40.9% [stage III/IV]). The detection rates of Fn on the tumor surface and in deep areas were 45.7% and 32.6%, while that of normal mucosa were 26.1% and 23.9%, respectively. Stage III/IV tumors showed high Fn surface area expression (66.7%). Fn intratumoral heterogeneity (34.8%) was higher than that of KRAS (4.3%; P < 0.001) and BRAF (2.2%; P < 0.001). The Ki-67 index in Fn-positive cases was higher than that in negative cases (93.9% vs 89.0%; P = 0.01).

Conclusions: Fusobacterium nucleatum was strongly present in CRC superficial areas at stage III/IV. The presence of Fn in the deep areas of adjacent normal mucosa also increased. The intratumoral heterogeneity of Fn is important in the use of Fn as a biomarker, as Fn is associated with CRC proliferative capacity.
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http://dx.doi.org/10.1111/jgh.15361DOI Listing
July 2021

Narrow band imaging under less-air condition improves the visibility of superficial esophageal squamous cell carcinoma.

BMC Gastroenterol 2020 Nov 19;20(1):389. Epub 2020 Nov 19.

Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan.

Background: The current virtual chromoendoscopy equipment cannot completely detect superficial squamous cell carcinoma (SCC) in the esophagus, despite its development in the recent years. Thus, in this study, we aimed to elucidate the appropriate air volume during endoscopic observation to improve the visibility of esophageal SCC.

Methods: This retrospective study included a total of 101 flat type esophageal SCCs identified between April 2017 and January 2019 at the Department of Gastrointestinal Oncology, Osaka International Cancer Institute. Video images of narrow band imaging (NBI) under both less-air and standard-air conditions were recorded digitally. Videos were evaluated by five endoscopists. Relative visibility between less-air and standard-air conditions of the brownish area, brownish color change of the epithelium, and dilated intrapapillary capillary loop (IPCL) were graded as 5 (definitely better under less-air condition) to 1 (definitely worse under less-air condition), with 3 indicating average visibility (equivalent to standard-air observation).

Results: The mean (standard deviation) visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs under less-air condition were 3.94 (0.58), 3.73 (0.57), and 4.13 (0.60), respectively, which were significantly better than that under standard-air condition (p < 0.0001). Esophageal SCC evaluated as ≥ 4 in the mean visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs accounted for 50% (51/101 lesions), 34% (34/101 lesions), and 67% (68/101 lesions), respectively.

Conclusions: The present results suggested that NBI with less air might improve the visibility of flat type esophageal SCC compared with NBI with standard air. Less-air NBI observation may facilitate the detection of flat type esophageal SCC.

Trial Registration: The present study is a non-intervention trial.
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http://dx.doi.org/10.1186/s12876-020-01534-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678292PMC
November 2020

Evaluation of complete cold forceps polypectomy resection rate for 3- to 5-mm colorectal polyps.

Dig Endosc 2021 Sep 18;33(6):948-954. Epub 2020 Dec 18.

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

Background And Study Aims: The propriety of cold forceps polypectomy (CFP) using jumbo biopsy forceps for diminutive polyps remains controversial. We conducted a prospective study to evaluate the complete CFP resection rate of 3-5-mm polyps using additional endoscopic mucosal resection (EMR) specimens following CFP.

Patients And Methods: Patients with 3-5-mm protruded or flat elevated colorectal polyps diagnosed endoscopically as adenomas or serrated lesions were prospectively enrolled. CFP using jumbo biopsy forceps was used to remove the eligible polyps and repeated until the absence of residuals were confirmed via image-enhanced endoscopy or chromoendoscopy. After CFP, saline was injected at the defect, and the marginal specimen of the defect was resected using EMR to histologically evaluate the residue. The primary outcome was the complete CFP resection rate, which was defined as no residue at the EMR site. Other outcomes were the number of CFP bites and the complete resection rate by lesion size.

