Details of a Researcher - YOSHII Shinji

Papers - YOSHII Shinji

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Hybrid Endoscopic Resection With Endo-knife and Snare for Colorectal Lesions: A Systematic Review and Meta-analysis

Shinji Yoshii, Takefumi Kikuchi, Yuki Hayashi, Masahiro Nojima, Hiro-o Yamano, Hiroshi Nakase

Techniques and Innovations in Gastrointestinal Endoscopy ( Elsevier BV ) 25 ( 2 ) 135 - 145 2023 [Refereed]

Efficacy and Safety of Complete Endoscopic Resection of Colorectal Neoplasia Using a Stepwise Endoscopic Protocol with SOUTEN, a Novel Multifunctional Snare.

Shinji Yoshii, Marina Kubo, Mio Matsumoto, Takefumi Kikuchi, Yasunari Takakuwa

Clinical endoscopy 53 ( 2 ) 206 - 212 2020.03 [Refereed] [International journal]

BACKGROUND/AIMS: A multifunctional snare SOUTEN has a sharp tip at the top of the snare loop that enables incision of the mucosa, dissection of the submucosal layer, and snaring of lesion. This study assessed the efficacy and safety of complete endoscopic resection of colorectal neoplasia using SOUTEN. METHODS: We analyzed the rates of gross en bloc resection and complete resections of 108 consecutive tumors from 69 patients resected by precutting endoscopic mucosal resection (precutting), hybrid endoscopic submucosal dissection (hybrid), or conventional endoscopic submucosal dissection (conventional) using SOUTEN. RESULTS: Out of the 108 tumors, 50 were resected by precutting, 27 were resected by hybrid after attempting precutting, and the remaining 31 were resected by conventional after attempting precutting and hybrid resections. The median tumor sizes were 14.5 mm for precutting, 16.4 mm for hybrid, and 21.1 mm for conventional. The success rate of gross en bloc resection and histological complete resection were 100% and 94.0% for precutting, 96.4% and 96.4% for hybrid, and 100% and 100% for conventional method, respectively. No procedure-related complication occurred. CONCLUSION: By using SOUTEN, precutting and hybrid were successfully performed on 10-30 mm tumors with a shorter procedure time than conventional without major complications.

Validity of endoscopic features for the diagnosis of Helicobacter pylori infection status based on the Kyoto classification of gastritis.

Yoshii S, Mabe K, Watano K, Ohno M, Matsumoto M, Ono S, Kudo T, Nojima M, Kato M, Sakamoto N

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 32 ( 1 ) 74 - 83 2019.07 [Refereed] [International journal]

OBJECTIVES: Evaluation of Helicobacter pylori infection status (non-infection, past infection, current infection) has become important. This study aimed to determine the usefulness of the Kyoto classification of gastritis for diagnosing H. pylori infection status by endoscopy. METHODS: In this prospective study, 498 subjects were recruited. Seven well-experienced endoscopists blinded to the history of eradication therapy performed the examinations. Endoscopic findings were assessed according to the Kyoto classification of gastritis: diffuse redness, regular arrangement of collecting venules (RAC), fundic gland polyp (FGP), atrophy, xanthoma, hyperplastic polyp, map-like redness, intestinal metaplasia, nodularity, mucosal swelling, white and flat elevated lesion, sticky mucus, depressive erosion, raised erosion, red streak, and enlarged folds. We established prediction models according to a machine learning procedure and compared them with general assessment by endoscopists using the Kyoto classification of gastritis. RESULTS: Significantly higher diagnostic odds were obtained for RAC (32.2), FGP (7.7), and red streak (4.7) in subjects with non-infection, map-like redness (12.9) in subjects with past infection, and diffuse redness (26.8), mucosal swelling (13.3), sticky mucus (10.2) and enlarged fold (8.6) in subjects with current infection. The overall diagnostic accuracy rate was 82.9% with the Kyoto classification of gastritis. The diagnostic accuracy of the prediction model was 88.6% for the model without H. pylori eradication history and 93.4% for the model with eradication history. CONCLUSIONS: The Kyoto classification of gastritis is useful for diagnosing H. pylori infection status based on endoscopic findings. Our prediction model is helpful for novice endoscopists. (UMIN000016674).

Factors Associated With Risk for Colorectal Cancer Recurrence After Endoscopic Resection of T1 Tumors

Shinji Yoshii, Masanori Nojima, Katsuhiko Nosho, Saori Omori, Takaya Kusumi, Hiroyuki Okuda, Hiroyuki Tsukagoshi, Masahiro Fujita, Hiroyuki Yamamoto, Masao Hosokawa

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY ( ELSEVIER SCIENCE INC ) 12 ( 2 ) 292 - + 2014.02 [Refereed] [International journal]

