Faculty Profiles - NAKAMURA, Masanao

Differentiation between pancreatic metastases from renal cell carcinoma and pancreatic neuroendocrine neoplasm using endoscopic ultrasound. International journal

Kunio Kataoka, Takuya Ishikawa, Eizaburo Ohno, Yasuyuki Mizutani, Tadashi Iida, Eri Ishikawa, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 21 ( 7 ) page： 1364 - 1370 2021.10

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

OBJECTIVES: Pancreatic metastases from renal cell carcinoma (PRCC) often appear many years after treatment of the primary tumor, and differentiation from pancreatic neuroendocrine neoplasm (PanNEN) can be challenging due to their hypervascularity. Here, we investigated the utility of endoscopic ultrasound (EUS) for differentiation of these conditions. METHODS: A retrospective analysis was performed in 17 and 79 consecutive patients with pathologically proven PRCC and non-functional PanNEN who were examined by EUS. In cases examined by EUS elastography or contrast-enhanced harmonic EUS (CH-EUS), the lesions were classified as stiff or soft, or into three vascular patterns as hypoechoic, isoechoic, and hyperechoic. CH-EUS images at 20 s, 40 s, 60 s, 3 min and 5 min were used for evaluation. EUS images were independently reviewed by two readers who were blinded to all clinical information. RESULTS: The patients with PRCC were significantly older than those with PanNEN (median, 71 (range, 45-81) vs. 58 (22-76), P = 0.001) and more often had multiple tumors (6/17 (35%) vs. 7/79 (9%), P = 0.010). In EUS findings, PRCC lesions significantly more frequently had a marginal hypoechoic zone (MHZ) (11/17 (65%) vs. 27/79 (34%), P = 0.028), being classified as soft (12/13 (92%) vs. 26/58 (45%), P = 0.002), and showed sustained hyperechoic vascular patterns at 5 min (7/8 (88%) vs. 4/59 (7%), P < 0.001) compared to PanNEN lesions. CONCLUSIONS: The presence of a MHZ, a soft lesion, and a sustained hyperechoic vascular pattern in EUS may be useful for differentiating PRCC from PanNEN.

DOI： 10.1016/j.pan.2021.07.001

【クローン病診療の診断から治療をマスターする】クローン病の活動性はどのように評価するのか? 内視鏡検査と検査のタイミング

喜田裕一, 山村健史, 前田啓子, 澤田つな騎, 石川恵里, 角嶋直美, 古川和宏, 中村正直

消化器・肝臓内科 Vol. 10 ( 4 ) page： 429 - 435 2021.10

炎症性腸疾患治療におけるアフェレシスの現状と未来難治性潰瘍性大腸炎における生物学的製剤とGMAの併用療法

中村正直, 山村健史, 前田啓子, 澤田つな騎, 石川恵里, 小杉智規, 丸山彰一, 梅田晋一, 服部憲史, 中山吾郎

日本アフェレシス学会雑誌 Vol. 40 ( Suppl. ) page： 49 - 49 2021.10

Endoscopic Ultrasound Elastography as a Novel Diagnostic Method for the Assessment of Hardness and Depth of Invasion in Colorectal Neoplasms. International journal

Masaya Esaki, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Hiroto Suzuki, Takeshi Kuno, Kentaro Yamada, Issei Hasegawa, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro

