Publications by authors named "Shu Hoteya"

117 Publications

Clinicopathological Differences between Eosinophilic Esophagitis and Asymptomatic Esophageal Eosinophilia.

Intern Med 2021 Oct 19. Epub 2021 Oct 19.

Department of Gastroenterology, Toranomon Hospital, Japan.

Objective According to consensus guidelines, eosinophilic esophagitis (EoE) is defined as a clinicopathological entity whose symptoms and histology must always be considered together. However, endoscopic findings typical of EoE are often seen in asymptomatic esophageal eosinophilia (aEE). We aimed to clarify the clinicopathological features of aEE. Methods We retrospectively compared cases of aEE and those of symptomatic EoE. Patients or Materials We reviewed 146 patients who underwent upper gastrointestinal endoscopy and were confirmed histopathologically to have esophageal eosinophil infiltration of at least 15 eosinophils per high-power field. They were divided into the aEE group (n=75) and the EoE group (n=71). Patients' clinicopathological findings were then collected and examined. Results The EoE group experienced dysphagia (47.9%), heartburn (40.8%), food impaction (40.8%), chest pain (16.9%), and other symptoms (8.5%). There was no significant difference between the two groups with regard to age, sex, current smoking status, or alcohol consumption. The aEE group had a significantly higher body mass index (p<0.01) and significantly lower frequency of concurrent allergic diseases (p<0.01) than the EoE group. No significant differences were found between the two groups with regard to the mean peripheral blood eosinophil count, non-specific immunoglobulin E concentration, peak eosinophil infiltration in the biopsy specimens, EoE histology scoring system, phenotype and location of typical endoscopic findings of EoE, or thickness of the esophagus wall or the mucosal and submucosal layer as measured by endoscopic ultrasonography. Two patients in the aEE group who were followed up without treatment subsequently developed esophageal symptoms. Conclusions aEE and EoE may have the same clinicopathological features.
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http://dx.doi.org/10.2169/internalmedicine.8241-21DOI Listing
October 2021

Risk Factors for Bleeding After Endoscopic Submucosal Dissection for Gastric Cancer in Elderly Patients Older Than 80 Years in Japan.

Clin Transl Gastroenterol 2021 Sep 24;12(9):e00404. Epub 2021 Sep 24.

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

Introduction: As the aging of people in a society advances, the number of elderly patients older than 80 years in Japan with gastric cancer continues to increase. Although delayed ulcer bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about characteristic risk factors for bleeding in elderly patients undergoing ESD. This study aimed to evaluate risk factors for delayed bleeding after ESD for gastric cancer in elderly patients older than 80 years.

Methods: We retrospectively evaluated the incidence of delayed bleeding after ESD in 10,320 patients with early-stage gastric cancer resected by ESD between November 2013 and January 2016 at 33 Japanese institutions and investigated risk factors for delayed bleeding in elderly patients older than 80 years.

Results: The incidence of delayed bleeding in elderly patients older than 80 years was 5.7% (95% confidence interval [CI]: 4.6%-6.9%, 95/1,675), which was significantly higher than that in nonelderly (older than 20 years and younger than 80 years) patients (4.5%, 4.1%-5.0%, 393/8,645). Predictive factors for ESD-associated bleeding differed between nonelderly and elderly patients. On multivariate analysis of predictive factors at the time of treatment, risk factors in elderly patients were hemodialysis (odds ratio: 4.591, 95% CI: 2.056-10.248, P < 0.001) and warfarin use (odds ratio: 4.783, 95% CI: 1.689-13.540, P = 0.003).

Discussion: This multicenter study found that the incidence of delayed bleeding after ESD in Japanese patients older than 80 years was high, especially in patients receiving hemodialysis and taking warfarin. Management of ESD to prevent delayed bleeding requires particular care in patients older than 80 years.
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http://dx.doi.org/10.14309/ctg.0000000000000404DOI Listing
September 2021

Antithrombotics increase bleeding after endoscopic submucosal dissection for gastric cancer: Nationwide propensity score analysis.

Dig Endosc 2021 Sep 26. Epub 2021 Sep 26.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Objectives: Post-operative bleeding is the most common adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Patients taking antithrombotic agents has increased. We evaluated the influence of antithrombotic agents on delayed bleeding in ESD for EGC.

