Publications by authors named "Tsuneo Oyama"

81 Publications

The potential for reducing alcohol consumption to prevent esophageal cancer morbidity in Asian heavy drinkers: a systematic review and meta-analysis.

Esophagus 2021 Oct 24. Epub 2021 Oct 24.

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34-7.47, I = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57-2.10, I = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.
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http://dx.doi.org/10.1007/s10388-021-00892-4DOI Listing
October 2021

Endoscopic diagnosis and treatment of superficial Barrett's esophageal adenocarcinoma: Japanese perspective.

Authors:
Tsuneo Oyama

Dig Endosc 2021 Oct 7. Epub 2021 Oct 7.

Department of Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan.

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http://dx.doi.org/10.1111/den.14147DOI Listing
October 2021

Fruit and vegetable consumption and risk of esophageal cancer in the Asian region: a systematic review and meta-analysis.

Esophagus 2021 Sep 25. Epub 2021 Sep 25.

Department of General Surgical Science, Division of Gastroenterological Surgery, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.

The consumption of fruit and vegetables was reported to be associated with a reduced risk of esophageal cancer (EC) in many studies of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) from different regions worldwide. Therefore, to provide precise information to reduce the risk of EC in Asia, we performed a systematic review and meta-analysis of studies conducted in the Asian region about fruit and vegetable consumption and the risk of EC. We searched the MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases from January 2010 to December 2020. The summary relative risk (SRR) and 95% CI were calculated using a random-effects model. In addition, I statistics were used to detect heterogeneity. Twenty-two studies were eligible for meta-analysis (16 case-control studies and 6 cohort studies). The SRR for the lowest versus highest fruit consumption was 0.64 (95% CI 0.53-0.77, I = 82%). That for the lowest versus highest vegetable consumption was 0.61 (95% CI 0.50-0.74, I = 81%). Based on subgroup analysis, a validated Food Frequency Questionnaire (FFQ) was significantly associated (SRR for fruit: 0.54; 95% CI 0.40-0.74, SRR for vegetable: 0.60; 95% CI 0.48-0.76) with low heterogeneity (I = 48% for fruit, I = 0% for vegetables). Egger's funnel plot asymmetry test demonstrated publication bias (P < 0.001 for fruit, P = 0.009 for vegetables). Fruit and vegetable consumption might be associated with a lower risk of EC in the Asian region. However, further substantial prospective studies with a validated FFQ and well-controlled important confounding factors are required to confirm the association.
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http://dx.doi.org/10.1007/s10388-021-00882-6DOI Listing
September 2021

Comprehensive registry of esophageal cancer in Japan, 2014.

Esophagus 2021 Sep 22. Epub 2021 Sep 22.

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

Background: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually.

Methods: We analyzed the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging.

Results: A total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system, because pStage IV included the patients with supraclavicular lymph-node metastasis (M1 LYM).

Conclusion: We hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan.
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http://dx.doi.org/10.1007/s10388-021-00879-1DOI 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

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

Esophagus 2021 Oct 30;18(4):713-723. Epub 2021 May 30.

Department of Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan.

Background: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms.

Methods: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter.

Results: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found.

Conclusion: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.
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http://dx.doi.org/10.1007/s10388-021-00841-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387266PMC
October 2021

Topical oro-dispersible budesonide tablets for stricture prevention after near circumferential ESD for esophageal squamous cell cancer - a case report.

Z Gastroenterol 2021 May 18;59(5):454-456. Epub 2021 Mar 18.

Department of Medicine and Gastroenterology, Academic Teaching Hospital, University of Bonn, Bonn, Germany.

Background:  Endoscopic resection is the treatment of choice for early esophageal cancers. However, resections comprising more than 70-80 % of the circumference are associated with a high risk of stricture formation. Currently, repetitive local injections and/or systemic steroids are given for prevention.

Case Report:  We present here the case of a 78-year-old male patient who had a near circumferential endoscopic submucosal dissection for a pT1a mm, L0, V0, R0, G2 esophageal squamous cell cancer. At the end of endoscopic resection, 80 mg of triamcinolone was injected locally. The patient was then treated with oro-dispersible budesonide tablets (2 × 1 mg/day) and nystatin (4 × 100 000 I.E.) for 8 weeks. This treatment resulted in complete healing without any stricture formation and did not result in any complications.

Discussion:  Treatment with orodispersible budesonide tablets could help prevent strictures after large endoscopic resections in the esophagus.
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http://dx.doi.org/10.1055/a-1409-1076DOI Listing
May 2021

Current Trends in Endoscopic Diagnosis and Treatment of Early Esophageal Cancer.

