Faculty Profiles - HASHIMOTO Shinichi

Papers - HASHIMOTO Shinichi

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Murakami M., Fujimori N., Nakata K., Nakamura M., Hashimoto S., Kurahara H., Nishihara K., Abe T., Hashigo S., Kugiyama N., Ozawa E., Okamoto K., Ishida Y., Okano K., Takaki R., Shimamatsu Y., Ito T., Miki M., Oza N., Yamaguchi D., Yamamoto H., Takedomi H., Kawabe K., Akashi T., Miyahara K., Ohuchida J., Ogura Y., Nakashima Y., Ueki T., Ishigami K., Umakoshi H., Ueda K., Oono T., Ogawa Y. . Machine learning-based model for prediction and feature analysis of recurrence in pancreatic neuroendocrine tumors G1/G2 . Journal of Gastroenterology58 ( 6 ) 586 - 597 2023.6

Language：Japanese Publisher：Journal of Gastroenterology

Background: Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors. Although the prognosis of resected PanNENs is generally considered to be good, a relatively high recurrence rate has been reported. Given the scarcity of large-scale reports about PanNEN recurrence due to their rarity, we aimed to identify the predictors for recurrence in patients with resected PanNENs to improve prognosis. Methods: We established a multicenter database of 573 patients with PanNENs, who underwent resection between January 1987 and July 2020 at 22 Japanese centers, mainly in the Kyushu region. We evaluated the clinical characteristics of 371 patients with localized non-functioning pancreatic neuroendocrine tumors (G1/G2). We also constructed a machine learning-based prediction model to analyze the important features to determine recurrence. Results: Fifty-two patients experienced recurrence (14.0%) during the follow-up period, with the median time of recurrence being 33.7 months. The random survival forest (RSF) model showed better predictive performance than the Cox proportional hazards regression model in terms of the Harrell’s C-index (0.841 vs. 0.820). The Ki-67 index, residual tumor, WHO grade, tumor size, and lymph node metastasis were the top five predictors in the RSF model; tumor size above 20 mm was the watershed with increased recurrence probability, whereas the 5-year disease-free survival rate decreased linearly as the Ki-67 index increased. Conclusions: Our study revealed the characteristics of resected PanNENs in real-world clinical practice. Machine learning techniques can be powerful analytical tools that provide new insights into the relationship between the Ki-67 index or tumor size and recurrence.

DOI： 10.1007/s00535-023-01987-8

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Hinokuchi Makoto, Hashimoto Shinichi, Kojima Issei, Nakamura Yoshitaka, Fujita Toshihiro, Iwashita Yuji, Arima Shiho, Tanoue Shiroh, Ohtsuka Takao, Ido Akio . Efficacy and safety of a novel anti-reflux metal stent during neoadjuvant chemotherapy for pancreatic cancer: A prospective multicenter exploratory study(タイトル和訳中) . Journal of Hepato-Biliary-Pancreatic Sciences30 ( 4 ) 532 - 541 2023.4

Language：English Publisher：John Wiley & Sons Australia, Ltd

新規ダックビル型逆流防止弁付き金属ステント(D-ARMS)による胆道ドレナージの安全性および有効性を前向きに評価した。ネオアジュバント化学療法施行予定のD-ARMS治療が実施された切除可能または境界切除可能膵癌患者33例(男性23例、中央値68歳)、従来の被覆自己拡張型金属ステント(CCSEMS)による治療が実施された38例(男性27例、中央値67.5歳)を解析対象とした。評価項目は技術的・臨床的成功、Recurrent biliary obstruction(RBO)発生率、RBO累積発生率とした。その結果、技術的成功率は両群ともに100%であり、臨床的成功率にも有意差は認められなかった(93.9%対89.5%、P=0.68)。多変量解析の結果、D-ARMSはRBO累積発生の独立した予測因子であった(P=0.03)。RBO累積発生率はCCSEMS群と比較してD-ARMS群で有意に低かった(P=0.04)。以上から、D-ARMSはネオアジュバント化学療法施行患者にとって安全かつ有用であることが示された。

Hinokuchi M., Hashimoto S., Kojima I., Nakamura Y., Fujita T., Iwashita Y., Arima S., Tanoue S., Ohtsuka T., Ido A. . Efficacy and safety of a novel anti-reflux metal stent during neoadjuvant chemotherapy for pancreatic cancer: A prospective multicenter exploratory study . Journal of Hepato-Biliary-Pancreatic Sciences30 ( 4 ) 532 - 541 2023.4