BACKGROUND & AIMS: More information is needed on the long-term outcomes of patients who undergo endoscopic resection of colorectal tumors. We evaluated recurrence of colorectal cancer (CRC) after endoscopic resection or a combination of endoscopic research and surgery for T1 colorectal tumors. METHODS: We conducted a retrospective study of 389 patients with T1 CRC treated by endoscopic resection from January 1989 to December 2008 in Sapporo, Japan. We compared outcomes between patients who underwent subsequent surgery (ER + SURG, n = 205) and those who did not (ER only, n = 184) and statistically adjusted baseline differences between the groups according to the propensity scores. RESULTS: There was almost no risk of cancer recurrence among patients without indications for surgery recommended by the Japanese Society for Cancer of the Colon and Rectum (these indications include tumors with vertical margins, deep submucosal invasion, lymphatic or venous invasion, poor differentiation, or high-grade budding). Among patients with indications for surgery, the cumulative risks of recurrence (CRRs) were 3.7% in the ER + SURG group and 20.1% in the ER only group (P = .001). However, the patients with only deep submucosal invasion had a low CRR, even without surgery (2.3% in the ER + SURG group and 3.4% in the ER only groups, P = .867). In contrast, patients with indications for surgery other than deep submucosal invasion (high-risk patients) had much better outcomes when they also underwent surgery (CRRs: 5.8% in the ER + SURG group vs 58.0% in the ER only group, P < .001). CONCLUSIONS: On the basis of a retrospective study of patients who underwent endoscopic resection for T1 CRC, those with tumors with only submucosal invasion are at low risk for cancer recurrence. However, patients with other high-risk tumor features have greater risks for cancer recurrence and benefit from subsequent surgery.

A rare case of delayed duodenal perforation due to an over-the-scope clip.

Yujiro Kawakami, Shinji Yoshii, Masahiro Taniguchi, Yoshiharu Masaki, Taro Sugawara, Yasutoshi Kimura, Hiroshi Nakase

Endoscopy 56 ( S 01 ) E331-E333 2024.12 [International journal]

Clinical performance of fecal calprotectin, lactoferrin, and hemoglobin for evaluating the disease activity of IBD and detecting colorectal tumors.

Tsukasa Yamakawa, Takakazu Miyake, Yoshihiro Yokoyama, Tomoe Kazama, Yuki Hayashi, Daisuke Hirayama, Shinji Yoshii, Hiro-O Yamano, Satoshi Takahashi, Hiroshi Nakase

JGH open : an open access journal of gastroenterology and hepatology 8 ( 6 ) e13077 2024.06 [International journal]

BACKGROUND AND AIM: Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all-in-one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. METHODS: In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. RESULTS: Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. CONCLUSION: Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.

【内視鏡治療後サーベイランスの現状-異時性多発病変を中心に】15ヵ月で急速な発育進展を来したと考えるSSL由来進行大腸癌の1例

山川司, 山野泰穂, 中村隼人, 三宅高和, 菅原太郎, 吉井新二, 長谷川匡, 仲瀬裕志

胃と腸 ( (株)医学書院 ) 59 ( 6 ) 883 - 887 2024.06

＜文献概要＞患者は80歳代,男性.肝腫瘤の精査目的のために当科に紹介され受診となり肝細胞癌と診断された.貧血があり大腸内視鏡検査を行ったところ,上行結腸に5mm大の0-IIa型病変を認めSSLと診断した.その後,高齢のため肝細胞癌は経過観察となっていたが,初回の内視鏡検査から15ヵ月後に血便を生じ,再度大腸内視鏡検査を行ったところ,上行結腸に進行大腸癌を認めた.病変の裾野には鋸歯状と考えられる開大した腺管構造を認め,腫瘍の遺伝子変異解析ではBRAF変異陽性であった.病理組織学的にも大腸鋸歯状病変由来の癌として矛盾せず,本症例は15ヵ月の経過で増大したSSL由来進行大腸癌と考えられた.

【大腸内視鏡治療-CP/EMR/ESD/Underwater関連手技の今】Precutting EMR/Hybrid ESD

吉井新二, 三宅高和, 山川司, 山野泰穂, 仲瀬裕志

臨床消化器内科 ( (株)日本メディカルセンター ) 39 ( 6 ) 655 - 662 2024.05

＜文献概要＞ESDの技術的困難性とEMRのサイズ制限を克服して一括切除をするために,粘膜切開・粘膜下層剥離とスネア切除を組み合わせたprecutting EMR/hybrid ESDは有用な手技である.Precutting EMRの適応は,スネアが滑って一括切除が難しい20mm程度までのEMR適応病変で,hybrid ESDは,スネアのサイズ制限から,30～40mm程度までのESD適応病変と考える.スネアリングする際は,粘膜下層が十分にトリミングされて深い溝がつくられていることが重要である.スネアリング時に病変部が落ち込んでくる場合は,分割切除になりやすいため,粘膜下層剥離を追加することが重要である.