Digestion Vol. 102 ( 5 ) page： 701 - 713 2021.9

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

INTRODUCTION: We aimed to compare the efficacy of endoscopic ultrasound elastography (EUS-EG) with that of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for the diagnosis of the depth of invasion in colorectal neoplasms. This is an important clinical issue as the depth of invasion is associated with the risk of metastasis. METHODS: Consecutive patients with suspected superficial colorectal neoplasms, evaluated by MCE, EUS, and EUS-EG, for whom endoscopic submucosal dissection was considered, were enrolled in 2018 (derivation study) and in 2019-2020 (validation study). The primary clinical endpoint was the diagnostic yield differentiating intramucosal and shallow submucosal neoplasms from deep submucosal (dSM) and advanced colorectal cancers. In addition, inter- and intra-observer agreements of the elastic score of colorectal neoplasm (ES-CRN) were evaluated by 2 expert and 2 non-expert endoscopists. RESULTS: Thirty-one (33 lesions) and 50 (55 lesions) patients were enrolled in the derivation and validation studies, respectively. Sensitivity, specificity, positive, and negative predictive values, and accuracy of assessment of the depth of submucosal or deeper invasion in the derivation and validation groups were as follows: EUS-EG, 100/88.2/86.7/100/93.3% and 77.8/86.1/73.7/88.6/83.3%; MCE, 66.7/94.4/90.9/77.3/81.8% and 84.2/91.4/84.2/91.4/88.9%; and EUS, 93.3/77.8/77.8/93.3/84.8% and 89.5/65.7/58.6/92.0/74.1%, respectively. For the 2 expert endoscopists, interobserver agreement for the ES-CRN (first and second assessments) in the derivation group was 0.84 and 0.78, respectively; these values were 0.73 and 0.49, respectively, for the 2 non-expert endoscopists. DISCUSSION/CONCLUSION: All 3 modalities presented similar diagnostic yield. Inter- and intra-observer agreements of the ES-CRN were substantial, even for non-expert endoscopists. Therefore, EUS-EG may be a useful modality in determining the depth of invasion in colorectal neoplasms.

DOI： 10.1159/000511589

Subjective Symptoms in Patients with Eosinophilic Esophagitis Are Related to Esophageal Wall Thickness and Esophageal Body Pressure. International journal

Koichi Muroi, Naomi Kakushima, Kazuhiro Furukawa, Eri Ishikawa, Tsunaki Sawada, Takuya Ishikawa, Keiko Maeda, Takeshi Yamamura, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Kohei Funasaka, Ryoji Miyahara, Mitsuhiro Fujishiro

Digestive diseases and sciences Vol. 66 ( 7 ) page： 2291 - 2300 2021.7

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

BACKGROUND: Endoscopic ultrasonography (EUS) and high-resolution manometry (HRM) can be used in the evaluation of eosinophilic esophagitis (EoE) for frequent symptoms such as dysphagia. However, the role of these examinations is not clear. AIMS: The aim of this study was to objectively evaluate the subjective symptoms of EoE patients with EUS and HRM. METHODS: Patients who had endoscopic findings indicative of EoE and matched the number of eosinophil infiltrates used as diagnostic criteria were recruited between September 2018 and August 2019. Evaluable subjects underwent EUS and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. The esophageal wall thickness (evaluated with EUS) and HRM parameters between patients with and without symptoms were retrospectively compared. Symptomatic patients were re-examined using EUS and HRM 6 months after treatment. RESULTS: A total of 35 patients (29 males, median age of 49 years) were divided into symptomatic (20 patients) and asymptomatic groups (15 patients). The esophageal wall was thicker, and the distal contractile integral (DCI) values were higher in the symptomatic group (P < 0.001). In addition, DCI values were positively correlated with esophageal wall thickness. After treatment, the GSRS scores showed an improving trend for each item. Esophageal wall thickness and DCI values were significantly decreased (Ps < 0.001). CONCLUSIONS: Esophageal wall thickening and increased esophageal body pressure may be involved in subjective symptoms. In addition, treatment may reduce esophageal thickness and pressure along with improvement of subjective symptoms.

DOI： 10.1007/s10620-020-06527-5

Endoscopic papillectomy for ampullary adenoma and early adenocarcinoma: Analysis of factors related to treatment outcome and long‐term prognosis

Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Tadashi Iida, Hiroyuki Tanaka, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Senju Hashimoto, Akihiro Itoh, Masatoshi Ishigami, Yoshiki Hirooka, Mitsuhiro Fujishiro

