Faculty Profiles - NAKAMURA, Masanao

The microbiome can predict mucosal healing in small intestine in patients with Crohn's disease.

Shun Hattori, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Kenta Yamamoto, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Yoshiki Hirooka, Mitsuhiro Fujishiro

Journal of gastroenterology Vol. 55 ( 12 ) page： 1138 - 1149 2020.12

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: Mucosal healing is the main treatment goal for Crohn's disease. In this situation, some patients have difficulty with endoscopic evaluation of the entire small intestine. Crohn's disease is closely associated with the gut microbiota, but the relationship between the microbiome and disease activity in the small intestine remains unclear. We examined the association between the microbiome and endoscopic findings in the small intestine and determined whether the microbiome can predict mucosal healing. METHODS: The patients with Crohn's disease who were scheduled for capsule or balloon-assisted endoscopy were included in this prospective study. Patients whose entire small intestine was evaluated were divided into two groups based on ulcerative findings. The microbiomes in the fecal samples were analyzed using 16S rRNA sequencing. RESULTS: The 38 enrolled patients were divided into the ulcer group (24) and mucosal healing group (14). The ulcer group exhibited lower α diversity. Six genera, namely Faecalibacterium (P = 0.008), Lachnospira (P = 0.009), Paraprevotella (P = 0.01), Dialister (P = 0.012), Streptococcus (P = 0.025), and Clostridium (P = 0.028) were enriched in the mucosal healing group. A predictive score for mucosal healing was defined using these six genera. The area under the curve was 0.795 and the sensitivity and specificity for predicting mucosal healing were 0.643 and 0.917, respectively. CONCLUSIONS: Fecal microbiome is corelated with disease activity in the entire small intestine in Crohn's disease patients. The predictive score proposed by microbiota characteristics was a potential biomarker for mucosal healing in the small intestine.

DOI： 10.1007/s00535-020-01728-1

Mutation analysis of gastrointestinal stromal tumors using RNA obtained via endoscopic ultrasound-guided fine-needle aspiration. International journal

Kohei Funasaka, Ryoji Miyahara, Kazuhiro Furukawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Yoshiki Hirooka, Naoki Ohmiya, Mitsuhiro Fujishiro

Translational oncology Vol. 13 ( 11 ) page： 100848 - 100848 2020.11

Language：Japanese Publishing type：Research paper (scientific journal)

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is useful for pathologically diagnosing gastrointestinal stromal tumor (GIST) before surgery. However, its role in mutation analysis remains unclear. To examine the feasibility of analyzing GIST mutations using mRNA obtained with EUS-FNA, we prospectively enrolled 41 patients with subepithelial lesion from which EUS-FNA was successfully acquired tissue sample. Thirty-two, 5, and 4 subepithelial lesions were diagnosed as GISTs, schwannomas, and leiomyomas, respectively. After RNA was extracted from FNA sample, RNA was converted to cDNA. Full-length sequence of the KIT cDNA amplified via the polymerase chain reaction (PCR) was successful in 31 (96.9%) out of 32 GIST and three out of 9 non-GIST (33.3%). The KIT mutation statuses of 31 GISTs in which KIT cDNA was amplified were successfully determined through directional sequencing. Furthermore, 15 of 16 surgically excised GISTs exhibited the same mutation status in both the EUS-FNA and resected samples. In vitro experiment, the minimum number of cells required to amplify full-length of KIT cDNA from RNA was one-tenth of that required to amplify KIT exon11 gene from DNA. This study clarifies that mutation analysis using RNA obtained with EUS-FNA is feasible and reliable. Moreover, our data would support that RNA-based mutation is superior to DNA-based mutation analysis in GIST.

DOI： 10.1016/j.tranon.2020.100848

Endoscopic Activity and Serum TNF-α Level at Baseline Are Associated With Clinical Response to Ustekinumab in Crohn’s Disease Patients Reviewed

Kentaro Murate, Keiko Maeda, Masanao Nakamura, Daisuke Sugiyama, Hirotaka Wada, Takeshi Yamamura, Tsunaki Sawada, Yasuyuki Mizutani, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Ryoji Miyahara, Masatoshi Ishigami, Hiroyoshi Nishikawa, Mitsuhiro Fujishiro

Inflammatory Bowel Diseases Vol. 26 ( 11 ) page： 1669 - 1681 2020.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

<title>Abstract</title>
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<title>Background and Aims</title>
The therapeutic efficacy and safety of ustekinumab for Crohn’s disease (CD) have been reported from randomized controlled trials and real-world data. However, there are few studies describing the identification of patients most suitable for ustekinumab therapy. The aim of this study was to prospectively evaluate the patients receiving ustekinumab and identify predictors of the treatment efficacy.