Language：Japanese Publisher：Journal of Hepato-Biliary-Pancreatic Sciences

Background/Purpose: The benefits of anti-reflux metal stents, used for treating biliary obstruction in patients receiving neoadjuvant chemotherapy (NAC) for pancreatic cancer, are yet unknown. Herein, the safety and efficacy of the novel duckbill-type anti-reflux metal stent (D-ARMS) were prospectively evaluated for biliary drainage. Additionally, the incidence of recurrent biliary obstruction (RBO) after placement of D-ARMS vs conventional covered self-expandable metal stents (CCSEMSs) was retrospectively compared. Methods: Patients who received D-ARMS (n = 33) for treatment of distal biliary obstruction before NAC between September 2019 and January 2021 and those that received CCSEMSs (n = 38) between January 2013 and August 2019 were included in the historical control group. Technical and clinical successes, rate of RBO, and cumulative incidence of RBO were compared between the two groups. Results: The technical success rate was 100% for both the D-ARMS and CCSEMS groups, and the clinical success rate were not significantly different (93.9% and 89.5%, respectively; P =.68). In the multivariate analysis, D-ARMS was identified as the independent factor for cumulative incidence of RBO (P =.03). The cumulative incidence of RBO was significantly lower in the D-ARMS group than that in the CCSEMS group (P =.04). Conclusions: D-ARMS is safe and effective for patients receiving NAC.

DOI： 10.1002/jhbp.1239

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Kabayama M., Sasaki F., Hidehito M., Fujino Y., Yano H., Tanaka A., Arima S., Tanoue S., Hashimoto S., Kanmura S., Hirade H., Nishiguchi A., Taguchi T., Ido A. . Effects of Sprayable, Highly Adhesive Hydrophobized Gelatin Microparticles on Endoscopic Submucosal Dissection: A Swine Model . Digestion104 ( 2 ) 137 - 147 2023.3

Language：Japanese Publisher：Digestion

Introduction: Sprayable wound dressings containing hydrophobized microparticles (hMPs) are characterized by strong adhesiveness. We examined the effect of hMPs derived from Alaska pollock gelatin on endoscopic submucosal dissection (ESD) ulcers. Methods: (1) In an in vivo model of miniature swine gastric ESD, gastric ulcers were created by ESD and then sprayed with hMPs or untreated followed by microscopic examination. (2) In an ex vivo ESD model of resected stomach, a pinhole-shaped perforation was created on the ESD ulcer of resected stomach; hMPs were then sprayed on the perforation; and air leakage and intragastric pressure were measured. (3) In an in vivo duodenal ESD model of miniature swine, duodenal artificial ESD ulcers with pinhole-shaped perforation were examined; ulcers were classified into hMPs-sprayed and nonsprayed groups, and inflammation in the intrinsic muscle layer and serosa were compared between the groups. Results: (1) Histological observation of submucosal tissues showed a decreased number of invading inflammatory cells in hMP-sprayed tissues compared with the control in miniature swine gastric ESD (p < 0.05). In addition, the rates of anti-alpha smooth muscle actin and type I collagen positivity were significantly lower in the hMPs group than in the control group (p < 0.05). (2) Intragastric pressure could not be measured in the nonsprayed group, whereas no air leakage was observed in the sprayed group when pressurized up to 26 mm Hg in the resected stomach model. (3) The sprayed group showed suppressed inflammation of the intrinsic muscular layer and serosa in both cases compared with the nonsprayed group in miniature swine duodenal ESD (p < 0.05). Conclusions: Sprayable, tissue-adhesive hMPs are a promising medical material for intraoperative and postoperative treatment of ESD-induced wound via anti-inflammation and strong adhesiveness.

DOI： 10.1159/000526650

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Iwaya H., Tanimoto A., Toyodome K., Kojima I., Hinokuchi M., Tanoue S., Hashimoto S., Kawahira M., Arima S., Kanmura S., Akahane T., Higashi M., Suzuki S., Ueno S., Ohtsuka T., Ido A. . Next-Generation Sequencing Analysis of Pancreatic Cancer Using Residual Liquid Cytology Specimens from Endoscopic Ultrasound—Guided Fine-Needle Biopsy: A Prospective Comparative Study with Tissue Specimens . Diagnostics13 ( 6 ) 2023.3