Methods: This was a post hoc analysis of nationwide, multicenter, retrospective cohort study in Japan. Altogether, 11,452 patients who underwent ESD for EGC in 33 institutions between November 2013 and October 2016 were enrolled. The primary outcome was the incidence of delayed bleeding in patients with or without antithrombotic agents. The secondary outcome was the incidence of delayed bleeding in those who took each antithrombotic agent and the cessation status of its use compared with each matched pair of patients. We used propensity matching and inverse probability of treatment weighting (IPTW) analyses.

Results: There were 1353 matched pairs of patients. The incidence of delayed bleeding was 2.8% and 10.7% in those without and with antithrombotic agents, respectively (odds ratio [OR] 4.15, 95% confidence interval [CI] 2.88-5.99; P < 0.001). The IPTW analysis showed similar results (OR 4.21, 95% CI 3.48-5.08; P < 0.001). Antiplatelets, anticoagulants, and their combination increased such incidence. Heparin bridging therapy had high OR (8.80), and the continuation (OR 3.46) and cessation (OR 2.95) of antithrombotic agent use had similar risk.

Conclusions: Antithrombotic agents increased the incidence of delayed bleeding in patients who underwent ESD for EGC. Continuing antithrombotics may be more appropriate than heparin bridging therapy.
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http://dx.doi.org/10.1111/den.14151DOI Listing
September 2021

Possibility of new shielding device for upper gastrointestinal endoscopy.

Endosc Int Open 2021 Oct 16;9(10):E1536-E1541. Epub 2021 Sep 16.

Department of Gastroenterology, Toranomon Hospital, Tokyo Japan.

Infection control is essential when performing endoscopic procedures, especially during the COVID-19 pandemic. Therefore, we have developed a new shielding device called STEP for infection control in upper gastrointestinal endoscopy. STEP consists of a mask worn by the patient and a drape that is connected to the mask and covers the endoscope. A suction tube attached to the mask prevents aerosols from spreading. The endoscopist operates the endoscope through the drape. Three endoscopists performed a total of 18 examinations using an upper endoscopy training model with and without STEP. Endoscopic images were evaluated by three other endoscopists, using a visual analog scale. We also simulated contact, droplet, and aerosol infection and evaluated the utility of STEP. All examinations were conducted without a problem. Mean procedure time was 126.3 ± 11.6 seconds with STEP and 122.3 ± 10.0 seconds without STEP. The mean visual analog score was 90.7 ± 10.1 with STEP and 90.4 ± 10.0 without STEP. In the contact model, adherence of simulated contaminants was 4.9 ± 1.4 % without STEP and 0 % with STEP. In the droplet model, the number of simulated contaminants attached to the paper was 338 273 ± 90 735 pixels without STEP and 0 with STEP. In the aerosol model, the total number of particles was 346 837 ± 9485 without STEP and was significantly reduced to 222 ± 174 with STEP. No effect on examination time or endoscopic image quality was observed when using STEP in upper gastrointestinal endoscopy. Using STEP reduced the diffusion of simulated contaminants in all three infection models.
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http://dx.doi.org/10.1055/a-1523-8959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445671PMC
October 2021

Clinicopathological features of Epstein-Barr virus-associated superficial early stage gastric cancer treated with endoscopic submucosal dissection.

Dig Liver Dis 2021 Sep 14. Epub 2021 Sep 14.

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

Background: Epstein-Barr virus (EBV) is known to be involved in gastric carcinogenesis. EBV-associated early gastric carcinoma (EBVEGC) has a lower incidence of lymph node involvement and could be an expanded indication for endoscopic submucosal dissection (ESD) treatment.

Aim: To clarify the prevalence and clinicopathological features of EBVEGC.

Methods: This study reviewed 618 lesions in 519 patients treated with ESD between 2014 and 2016. Tissue microarray sections were subjected to in situ hybridization staining for EBV-encoded small RNA transcripts (EBER). Lesions positive for EBER were compared with control lesions and were retrospectively analyzed.

Results: 12 (1.9%) of the 618 lesions were EBVEGC. EBVEGCs were more frequently located near the atrophic border than control lesions in the middle or upper stomach and were reddish. EBVEGC invasion was deeper and more often histologically undifferentiated. On narrow-band imaging magnifying endoscopy, the EBVEGC group significantly more often showed an endoscopic lace pattern, defined as an absent or obscure microsurface pattern and a microvascular pattern of a tiny, dense, and irregular subepithelial capillary network. The rate of curative resection was significantly lower in the EBVEGC group.