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<title>Methods</title>
Patients with moderate to severe active CD scheduled to receive ustekinumab were enrolled. The responders and nonresponders were compared at weeks 0, 8, 24, and 48 by evaluating patient demographics, simple endoscopic scores (SES-CD), ustekinumab and cytokine concentrations, and cellular fractions.

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<title>Results</title>
The clinical response and clinical remission rates in the 22 enrolled patients were 59.1% and 31. 8% at week 8, 68.2% and 45.5% at week 24, and 54.4% and 40.9% at week 48, respectively. There were no significant differences in patients’ demographic and disease characteristics at baseline between responders and nonresponders. A combination of low SES-CD and high serum TNF-α concentration at baseline showed a good correlation with the clinical response. Serum TNF-α concentration was decreased because of the therapy. The ratio of CD4+TNF-α cells at baseline was significantly higher in responders than in nonresponders; however, the ratios of CD45+CD11b+TNF-α and CD45+CD11c+TNF-α cells were not different. The ratio of CD4+ TNF-α cells decreased with the treatment in the responders but not in the nonresponders.

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<sec>
<title>Conclusions</title>
The combination of 2 factors, namely higher serum TNF-α concentration and lower SES-CD at baseline, may assist clinicians in selecting the appropriate therapy for patients with moderate to severe CD.

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DOI： 10.1093/ibd/izaa086

What is the role of measuring shear wave dispersion using shear wave elastography in pancreatic parenchyma?

Hirotaka Suzuki, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Senju Hashimoto, Masanao Nakamura, Ryoji Miyahara, Masatoshi Ishigami, Yoshiki Hirooka, Mitsuhiro Fujishiro

JOURNAL OF MEDICAL ULTRASONICS Vol. 47 ( 4 ) page： 575 - 581 2020.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Purpose Shear wave elastography (SWE) using transabdominal ultrasonography (US) is widely used for diagnosis of tissue stiffness. Ultrasound shear wave dispersion (SWD) enables evaluation of tissue viscosity using SWE. The objective of this study was to investigate the reliability and clinical significance of SWD in pancreatic screening. Methods SWE and SWD were measured in 76 patients examined by US in pancreatic screenings performed between November 2017 and November 2018. The median pancreatic elastic modulus (PEM) and dispersion slope were obtained from at least five measurements. The reproducibility of these values and their correlations with patient characteristics, pancreatic echogenicity, and the pancreas-to-spleen attenuation ratio (P/S) on plain CT, which is associated with fatty change in pancreatic parenchyma, were investigated retrospectively. Results The median PEM and dispersion slope were 7.4 kPa and 15.7 (m/sec)/kHz, respectively, and both values had high intraclass correlation coefficients, showing high reproducibility (rho = 0.869 and rho = 0.867, respectively). The interquartile range/median value of PEM and dispersion slope were 0.36 and 0.28, respectively. PEM had a positive correlation with age (r(s) = 0.348,p = 0.002), and dispersion slope was positively correlated with age (r(s) = 0.278,p = 0.016) and BMI (r(s) = 0.397,p < 0.001). The hyperechoic pancreas had significantly higher PEM (6.6 vs. 7.8 kPa,p = 0.037) and dispersion slope (13.2 vs. 16.3 (m/sec)/kHz,p < 0.001). On plain CT performed in 50 patients, the P/S was not correlated with PEM (r(s) = - 0.180,p = 0.221), but was inversely correlated with dispersion slope (r(s) = - 0.338,p = 0.019). Conclusion Measurement of SWD in pancreatic screening was highly reproducible and may permit objective evaluation of fatty change of the pancreas.

DOI： 10.1007/s10396-020-01033-7

Comparison of different virtual chromoendoscopy classification systems for the characterization of colorectal lesions. International journal

Leonardo Zorron Cheng Tao Pu, Takeshi Yamamura, Masanao Nakamura, Doreen S C Koay, Amanda Ovenden, Suzanne Edwards, Alastair D Burt, Yoshiki Hirooka, Mitsuhiro Fujishiro, Rajvinder Singh

JGH open : an open access journal of gastroenterology and hepatology Vol. 4 ( 5 ) page： 818 - 826 2020.10

Language：Japanese Publishing type：Research paper (scientific journal)