Digestive Endoscopy Vol. 33 ( 5 ) page： 858 - 869 2021.7

【消化管がん検診・スクリーニングの手引き】(第VI章)下部消化管の検診でしばしば遭遇する腫瘍性疾患大腸ポリープ

山村健史, 中村正直, 前田啓子, 澤田つな騎, 石川恵里, 角嶋直美, 古川和宏, 川嶋啓揮, 藤城光弘

臨床消化器内科 Vol. 36 ( 8 ) page： 1022 - 1028 2021.7

Language：Japanese Publisher：(株)日本メディカルセンター

＜文献概要＞大腸がんは本邦でがん罹患数1位,がん死亡数2位と増加傾向を示しており,世界でもがん疾患のなかで大きな割合を占めている.大腸がんは検診による死亡抑制効果が実証されており,世界の多くの地域で実施されている.本邦では便潜血免疫法(fecal immunohistochemical test;FIT)が開発され,1992年から対策型検診として行われているが,検診受診率および精検受診率の低さが問題として挙げられている.一方,任意型検診では全大腸内視鏡(total colonoscopy;TCS)を用いることができるが,対策型検診として組み込むには安全性と質の担保,医療者側の検査処理能力,費用効果,アドヒアランスなど多くの課題が残されている.しかし大腸内視鏡による腺腫性ポリープ切除は,大腸がんの罹患率・死亡率を減少させることが報告されており,TCSが早期発見・治療に関しては非常に有効な手段であることに異論はないと思われる.大腸がんは検診により死亡抑制効果を期待できるうえに内視鏡的腺腫性ポリープ切除術により死亡率・罹患率を減少させることなど,二次予防の効果(早期発見・早期治療)も高いことが特徴であり,検診で遭遇する大腸ポリープを適切に取り扱うことは大変重要な課題である.本稿ではガイドラインを中心にして,大腸ポリープの取り扱いについて解説する.

Comparison of High-Resolution Manometry in Patients Complaining of Dysphagia among Patients with or without Diabetes Mellitus. International journal

Koichi Muroi, Ryoji Miyahara, Kohei Funasaka, Kazuhiro Furukawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Takeshi Onoue, Hiroshi Arima, Yoshiki Hirooka, Mitsuhiro Fujishiro

Digestion Vol. 102 ( 4 ) page： 554 - 562 2021.6

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

INTRODUCTION: Dysphagia is a common symptom that occurs in patients with diabetes mellitus (DM). There have been few prospective observational studies on esophageal motility disorders in DM using high-resolution manometry (HRM). This study aimed to clarify the characteristics of esophageal motility disorders using HRM in patients with dysphagia and compare them between DM and non-DM patients. METHODS: Patients with dysphagia were prospectively recruited between October 2018 and July 2019. Patients (n = 89) underwent esophagogastroduodenoscopy and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Manometry parameters and motility disorder classifications were compared between DM and non-DM patients. We also investigated the differences in clinical backgrounds and questionnaire scores among DM patients with normal and abnormal manometry results. RESULTS: A higher prevalence of esophageal motility disorder was observed in DM patients (60%, 21/35) compared to non-DM patients (29.6%, 16/54) (p = 0.001). The prevalence of minor disorders such as ineffective esophageal motor disorder and fragmented peristalsis was significantly higher (45 vs. 11%), and the distal contractile integral, integrated relaxation pressure, and contractile front velocity values were lower in the DM group. Among DM patients, those with abnormal esophageal motility had a significantly higher prevalence of neuropathy, retinopathy, and nephropathy, as well as higher reflux or constipation scores on the GSRS, than those with normal results. CONCLUSIONS: Among patients with dysphagia, the frequency of minor esophageal motility disorders was higher in DM patients than in non-DM patients. Abnormal esophageal motility related to poor esophageal clearance was associated with higher prevalence of diabetic complications.

DOI： 10.1159/000510081

Long-Term Prognostic Predictors of Esophageal Squamous Cell Carcinoma Potentially Indicated for Endoscopic Submucosal Dissection. International journal

Tomohiko Suzuki, Kazuhiro Furukawa, Kohei Funasaka, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Ryoji Miyahara, Mitsuhiro Fujishiro