Conclusions: Only 1.9% of the ESD specimens were EBV-positive. Endoscopic features could raise clinical suspicion of EBV infection.
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http://dx.doi.org/10.1016/j.dld.2021.08.023DOI 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

Influence of hospital volume on bleeding after endoscopic submucosal dissection for early gastric cancer in Japan: a multicenter propensity score-matched analysis.

Surg Endosc 2021 Sep 7. Epub 2021 Sep 7.

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

Background: Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume.

Methods: Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching.

Results: A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups.

Conclusions: The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD.
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http://dx.doi.org/10.1007/s00464-021-08721-6DOI Listing
September 2021

Endoscopic treatment for duodenal neoplasms.

Authors:
Shu Hoteya

Dig Endosc 2021 Sep 6. Epub 2021 Sep 6.

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1111/den.14110DOI Listing
September 2021

Real-World Experience of Endoscopic Submucosal Dissection for Ulcerative Colitis-Associated Neoplasia.

Inflamm Intest Dis 2021 May 18;6(2):70-77. Epub 2021 Mar 18.

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

Introduction: Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Some studies have recently investigated endoscopic resection of UC-associated neoplasia (UCAN), but the indications for endoscopic resection of UCAN remain controversial. This study sought to clarify the problems encountered in endoscopic submucosal dissection (ESD) for UCAN.

Methods: Seventeen lesions in 12 patients with UCAN (UCAN group) and 913 epithelial lesions in 824 control patients without UC (non-UC group) were evaluated. Both groups underwent ESD between January 2010 and December 2017 at Toranomon Hospital, Tokyo, Japan. Treatment outcomes of the 2 groups were compared retrospectively.

Results: Univariate analysis showed that the mean tumor size was significantly smaller in the UCAN group than in the non-UC group (25.1 ± 26.7 mm vs. 31.9 ± 19.0; = 0.0023); however, the R0 resection rate was significantly lower in the UCAN group (70.6 vs. 92.9%; = 0.001). Multivariate analysis showed a significantly lower negative horizontal margin rate in the UCAN group (odds ratio 11.3, 95% confidence interval 3.588-34.525; = 0.000).

Discussion/conclusion: ESD for UCAN is associated with a low-negative horizontal margin rate. When performing ESD for UCAN, it is important to evaluate the accuracy of the UCAN demarcation line, especially for flat lesions, using white-light imaging and chromoendoscopy as well as other modalities, including biopsy of surrounding tissues.
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http://dx.doi.org/10.1159/000512292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160563PMC
May 2021

Metachronous carcinogenesis of superficial esophagus squamous cell carcinoma after endoscopic submucosal dissection: incidence and risk stratification during long-term observation.

Esophagus 2021 Oct 11;18(4):806-816. Epub 2021 May 11.

Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.

Background: This study aimed to reveal long-term outcomes, such as incidence of metachronous esophageal and head and neck squamous cell carcinomas and overall survival rate, through long-term observation of patients with esophageal carcinoma post-endoscopic submucosal dissection.

Methods: Risk of metachronous carcinogenesis was evaluated in 88 patients with intramucosal esophageal carcinoma (without history of metachronous esophageal or head and neck squamous cell carcinomas) who underwent endoscopic submucosal dissection from 2007 to 2008 and were endoscopically observed for > 3 years. Histologically, the papillary vessel is defined as the clock gear-like structure composed of capillaries directly penetrating the epithelium (starting from the lamina propria) and covering at least two-thirds of it, around which the tumor cells are arranged in a spiral pattern.

Results: Median endoscopic follow-up period was 11.0 years. Cumulative 2-, 5-, and 10-year metachronous esophageal carcinoma rates were 11.4%, 20.6%, and 39.3%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple Lugol-voiding lesions (LVLs) as the single significant independent predictor. Cumulative 2-, 5-, and 10-year metachronous head and neck squamous cell carcinoma rates were 6.9%, 10.4%, and 19.6%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple LVLs, Brinkman index, papillary vessel, and younger age as significant predictive factors. Overall post-endoscopic submucosal dissection survival rates were 98.8% and 87.5% at 5 and 10 years, respectively.

Conclusion: Patients with a history of esophageal carcinoma remain at risk for metachronous carcinogenesis even > 5 years after endoscopic submucosal dissection. Thus, long-term follow-up is important.
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http://dx.doi.org/10.1007/s10388-021-00848-8DOI Listing
October 2021

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

J Gastroenterol Hepatol 2021 Oct 26;36(10):2769-2777. Epub 2021 May 26.

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
October 2021

Feasibility of ultrathin endoscope for esophageal endoscopic submucosal dissection.