Language：Japanese Publisher：Diagnostics

This study evaluated the feasibility and clinical utility of liquid-based cytology (LBC) specimens via endoscopic ultrasound–guided fine-needle biopsy (EUS-FNB) for next-generation sequencing (NGS) of pancreatic cancer (PC). We prospectively evaluated the performance of DNA extraction and NGS using EUS-FNB samples obtained from PC. Thirty-three consecutive patients with PC who underwent EUS-FNB at our hospital were enrolled. DNA samples were obtained from 96.8% of the patients. When stratified with a variant allele frequency (VAF) > 10% tumor burden, the NGS success rate was 76.7% (n = 23) in formalin-fixed paraffin-embedded (FFPE), 83.3% (n = 25) in LBC, and 76.7% (n = 23) in frozen samples. The overall NGS success rate was 86.7% (n = 26) using FFPE, LBC, or frozen samples. The detection rates for the main mutated genes were as follows: 86.7% for KRAS, 73.3% for TP53, 66.7% for CDKN2A, 36.7% for SMAD4, and 16.7% for ARID1A. LBC had the highest median value of VAF (23.5%) for KRAS and TP53. PC mutation analysis using NGS was successfully performed using LBC compared with FFPE and frozen samples. This approach provides an alternative and affordable source of molecular testing materials.

DOI： 10.3390/diagnostics13061078

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Hashimoto S., Iwashita Y., Taguchi H., Tanoue S., Ohi T., Shibata R., Haraguchi T., Kamikihara Y., Toyodome K., Kojima I., Araki N., Tsuneyoshi K., Nakamura Y., Fujita T., Hinokuchi M., Iwaya H., Arima S., Sasaki F., Kanmura S., Ido A. . Comparison of recurrent biliary obstruction with the use of metal and plastic stents in EUS-guided biliary drainage: A propensity score-matched analysis . Endoscopic Ultrasound12 ( 1 ) 64 - 73 2023.1

Language：Japanese Publisher：Endoscopic Ultrasound

Background and Objectives: In transpapillary biliary drainage, metal stents (MSs) exhibit a lower incidence of a biliary obstruction than plastic stents (PSs). However, few studies have compared recurrent biliary obstruction (RBO) when MSs and PSs are used in EUS-guided hepaticogastrostomy (EUS-HGS) and choledochoduodenostomy (EUS-CDS). We retrospectively evaluated the RBO for both stents in each procedure. Patients and Methods: Between November 2012 and December 2020, 85 and 53 patients who underwent EUS-HGS and EUS-CDS for unresectable malignant biliary obstruction, respectively, were enrolled. Factors associated with RBO were assessed. Clinical outcomes were compared between the MS and PS groups using propensity score matching. Results: The clinical success rate and procedure-related adverse events were similar in the MS and PS groups. Multivariate analysis identified the use of PS as a factor associated with RBO (EUS-HGS, P = 0.03; EUS-CDS, P = 0.02). After matching, the median time to RBO in EUS-HGS (MS: 313; PS: 125 days; P = 0.01) in the MS group was longer than that in the PS group. The cumulative incidence of RBO at 1, 3, and 6 months in the MS group was significantly lower than that in the PS group for EUS-HGS (MS: 4.0%, 8.2%, and 8.2%; PS: 12.4%, 24.9%, and 39.5%, respectively, P = 0.01). Conclusions: MS exhibited a lower rate of RBO than PS for EUS-HGS and EUS-CDS.

DOI： 10.4103/EUS-D-21-00251

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Fujisaki Y., Fukukura Y., Kumagae Y., Ejima F., Yamagishi R., Nakamura S., Kamizono J., Kurahara H., Hashimoto S., Yoshiura T. . Value of Dual-Energy Computed Tomography for Detecting Small Pancreatic Ductal Adenocarcinoma . Pancreas51 ( 10 ) 1352 - 1358 2022.11

Language：Japanese Publisher：Pancreas

Objective The aim of the study is to evaluate the usefulness of virtual monoenergetic imaging (VMI) generated from dual-energy computed tomography (DECT) in detecting small pancreatic ductal adenocarcinomas (PDACs). Methods This study included 82 patients pathologically diagnosed with small PDAC (≤30 mm) and 20 without pancreatic tumors who underwent triple-phase contrast-enhanced DECT. To assess diagnostic performance for small PDAC detection via a receiver operating characteristic analysis, 3 observers reviewed 2 image sets (conventional computed tomography [CT] set and combined image set [conventional CT + 40-keV VMI from DECT]). The tumor-To-pancreas contrast-To-noise ratio was compared between conventional CT and 40-keV VMI from DECT. Results The area under the receiver operating characteristic curve of the 3 observers were 0.97, 0.96, and 0.97 in conventional CT set and 0.99, 0.99, and 0.99 in combined image set (P = 0.017-0.028), respectively. The combined image set yielded a better sensitivity than the conventional CT set (P = 0.001-0.023), without a loss of specificity (all P > 0.999). The tumor-To-pancreas contrast-To-noise ratios of 40-keV VMI from DECT were approximately threefold higher than those of conventional CT at all phases. Conclusions The addition of 40-keV VMI from DECT to conventional CT had better sensitivity for detecting small PDACs without compromising specificity.