Cancers (Basel) 2021 Feb 11;13(4). Epub 2021 Feb 11.

Department of Medicine, Evangelisches Diakoniekrankenhaus Freiburg, Academic Teaching Hospital, University of Freiburg, D-79110 Freiburg, Germany.

Diagnosis of esophageal adenocarcinoma mostly occurs in the context of reflux disease or surveillance of Barrett's metaplasia. Optimal detection rates are obtained with high definition and virtual or dye chromoendoscopy. Smaller lesions can be treated with endoscopic mucosal resection. Endoscopic submucosal dissection (ESD) is an option for larger lesions. Endoscopic resection is considered curative (i.e., without significant risk of lymph node metastasis) if histopathology confirms en bloc and R0 resection of a well-differentiated (G1/2) tumor without infiltration of lymphatic or blood vessels and the maximal submucosal infiltration depth is 500µm. Ablation of remaining Barrett's metaplasia is important, to reduce the risk of metachronous cancer. Esophageal squamous cell cancer is associated with different risk factors, and most of the detected lesions are diagnosed during upper gastrointestinal endoscopy for other indications. Virtual high definition and dye chromoendoscopy with Lugol's solution are used for screening and evaluation. ESD is the preferred resection technique. The criteria for curative resection are similar to Barrett's cancer, but the maximum infiltration depth must not exceed lamina propria mucosae. Although a submucosal infiltration depth of up to 200 µm carries a substantial risk of lymph node metastasis, ESD combined with adjuvant chemo-radiotherapy gives excellent results. The complication rates of endoscopic resection are low, and the functional outcomes are favorable compared to surgery.
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http://dx.doi.org/10.3390/cancers13040752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916931PMC
February 2021

Long-term follow-up after colorectal endoscopic submucosal dissection in 182 cases.

Endosc Int Open 2021 Feb 3;9(2):E258-E262. Epub 2021 Feb 3.

Department of Medicine and Gastroenterology, Gemeinschaftskrankenhaus Bonn, Academic Teaching Hospital, University of Bonn, Bonn, Germany.

 We previously reported a case series of our first 182 colorectal endoscopic submucosal dissections (ESDs). In the initial series, 155 ESDs had been technically feasible, with 137 en bloc resections and 97 en bloc resections with free margins (R0). Here, we present long-term follow-up data, with particular emphasis on cases where either en bloc resection was not achieved or en bloc resection resulted in positive margins (R1).  Between September 2012 and October 2015, we performed 182 consecutive ESD procedures in 178 patients (median size 41.0 ± 17.4 mm; localization rectum vs. proximal rectum 63 vs. 119). Data on follow-up were obtained from our endoscopy database and from referring physicians.  Of the initial cohort, 11 patients underwent surgery; follow-up data were available for 141 of the remaining 171 cases (82,5 %) with a median follow-up of 2.43 years (range 0.15-6.53). Recurrent adenoma was observed in 8 patients (n = 2 after margin positive en bloc ESD; n = 6 after fragmented resection). Recurrence rates were lower after en bloc resection, irrespective of involved margins (1.8 vs. 18,2 %; P < 0.01). All recurrences were low-grade adenomas and could be managed endoscopically.  The rate of recurrence is low after en bloc ESD, in particular if a one-piece resection can be achieved. Recurrence after fragmented resection is comparable to published data on piecemeal mucosal resection.
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http://dx.doi.org/10.1055/a-1321-1271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857971PMC
February 2021

Risk of colonoscopic post-polypectomy bleeding in patients after the discontinuation of antithrombotic therapy.

Turk J Gastroenterol 2020 11;31(11):752-759

Department of Community Care, Saku Central Hospital, Saku, Japan.

Background/aims: Few studies have examined the incidence of post-polypectomy bleeding (PPB) after discontinuation of antithrombotic therapies. Therefore, this study aimed to evaluate the incidence of PPB and thromboembolic events in patients whose antithrombotic agents were discontinued before colonoscopy.

Materials And Methods: We retrospectively selected all patients who underwent colon polypectomy at a community hospital. A total of 282 patients (540 polypectomies) discontinued antithrombotic agents (group 1), and 1,648 patients (2,827 polypectomies) did not take antithrombotic agents (group 2). The cessation periods before and after polypectomies were 4 and 3 days for warfarin, 5 and 3 days for anti-platelet agents, and 7 and 5 days of combination therapy, respectively. Main outcome measurements were the incidence of PPB and thromboembolic events.