Endosc Int Open 2021 Apr 13;9(4):E606-E609. Epub 2021 Apr 13.

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

Endoscopic submucosal dissection (ESD) is widely performed for superficial esophageal cancer, but stricture after extensive resection is a major clinical problem. Using an ultrathin endoscope would enable endoscopists to approach lesions beyond the stricture. We evaluated the feasibility of an ultrathin endoscope for esophageal ESD. To perform ESD with an ultrathin endoscope, we developed a transparent hood and ESD knife. A total of 24 esophageal ESDs were performed by two endoscopists with excised and live porcine esophaguses. A GIF-Q260 J and Dual knife were used in the conventional group and the GIF-XP260NS and a newly developed knife were used in the ultrathin group. En bloc resection rates, perforation rates, and procedure times were compared. All 24 lesions were resected en bloc without perforation. The mean procedure time was longer in the ultrathin group, although not significantly so (274.3 ± 81.8 s vs 435.8 ± 313.9 s, respectively;  = 0.22). Although the procedure time was longer in the ultrathin group, en bloc resection was performed without any perforation. The findings indicate that esophageal ESD with an ultrathin endoscope is feasible.
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http://dx.doi.org/10.1055/a-1352-3805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043804PMC
April 2021

Current status of diagnostic and therapeutic colonoscopy in Japan: The Japan Endoscopic Database Project.

Dig Endosc 2021 Mar 27. Epub 2021 Mar 27.

JED (Japan Endoscopy Database) Project Committee, Japan Gastroenterological Endoscopy Society, Tokyo, Japan.

Objectives: The Japan Endoscopy Database Project was initiated to develop the world's largest endoscopy data repository. This study describes the first phase of the colonoscopy project in Japan.

Methods: Data were aggregated offline by integrating information from the endoscopy database software from January 2015 through March 2017. The study population included all patients who underwent colonoscopy at eight centers.

Results: A total of 31,395 patients who underwent 38,497 colonoscopy procedures were registered. The majority of procedures were performed for screening (n = 14,156), followed by fecal immunochemical test positivity (n = 3960), abdominal symptoms (n = 3864), post-colorectal surgery surveillance (n = 3431), post-endoscopic treatment surveillance (n = 3757), thorough pre-treatment examination (n = 2822), and therapeutic purposes (n = 6507). In the screening group, advanced cancers, early cancers, and adenomas were diagnosed endoscopically in 2.1%, 1.3%, and 28.7% of cases, respectively, while in the fecal immunochemical test-positive group, they were diagnosed in 2.5%, 1.9%, and 41.6% of cases, respectively. The incidence of complications was 0.177% and 0.152% in the screening and fecal immunochemical test-positive groups, respectively. The therapeutic procedures included 1446 cold forceps polypectomy procedures, 4770 cold snare polypectomy procedures, 368 hot biopsies, 2998 hot snare polypectomy procedures, 9775 endoscopic or piecemeal endoscopic mucosal resections, and 1660 endoscopic submucosal dissections. A total of 173 procedure-related complications (0.82%) occurred in 21,017 therapeutic procedures performed in 15,744 patients.

Conclusions: The first phase of the Japan Endoscopy Database Project established the proportions of the diagnostic and therapeutic colonoscopy procedures, and complication rates in real-world settings.
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http://dx.doi.org/10.1111/den.13980DOI Listing
March 2021

Cytomegalovirus ileitis with protein-losing enteropathy in an immunocompetent adult.

Clin J Gastroenterol 2021 Aug 20;14(4):1060-1066. Epub 2021 Mar 20.

Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.

Symptomatic cytomegalovirus (CMV) infection in immunocompetent hosts has traditionally been considered to have a benign, self-limited course, and those who need intensive therapy are rare. Moreover, there are few reports of CMV infection with protein-losing enteropathy (PLE). We present an immunocompetent 74-year-old woman with CMV ileitis with PLE, which was diagnosed due to severe hypoalbuminemia and edema of the lower extremities. The patient was not immunocompromised, because a human immunodeficiency virus (HIV) antibody test was negative and she had not been taking immunosuppressants. Imaging tests including colonoscopy revealed ileitis with shallow widespread ulcers. Tc-human serum albumin (HAS-D) scintigraphy suggested a possibility of protein loss in the ileum based on selective accumulation of nuclides in the right abdomen. Histological findings of the biopsy showed ulcerative mucosa with abnormal cells, which had enlarged nuclei with intranuclear inclusion bodies, including typical Cowdry A type. In immunohistochemistry, these cells were positive for anti-CMV staining. She was successfully treated with medical treatments including intravenous injection of ganciclovir (GCV) (500 mg/day). We described an extremely rare case of CMV ileitis with PLE in an immunocompetent adult who was treated successfully with medical treatments, including GCV.
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http://dx.doi.org/10.1007/s12328-021-01382-xDOI Listing
August 2021

Large Fundic Gland Polyp Associated with Long-Term Proton Pump Inhibitor Administration Mimicking Gastric-Type Neoplasm.