Background and Aim: Commonly used classifications for colorectal lesions (CLs) include the Narrow Band Imaging (NBI) International Colorectal Endoscopic (NICE) and Japan NBI Expert Team (JNET) classifications. However, both lack a sessile serrated adenoma/polyp (SSA/P) category. This has been addressed by the modified Sano's (MS) and Workgroup serrAted polypS and Polyposis (WASP) classifications. This study aims to compare the accuracy of wNICE and wJNET (WASP added to both) with the stand-alone MS classification. Methods: Patients undergoing colonoscopy at an Australian tertiary hospital who had at least one CL detected were prospectively enrolled. In the exploratory phase, CLs were characterized in real time with NBI and magnification using all classifications. In the validation phase, CLs were assessed with both NBI and Blue Laser Imaging (BLI) by four external endoscopists in Japan. The primary outcome was the comparison of wJNET and MS. Secondary outcomes included comparisons among all classifications and the calculation of interrater reliability. Results: A total of 483 CLs were evaluated in real time in the exploratory phase, and four sets of 30 CL images (80 on NBI and 40 on BLI) were scored in the validation phase. For high-confidence diagnoses, MS accuracy was superior to wJNET in both the exploratory (86% vs 79%, P < 0.05) and validation (85% vs 69%, P < 0.05) phases. The interrater reliability was substantial for all classifications (κ = 0.74, 0.69, and 0.63 for wNICE, wJNET, and MS, respectively). Conclusions: MS classification achieved the highest accuracy in both the exploratory and validation phases. MS can differentiate serrated and adenomatous polyps as a stand-alone classification.

DOI： 10.1002/jgh3.12382

Computer-aided diagnosis for characterization of colorectal lesions: comprehensive software that includes differentiation of serrated lesions. International journal

Leonardo Zorron Cheng Tao Pu, Gabriel Maicas, Yu Tian, Takeshi Yamamura, Masanao Nakamura, Hiroto Suzuki, Gurfarmaan Singh, Khizar Rana, Yoshiki Hirooka, Alastair D Burt, Mitsuhiro Fujishiro, Gustavo Carneiro, Rajvinder Singh

Gastrointestinal endoscopy Vol. 92 ( 4 ) page： 891 - 899 2020.10

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: Endoscopy guidelines recommend adhering to policies such as resect and discard only if the optical biopsy is accurate. However, accuracy in predicting histology can vary greatly. Computer-aided diagnosis (CAD) for characterization of colorectal lesions may help with this issue. In this study, CAD software developed at the University of Adelaide (Australia) that includes serrated polyp differentiation was validated with Japanese images on narrow-band imaging (NBI) and blue-laser imaging (BLI). METHODS: CAD software developed using machine learning and densely connected convolutional neural networks was modeled with NBI colorectal lesion images (Olympus 190 series - Australia) and validated for NBI (Olympus 290 series) and BLI (Fujifilm 700 series) with Japanese datasets. All images were correlated with histology according to the modified Sano classification. The CAD software was trained with Australian NBI images and tested with separate sets of images from Australia (NBI) and Japan (NBI and BLI). RESULTS: An Australian dataset of 1235 polyp images was used as training, testing, and internal validation sets. A Japanese dataset of 20 polyp images on NBI and 49 polyp images on BLI was used as external validation sets. The CAD software had a mean area under the curve (AUC) of 94.3% for the internal set and 84.5% and 90.3% for the external sets (NBI and BLI, respectively). CONCLUSIONS: The CAD achieved AUCs comparable with experts and similar results with NBI and BLI. Accurate CAD prediction was achievable, even when the predicted endoscopy imaging technology was not part of the training set.

DOI： 10.1016/j.gie.2020.02.042

Low ETV1 mRNA expression is associated with recurrence in gastrointestinal stromal tumors. International journal

Keiichi Sakamaki, Kohei Funasaka, Ryoji Miyahara, Kazuhiro Furukawa, Takeshi Yamamura, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro, Hidemi Goto

Scientific reports Vol. 10 ( 1 ) page： 14767 - 14767 2020.9

Language：Japanese Publishing type：Research paper (scientific journal)

Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples (P < 0.0001). Sixty-four GISTs were stratified into high or low ETV1 mRNA expression groups based on the median relative abundance of ETV1 mRNA. The multivariate analysis showed that low ETV1 expression, as well as tumor size and mitotic index, was an independent factor of recurrence (hazard ratio: 8.1). Patients with high ETV1 expression achieved significantly longer recurrence-free survival (RFS) times than those with low ETV1 expression (P = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.