Results: Immediate PPB rates were 3.9% (11/282) in group 1 and 4.6% (76/1648) in group 2 (adjusted odds ratio [OR], 0.85; 95% confidence interval [CI], 0.42-1.72; p=0.65). Delayed PPB rates were 1.4% (4/282) in group 1 and 1.1% (18/1648) in group 2 (adjusted OR, 1.24; 95% CI, 0.36-4.24; p=0.732). No thromboembolic events were observed in either group.

Conclusion: Our cessation periods were appropriate, and further shortening of these periods is possible.
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http://dx.doi.org/10.5152/tjg.2020.19428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759232PMC
November 2020

Endoscopic prediction of submucosal invasion in Barrett's cancer with the use of artificial intelligence: a pilot study.

Endoscopy 2021 09 16;53(9):878-883. Epub 2020 Nov 16.

III Medizinische Klinik, Universitätsklinikum Augsburg, Augsburg Germany.

Background: The accurate differentiation between T1a and T1b Barrett's-related cancer has both therapeutic and prognostic implications but is challenging even for experienced physicians. We trained an artificial intelligence (AI) system on the basis of deep artificial neural networks (deep learning) to differentiate between T1a and T1b Barrett's cancer on white-light images.

Methods: Endoscopic images from three tertiary care centers in Germany were collected retrospectively. A deep learning system was trained and tested using the principles of cross validation. A total of 230 white-light endoscopic images (108 T1a and 122 T1b) were evaluated using the AI system. For comparison, the images were also classified by experts specialized in endoscopic diagnosis and treatment of Barrett's cancer.

Results: The sensitivity, specificity, F1 score, and accuracy of the AI system in the differentiation between T1a and T1b cancer lesions was 0.77, 0.64, 0.74, and 0.71, respectively. There was no statistically significant difference between the performance of the AI system and that of experts, who showed sensitivity, specificity, F1, and accuracy of 0.63, 0.78, 0.67, and 0.70, respectively.

Conclusion: This pilot study demonstrates the first multicenter application of an AI-based system in the prediction of submucosal invasion in endoscopic images of Barrett's cancer. AI scored equally to international experts in the field, but more work is necessary to improve the system and apply it to video sequences and real-life settings. Nevertheless, the correct prediction of submucosal invasion in Barrett's cancer remains challenging for both experts and AI.
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http://dx.doi.org/10.1055/a-1311-8570DOI Listing
September 2021

Comprehensive registry of esophageal cancer in Japan, 2013.

Esophagus 2021 Jan 13;18(1):1-24. Epub 2020 Oct 13.

Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Esophageal cancer is the eighth most common cause of cancer mortality in Japan. More than 11,000 people had died from esophageal cancer in 2018. The Japan Esophageal Society has collected the data on patients' characteristics, performed treatment, and outcomes annually.

Methods: We analyzed the data of patients who had first visited the participating hospitals in 2013. In 2019, the data collection method was changed from an electronic submission to a web-based data collection using the National Clinical Database (NCD). Japanese Classification of Esophageal Cancer 10th by the Japan Esophageal Society (JES) and UICC TNM Classification 7th were used for cancer staging RESULTS: A total of 8019 cases were registered from 334 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.8% and 6.3%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, or esophagectomy were 88.3%, 32.4%, 24.4%, and 59.3%, respectively. Esophagectomy was performed in 4910 cases. The operative and the hospital mortality rates were 0.77% and 1.98%, respectively. The survival curves showed a good discriminatory ability both in the clinical and pathologic stages by the JES system. The 5-year survival rate of patients with pStage IV in the UICC classification that included patients with supraclavicular node metastasis was better than that of patients with pStage IVb in JES classification.

Conclusion: We hope this report contributes to improving all aspects of the diagnosis and treatment of esophageal cancer in Japan.
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http://dx.doi.org/10.1007/s10388-020-00785-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794110PMC
January 2021

Usefulness and Limitations of a Serum Screening System to Predict the Risk of Gastric Cancer.

Intern Med 2020 Jun 19;59(12):1473-1480. Epub 2020 Mar 19.

Department of Gastroenterology, Saku Central Hospital Advanced Care Center, Japan.