Case Rep Gastroenterol 2021 Jan-Apr;15(1):123-130. Epub 2021 Feb 3.

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

A 57-year-old man with a 10-year history of proton pump inhibitor (PPI) use presented with multiple fundic gland polyps (FGPs) including one >20 mm, whitish, semi-pedunculated polyp. Black spots and cobblestone-like mucosa were also observed in the stomach upon endoscopy; therefore, the lesion was considered to result from long-term PPI administration. Endoscopically, we diagnosed this polyp as a neoplastic lesion with gastric phenotype rather than a non-neoplastic lesion. Biopsy revealed an atypical glandular lesion that was indeterminate for neoplasia; therefore, we performed en bloc resection via endoscopic submucosal dissection (ESD) of the 22 × 22 × 10 mm-sized polyp. Histologically, the polyp was composed of hyperplastic foveolar epithelia in the upper half of the mucosa and hyperplastic fundic glands in the lower half of the mucosa, with luminal dilatation and parietal cell protrusion. The pathological diagnosis for this ESD specimen was FGP associated with PPI administration. We herein describe this rare case of a large FGP in -uninfected gastric mucosa associated with long-term PPI administration, which was mimicking gastric-type neoplasm and resected by endoscopy.
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http://dx.doi.org/10.1159/000512399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923705PMC
February 2021

The Evaluation of Esophageal Endoscopic Findings in Patients with Functional Esophagogastric Junction Outflow Obstruction.

Intern Med 2021 Aug 8;60(16):2537-2543. Epub 2021 Mar 8.

Department of Gastroenterology, Toranomon Hospital, Japan.

Objective Esophagogastric junction outflow obstruction (EGJOO) is a diagnosis of unclear significance that has become increasingly common with recent advances in high-resolution manometry (HRM). EGJOO can be divided into mechanical or functional obstruction. Functional EGJOO is considered an incomplete phenotype or an early stage of achalasia. However, little is known about the endoscopic findings in patients with functional EGJOO. Thus, we aimed to elucidate the endoscopic findings in patients with functional EGJOO and to identify patients at high risk for achalasia. Methods This was a single-center retrospective study. A total of 259 patients underwent esophagogastroduodenoscopy (EGD) along with HRM for upper gastrointestinal symptoms without any obstructive lesions or stricture between July 2013 and September 2019 in our institute. Among them, 31 patients were diagnosed with EGJOO. After excluding patients who had undergone previous endoscopic treatment, those who were diagnosed with eosinophilic esophagitis and those who had undergone EGD at other institutes, 23 patients were finally included with a diagnosis of functional EGJOO. The endoscopic findings were evaluated by three endoscopists. Results Five patients (21.7%) had an esophageal rosette sign (ERS). No patients had grade IV gastroesophageal flap valve, esophageal mucosal breaks, or abnormal retention of liquid or food in the esophagus. Manometric findings revealed that the median distal contractile integral value was significantly higher in patients with an ERS (n=5) than in those without it (n=18). Conclusion There were some patients with functional EGJOO who had an ERS, which is the characteristic endoscopic finding in achalasia.
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http://dx.doi.org/10.2169/internalmedicine.6715-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429279PMC
August 2021

Use of scopolamine butylbromide to facilitate specimen fixation after endoscopic submucosal dissection.

Rev Esp Enferm Dig 2021 Sep;113(9):688-689

Gastroenterology, Toranomon Hospital.