Results: Eighty patients with 120 polyps were enrolled. The mean polyp size was 4.1 ± 0.7 mm. The overall complete resection rate was 96.7% (95% confidence interval [CI], 91.7-98.7), and the rates for 3-, 4- and 5-mm polyps were 100% (95% CI, 86.7-100), 96.0% (95% CI, 86.5-98.9) and 95.5% (95% CI, 85.1-98.8), respectively. The one-bite CFP rates were 92%, 60% and 31% for the 3-, 4- and 5-mm polyps, respectively.

Conclusions: The complete CFP resection rate for 3-5-mm polyps was acceptable, although the one-bite clearance rate decreased as the polyp size increased (UMIN000028841).
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http://dx.doi.org/10.1111/den.13895DOI Listing
September 2021

Factors Predicting a Favorable Disease Course Without Anti-TNF Therapy in Crohn's Disease Patients.

Acta Med Okayama 2020 Aug;74(4):265-274

Department of Gastroenterology, Mitsui Memorial Hospital, Chiyoda-ku, Tokyo 101-8643, Japan.

Determining factors that predict a favorable disease course without anti-tumor necrosis factor (TNF) agents would help establish a more cost-effective strategy for Crohn's disease (CD). A retrospective chart review was performed for CD patients with disease durations > 10 years who had not received anti-TNF agents as first-line therapy. Patients were divided into 2 groups: those who received neither anti-TNF agents nor bowel resection (G1), and those who had received an anti-TNF agent and/or bowel resection (G2). The patient backgrounds, therapies and clinical courses were compared between the groups. A total of 62 CD patients met the inclusion criteria (males: 71%; median duration of follow-up: 19 years). Six patients were included in G1; they were significantly less likely to have upper gastrointestinal lesions than G2 (p=0.007). A multivariate analysis revealed that the significant factors for avoidance of bowel resection without anti-TNF treatment were non-stricturing and non-penetrating behaviors, and absence of upper gastrointestinal lesions at the diagnosis (hazard ratios 0.41 and 0.52; p=0.004 and 0.04, respectively). In consideration of the long treatment course of CD, patients with non-stricturing and non-penetrating behaviors and no upper gastrointestinal lesions should not be treated with anti-TNF agents as first-line therapy.
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http://dx.doi.org/10.18926/AMO/60363DOI Listing
August 2020

Continued Aspirin Treatment May Be a Risk Factor of Delayed Bleeding after Gastric Endoscopic Submucosal Dissection under Heparin Replacement: A Retrospective Multicenter Study.

Intern Med 2020 Nov 7;59(21):2643-2651. Epub 2020 Jul 7.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.

Objective Gastric endoscopic submucosal dissection (ESD) under heparin replacement (HR) of warfarin reportedly has a high risk of delayed bleeding (24-57%). It is possible that the delayed bleeding risk may have changed over the years. We evaluated the current risk of delayed bleeding after gastric ESD under HR of anticoagulant agents. Methods We retrospectively reviewed the delayed bleeding rate and analyzed the risk factors for delayed bleeding. Patients Consecutive patients who underwent gastric ESD under HR of anticoagulant agents from July 2015 to June 2017. Results A total of 32 patients with a solitary early gastric cancer and taking anticoagulant agents were analyzed, including 24 patients on warfarin (the warfarin group) and 8 patients on direct oral anticoagulants (the DOAC group). Three (9.4%) patients experienced delayed bleeding: three (12.5%) patients in the warfarin group and no patients in the DOAC group. Continued aspirin treatment was identified to be a risk factor of delayed bleeding (p=0.01). Conclusion Careful management may be required for patients undergoing gastric ESD under continued aspirin treatment in addition to HR of anticoagulant agents; although the delayed bleeding risk after gastric ESD under HR of anticoagulant agents might have decreased over the years.
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http://dx.doi.org/10.2169/internalmedicine.4998-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691037PMC
November 2020

Dynamics of endoscopic snares: a new approach towards more practical and objective performance evaluation.