Digestion Vol. 102 ( 4 ) page： 563 - 571 2021.6

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

INTRODUCTION: Patients with esophageal squamous cell carcinoma (ESCC) have various comorbidities. Thus, it is necessary to determine the appropriateness of performing treatment based on the patient's general condition. AIM: This study aimed to clarify the prognostic predictors of ESCC indicated for endoscopic submucosal dissection (ESD). METHODS: This retrospective study enrolled 241 patients with superficial ESCC endoscopically diagnosed as ESD-indicated lesions at the Nagoya University Hospital between January 2007 and December 2017. We evaluated the 3- and 5-year overall survival (OS) rates and prognostic predictors, such as the Prognostic Nutritional Index (PNI), Charlson Comorbidity Index (CCI), Psoas Muscle Index, and Controlling Nutritional Status score. Furthermore, we created a score-based classification using the prognostic predictors identified by multivariate analysis, and the 3- and 5-year OS rates were compared among the calculated scores. RESULTS: In the multivariate analysis, PNI < 45 (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.28-4.46; p = 0.006) and CCI ≥ 3 (HR: 4.42; 95% CI: 2.40-8.12; p < 0.001) were significantly associated with the OS. Based on the HR, 0 and 1 were assigned to PNI and 0, 2, and 4 were assigned to CCI, and the score classification of 0-5 points was created. The 3- and 5-year OS rates in patients with a score 3 were significantly higher than in those with scores 4 and 5. As a result of scoring, the prognosis was stratified; the 3- and 5-year OS rates in patients with scores 4 and 5, that is, CCI ≥ 6, were clearly low, at approximately 10%. CONCLUSIONS: CCI and PNI can be prognostic predictors of patients with superficial ESCC indicated for ESD. Observation without ESD might be an acceptable strategy among patients with CCI ≥ 6.

DOI： 10.1159/000510091

Immunohistochemical staining for IMP3 in patients with duodenal papilla tumors: assessment of the potential for diagnosing endoscopic resectability and predicting prognosis. International journal

Hiroyuki Tanaka, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Tadashi Iida, Eri Ishikawa, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Yoshie Shimoyama, Ryoji Miyahara, Naoto Kawabe, Teiji Kuzuya, Senju Hashimoto, Masatoshi Ishigami, Yoshiki Hirooka, Mitsuhiro Fujishiro

BMC gastroenterology Vol. 21 ( 1 ) page： 224 - 224 2021.5

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

BACKGROUND: Endoscopic papillectomy of duodenal papillary tumors (PT) is indicated for adenomas or well-differentiated adenocarcinomas that do not involve the sphincter of Oddi. However, there is currently no reliable pre-operative method to diagnose the infiltration in the sphincter of Oddi.' Insulin-like growth factor 2 mRNA protein 3 (IMP3) staining is reportedly associated with advanced disease stage and clinical outcomes in many carcinomas. The aim of this retrospective study was to investigate the ability of diagnosing sphincter of Oddi involvement in PT and predicting the prognoses using IMP3 immunohistochemistry. METHODS: Twenty-five resected specimens from patients with PT and 24 biopsy specimens from the same patients excluding one were immunostained for IMP3. The percentage of positive cells in the tumor was evaluated and compared with the final pathological diagnosis and prognosis. RESULTS: The final pathological diagnoses were adenoma in 5 patients and adenocarcinoma in 20 patients (no sphincter of Oddi involvement in 5 and involvement in 15). The ability to diagnose sphincter of Oddi involvement based on the percentage of IMP3-positive cells in resected specimens and tissue biopsies was the area under the curve 0.8 and 0.78, respectively, of the receiver operating characteristic curve, and the accuracies were 80.0% and 75.0% (cutoff value: 10%), respectively. Moreover, patients with an IMP3-positive cell rate of ≥ 10% had a significantly worse prognosis (log-rank test P = 0.01). CONCLUSION: IMP3 immunostaining of resected and biopsy specimens from PT patients enables the diagnosis of sphincter of Oddi involvement objectively and is also effective in predicting the prognosis.

DOI： 10.1186/s12876-021-01811-8

Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. International journal

Kota Uetsuki, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Tadashi Iida, Kenta Yamamoto, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Yoshiki Hirooka, Mitsuhiro Fujishiro