DOI： 10.1038/s41598-020-71719-y

芳川昌功, 川嶋啓揮, 大野栄三郎, 石川卓哉, 小屋敏也, 田中浩敬, 酒井大輔, 飯田忠, 西尾亮, 鈴木博貴, 植月康太, 八鹿潤, 山田健太, 澤田つな騎, 前田啓子, 山村健史, 古川和宏, 舩坂好平, 中村正直, 宮原良二, 廣岡芳樹

肝胆膵治療研究会誌 Vol. 16 ( 1 ) page： 93 - 93 2020.9

Reappraisal of Primary Epstein-Barr Virus (EBV)-positive Diffuse Large B-Cell Lymphoma of the Gastrointestinal Tract: Comparative Analysis Among Immunosuppressed and Nonimmunosuppressed Stage I and II-IV Patients. Reviewed International journal

Shouhei Miyagi, Eri Ishikawa, Masanao Nakamura, Kazuyuki Shimada, Takeshi Yamamura, Kazuhiro Furukawa, Tsutomu Tanaka, Seiyo Mabuchi, Yuta Tsuyuki, Kei Kohno, Ayako Sakakibara, Akira Satou, Seiichi Kato, Mitsuhiro Fujishiro, Shigeo Nakamura

The American journal of surgical pathology Vol. 44 ( 9 ) page： 1173 - 1183 2020.9

Language：Japanese Publishing type：Research paper (scientific journal)

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoproliferation encompasses a broad range of clinicopathologic findings, including specific subtypes, for example, EBV mucocutaneous ulcer. Here we reassessed 36 cases of primary EBV diffuse large B-cell lymphomas (16 men and 20 women; median age, 69.5 y; range, 35 to 84 y), including 8 immunosuppressed patients (Lugano stage II-IV; median age, 74 y), 7 nonimmunosuppressed patients with stage I disease (median age, 69 y), and 21 nonimmunosuppressed patients with stage II-IV disease (median age, 69 y). All immunosuppressed patients exhibited iatrogenic immunodeficiency and an ulcerative appearance, with ulcer sites including the stomach (1 patient), small intestine (6 patients), and rectum (1 patient). Four patients were in the setting of treated lymphoma-associated immunosuppression. Immunosuppressed patients had higher incidences of intestinal involvement (P=0.001) and perforation (n=2) compared with advanced stage nonimmunosuppressed patients. Among nonimmunosuppressed stage I patients, lesions were restricted to the stomach, none showed multiple lesions or elevated serum lactate dehydrogenase, and the overall survival curve plateaued, although it was not statistically significant (P=0.0581). One nonimmunosuppressed stage I patient with a polypoid lesion exhibited spontaneous regression within 2 months after diagnosis, while another with bulky disease pursued an aggressive clinical course. Nonimmunosuppressed stage I cases without bulky masses may be considered EBV mucocutaneous ulcer with local progression. Our results demonstrated that primary EBV gastrointestinal diffuse large B-cell lymphoma could be delineated into 3 groups based on immune status and clinical stage, revealing distinguishing features useful as a pragmatic guide for diagnostic and therapeutic approaches.

DOI： 10.1097/PAS.0000000000001499

Learning curve for mastery of colorectal endoscopic submucosal dissection: Perspectives from a large Japanese cohort. International journal

Leonardo Zorron Cheng Tao Pu, Takeshi Yamamura, Masanao Nakamura, Masaya Esaki, Uayporn Kaosombatwattana, Miguel R Rodriguez, Suzanne Edwards, Alastair D Burt, Rajvinder Singh, Yoshiki Hirooka, Mitsuhiro Fujishiro

JGH open : an open access journal of gastroenterology and hepatology Vol. 4 ( 4 ) page： 611 - 616 2020.8

Language：Japanese Publishing type：Research paper (scientific journal)