Endosc Int Open 2020 Jun 25;8(6):E792-E795. Epub 2020 May 25.

Department of Next Generation Endoscopic Intervention (Project ENGINE), Osaka University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.1055/a-1145-3308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247903PMC
June 2020

Observer agreement for the diagnosis of intestinal acute graft-vs.-host disease based on the presence of villous atrophy in the terminal ileum.

Exp Ther Med 2020 Apr 21;19(4):3076-3080. Epub 2020 Feb 21.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Intestinal graft-vs.-host disease (GVHD) is a serious complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Villous atrophy in the terminal ileum is considered a useful diagnostic indicator for GVHD. However, the inter- and intra-observer agreement regarding the ileocolonoscopic findings indicative of acute intestinal GVHD, i.e., villous atrophy in the terminal ileum, are currently insufficient in multiple institutions. Thus, the present study aimed to investigate the incidence of villous atrophy in the terminal ileum to diagnose acute intestinal GVHD and determine the inter- and intra-observer agreement regarding this result for experienced endoscopists from multiple institutions. Consecutive patients who underwent allo-HSCT were referred to our institution between May 2008 and September 2015. A total of 54 patients underwent total ileocolonoscopy after allo-HSCT due to suspected intestinal acute GVHD. Subsequently, three observers from different institutions evaluated the cases for the presence of villous atrophy in the terminal ileum. In this study, the pathology results were a gold standard to evaluate the predictive value of ileocolonoscopy detection. Definitive pathological and non-pathological GVHD was diagnosed in 22 and 32 cases, respectively. The results of examining whether villous atrophy could predict GVHD were as follows. For three observers (A, B and C), the sensitivity of villous atrophy in the terminal ileum was 86.4, 77.3 and 79.2%, respectively, whereas the specificity was 62.5, 62.5 and 86.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of villous atrophy for GVHD were as follows: The PPV of appearance was 61.3, 58.6 and 82.6%, respectively, whereas the NPV was 87.0, 80.0 and 83.9%, respectively. Kappa coefficients for the inter-observer reliability were 0.85, 0.63 and 0.63 for observers A and B, A and C, and B and C, respectively. The intra-observer kappa coefficient was 0.88 for observer A, 0.73 for observer B and 0.75 for observer C. A substantial observer agreement was achieved for the analysis of villous atrophy in the terminal ileum and the agreement for the predictive histological diagnosis was also excellent. Based on the results of the present study, identification of villous atrophy in the terminal ileum was a clinically effective diagnostic parameter, even if different endoscopists were involved in the diagnosis at multiple institutions. The present study was registered as a trial with the University Hospital Medical Information Network (UMIN; registration no. UMIN000025390).
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http://dx.doi.org/10.3892/etm.2020.8538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086216PMC
April 2020

Switching between Three Types of Mesalazine Formulation and Sulfasalazine in Patients with Active Ulcerative Colitis Who Have Already Received High-Dose Treatment with These Agents.

J Clin Med 2019 Dec 2;8(12). Epub 2019 Dec 2.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Background And Aim: Oral mesalazine and sulfasalazine (SASP) are key drugs for treating ulcerative colitis (UC). The efficacy of switching from one of the several mesalazine formulations to another is largely unknown. This study assessed the efficacy of switching among three types of mesalazine formulation and SASP for UC therapy.

Methods: UC patients receiving high-dose mesalazine/SASP who switched to other formulations due to disease activity were considered eligible. Efficacy was evaluated 2, 6, and 12 months after switching.

Results: A total of 106 switches in 88 UC patients were analyzed. The efficacy at 2 months after switching was observed in 23/39 (59%) cases from any mesalazine formulation to SASP, in 18/55 (33%) cases from one mesalazine to another, and in 2/12 (17%) cases from SASP to any mesalazine formulation. Nine of 43 effective cases showed inefficacy or became intolerant post-switching. Delayed efficacy more than two months after switching was observed in four cases. Steroid-free remission was achieved in 42/106 (39%) cases-within 100 days in 35 of these cases (83%).