BMC gastroenterology Vol. 21 ( 1 ) page： 211 - 211 2021.5

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

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is associated with the outcome of pancreatic disease. However, there is no method for assessing PEI that can be used noninvasively and easily for outpatient. It has been reported that changes in intestinal bacteria caused by PEI may increase breath hydrogen concentration (BHC) levels during glucose or lactose loading. We have evaluated the usefulness of fasting breath hydrogen concentration (FBHC) measurement without glucose loading for the evaluation of PEI. METHODS: Sixty patients underwent FBHC measurement, BT-PABA testing, and microbiome analysis. They were classified into PEI group (PABA excretion rate < 73.4%, n = 30) and non-PEI group (n = 30). The FBHC of the two groups were compared, and the diagnostic ability of PEI by them was evaluated. The 16 s rRNA (V3-V4) from fecal samples was analyzed by MiSeq. RESULTS: FBHC levels was higher in the PEI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001). FBHC was negatively correlated with PABA excretion rate (r = - 0.523, P < 0.001). The cutoff value of FBHC of 10.7 ppm (95% CI: 0.678-0.913, P < 0.001) showed a sensitivity of 73.3% and specificity of 83.3% for PEI diagnosis. In the PEI group, there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05). CONCLUSION: FBHC shows good potential as a simple and repeatable test for the diagnosis of PEI. The elevated FBHC levels may be caused by hydrogen-producing bacteria such as Clostridium.

DOI： 10.1186/s12876-021-01776-8

New modality for the quantitative evaluation of tissue elasticity using a forward-viewing radial-array echoendoscope for colorectal neoplasms. International journal

Masaya Esaki, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Kazuhiro Furukawa, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro

International journal of colorectal disease Vol. 36 ( 5 ) page： 919 - 927 2021.5

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

PURPOSE: Sound speed correction (SSC) is a non-invasive modality that quantifies the hardness of neoplasms. The aim of our study was to evaluate the usefulness of SSC for the diagnostic accuracy of colorectal neoplasms and to differentiate the depth of invasion. METHODS: Forty colorectal neoplasms, contributed by 40 patients, were included in the analysis. The primary outcome was the diagnostic ability of SSC for the depth of invasion of colorectal neoplasms, with the secondary endpoint being the clinical efficacy of SSC to distinguish between a neoplasm and normal mucosa. RESULTS: The median sound speeds for colorectal neoplasms and normal mucosa were 1580 m/s and 1515 m/s, respectively (p < 0.001), with a median sound speed of 1583 m/s for lesions with a depth shallower than that of the muscularis propria and 1610 m/s for depths deeper than that of the muscularis propria (p = 0.002). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80.0%, 100%, 100%, 83.3%, 90.0%, and 100%, respectively, for the diagnosis of neoplasms (using a cut-off sound speed of 1557 m/s) and 100%, 77.8%, 33.3%, 100%, 80.0%, respectively, for the diagnosis of the depth of invasion (using a cut-off of 1590 m/s). CONCLUSION: We identified absolute sound speeds for colorectal neoplasms and the depth of invasion of neoplasms which yielded a good diagnostic performance. SSC provides an objective evaluation of colorectal neoplasms and the depth of invasion of neoplasms and, thus, might be a useful modality in practice. TRIAL REGISTRATION: UMIN000038235 , Date of registration; October 8, 2019.

DOI： 10.1007/s00384-020-03790-w

Diagnostic performance of endoscopic ultrasonography-guided elastography for solid pancreatic lesions: Shear-wave measurements versus strain elastography with histogram analysis. International journal

Eizaburo Ohno, Hiroki Kawashima, Takuya Ishikawa, Tadashi Iida, Hirotaka Suzuki, Kota Uetsuki, Jun Yashika, Kenta Yamada, Masakatsu Yoshikawa, Noriaki Gibo, Toshinori Aoki, Kunio Kataoka, Hiroshi Mori, Takeshi Yamamura, Kazuhiro Furukawa, Masanao Nakamura, Yoshiki Hirooka, Mitsuhiro Fujishiro

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society Vol. 33 ( 4 ) page： 629 - 638 2021.5