Objective The aim of the present study was to evaluate the effectiveness and limitations of a serum screening system for predicting the risk of gastric cancer. Methods Serum pepsinogen I (PG I)/pepsinogen II (PG II) and Helicobacter pylori (HP) antibody levels were measured. Subjects were classified into four groupsaccording to their serological status (the ABC classification system). The grade of atrophic gastritis was assessed endoscopically. We evaluated gastric cancer detection rates according to the ABC classification system and the endoscopic grade of atrophy. Patients Individuals who underwent esophagogastroduodenoscopy (EGD) in a health check were prospectively enrolled in the present study. Results According to the ABC classification system, the gastric cancer detection rates in groups A, B, C, and D were 0.07% (4/6,105), 0.5% (8/1,739), 0.8% (16/2,010), and 1.1% (3/281), respectively. The gastric cancer detection rates in subjects with no atrophy, closed type (C-type) atrophy, and open type (O-type) atrophy were 0% (0/4,567), 0.2% (4/2,581), and 0.9% (27/2,987), respectively. In group A (HP(-)/PG(-)), the proportions of subjects with no atrophy, C-type atrophy, and O-type atrophy were 71.2%, 22.8%, and 6.0%, respectively. In group A, the gastric cancer detection rates in subjects with no atrophy, C-type atrophy, and O-type atrophy were 0%, 0.07%, and 0.8%, respectively. Conclusion The ABC classification system is useful for predicting the risk of gastric cancer. However, this system was limited in group A, which included individuals with a high risk of developing gastric cancer. An endoscopic diagnosis of atrophy may be more effective than the ABC classification system for predicting the risk of gastric cancer.
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http://dx.doi.org/10.2169/internalmedicine.3521-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364258PMC
June 2020

Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer.

Dig Endosc 2020 May;32(4):452-493

Japan Gastroenterological Endoscopy Society, Tokyo, Japan.

The Japan Gastroenterological Endoscopy Society has developed endoscopic submucosal dissection/endoscopic mucosal resection guidelines. These guidelines present recommendations in response to 18 clinical questions concerning the preoperative diagnosis, indications, resection methods, curability assessment, and surveillance of patients undergoing endoscopic resection for esophageal cancers based on a systematic review of the scientific literature.
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http://dx.doi.org/10.1111/den.13654DOI Listing
May 2020

Endoscopic hand-suturing is feasible, safe, and may reduce bleeding risk after gastric endoscopic submucosal dissection: a multicenter pilot study (with video).

Gastrointest Endosc 2020 05 7;91(5):1195-1202. Epub 2020 Jan 7.

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

Background And Aims: Endoscopic hand-suturing (EHS) provides secure intraluminal mucosal closure and should decrease the risk of adverse events after gastric endoscopic submucosal dissection (ESD). We prospectively investigated the feasibility and safety of EHS after gastric ESD, particularly for preventing post-ESD bleeding.

Methods: Patients scheduled for gastric ESD at 3 institutions were prospectively recruited. Just after ESD, the mucosal defect was closed by EHS. The primary outcome was endoscopic assessment of adequately sustained closure of the defect on postoperative day 3. Endoscopy was performed to assess maintenance of the closure for the primary outcome. During postoperative weeks 3 to 4, patients were interviewed as outpatients about any occurrence of delayed bleeding.

Results: Data from 30 patients (15 each who did or did not take antithrombotic agents) were analyzed. Mucosal closure by EHS was completed in 29 of 30 cases (97%) and was well maintained on postoperative day 3 in 25 cases (84%). Emergency endoscopy was required for major postoperative bleeding in 3 cases (10%), including 1 in which suturing had been incomplete. Excluding 1 patient with a remnant stomach, the other 24 with sustained closure had no bleeding, regardless of whether they did or did not take antithrombotic agents (0/11 and 0/13, respectively). No serious adverse events occurred during EHS.

Conclusions: Results show that EHS is feasible and safe with favorable outcomes. Provided that mucosal suturing is successfully completed and sustained, post-ESD bleeding can be decreased even in patients undergoing antithrombotic therapy. (Clinical trial registration number: UMIN 000033988.).
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http://dx.doi.org/10.1016/j.gie.2019.12.046DOI Listing
May 2020

Distribution of lanthanum carbonate in the gastric mucosa confirmed by electron microscopy with a magnified endoscopy: a case report and literature review.

Clin J Gastroenterol 2020 Jun 3;13(3):365-371. Epub 2019 Dec 3.

Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan.