Endoscopic submucosal dissection (ESD) is a technique for the en bloc resection of early neoplastic lesions in the gastrointestinal tract. A step that must be carried out after excision is the pinning down of the specimen on a support plate such as a cork board to avoid artifacts because of tissue contraction. After ESD lesion borders usually curl up from contraction, hence this procedure must be carefully performed to prevent damaging the specimen. Recently, Nishizawa T, et al. reported that dropping adrenaline onto the lesion results in edge relaxation, which facilitates fixation. However, the use of other drugs-such as Buscapine-that induce gastrointestinal smooth muscle relaxation, potentially with similar effects, has not been described. Below, two ESD specimens from two different institutions are shown. These specimens correspond to gastric lesions. Buscapine is applied on their surface and the edges become relaxed, thus facilitating stretching and thus fixation. In conclusion, the use of Buscapine may help in the processing of excised lesions by facilitating pinning out and reducing damage risk for specimens.
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http://dx.doi.org/10.17235/reed.2021.7821/2021DOI Listing
September 2021

Efficacy of vonoprazan for refractory reflux esophagitis after esophagectomy.

Dig Dis 2021 Feb 10. Epub 2021 Feb 10.

Background: Refractory reflux esophagitis (RRE), unresponsive to conventional proton-pump inhibitors (PPIs) is a complication in esophagectomy with gastric pull-up. Vonoprazan, a novel potassium-competitive acid blocker, has been available in Japan since 2015. Here, we investigated the efficacy of vonoprazan on PPI-resistant RRE after esophagectomy with gastric pull-up.

Methods: This was a single-center retrospective study. We used the revised Los Angeles (r-LA) classification based on the Los Angeles (LA) classification and the modified Los Angeles (m-LA) classification to evaluate abnormal forms of mucosal breaks such as spreading laterally consistently. Patients who underwent esophagectomy with gastric pull-up and had RRE grade B-D as per the r-LA classification, despite using standard dose PPIs or double-dose of rabeprazole, were included. Sixteen patients who switched to vonoprazan (20 mg/day) and 14 patients who continued PPIs were assigned to the vonoprazan and PPI groups, respectively. Endoscopic observations were reviewed by three endoscopists using the r-LA classification to ensure consistent diagnosis, while treatment arm and patient information were blinded to evaluators. We defined mucosal breaks that improved by at least one grade after treatment as improved mucosa and recovery to grade M or N as mucosal healing.

Results: The percentage of patients with improved mucosa in the vonoprazan and PPI groups was 81.3% and 14.3%, respectively (p<0.001). The rate of mucosal healing was 68.8% and 7.1%, respectively (p=0.001).

Conclusions: Vonoprazan significantly improved PPI-resistant RRE after esophagectomy with gastric pull-up.
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http://dx.doi.org/10.1159/000515146DOI Listing
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

Management and outcomes of resectable gastric conduit cancer: a retrospective comparative study of 51 cases.

Langenbecks Arch Surg 2021 Aug 6;406(5):1433-1441. Epub 2021 Jan 6.

Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.

Purpose: Although gastric conduit cancer (GCC) arising after esophagectomy is increasingly being reported, therapeutic strategies for resectable GCC have yet to be optimized. We investigated clinicopathological features of patients undergoing endoscopic versus more invasive surgical treatments for GCC and compared their outcomes.

Methods: Fifty-one patients, who had a history of esophagectomy with gastric conduit reconstruction for esophageal cancer and underwent resection for metachronous GCC, were identified. Their characteristics and outcomes were retrospectively reviewed.

Results: There were 48 males and three females, ranging in age from 46-86 years. Twelve patients underwent surgery for GCC (group S) and 39 underwent only endoscopic resection (group E). The most common cause of death was pneumonia (10/51, 19.6%). Neither overall survival nor cumulative incidence of pneumonia-caused death differed significantly between the two groups (P = 0.60, 0.84, respectively). In group S, partial gastrectomy was performed in four cases and total gastrectomy in seven. Partial resections, including three antrectomy without sternotomy or intrathoracic procedures, were completed with significantly shorter operative durations than total resections (median 208 vs 513 min, P = 0.012). GCC recurrence was experienced in two cases: one undergoing open approach partial resection of the corpus and the other thoracoscopic total gastrectomy.

Conclusion: Even compared with endoscopic treatment, outcomes following surgery for GCC appeared to be acceptable. Open approach total gastric gastrectomy could be the most radical modality, while other less invasive alternatives, e.g., antrectomy, are also an option. Clinicians may select a treatment strategy balancing radicality and patient status, reflecting tolerance to invasive procedures.
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http://dx.doi.org/10.1007/s00423-020-02053-0DOI Listing
August 2021

Secondary esophageal squamous cell carcinoma after hematopoietic stem cell transplantation.

J Cancer Res Clin Oncol 2021 Jul 2;147(7):2137-2144. Epub 2021 Jan 2.

Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.