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

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS) elastography (EUS-EG) is a minimally invasive diagnostic method for evaluating tissue elasticity. The aim of this study was to evaluate the feasibility of newly developed EUS shear-wave measurement (EUS-SWM) and to compare diagnostic performance between EUS-SWM and the conventional strain elastography (SE) for the measurement of elasticity of solid pancreatic lesions (SPLs). METHODS: From December 2017 until August 2019, we retrospectively reviewed 64 consecutive cases with SPLs who underwent both EUS-SWM and SE. EUS-SWM was used to measure the shear-wave velocity, Vs (m/s), and the unique measurement reliability index, VsN (%), in the target lesion. SE images were assessed by strain histogram (SH) analysis, and the mean strain value of the elasticity index was measured. We evaluated the diagnostic performance of EUS-SWM and SE with SH to characterize the SPLs. RESULTS: The Vs (m/s) values of SPLs were 2.19 for pancreatic cancer (PC), 1.31 for pancreatic neuroendocrine neoplasm (PanNEN), 2.56 for mass-forming pancreatitis (MFP) and 1.58 for metastatic tumors. Vs showed no significant difference based on the disease. The mean strain values were 45.5 for PC, 47.3 for PanNEN, and 74.5 for MFP. In the comparison of tissue elasticity between PC and MFP, Vs showed no significant difference (P = 0.5687); however, the mean strain value was significantly lower in PC cases (45.4 vs 74.5: P = 0.0007). CONCLUSION: Endoscopic ultrasound SWM tended to be unstable for the measurement of elasticity of SPLs, and conventional SE with SH was superior for their characterization.

DOI： 10.1111/den.13791

膵癌診療における超音波の位置づけ膵癌診断におけるEUS-FNB時の実体顕微鏡を用いた肉眼的検体評価の有用性

石川卓哉, 川嶋啓揮, 大野栄三郎, 鈴木博貴, 本多隆, 中村正直, 石津洋二, 山本健太, 宜保憲明, 藤城光弘

超音波医学 Vol. 48 ( Suppl. ) page： S302 - S302 2021.4

Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice. International journal

Takahiro Nishikawa, Keiko Maeda, Masanao Nakamura, Takeshi Yamamura, Tsunaki Sawada, Yasuyuki Mizutani, Takanori Ito, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Ryoji Miyahara, Hiroki Kawashima, Takashi Honda, Masatoshi Ishigami, Tokunori Yamamoto, Seiji Matsumoto, Yuji Hotta, Mitsuhiro Fujishiro

Digestive diseases and sciences Vol. 66 ( 4 ) page： 1034 - 1044 2021.4

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

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. AIMS: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. METHODS: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. RESULTS: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. CONCLUSIONS: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.

DOI： 10.1007/s10620-020-06359-3

Utility of multiphase contrast enhancement patterns on CEH-EUS for the differential diagnosis of IPMN-derived and conventional pancreatic cancer. International journal

Jun Yashika, Eizaburo Ohno, Takuya Ishikawa, Tadashi Iida, Hirotaka Suzuki, Kota Uetsuki, Kenta Yamada, Masakatsu Yoshikawa, Noriaki Gibo, Yoshie Shimoyama, Eri Ishikawa, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Yoshiki Hirooka, Hiroki Kawashima, Mitsuhiro Fujishiro

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 21 ( 2 ) page： 390 - 396 2021.3

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

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is reported as a high-risk factor for pancreatic cancer (PC) that includes IPMN-derived cancers (IPMC) and the development of invasive pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMN. Since invasive IPMC and PDAC exhibit different oncological behaviors, their differentiation is clinically important. We aimed to investigate the use of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) for the differential diagnosis between invasive IPMC and PDAC. METHODS: This study involved 183 consecutive patients with PC (invasive IPMC: 42, PDAC concomitant with IPMN: 9, without IPMN: 132) who underwent CEH-EUS preoperatively. While investigating the patterns, enhanced effects in the solid part of the tumor were compared with those in the surrounding pancreatic parenchyma after administration of Sonazoid® and evaluated as hyperenhanced, isoenhanced, or hypoenhanced. We retrospectively compared the enhanced pattern of CEH-EUS by using multiphasic analysis and clinicopathological factors between invasive IPMC and PDAC. RESULTS: In multiphase evaluations at 20, 40 and 60 s in CEH-EUS, 75.2% (106/141) of PDACs were hypoenhanced (-) at ≥2 of the 3 time points, with significant differences from those of invasive IPMC (P < 0.001). The solid tumor diameter was significantly larger in PDAC than in invasive IPMC, and the tumor stage and preoperative serum carbohydrate antigen 19-9 level were higher. After propensity score matching of stage and solid tumor diameter, contrast enhancement patterns were significantly more persistent in invasive IPMC than in PDAC (P = 0.0013). CONCLUSIONS: Multiphase evaluation using CEH-EUS is a useful method for differentiating between invasive IPMC and PDAC.