We describe the case of a 70-year-old man with diabetic nephropathy undergoing hemodialysis. Four years following hemodialysis, he started taking lanthanum carbonate 1500 mg/day and lansoprazole 30 mg/day. Nine years following hemodialysis, he underwent screening esophagogastroduodenoscopy, which demonstrated the presence of the whitish cobblestone-like mucosa in the gastric corpus and multiple reddish depressed lesions with annular whitish mucosa in the antrum. With magnified narrow-band imaging endoscopy, a yellowish-white substance was observed in the villous structure, and subepithelial vessels were observed on the yellowish-white substance. Biopsies were taken from the whitish cobblestone-like mucosa of the upper corpus, a reddish depressed part of the antrum. Histologically, aggregates of cells containing amphophilic fine granular material were found in the mucosal interstitium. These cells stained positive for CD68 and were identified as histiocytes. Since he had been taking lanthanum carbonate for 5 years, we considered the possibility of histiocyte-mediated phagocytosis of lanthanum. Digital mapping via scanning electron microscopy with energy-dispersive X-ray spectrometry showed the presence of lanthanum and phosphorus in the interstitium and cytoplasm of histiocytes. The white, rough mucosa in the gastric body appeared 6 months following the commencement of lanthanum administration and still exists 3 years and 5 months after discontinuation of lanthanum.
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http://dx.doi.org/10.1007/s12328-019-01076-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239835PMC
June 2020

Laparoscopy and endoscopy cooperative surgery is a safe and effective novel treatment for duodenal neuroendocrine tumor G1.

Endoscopy 2020 02 17;52(2):E68-E70. Epub 2019 Sep 17.

Department of Pathology, Saku Central Hospital Advanced Care Center, Saku, Japan.

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http://dx.doi.org/10.1055/a-0999-5172DOI Listing
February 2020

Is Additional Surgery Always Sufficient for Preventing Recurrence After Endoscopic Submucosal Dissection with Curability C-2 for Early Gastric Cancer?

Ann Surg Oncol 2019 Oct 24;26(11):3636-3643. Epub 2019 Jul 24.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: When a lesion does not meet the curative criteria of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), referred to as non-curative resection or curability C-2 in the guidelines, an additional surgery is the standard therapy because of the risk of lymph node metastasis (LNM).

Objective: This study aimed to identify high-risk patients for recurrence after additional surgery for curability C-2 ESD of EGC.

Methods: This multicenter retrospective cohort study enrolled 1064 patients who underwent additional surgery after curability C-2 ESD for EGC. We evaluated the recurrence rate and the risk factors for recurrence after additional surgery in these patients.

Results: The 5-year recurrence rate after additional surgery was 1.3%. Multivariate Cox analysis revealed that the independent risk factors for recurrence after additional surgery were LNM (hazard ratio [HR] 32.47; p < 0.001) and vascular invasion (HR 4.75; p = 0.014). Moreover, patients with both LNM and vascular invasion had a high rate of recurrence after additional surgery (24.6% in 5 years), with a high HR (119.32) compared with those with neither LNM nor vascular invasion. Among patients with no vascular invasion, a high rate of recurrence was observed in those with N2/N3 disease according to the American Joint Committee on Cancer TNM staging system (27.3% in 5 years), in contrast with no recurrence in those with N1 disease.

Conclusions: Patients with both LNM (N1-N3) and vascular invasion, as well as those with N2/N3 disease but no vascular invasion, would be candidates for adjuvant chemotherapy after additional surgery for curability C-2 ESD of EGC.
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http://dx.doi.org/10.1245/s10434-019-07579-2DOI Listing
October 2019

Comprehensive registry of esophageal cancer in Japan, 2012.

Esophagus 2019 07 16;16(3):221-245. Epub 2019 May 16.

Department of Diagnostic Radiology and Radiation Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

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http://dx.doi.org/10.1007/s10388-019-00674-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592979PMC
July 2019

Age Affects Clinical Management after Noncurative Endoscopic Submucosal Dissection for Early Gastric Cancer.

Dig Dis 2019 16;37(6):423-433. Epub 2019 May 16.

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

Background: Additional surgery is recommended after noncurative endoscopic submucosal dissection (ESD) for early gastric cancer due to the risk of lymph node metastasis. However, age may affect the clinical management of these patients.

Objectives: The aim of our retrospective multicenter study was to clarify whether age affects decision-making after noncurative ESD and if the decision affects long-term outcomes.

Methods: Age was classified as follows: non-elderly, <70 years (n = 811); elderly, 70-79 years (n= 760); and super-elderly, ≥80 years (n = 398). Age associations with the selection for additional surgery were evaluated using logistic regression analysis. Long-term outcomes were also evaluated in each age group.

Results: Age was inversely related to the rate of additional surgery, which ranged from 70.0% in the non-elderly group to 20.1% in the super-elderly group (p < 0.001). On multivariate analysis, age <70 years (versus age ≥80 years) was associated with the -selection of additional surgery (OR 18.6). Overall survival (OS) in patients who underwent additional surgery was -significantly higher in the non-elderly and elderly groups (p< 0.001), whereas the difference was not significant in the super-elderly group (p = 0.23).