DOI： 10.1097/MPA.0000000000002207

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Kitano M., Yoshida M., Ashida R., Kita E., Katanuma A., Itoi T., Mikata R., Nishikawa K., Matsubayashi H., Takayama Y., Kato H., Takenaka M., Ueki T., Kawashima Y., Nakai Y., Hashimoto S., Shigekawa M., Nebiki H., Tsumura H., Okabe Y., Ryozawa S., Harada Y., Mitoro A., Sasaki T., Yasuda H., Miura N., Ikemoto T., Ozawa E., Shioji K., Yamaguchi A., Okuzono T., Moriyama I., Hisai H., Fujita K., Goto T., Shirahata N., Iwata Y., Okabe Y., Hara K., Hashimoto Y., Kuwatani M., Isayama H., Fujimori N., Masamune A., Hatamaru K., Shimokawa T., Okazaki K., Takeyama Y., Yamaue H., Abue M., Aiura K., Akashi T., Akiyama T., Aoyagi H., Araki M., Arizumi T., Aruga Y., Asada M., Asai S., Baba T., Ban S., Chinen K., Doi S., Eguchi T., Endo M., Endo S., Ezaki T., Fujii K., Fujii M., Fujimori M., Fujimoto Y., Fujita Y., Fujita Y., Fukasawa M., Fukuba N., Fukuchi S., Fukuda K., Furukawa M., Furumatsu K., Hakamada K., Hanada K., Harada K., Harano M., Hashigo S., Hashiguchi K., Hayashi K., Hayashi N., Hayatsu S., Hijioka S., Hirano A., Hirao M., Hirooka Y., Hirota M., Horino K., Hotta Y., Ijima M., Ikuta Y., Imakiire K., Imamura T., Inatomi O. . Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: Nationwide survey in Japan . Digestive Endoscopy34 ( 7 ) 1442 - 1455 2022.11

Language：Japanese Publisher：Digestive Endoscopy

Objectives: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. Methods: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. Results: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P = 0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P = 0.037). Conclusions: Needle tract seeding appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

DOI： 10.1111/den.14346

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Kitano Masayuki, Yoshida Makoto, Ashida Reiko, Kita Emiri, Katanuma Akio, Itoi Takao, Mikata Rintaro, Nishikawa Kenichiro, Matsubayashi Hiroyuki, Takayama Yukiko, Kato Hironari, Takenaka Mamoru, Ueki Toru, Kawashima Yohei, Nakai Yousuke, Hashimoto Shinichi, Shigekawa Minoru, Nebiki Hiroko, Tsumura Hidetaka, Okabe Yosinobu, Ryozawa Shomei, Harada Yoshiyuki, Mitoro Akira, Sasaki Tamito, Yasuda Hiroaki, Miura Natsuki, Ikemoto Tetsuya, Ozawa Eisuke, Shioji Kazuhiko, Yamaguchi Atsushi, Okuzono Toru, Moriyama Ichiro, Hisai Hiroyuki, Fujita Koichi, Goto Takuma, Shirahata Nakao, Iwata Yoshinori, Okabe Yoshihiro, Hara Kazuo, Hashimoto Yusuke, Kuwatani Masaki, Isayama Hiroyuki, Fujimori Nao, Masamune Atsushi, Hatamaru Keiichi, Shimokawa Toshio, Okazaki Kazuichi, Takeyama Yoshifumi, Yamaue Hiroki . 超音波内視鏡ガイド下膵臓腫瘍組織採取後の穿刺経路播種　日本で行った全国調査(Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: Nationwide survey in Japan) . Digestive Endoscopy34 ( 7 ) 1442 - 1455 2022.11

Language：English Publisher：John Wiley & Sons Australia, Ltd

原発膵臓腫瘍に対する超音波内視鏡ガイド下組織採取(EUS-TA)後の穿刺経路播種(NTS)の現状を、日本の全国調査を基に明らかにした。EUS-TA後に膵臓腫瘍の外科的切除を施行された患者12109例を対象に、NTSの全発生率を調査した。また当該患者を、膵管腺癌(PDAC)とその他の膵臓腫瘍群、PDACに対する経胃的および経十二指腸的EUS-TAを行った患者群に分け、播種発生率を比較した。さらにNTS患者の特徴と予後も評価した。NTSの全発生率は0.330%で、PDAC患者で有意に高かった。NTSは、経胃的EUS-TA施行患者の0.857%で観察されたが、経十二指腸的EUS-TA施行患者では観察されなかった。PDACのEUS-TA後にNTSを発生した患者38例(男性23例、女性15例、年齢中央値71歳)では、36例の原発腫瘍が膵体および膵尾部に位置し、EUS-TAからNTSの発生まで時間中央値は19.3ヵ月、生存期間中央値は44.7ヵ月であった。またNTSの97.4%が胃壁にあり、65.8%が切除された。患者生存率は、NTS切除非施行患者よりもNTS切除施行患者の方が有意に長かった。NTSは経胃的EUS-TA後のPDAC患者の約0.9%で検出されたが、経十二指腸的EUS-TA施行患者では検出されなかった。