Conclusions: Switching from mesalazine to SASP was effective in more than half of cases. The efficacy of switching between mesalazine formulations was lower but may be worth attempting in clinical practice from a safety perspective.
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http://dx.doi.org/10.3390/jcm8122109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970226PMC
December 2019

Blue laser imaging and linked color imaging improve the color difference value and visibility of colorectal polyps in underwater conditions.

Dig Endosc 2020 Jul 14;32(5):791-800. Epub 2020 Jan 14.

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

Background And Aim: Underwater endoscopic mucosal resection (UEMR) has become widespread for treating colorectal polyps. However, which observational mode is best suited for determining polyp margins underwater remains unclear. To determine the best mode, we analyzed three imaging modes: white light imaging (WLI), blue laser imaging (BLI) and linked color imaging (LCI).

Methods: Images of consecutive colorectal polyps previously examined by these three modes before UEMR were analyzed according to the degree of underwater turbidity (transparent or cloudy). Color differences between the polyps and their surroundings were calculated using the Commission Internationale d'Eclairage Lab color space in which 3-D color parameters were expressed. Eight evaluators, who were blinded to the histology, scored the visibility from one (undetectable) to four (easily detectable) in both underwater conditions. The color differences and visibility scores were compared.

Results: Seventy-three polyps were evaluated. Sixty-one polyps (44 adenomatous, 17 serrated) were observed under transparent conditions, and 12 polyps (seven adenomatous, five serrated) were observed under cloudy conditions. Under transparent conditions, color differences for the BLI (8.5) and LCI (7.9) were significantly higher than that of WLI (5.7; P < 0.001). Visibility scores for BLI (3.6) and LCI (3.4) were also higher than that of WLI (3.1; P < 0.0001). Under cloudy conditions, visibility scores for LCI (2.9) and WLI (2.7) were significantly higher than that of BLI (2.2; P < 0.0001 and P = 0.04, respectively).

Conclusions: BLI and LCI were better observational modes in transparent water; however, BLI was unsuitable for cloudy conditions.
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http://dx.doi.org/10.1111/den.13581DOI Listing
July 2020

Endocytoscopic images of malignant lymphoma located at the terminal ileum.

Ann Gastroenterol 2019 Nov-Dec;32(6):655. Epub 2019 Sep 23.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

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http://dx.doi.org/10.20524/aog.2019.0416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826065PMC
September 2019

Endoscopic appearance of esophageal xanthoma.

Endosc Int Open 2019 Oct 1;7(10):E1214-E1220. Epub 2019 Oct 1.

Department of Gastrointestinal Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan.

 Esophageal xanthomas are considered to be rare, and their endoscopic diagnosis has not been fully elucidated. The aim of the present study was to determine the characteristics of the endoscopic appearance of esophageal xanthomas.  This was a retrospective study of consecutive patients with histologically diagnosed esophageal xanthomas at a referral cancer center in Japan. The endoscopic appearance, by magnifying or image-enhanced endoscopy, and histological findings of esophageal xanthomas were investigated.  Seven patients (six men and one woman) were enrolled. All of the patients had a solitary lesion, and the median size was 2 mm (range, 1 - 5 mm). Conventional white-light endoscopy showed the lesions as flat areas with yellowish spots in four cases and slightly elevated yellowish lesions in three cases. Magnifying endoscopy, performed in six patients, revealed the lesions as areas with aggregated minute yellowish spots with tortuous microvessels inside. Magnifying narrow-band imaging contrasted the yellowish spots and microvessels better than white-light endoscopy. In all lesions, histological examination showed that the yellowish spots corresponded to papillae filled with foam cells. The foam cells were strongly immunopositive for CD68, and in all lesions, CD34-positive intrapapillary capillaries surrounded the aggregated foam cells. The different morphologies of the flat and slightly elevated lesions corresponded to different densities of papillae filled with foam cells.  Magnifying endoscopy revealed minute yellowish spots with tortuous microvessels inside. These correspond well with histological findings and so may be useful in the diagnosis of esophageal xanthomas.
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http://dx.doi.org/10.1055/a-0966-8544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773585PMC
October 2019

Feasibility of underwater endoscopic mucosal resection and management of residues for superficial non-ampullary duodenal epithelial neoplasms.