Conclusions: Despite the fact that almost 80% of super-elderly patients did not undergo additional surgery, the difference of OS between patients with and without additional surgery was not significant only in patients ≥80 years. Therefore, establishment of criteria for selecting treatment methods after noncurative ESD in elderly patients is required.
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http://dx.doi.org/10.1159/000499538DOI Listing
December 2019

Efficacy of Endoscopic Resection and Selective Chemoradiotherapy for Stage I Esophageal Squamous Cell Carcinoma.

Gastroenterology 2019 08 20;157(2):382-390.e3. Epub 2019 Apr 20.

Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address:

Background & Aims: Esophagectomy is the standard treatment for stage I esophageal squamous cell carcinoma (ESCC). We conducted a single-arm prospective study to confirm the efficacy and safety of selective chemoradiotherapy (CRT) based on findings from endoscopic resection (ER).

Methods: We performed a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC from December 2006 through July 2012; 176 patients underwent ER. Based on the findings from ER, patients received the following: no additional treatment for patients with pT1a tumors with a negative resection margin and no lymphovascular invasion (group A); prophylactic CRT with 41.4 Gy delivered to locoregional lymph nodes for patients with pT1b tumors with a negative resection margin or pT1a tumors with lymphovascular invasion (group B); or definitive CRT (50.4 Gy) with a 9-Gy boost to the primary site for patients with a positive vertical resection margin (group C). Chemotherapy comprised 5-fluorouracil and cisplatin. The primary end point was 3-year overall survival in group B, and the key secondary end point was 3-year overall survival for all patients. If lower limits of 90% confidence intervals for the primary and key secondary end points exceeded the 80% threshold, the efficacy of combined ER and selective CRT was confirmed.

Results: Based on the results from pathology analysis, 74, 87, and 15 patients were categorized into groups A, B, and C, respectively. The 3-year overall survival rates were 90.7% for group B (90% confidence interval, 84.0%-94.7%) and 92.6% in all patients (90% confidence interval, 88.5%-95.2%).

Conclusions: In a prospective study of patients with T1b (SM1-2) N0M0 thoracic ESCC, we confirmed the efficacy of the combination of ER and selective CRT. Efficacy is comparable to that of surgery, and the combination of ER and selective CRT should be considered as a minimally invasive treatment option. UMIN-Clinical Trials Registry no.: UMIN000000553.
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http://dx.doi.org/10.1053/j.gastro.2019.04.017DOI Listing
August 2019

Implementation of endoscopic submucosal dissection for early upper gastrointestinal tract cancer after primary experience in colorectal endoscopic submucosal dissection.

Endosc Int Open 2019 Apr 21;7(4):E446-E451. Epub 2019 Mar 21.

Department of Medicine and Gastroenterology, Gemeinschaftskrankenhaus Bonn, Academic Teaching Hospital, University of Bonn, Bonn, Germany.

 Current guidelines recommend endoscopic submucosal dissection (ESD) as a treatment option for early cancers of the upper gastrointestinal tract with absent or minimal risk of lymph node metastasis. However, due to the low prevalence of these entities, it is difficult to achieve a competence level for ESD of upper gastrointestinal tract cancers in the Western World. Here, we present single-center data on the implementation of upper gastrointestinal ESD after previous experience with 89 colorectal ESD cases.  Retrospective case series of 39 consecutive patients with early cancers of the esophagus (n = 13) or cardia and stomach (n = 26) treated with ESD over a 4-year period.  ESD was technically feasible in all cases with en bloc, R0, and curative resection rates of 100 %, 76.9 %, and 71.8 %, respectively, and a mean procedure time of 100 minutes (30 - 360 minutes). After an initial 20 procedures, the R0 and curative resection rates increased from 65.0 % to 89.5 %, and from 60.0 % to 84.2 %, respectively. Complications were observed in four patients (10.3 %): three perforations, one case of delayed bleeding, and one esophageal stricture. No case required emergency surgery; the 30-day mortality rate was 0 %.  In this modest case series from Europe, we observed an effectiveness and complication rate for ESD for early esophageal and gastric cancer that are comparable to other series from Europe but also to more abundant data from Asia. The results indicate that even small numbers of upper gastrointestinal cancers can be managed adequately in centers with expertise in colorectal ESD.
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http://dx.doi.org/10.1055/a-0854-3610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428673PMC
April 2019

Long-term outcomes after non-curative endoscopic submucosal dissection for early gastric cancer according to hospital volumes in Japan: a multicenter propensity-matched analysis.

Surg Endosc 2019 12 25;33(12):4078-4088. Epub 2019 Feb 25.