Yokoyama S., Iwaya H., Akahane T., Hamada T., Higashi M., Hashimoto S., Tanoue S., Ohtsuka T., Ido A., Tanimoto A. . Sequential evaluation of MUC promoter methylation using next-generation sequencing-based custom-made panels in liquid-based cytology specimens of pancreatic cancer . Diagnostic Cytopathology50 ( 11 ) 499 - 507 2022.11

Language：Japanese Publisher：Diagnostic Cytopathology

Background: As liquid-based cytology (LBC) specimens preserve high-quality DNA, clinical sequencing of LBC specimens using next-generation sequencing (NGS) is becoming a common strategy. This study aimed to evaluate the feasibility of NGS-based custom-made panels for evaluating MUC promoter methylation in LBC specimens. Methods: Thirty-one patients with pancreatic cancer were enrolled in the study. Cancer tissue samples were obtained using endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB). LBC, formalin-fixed paraffin-embedded (FFPE), and fresh frozen specimens were prepared for DNA extraction after pathological diagnosis. These specimens were then subjected to NGS analysis using custom-made cancer gene screening and methylation panels comprising 28 cancer-related genes and 13 gene promoter regions, including MUC1, MUC2, and MUC4. Results: The success rate of NGS using the cancer gene panel was comparable among the LBC, FFPE, and frozen specimens, and the presence of cancer cell-derived somatic mutations in each specimen was confirmed. The specimens were then tested using a methylation panel that revealed the sequential methylation status of CpG islands located in the promoter regions of MUC genes. The methylation status results obtained from LBC specimens were almost comparable with those from FFPE and frozen specimens. Conclusions: MUC and other gene methylation analyses using an NGS-based panel were successfully performed in residual LBC specimens obtained by EUS-FNA/FNB. Therefore, this approach provides an alternative source of molecular tests for gene mutations and methylation, especially in the pancreatic cancers, which are often unresectable and unsuitable for obtaining FFPE specimens.

DOI： 10.1002/dc.25022

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Maeda H., Sasaki F., Kabayama M., Iwaya H., Komaki Y., Arima S., Tanoue S., Hashimoto S., Kanmura S., Miyashita K., Ohori J., Yamashita M., Ido A. . Efficacy of endoscopic ultrasonography in evaluating tumor thickness in patients with superficial pharyngeal carcinoma: A pilot study . Auris Nasus Larynx49 ( 3 ) 495 - 503 2022.6

Language：Japanese Publisher：Auris Nasus Larynx

Objectives: A histopathological tumor thickness of ≥1000 μm has been reported as one of many risk factors for recurrent lymph node metastasis in superficial pharyngeal cancer (SPC). However, methods for assessing this risk factor preoperatively have not yet been established. Hence, the current study aimed to evaluate the efficacy of endoscopic ultrasonography (EUS) in measuring tumor thickness preoperatively in patients with SPC. Methods: This single-center retrospective study included 44 consecutive patients with 47 lesions who underwent endoscopic submucosal dissection (ESD). Prior to surgery, EUS examination was performed while under general anesthesia. Further, microvascular irregularity in the target lesion was evaluated using the Japan Esophageal Society (JES) magnification endoscopic classification system. Results: A significant correlation was noted between histopathological and EUS tumor thickness (Spearman's correlation r == 0.879, p < 0.001). In tumors ≥1000 µm thick on histopathology, the cutoff value for EUS tumor thickness was 2.6 mm, and the following values were obtained: sensitivity, 100%; specificity, 81.8%; positive predictive value (PPV), 70%; negative predictive value (NPV), 100%; and accuracy, 87.2%. In B2 lesions ≥1000-μm thick, the following values were obtained: sensitivity, 85.7%; specificity, 90.9%; PPV, 80%; NPV, 93.8%; and accuracy, 89.4%. The diagnostic accuracy rate of combined EUS and the JES magnifying endoscopic classification system was 95.7%. Conclusions: Tumor thickness assessed using EUS was effective in diagnosing histopathological tumor thickness of ≥1000 μm. The combined use of EUS and the JES magnifying endoscopic classification system may be useful for assessing preoperative risk factors for lymph node metastasis in SPC.