Dig Endosc 2020 May 15;32(4):565-573. Epub 2019 Nov 15.

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

Background And Aim: Underwater endoscopic mucosal resection (UEMR) is effective for superficial non-ampullary duodenal epithelial neoplasms (SNADEN). However, the incidence of residual lesion after UEMR, especially for large lesions (≥20 mm), and their prognosis remain unclear. We aimed to assess the incidence of residual lesions and further outcomes after UEMR for SNADEN.

Methods: We carried out a retrospective study at a tertiary cancer institute. Candidates for the study were systematically retrieved from an endoscopic and pathological database from January 2013 to April 2018.

Results: A total of 162 SNADEN resected with UEMR were analyzed. Median (range) procedure time was 5 (1-70) min. En bloc resection rates for large lesions (≥20 mm) and small lesions (<20 mm) were 14% and 79%, respectively. Intraprocedural bleeding occurred in one (0.6%) case, but no intraprocedural perforation occurred during the study. Delayed bleeding occurred in two (1.2%) cases and delayed perforation occurred in one (0.6%) case. A total of 157 (97%) lesions were followed up by at least one endoscopic examination. Of these lesions, residual lesions were recognized in seven cases (5%). Additional UEMR was carried out in five lesions and underwater cold snare polypectomy in one lesion. One lesion was observed without additional treatment. After salvage intervention, no cases experienced further residual lesions.

Conclusion: Although UEMR for SNADEN can be relevant when other efficacious procedures are unavailable, careful follow up for residual lesions is required especially after piecemeal resection for large lesions.
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http://dx.doi.org/10.1111/den.13541DOI Listing
May 2020

Underwater endoscopic papillectomy using double-balloon endoscopy.

Endoscopy 2020 02 9;52(2):E55-E56. Epub 2019 Sep 9.

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

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http://dx.doi.org/10.1055/a-0992-9084DOI Listing
February 2020

Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4 T cells through AMPK activation.

Sci Rep 2019 08 15;9(1):11934. Epub 2019 Aug 15.

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4 T cells in T cell transfer IBD models in which SCID mice had been injected with CD4CD45RB T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4 T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4 T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4 T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.
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http://dx.doi.org/10.1038/s41598-019-48331-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695484PMC
August 2019

Differentiation between duodenal neoplasms and non-neoplasms using magnifying narrow-band imaging - Do we still need biopsies for duodenal lesions?

Dig Endosc 2020 Jan 20;32(1):84-95. Epub 2019 Aug 20.

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

Objectives: Endoscopic biopsies for nonampullary duodenal epithelial neoplasms (NADENs) can induce submucosal fibrosis, making endoscopic resection difficult. However, no biopsy-free method exists to distinguish between NADENs and non-neoplasms. We developed a diagnostic algorithm for duodenal neoplasms based on magnifying endoscopy findings and evaluated the model's diagnostic ability.

Methods: Magnified endoscopic images and duodenal lesion histology were collected consecutively between January 2015 and April 2016. Diagnosticians classified the surface patterns as pit, groove or absent. In cases of nonvisible surface patterns, the vascular pattern was evaluated to determine regularity or irregularity. The correlation between our algorithm (pit-type or absent with irregular vascular pattern) and the lesion histology were evaluated. Four evaluators, who were blinded to the histology, also classified the endoscopic findings and evaluated the diagnostic performance and interobserver agreement.