Background: We evaluated cases of esophageal squamous cell carcinoma (ESCC) that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our institution.

Methods: Allo-HSCT was performed in 1534 patients (1776 cases) at our institution from 2001 to 2016. Overall, 602 patients were confirmed to have survived for 2 or more years and 154 underwent upper gastrointestinal endoscopy at least 1-year post-transplantation. ESCC was discovered in 17 patients (1.1%), 15 of whom had 31 lesions discovered at our institution (ESCC group). A retrospective comparative study was conducted with the remaining 137 patients for whom no ESCC was noted (non-ESCC group), and we also evaluated the clinicopathological characteristics of the ESCC group.

Results: History of TBI (total body irradiation) and bone marrow transplant was significantly higher in the ESCC group. The mean time from transplantation to detection of ESCC was 82.3 months. Localization was upper thoracic in 12 cases, middle thoracic in 10, cervical in 4, lower thoracic in 3, and upper to lower thoracic in 2. Treatment comprised endoscopic submucosal dissection in 23 cases, surgery in 4, untreated due to worsening primary disease in 3, and chemoradiotherapy in 1.

Conclusions: In this study, lesions were located in the cervical to upper thoracic esophagus in approximately 60% of all secondary ESCC cases after allo-HSCT. History of TBI and bone marrow transplantation are high risk of ESCC, and proactive screening endoscopy is desirable.
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http://dx.doi.org/10.1007/s00432-020-03500-7DOI Listing
July 2021

The Long-term Efficacy of Endoscopic Submucosal Dissection in the Treatment of Symptomatic Mucosal Prolapse Syndrome.

Intern Med 2021 Apr 28;60(7):1005-1009. Epub 2020 Oct 28.

Department of Gastroenterology, Toranomon Hospital, Japan.

Mucosal prolapse syndrome (MPS) is a benign inflammatory disease of the rectum that causes symptoms such as blood-stained stools and anemia. However, there is no treatment with a proven long-term efficacy for MPS. A 53-year-old man presented with blood-stained stools and anemia due to MPS and was treated conservatively for 1 year. However, his symptoms did not improve. We performed endoscopic submucosal dissection (ESD) for MPS. He has had no symptoms for six years after ESD, and the recurrence of MPS was not seen on endoscopy. This case shows that ESD can be effective for the long-term treatment of symptomatic MPS.
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http://dx.doi.org/10.2169/internalmedicine.6015-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079919PMC
April 2021

Shielding method for the endoscopic procedures during the COVID-19 pandemic.

Dig Endosc 2020 Nov 5;32(7):e160-e161. Epub 2020 Oct 5.

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1111/den.13821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675636PMC
November 2020

Effectiveness of Chemoradiotherapy for Metachronous Esophageal Squamous Cell Carcinoma.

Digestion 2021 29;102(4):622-629. Epub 2020 Sep 29.

Department of Gastroenterology, Tokyo Metropolitan Cancer and infectious Diseases Center Komagome Hospital, Tokyo, Japan.

Introduction: Multiple Lugol-voiding lesions (LVLs) in the esophagus increase the risk of synchronous and metachronous development of esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) following endoscopic submucosal dissection (ESD) may reduce the incidence of metachronous ESCC, but few studies have investigated this. Therefore, we retrospectively examined the effect of CRT on metachronous ESCC and multiple esophageal dysplasias visible as multiple LVLs.

Methods: This study reviewed 146 patients who underwent esophageal ESD and were determined pathologically to have noncurative resection. They were divided into 2 groups: those who received additional CRT (CRT group; n = 64) and those without additional treatment (control group; n = 82). Incidence of metachronous ESCC was analyzed using propensity scores to adjust for patient characteristics. The number of multiple LVLs was also examined.

Results: The CRT group was significantly younger than the control group (mean 66.6 vs. 70.6 years, p = 0.011), had significantly deeper tumor invasion (p = 0.013), and had a significantly higher rate of lymphovascular invasion (47.8 vs. 12.2%, p < 0.001). The CRT group also had a significantly higher improvement rate of multiple LVLs (58.1 vs. 2.0%, p < 0.001). The LVLs after CRT had a distinctive irregular crack-shaped appearance. Metachronous ESCC was found in 7 patients (10.9%) in the CRT group and in 17 patients (20.7%) in the control group (p = 0.113). In propensity score-adjusted logistic regression analysis, the odds ratio for metachronous ESCC in the CRT group was 0.316 (p = 0.023). The occurrence rate was significantly lower in the CRT group than in the control group.