DOI： 10.1016/j.anl.2021.11.003

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Maeda Hidehito, Sasaki Fumisato, Kabayama Masayuki, Iwaya Hiromichi, Komaki Yuga, Arima Shiho, Tanoue Shiroh, Hashimoto Shinichi, Kanmura Shuji, Miyashita Keiichi, Ohori Junichiro, Yamashita Masaru, Ido Akio . 咽頭表在癌患者での腫瘍厚評価における超音波内視鏡検査の有効性　パイロット試験(Efficacy of endoscopic ultrasonography in evaluating tumor thickness in patients with superficial pharyngeal carcinoma: A pilot study) . Auris・Nasus・Larynx49 ( 3 ) 495 - 503 2022.6

Language：English Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会

咽頭表在癌では腫瘍の厚さがリンパ節転移再発の危険因子の一つであることが報告されている。その厚さを術前に測定する目的で超音波内視鏡検査(EUS)が示す有用性を評価した。2010年12月～2018年3月に当院で咽頭表在癌に対し内視鏡的粘膜下層剥離術を施行し、その直前に全身麻酔下でEUSも実施していた連続患者44名(男性43名、平均67.8±8.7歳)の47病変を組み入れた。EUSで測定した腫瘍厚と、術後、病理組織学的に評価された腫瘍厚とは有意に相関していた(Spearmanの相関係数r=0.88、p<0.001)。病理評価の厚が1000μm以上であることの予測に最適となるEUS測定厚のカットオフ値を受信者動作特性(ROC)解析で求めたところ2.6mmと決定された。そのカットオフ値が示した感度は100%、特異度は82%、陽性的中率は70%、陰性的中率は100%、精度は89%となった。さらに日本食道学会の拡大内視鏡分類システムをEUSと組み合わせて使用した場合、その診断精度は96%となった。EUS評価による腫瘍厚は、病理組織学的計測での腫瘍厚が1000μm以上であることを診断するのに有効であった。咽頭表在癌に対しEUSと拡大内視鏡分類システムを併用すれば、リンパ節転移再発の術前危険因子の評価に有用であると考えられた。

Komaki Y., Kanmura S., Yutsudo K., Kuwazuru K., Komaki F., Tanaka A., Maeda H., Arima S., Tanoue S., Sasaki F., Hashimoto S., Horiuchi M., Ido A. . Clinical features of obscure gastrointestinal bleeding undergoing capsule endoscopy: A retrospective cohort study . PLoS ONE17 ( 3 March ) e0265903 2022.3

Language：Japanese Publisher：PLoS ONE

Background Capsule endoscopy has been widely used to investigate obscure gastrointestinal bleeding (OGIB) in the small intestine since its approval in 2001. However, the clinical features of OGIB remain unclear. Aim We retrospectively examined the clinical features and risk factors of OGIB in patients who underwent capsule endoscopy in our hospital. Methods We included 420 of the 431 patients who underwent capsule endoscopy from June 2014 to May 2021, in whom the small intestine could be observed. We retrospectively compared the clinical features and treatment of OGIB cases, with or without active small bowel bleeding (n = 173), with other cases (n = 247). Patient sex, age, diabetes mellitus, and heart failure histories were matched for the analysis. Results The male/female ratio was 247/173 and the average age was 51.54 years. In multivariate analysis, the use of direct oral anticoagulants was significant (P = 0.016), and vascular lesions (P = 0.018) were observed in OGIB cases. When OGIB cases with and without active small bowel bleeding were compared, serum albumin level was lower in cases with active bleeding (P = 0.031). When treatment of OGIB cases were compared, those without vascular lesions could be treated conservatively (P = 0.0047). In the 1:1 propensity score matching analysis, serum creatinine level was elevated in cases of active bleeding (P = 0.029), and cases without vascular lesions were treated conservatively (P = 0.010). Conclusions Use of direct oral anticoagulants is frequently associated with OGIB. OGIB patients without vascular lesions may be treated conservatively.

DOI： 10.1371/journal.pone.0265903

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橋元慎一, 柿原敦子, 児島一成, 松岡慧, 荒木紀匡, 樋之口真, 有馬志穂, 田ノ上史郎, 井戸章雄 . 特集内視鏡的乳頭切除術まるわかり [各論] EP後の晩期偶発症とその治療 . 消化器内視鏡34 ( 1 ) 109 - 114 2022.1

Tanoue S., Kanmura S., Hinokuchi M., Arima S., Sasaki F., Hashimoto S., Ido A. . Role of apoptosis inhibitor of macrophages in patients with IgG4-related disease/autoimmune pancreatitis and the clinical characteristics associated with this condition . Biomedical Reports17 ( 4 ) 82 2022