Results: Endoscopic images of 114 lesions were evaluated (70 NADENs and 44 non-neoplasms, 31 in the superior and 83 in the descending and horizontal duodenum). Of the NADEN surface patterns, 88% (62/70) were pit-type, while 79% (35/44) of the non-neoplasm surface patterns were groove-type. Our diagnostic algorithm for differentiating NADENs from non-neoplasms was high (sensitivity 96%, specificity 95%) in the descending and horizontal duodenum. The evaluators' diagnostic performances were also high, and interobserver agreement for the algorithm was good between each diagnostician and evaluator (κ = 0.60-0.76).

Conclusion: Diagnostic performance of our algorithm sufficiently enabled eliminating endoscopic biopsies for diagnosing the descending and horizontal duodenum.
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http://dx.doi.org/10.1111/den.13485DOI Listing
January 2020

Underwater endoscopic mucosal resection for a tumor located in the free jejunal graft.

Ann Gastroenterol 2019 Jul-Aug;32(4):424. Epub 2019 May 8.

Department of Gastroenterology, Iwakuni Clinical Center, National Hospital Organization, Yamaguchi (Junki Toyosawa, Yasushi Yamasaki, Tsuyoshi Fujimoto, Shouichi Tanaka).

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http://dx.doi.org/10.20524/aog.2019.0383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595932PMC
May 2019

The effects of a participatory structured group educational program on the development of CKD: a population-based study.

Clin Exp Nephrol 2019 Aug 27;23(8):1031-1038. Epub 2019 Apr 27.

Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Chou, Kida-Gun, Kagawa, 761-0793, Japan.

Background: The type of lifestyle guidance that is effective for preventing development of chronic kidney disease (CKD) is unknown. Here, we aim to investigate the effects of a participatory structured group education (SGE) program on the development of CKD in a population-based study.

Methods: We retrospectively analyzed 1060 adult special health check-up examinees with CKD. Examinees with an estimated glomerular filtration rate (eGFR) from 50 to 60 mL/min/1.73 m and/or proteinuria 1+ were encouraged to attend an SGE program. The SGE program included participatory small group discussions on the attendees' remaining risk factors. The primary outcome of this study was the change in eGFR per year.

Results: The changes in eGFR in examinees who attended the SGE program (n = 209, + 2.9 mL/min/1.73 m [95% confidence interval (CI) + 1.9 to  + 3.9]) significantly improved compared with control (n = 383, + 1.2 mL/min/1.73 m [95% CI + 0.5 to + 1.9], p = 0.006). Attending an SGE program was independently and positively related to the changes in eGFR at 1 year after attendance, after adjusting for classical covariates (β = 1.55 [95% CI 0.37-2.73], p = 0.01). Attending an SGE program was effective for the examinees with a lower eGFR compared with those with only proteinuria.

Conclusions: Our SGE program showed the beneficial effects of preventing the development of CKD, independent of classical factors. The type of SGE program that is more effective for preventing development of CKD should be investigated in a long-term analysis.
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http://dx.doi.org/10.1007/s10157-019-01738-1DOI Listing
August 2019

Comparison of Two Electrosurgical Modes for Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms: A Prospective Randomized Study.

Acta Med Okayama 2019 Feb;73(1):81-84

Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558,

Endoscopic submucosal dissection (ESD) is reportedly one of the standard treatment strategies for large superficial colorectal neoplasms in Japan because of its high en bloc resection rate. A few technical issues regarding ESD should be considered, one of which is the selection of the Endo-cut I mode versus the Swift-coagulation mode as the electrosurgical unit mode setting during submucosal dissection. We seek to determine which of these two modes is more suitable for submucosal dissections of colorectal tumors with regard to procedure time and safety.
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http://dx.doi.org/10.18926/AMO/56463DOI Listing
February 2019

Response to Galán-Puchades and Fuentes.

Am J Gastroenterol 2019 02;114(2):357

Department of Respiratory Medicine, Tsuyama chuo Hospital, Tsuyama, Japan.

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http://dx.doi.org/10.14309/ajg.0000000000000118DOI Listing
February 2019
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