Department of Gastroenterology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

Background: There is a lack of data regarding the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) without curative resection, and the relationship of these outcomes with hospital volumes remains unclear. This study evaluated long-term outcomes of patients who underwent ESD for EGC without curative resection according to hospital volumes in Japan.

Methods: This multicenter retrospective study evaluated 1,969 patients who did not meet the criteria of the Japanese Gastric Cancer Association for curative resection between January 2000 and August 2011. Hospitals were classified according to the annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). Clinicopathological features, overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared across groups after a generalized propensity score matching analysis.

Results: In 495 pairs of generalized propensity score-matched patients, the 5-year OS, DSS, and RFS rates were 81.5%, 97.9%, and 97.6% for LMVG; 86.9%, 98.2%, and 97.0% for HVG; and 85.4%, 98.5%, and 97.6% for VHVG, respectively. The 5-year DSS and RFS rates did not significantly differ among the three groups. However, 5-year OS was significantly worse in the LMVG than in the HVG and VHVG (P < 0.001 and P = 0.008, respectively).

Conclusions: DSS and RFS in patients with EGC who did not meet the criteria for curative resection did not differ across hospital volumes in Japan. Even in cases in which ESD for EGC involved non-curative resection, the procedure is feasible across Japanese hospitals with different volumes.
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http://dx.doi.org/10.1007/s00464-019-06710-4DOI Listing
December 2019

Multicenter prospective study on the histological diagnosis of gastric cancer by narrow band imaging-magnified endoscopy with and without acetic acid.

Endosc Int Open 2019 Feb 18;7(2):E155-E163. Epub 2019 Jan 18.

Department of Gastroenterology, Nara City Hospital, Higashikidera-cho, Nara, Japan.

 The usefulness of endoscopy for diagnosing histological type remains unclear. This study aimed to examine the diagnostic accuracy of white light endoscopy (WLE), magnified endoscopy with narrow band imaging (NBI-ME), and NBI-ME with acetic acid enhancement (NBI-AA) for histological type of gastric cancer.  Patients with depressed-type gastric cancers resected by endoscopic submucosal dissection were prospectively enrolled, and 221 cases were analyzed. Histological type was diagnosed by WLE, followed by NBI-ME and NBI-AA. Histological type was classified into differentiated adenocarcinoma and undifferentiated adenocarcinoma. Histological type was diagnosed based on lesion color in WLE, surface patterns (pit, villi, and unclear) and vascular irregularities in NBI-ME, and surface patterns in NBI-AA.  Histological types of target areas were differentiated adenocarcinoma and undifferentiated adenocarcinoma in 206 and 15 cases, respectively. Diagnostic accuracy of WLE, NBI-ME, and NBI-AA for the histological type was 96.4 % (213/221), 96.8 % (214/221), and 95.5 % (211/221), respectively. No significant differences were observed among modalities. Positive predictive value based on endoscopic findings in NBI-ME was 98.0 % (149/152) for the villi pattern, 100 % (19/19) for the irregular pit pattern, 100 % (9/9) for the unclear surface pattern with a vascular network, 90.3 % (28/31) for the unclear surface pattern with mild vascular irregularity, and 88.9 % (8/9) for the unclear surface pattern with severe vascular irregularity.  NBI-ME and NBI-AA did not show any advantages over WLE for diagnostic accuracy. Villi pattern, irregular pit pattern, and vascular network may be useful for identifying differentiated adenocarcinoma.
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http://dx.doi.org/10.1055/a-0806-7275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338541PMC
February 2019

Long-term outcomes of endoscopic resection and metachronous cancer after endoscopic resection for adenocarcinoma of the esophagogastric junction in Japan.

Gastrointest Endosc 2019 06 18;89(6):1120-1128. Epub 2018 Dec 18.

Department of Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan.

Background And Aims: Endoscopic resection (ER) of superficial adenocarcinoma of the esophagogastric junction (AEGJ) has been shown to be safe and effective. However, long-term data in patients undergoing ER for superficial AEGJ in Japan are still limited. The aim of this study was to determine the effect of ER on survival and occurrence of metachronous cancer of patients with superficial AEGJ.

Methods: A retrospective analysis of patients who underwent or endoscopic submucosal dissection (ESD) for superficial AEJG in 13 centers in Japan was performed. The patients were classified as either low risk or high risk for lymph node metastasis based on histologic features. The incidence of metachronous AEGJ as well as overall survival and disease-specific survival rates were calculated.