Language：Japanese Publisher：Biomedical Reports

Type 1 autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related disease (IgG4-RD) and is a unique chronic inflammatory disease characterized by fibrosis. IgG4-RD is caused by an autoimmune mechanism that mimics malignant tumors and inflammatory disorders. Apoptosis inhibitor of macrophages (AIM) can function as a biomarker of autoimmune or inflammatory diseases with tissue fibrosis, including in inflammatory bowel disease and chronic liver disease. Therefore, the aim of the present study was to clarify the role of serum AIM levels and the clinical characteristics of patients with IgG4-RD and AIP. For this purpose, serum AIM concentrations were assessed using ELISA and the association between AIM and the laboratory and clinical data from patients with IgG4-RD/AIP, patients with pancreatic cancer (PC) and healthy controls (HCs), was determined. The results demonstrated that the serum AIM concentrations were not associated with the laboratory data. However, the serum AIM levels were significantly elevated in patients with AIP compared with the HCs and patients with PC. Furthermore, the serum AIM levels significantly decreased following steroid therapy in patients with AIP who were in remission. Overall, the present study demonstrates that serum AIM levels may be a potentially useful biomarker for the differential diagnosis of AIP and for evaluating the therapeutic reactivity of affected patients.

DOI： 10.3892/br.2022.1565

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Kozono M., Tanoue S., Kiyama K., Jikuya K., Kawahira M., Hinokuchi M., Iwaya H., Arima S., Hashimoto S., Hiwatashi K., Fukuda Y., Sakoda M., Higashi M., Tokushige K., Ido A. . A case of immunoglobulin G4-related sclerosing mesenteritis without other organ involvement . Clinical Journal of Gastroenterology14 ( 5 ) 1411 - 1418 2021.10

Language：Japanese Publisher：Clinical Journal of Gastroenterology

A 64-year-old man presented to our hospital with abdominal pain and 4–5 episodes of watery diarrhea per day for 2 months. Abdominal ultrasound examination revealed a mass in the peritoneal cavity, and computed tomography showed a 13.4 cm mass in the mesentery and a 3 cm mass in the mesocolon. The patient underwent laparoscopic partial resection for diagnosis. Microscopically, abundant fibrosis and numerous immunoglobulin (Ig) G4-positive plasma cells were observed. The serum level of IgG4 was 665 mg/dl postoperatively. These findings suggested that the lesion was consistent with IgG4-related sclerosing mesenteritis. Oral steroids resulted in rapid disappearance of symptoms and a decrease in masses. Recently, sclerosing mesenteritis are reported as IgG4-related disease or mimicking IgG4-related disease but multiple lesions rarely occur in the same organ. We report a case of IgG4-related sclerosing mesenteritis with multiple lesions without involvement of other organs, such as the pancreas and salivary glands.

DOI： 10.1007/s12328-021-01451-1

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PubMed

Kozono Masaya, Tanoue Shiroh, Kiyama Kanna, Jikuya Kenichi, Kawahira Machiko, Hinokuchi Makoto, Iwaya Hiromichi, Arima Shiho, Hashimoto Shinichi, Hiwatashi Kiyokazu, Fukuda Yoshio, Sakoda Masahiko, Higashi Michiyo, Tokushige Koichi, Ido Akio . 他臓器侵襲を伴わない免疫グロブリンG4関連硬化性腸間膜炎の1例(A case of immunoglobulin G4-related sclerosing mesenteritis without other organ involvement) . Clinical Journal of Gastroenterology14 ( 5 ) 1411 - 1418 2021.10

Language：English Publisher：シュプリンガー・ジャパン(株)

症例は64歳男性で、2ヵ月前から臍部周辺の腹痛と毎週4～5回の水様便を呈して当院を受診した。身体所見では腹部は軟性で軽度圧痛があり、頻回な腸管運動がみられた。また、臨床検査で軽度貧血、CRPの軽度上昇、可溶性IL-2の増加が認められた。腹部超音波検査にて腹腔内に10cm大の腫瘤が検出され、造影CTでは上腸間膜と横行結腸間膜に軟部組織腫瘤を認め、多発性の小結節が腫瘤周囲に存在していた。このほか、MRI検査にてT1強調像で低信号、脂肪抑制T2強調像で軽度高信号を呈する上腸間膜腫瘤が認められた。なお、造影CTでは他臓器侵襲は確認されず、PET-CTは施行しなかった。腹腔鏡アプローチにて病理診断を行ったところ、術中所見では小腸間膜に腫瘍を認め腹膜腫瘤を形成しており可動性に乏しかった。腫瘍末梢側に多数の黄色結節がみられ、術中迅速病理検査で非定型細胞が検出された。組織診では多量のIgG4陽性形質細胞が中隔に観察され、IgG4関連硬化性腸間膜炎を示唆する所見であった。経口ステロイド療法としてプレドニゾロン0.5mg/kgを開始したところ、下痢と腹部症状は急速に改善し、1ヵ月後には完全消失が得られた。治療開始6ヵ月後、症状の再燃や腫瘤の再増殖は認めていない。