Background and Aim: Endoscopic submucosal dissection (ESD) is a challenging procedure. A dissection speed of ≥9 cm2/h has been acknowledged as a mark for expertise, alongside a complication rate of ≤5% and en bloc resection rate of ≥90%. However, there is lack of objective information on whether the three measures correlate with each other. This study aims to evaluate the dissection speed, safety, and efficacy of colorectal ESDs performed by experts and trainees. Methods: Consecutive patients undergoing colorectal ESD at a Japanese hospital (2006-2017) were included in a prospectively collected database. Information on patient demographics, proceduralist, and intra-/postprocedure data was retrieved. The primary outcome was the comparison in dissection speed. The secondary outcomes included differences in safety and efficacy. Log-linear regression models adjusted for confounders (e.g. R0 resection) were used to assess the differences in dissection speed. Results: Five hundred ninety procedures (514 patients) performed by 26 endoscopists were analyzed. Experts performed a higher number of difficult lesions (e.g. F2 fibrosis) but achieved higher dissection speed (10.3 vs 6.7 cm2/h). The difference was statistically significant for both unadjusted and adjusted models (P < 0.0001). The en bloc resection rates were similar for both groups (experts = 95.6%; trainees = 94.7%, P = 0.61). Although nonexperts damaged more of the muscularis propria (18.6 vs 12.5%, P = 0.04), this did not translate into a significant difference in perforation (experts = 3.7%; trainees = 6.9%, P = 0.09) or delayed bleeding (experts = 2.9%; trainees = 4.4%, P = 0.34). The dissection speed steadily increased with expertise. Conclusion: Although dissection speed for colorectal ESD was significantly higher for experts, ESDs could be safely and efficaciously performed by ESD trainees.

DOI： 10.1002/jgh3.12298

Polyp Detection Rate as a Surrogate for Adenoma and Sessile Serrated Adenoma/Polyp Detection Rates. International journal

Leonardo Zorron Cheng Tao Pu, Gurfarmaan Singh, Khizar Rana, Masanao Nakamura, Takeshi Yamamura, Sudarshan Krishnamurthi, Amanda Ovenden, Suzanne Edwards, Andrew Ruszkiewicz, Yoshiki Hirooka, Mitsuhiro Fujishiro, Alastair D Burt, Rajvinder Singh

Gastrointestinal tumors Vol. 7 ( 3 ) page： 74 - 82 2020.7

Language：Japanese Publishing type：Research paper (scientific journal)

Introduction: Quality measures for colonoscopy such as adenoma detection rate (ADR) have been proposed to be surveilled for ensuring minimum standards. However, its direct measurement is time consuming and often neglected. Extrapolating ADR and other quality measures from polyp detection rate (PDR) can be a pragmatic alternative. Objective: To determine quotients for estimating ADR and sessile serrated adenoma/polyp detection rate (SSA/P-DR) from PDR in an Australian cohort. Methods: Consecutive adult patient colonoscopies during a 1-year period were retrospectively assessed in a single Australian tertiary endoscopy center. Adenoma detection quotient (ADQ) and SSA/P detection quotient (SSA/P-DQ) were defined as the division of ADR and SSA/P-DR by PDR, respectively. The primary outcome was the number of procedures to achieve a stable cumulative ADQ and SSA/P-DQ. Secondary outcomes included evaluation of ADQ and SSA/P-DQ in different subsets. Results: In total, 2,657 colonoscopies were performed by 15 endoscopists in 2016. The ADR, SSA/P-DR, and PDR found were 32.2, 6.7, and 47.3%, respectively. The ADQ and SSA/P-DQ values found were 0.68 and 0.14, respectively. After approximately 500 procedures, both ADQ and SSA/P-DQ became stable. Interclass correlation coefficient (ICC) for the prediction of ADR from ADQ was excellent for all endoscopists that performed >177 procedures in that year (ICC 0.84). Conclusions: ADQ and SSA/P-DQ values were consistent when over 500 procedures were analyzed. ADQ had an excellent correlation with ADR when >177 procedures per endoscopist were evaluated.

DOI： 10.1159/000505622

【消化器疾患とステント治療】胃・十二指腸狭窄に対するステント治療

鈴木智彦, 鈴木孝弘, 森裕, 石川卓哉, 古川和宏, 石川恵里, 澤田つな騎, 前田啓子, 山村健史, 大野栄三郎, 中村正直, 川嶋啓揮, 藤城光弘

消化器・肝臓内科 Vol. 8 ( 1 ) page： 18 - 25 2020.7

Use of Immunostaining for the diagnosis of Lymphovascular invasion in superficial Barrett's esophageal adenocarcinoma. International journal

Isao Hosono, Ryoji Miyahara, Kazuhiro Furukawa, Kohei Funasaka, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Takio Yokoi, Tetsuya Tsukamoto, Yoshiki Hirooka, Mitsuhiro Fujishiro

BMC gastroenterology Vol. 20 ( 1 ) page： 175 - 175 2020.6

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: The prevalence of Barrett's esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA. METHODS: We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2-40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment. RESULTS: H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2-40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively. CONCLUSIONS: Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens.

DOI： 10.1186/s12876-020-01319-7