Results: A total of 372 patients who underwent ER were included, in which 277 patients were low risk and 95 high risk for lymph node metastasis. Five-year cumulative incidences of local recurrence were 13% and .5% in the EMR and ESD groups, respectively (P < .01). Six AEGJ deaths were observed in the high-risk group and none in the low-risk group. The 5-year overall survival rates in the low-risk group without additional treatment, the high-risk group with additional treatment, and the high-risk group without additional treatment were 93.9%, 77.7%, and 81.6%, respectively. The 5-year disease-specific survival rates in the 3 groups were 100%, 94.4%, and 92.8%, respectively. The 5-year cumulative incidence of metachronous AEGJ in 316 patients without additional treatment was 1.1%.

Conclusions: Favorable long-term outcomes with ER were observed in patients with AEGJ who met the low-risk criteria for lymph node metastasis. ESD was a reasonable and effective treatment in Japanese patients.
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http://dx.doi.org/10.1016/j.gie.2018.12.010DOI Listing
June 2019

Recurrence Patterns and Outcomes of Salvage Surgery in Cases of Non-Curative Endoscopic Submucosal Dissection without Additional Radical Surgery for Early Gastric Cancer.

Digestion 2019 14;99(1):52-58. Epub 2018 Dec 14.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background/aims: The outcomes of salvage surgery for recurrence after non-curative endoscopic submucosal dissection (ESD) without additional radical surgery for early gastric cancer (EGC) remain unclear. We determined the recurrence patterns and outcomes of salvage surgery in such cases using data from a multicenter, retrospective study.

Methods: Of 15,785 patients who underwent ESD for EGC at 19 participating institutions between January 2000 and August 2011, 1,969 failed to meet the current curative criteria after ESD. Of these, 905 patients received no additional treatment. We evaluated the pattern of recurrence, clinical course after salvage surgery, and long-term survival rate for these patients.

Results: Over a median 64-month follow-up period, recurrence was detected in 27 patients. Two patients with missing data were excluded. Three, seven, and 15 (60%) patients showed intragastric relapse, regional lymph node metastasis, and distant metastasis, respectively. The first line of treatment for recurrence in 1, 7, 6, and 11 patients was endoscopic treatment, salvage surgery, chemotherapy, and best supportive care, respectively. One patient survived without recurrence for 31 months after salvage surgery, one died of acute myocardial infarction 1 month after salvage surgery, and 5 showed recurrence at 0, 2, 3, 5, and 30 months after salvage surgery and eventually succumbed to the disease. The median survival times for all patients with recurrence and the 7 patients who underwent salvage surgery were 5 months after recurrence and 7 months after salvage surgery, respectively.

Conclusion: The survival rate after salvage surgery for recurrence after non-curative ESD without additional radical surgery for EGC is quite low, with distant metastasis being the most common recurrence pattern in these cases.
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http://dx.doi.org/10.1159/000494413DOI Listing
April 2019

Different risk factors between early and late cancer recurrences in patients without additional surgery after noncurative endoscopic submucosal dissection for early gastric cancer.

Gastrointest Endosc 2019 05 19;89(5):950-960. Epub 2018 Nov 19.

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

Background And Aims: Cancer recurrence is observed in some patients without additional radical surgery after endoscopic submucosal dissection (ESD) that does not fulfill the curability criteria for early gastric cancer (EGC), categorized as "noncurative resection" or "curability C-2" in the guidelines. However, time to cancer recurrence is different in such patients. Thus, we aimed to identify the risk factors of early and late cancer recurrences in these patients.

Methods: Between 2000 and 2011, this multicenter study analyzed 905 patients who were followed up without additional radical surgery after ESD for EGC categorized as curability C-2. We evaluated the risk factors for early and late cancer recurrences, separately, after ESD. The cut-off value was defined at 2 years.

Results: Time to cancer recurrence in the enrolled patients showed a bimodal pattern, and the 5-year cancer recurrence rate was 3.2%. Multivariate Cox analyses revealed that lymphatic invasion (hazard ratio [HR], 8.56; P = .003) was the sole independent risk factor for early cancer recurrence. Regarding late cancer recurrence, vascular invasion (HR, 4.50; P = .039) was an independent risk factor, and lymphatic invasion tended to be a risk factor (HR, 3.63; P = .069).

Conclusions: This multicenter study with a large cohort demonstrated that lymphatic invasion is mainly associated with early cancer recurrence; however, vascular invasion was a risk factor only for late recurrence in patients without additional treatment after ESD for EGC categorized as curability C-2. This finding may contribute to decision making for treatment strategies after ESD, especially for patients with a relatively short life expectancy.
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http://dx.doi.org/10.1016/j.gie.2018.11.015DOI Listing
May 2019
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