Iwaya H, Kojima I, Hinokuchi M, Hashimoto S, Tanoue S, Kanmura S, Ido A . Novel biliary stenting with an antireflux system for distal biliary obstruction in a patient with a surgically altered anatomy. . Endoscopy international open9 ( 10 ) E1561 - E1562 2021.10

Kuwatani M., Kawakubo K., Sugimori K., Inoue H., Kamada H., Ishiwatari H., Kato S., Iwashita T., Yoshida M., Hashimoto S., Itonaga M., Mizukami Y., Nomura Y., Katanuma A., Sakamoto N. . Trial protocol: A randomised controlled trial to verify the non-inferiority of a partially covered self-expandable metal stent to an uncovered self-expandable metal stent for biliary drainage during neoadjuvant therapy in patients with pancreatic cancer with obstructive jaundice (PUN-NAC trial) . BMJ Open11 ( 7 ) e045698 2021.7

Language：Japanese Publisher：BMJ Open

Introduction Neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy (NAC/NACRT) for resectable/borderline resectable pancreatic cancers was recently performed to improve clinical outcomes and led to good results, although it remains controversial whether NAC/NACRT is beneficial for resectable pancreatic cancer. A few recent studies revealed longer patency and lower cost related to the stent occlusion of a metal stent than those of a plastic stent during NAC/NACRT. It also remains controversial which type of self-expandable metal stent (SEMS) is the most suitable for patients with resectable/borderline resectable pancreatic cancer during NAC/NACRT: an uncovered SEMS (USEMS), a fully covered SEMS (FCSEMS) or a partially covered SEMS (PCSEMS). So far, two randomised controlled trials indicated that a USEMS and an FCSEMS were similar in preoperative stent dysfunction and adverse event rate. Thus, we aimed to verify the non-inferiority of a PCSEMS to a USEMS in this multicentre randomised controlled trial. Methods and analysis We designed a multicentre randomised controlled trial, for which we will recruit 100 patients with resectable/borderline resectable pancreatic cancer and distal biliary obstruction scheduled for NAC/NACRT from 13 high-volume institutions. Patients will be randomly allocated to the PCSEMS group or USEMS group. The primary outcome measure is the preoperative biliary event rate. Data will be analysed after completion of the study. We will calculate the 95% CIs of the incidence of preoperative biliary events in each group and analyse whether the difference between them is within the non-inferiority margin (10%). Ethics and dissemination This study has been approved by the institutional review board of Hokkaido University Hospital. The results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. Trial registration number UMIN000041737; jRCT1012200002.

DOI： 10.1136/bmjopen-2020-045698

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Taguchi H., Otsuka T., Shimokawa M., Arima S., Hashimoto S., Ido A., Koga F., Ueda Y., Nakazawa J., Komori A., Otsu S., Fukahori M., Makiyama A., Honda T., Shibuki T., Mizuta T., Mitsugi K., Nio K., Ide Y., Ureshino N., Shirakawa T. . Gemcitabine plus nanoparticle albumin-bound paclitaxel versus FOLFIRINOX for recurrent pancreatic cancer after resection . Anticancer Research41 ( 7 ) 3573 - 3582 2021.7

Language：Japanese Publisher：Anticancer Research

Background/Aim: The aim of the study was to evaluate gemcitabine plus nanoparticle albumin-bound paclitaxel (GnP) and FOLFIRINOX for recurrent pancreatic cancer (rPC) after resection. Patients and Methods: Forty-four patients with rPC and 211 with de novo metastatic pancreatic cancer (mPC) who received GnP or FOLFIRINOX as first-line chemotherapy were retrospectively analyzed. Results: On crude analysis, the median overall survival (OS) was significantly longer in the rPC group than in the mPC group (14.0 vs. 10.6 months, respectively; p=0.02). However, the difference was not significant on adjusted analysis using the Cox proportional hazards model (adjusted p=0.90). Patients receiving FOLFIRINOX (n=10) and GnP (n=34) in the rPC group had comparable OS (medians, 12.2 vs. 14.4 months, respectively; p=0.82) even after adjusting for covariates using the Cox model (adjusted p=0.18). Conclusion: The outcomes of patients in the rPC and mPC groups were comparable following chemotherapy. Both FOLFIRINOX and GnP may be reasonable options for treating rPC.

DOI： 10.21873/anticanres.15145

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PubMed

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