Discussion/conclusion: CRT may be effective in preventing metachronous ESCC.
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http://dx.doi.org/10.1159/000510368DOI Listing
August 2021

Artificial Intelligence System to Determine Risk of T1 Colorectal Cancer Metastasis to Lymph Node.

Gastroenterology 2021 03 24;160(4):1075-1084.e2. Epub 2020 Sep 24.

Graduate School of Informatics, Nagoya University, Nagoya, Japan.

Background & Aims: In accordance with guidelines, most patients with T1 colorectal cancers (CRC) undergo surgical resection with lymph node dissection, despite the low incidence (∼10%) of metastasis to lymph nodes. To reduce unnecessary surgical resections, we used artificial intelligence to build a model to identify T1 colorectal tumors at risk for metastasis to lymph node and validated the model in a separate set of patients.

Methods: We collected data from 3134 patients with T1 CRC treated at 6 hospitals in Japan from April 1997 through September 2017 (training cohort). We developed a machine-learning artificial neural network (ANN) using data on patients' age and sex, as well as tumor size, location, morphology, lymphatic and vascular invasion, and histologic grade. We then conducted the external validation on the ANN model using independent 939 patients at another hospital during the same period (validation cohort). We calculated areas under the receiver operator characteristics curves (AUCs) for the ability of the model and US guidelines to identify patients with lymph node metastases.

Results: Lymph node metastases were found in 319 (10.2%) of 3134 patients in the training cohort and 79 (8.4%) of /939 patients in the validation cohort. In the validation cohort, the ANN model identified patients with lymph node metastases with an AUC of 0.83, whereas the guidelines identified patients with lymph node metastases with an AUC of 0.73 (P < .001). When the analysis was limited to patients with initial endoscopic resection (n = 517), the ANN model identified patients with lymph node metastases with an AUC of 0.84 and the guidelines identified these patients with an AUC of 0.77 (P = .005).

Conclusions: The ANN model outperformed guidelines in identifying patients with T1 CRCs who had lymph node metastases. This model might be used to determine which patients require additional surgery after endoscopic resection of T1 CRCs. UMIN Clinical Trials Registry no: UMIN000038609.
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http://dx.doi.org/10.1053/j.gastro.2020.09.027DOI Listing
March 2021

Double Early Rectal Cancer Arising from Multiple Inflammatory Cloacogenic Polyps Resected by Endoscopic Submucosal Dissection.

Intern Med 2021 Feb 19;60(4):533-537. Epub 2020 Sep 19.

Department of Gastroenterology, Toranomon Hospital, Japan.

A 45-year-old man visited our institution due to the onset of hematochezia. He had a previous episode nine years earlier and colonoscopy at that time revealed multiple polyps, which were consistent with inflammatory cloacogenic polyps (ICPs) on the dentate line. Colonoscopy was performed again and two of the ICPs had grown. Both lesions were pathologically diagnosed as adenocarcinomas based on biopsies. Endoscopic submucosal dissection (ESD) was performed and the two lesions were diagnosed as double well-differentiated adenocarcinomas arising from ICPs. To our knowledge, this is the first reported case of double early rectal cancer in ICPs, which were followed endoscopically and successfully resected with ESD.
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http://dx.doi.org/10.2169/internalmedicine.5686-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946511PMC
February 2021

New safety measure for the endoscopic procedures during the COVID-19 pandemic: New STEP.

VideoGIE 2020 Dec 17;5(12):634-636. Epub 2020 Sep 17.

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.vgie.2020.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495179PMC
December 2020

Esophageal Hematoma Associated with the Bolus Ingestion of Hot Coffee.

Intern Med 2020 Nov 7;59(21):2701-2704. Epub 2020 Jul 7.

Department of Gastroenterology, Toranomon Hospital, Japan.

A 59-year-old woman presented with pharyngeal discomfort and dysphagia starting the previous day. Esophagogastroduodenoscopy revealed a longitudinal reddish area and hematoma mainly on the left wall of the esophagus. On the previous day, she had felt a piece of meat sticking in her throat while eating; she therefore rapidly gulped down some hot coffee to hasten the passage of the meat. Based on the history, we diagnosed her endoscopic findings as esophageal hematoma and thermal injury associated with hot coffee. We herein describe a case of an acute esophageal hematoma and thermal injury and the clinical course following endoscopy.
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http://dx.doi.org/10.2169/internalmedicine.5110-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691044PMC
November 2020
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