DOI： 10.1016/j.pan.2020.12.022

Endoscopic ultrasound elastography for small solid pancreatic lesions with or without main pancreatic duct dilatation. International journal

Kunio Kataoka, Takuya Ishikawa, Eizaburo Ohno, Tadashi Iida, Hirotaka Suzuki, Kota Uetsuki, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 21 ( 2 ) page： 451 - 458 2021.3

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

BACKGROUND: /Objectives: Endoscopic ultrasound elastography (EUS-EG) is useful for diagnosis of small solid pancreatic lesions (SPLs), particularly in excluding pancreatic cancer (PC), but its dependence on main pancreatic duct dilatation (MPDD) has not been examined. We aimed to investigate EUS-EG for diagnosis of small SPLs with and without MPDD. METHODS: Patients with pathologically diagnosed SPLs of ≤20 mm were included and retrospectively analyzed. Using the blue:green ratio, an EUS-EG image was classified as blue-dominant, equivalent, or green-dominant. Using multiple EUS-EG images per patient, a lesion with a greater number of blue-dominant than green-dominant images was classified as stiff, and the others as soft. EUS-EG images in random order were judged by three raters. Considering stiff SPLs as PC, diagnostic performance of EUS-EG was examined for SPLs with and without MPDD. RESULTS: Of 126 cases analyzed, 65 (52%) were diagnosed as PC, and 63 (50%) had MPDD. A total of 1077 EUS-EG images were examined (kappa coefficient = 0.783). Lesions were classified as stiff in 91 cases and soft in 35 (kappa coefficient = 0.932). The ratio of stiff to soft lesions was significantly higher in PC than in non-PC (62:3 vs. 29:32, P < 0.001). The sensitivity, specificity, and negative predictive value of a stiff lesion with vs. without MPDD for diagnosis of PC were 94%, 23%, and 50% vs. 100%, 60%, and 100%, respectively. CONCLUSIONS: Using the EUS-EG stiffness classification for small SPLs, PC can be excluded with high confidence and concordance for a soft lesion without MPDD.

DOI： 10.1016/j.pan.2020.12.012

Clinical characteristics and long-term prognosis of autoimmune pancreatitis with renal lesions. International journal

Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Tadashi Iida, Hirotaka Suzuki, Kota Uetsuki, Jun Yashika, Kenta Yamada, Masakatsu Yoshikawa, Noriaki Gibo, Toshinori Aoki, Kunio Kataoka, Hiroshi Mori, Takeshi Yamamura, Kazuhiro Furukawa, Masanao Nakamura, Yoshiki Hirooka, Mitsuhiro Fujishiro

Scientific reports Vol. 11 ( 1 ) page： 406 - 406 2021.1

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

Autoimmune pancreatitis (AIP) is recognized as the pancreatic manifestation of a systemic IgG4-related disease that can involve various organs, including the kidney. However, renal lesions tend to be overlooked when AIP is diagnosed, and the clinical characteristics and long-term prognosis of AIP with renal lesions are unclear. We retrospectively reviewed 153 patients with AIP diagnosed at our hospital with a median follow-up period of 41 months (interquartile range, 10-86) and classified them into two groups: the KD group (n = 17), with characteristic renal imaging features, and the non-KD group (n = 136). Serum IgG4 levels were significantly higher in the KD group (663 vs. 304.5 mg/dl, P = 0.014). No differences were observed between the two groups in terms of steroid treatment [14/17 (82.4%) vs. 112/136 (82.4%), P = 1] or in the number of patients who exhibited exacerbation of renal function during treatment [1/17 (5.9%) vs. 8/136 (5.9%), P = 1]. However, the cumulative relapse rate was significantly higher in the KD group [61% vs. 21.9% (3 years), P < 0.001]. Patients in the KD group had different clinical features with high relapse rates compared with those in the non-KD group, and thus, it is important to confirm the presence of renal lesions in AIP patients.

DOI： 10.1038/s41598-020-79899-3