ESD後穿孔における縫縮困難例への対策

山川司, 吉井新二, 秋田浩太朗, 三宅高和, 川上裕次郎, 柾木喜晴, 山野泰穂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 66 ( Suppl.1 ) 1019 - 1019 2024.04

内視鏡用軟性持針器を用いた内視鏡的手縫い縫合の導入経験

山川司, 吉井新二, 三宅高和, 山野泰穂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 66 ( 3 ) 286 - 292 2024.03

早期消化管癌に対する内視鏡治療後の粘膜欠損部に対して,後藤らにより内視鏡用軟性持針器と逆戻り防止弁付き縫合糸を用いた内視鏡的手縫い縫合法(endoscopic hand-suturing;EHS)が開発された.当科にて内視鏡用軟性持針器を用いてEHSを施行した5症例(胃3症例,大腸2症例)を検証した.EHSは全例で完遂でき縫合時間も既報と遜色ない結果であった.導入初期には胃症例で創部離開を1例認めたものの,全例で治療後の合併症は認めなかった.各病変の縫縮に要した時間は切除時間と同程度であったが,経験症例数が増えるに従って1針あたりの縫合時間は短縮傾向であった.EHSは様々な臨床応用が期待されるが,新規導入にあたってはトレーニングモデルを活用し十分な準備が必要である.(著者抄録)

An Analysis of Delayed Bleeding in Cases of Colorectal Endoscopic Submucosal Dissection Due to Types of Direct Oral Anticoagulants in Japan.

Naohisa Yoshida, Yoshikazu Hayashi, Daichi Togo, Shiro Oka, Kazunori Takada, Shusei Fukunaga, Yoshinori Morita, Takemasa Hayashi, Kazuhiro Kozuka, Yosuke Tsuji, Takashi Murakami, Takeshi Yamamura, Yoriaki Komeda, Yoji Takeuchi, Kensuke Shinmura, Hiroko Fukuda, Shinji Yoshii, Shoko Ono, Shinichi Katsuki, Kazumasa Kawashima, Daiki Nemoto, Hiroyuki Yamamoto, Yutaka Saito, Naoto Tamai, Aya Iwao, Yuki Itoi, Shigetsugu Tsuji, Yoshikazu Inagaki, Yutaka Inada, Koichi Soga, Daisuke Hasegawa, Takaaki Murakami, Hiroyuki Yoriki, Kohei Fukumoto, Takayuki Motoyoshi, Yasuki Nakatani, Yasushi Sano, Mikitaka Iguchi, Shigehiko Fujii, Hiromitsu Ban, Keita Harada, Koichi Okamoto, Hitoshi Nishiyama, Fumisato Sasaki, Kazujhiro Mizukami, Takashi Shono, Ryo Shimoda, Tadashi Miike, Naoyuki Yamaguchi

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 22 ( 2 ) 271 - 282 2024.02 [International journal]

BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.

Systemic Mastocytosis Observed by Image-Enhanced Endoscopy.

Ryota Seto, Shinji Yoshii, Tomoe Kazama, Tsukasa Yamakawa, Shintaro Sugita, Hiro-O Yamano, Hiroshi Nakase

The American journal of gastroenterology 118 ( 12 ) 2114 - 2114 2023.12 [International journal]

Jejunal Angiodysplasia in an Elderly Patient with Aortic Stenosis: Significance of Von Willebrand Factor as an Etiologic Factor.

Toshiyuki Kubo, Shinji Yoshii, Hiro-O Yamano, Masato Saito, Koichi Sakata, Shintaro Sugita, Tadashi Hasegawa, Hisanori Horiuchi, Hiroshi Nakase

Internal medicine (Tokyo, Japan) 62 ( 14 ) 2059 - 2062 2023.07 [Domestic journal]

Heyde's syndrome is a disease in which patients with aortic stenosis (AS) bleed from angiodysplasia. An 80-year-old woman with a history of severe AS was referred to our hospital with melena and anemia. The patient underwent jejunal resection after repeated blood transfusions. A pathological examination revealed angiodysplasia, and the patient's plasma lacked high-molecular-weight von Willebrand factor (VWF) multimers, leading to the diagnosis of Heyde's syndrome. The patient underwent transcatheter aortic valve implantation (TAVI) one year after the diagnosis, and the VWF index recovered. This is a valuable case in which the pathological analysis of angiodysplasia associated with Heyde's syndrome was possible.

Red blood cell distribution width as a novel marker for predicting bleeding after endoscopic resection for early gastric cancer.

Takada Yumemi, Shinji Yoshii, Tsukasa Yamakawa, Yuki Hayashi, Takakazu Miyake, Yoshihiro Yokoyama, Gota Sudo, Kei Mitsuhashi, Masanori Nojima, Hiro-O Yamano, Hiroshi Nakase

DEN open 3 ( 1 ) e123 2023.04 [International journal]

OBJECTIVES: Endoscopic resection (ER) is a minimally invasive treatment for early gastric cancer (EGC); however, there is a high occurrence of bleeding. This study aimed to clarify the significance of red blood cell distribution width (RDW) as a predictive risk factor for bleeding after ER for EGC. METHODS: We conducted a retrospective study based on data for patients who underwent ER for EGC from 2019 to 2021. This study included 79 lesions in 54 patients who underwent ER for EGC. The primary outcome was the association between RDW before ER and bleeding within 28 days of treatment. Receiver operating characteristic (ROC) curves were constructed, wherein areas under the curve (AUCs) and 95% confidence intervals were calculated to compare the discriminatory power of RDW for predicting bleeding. RESULTS: Endoscopic submucosal dissection was used as the resection method for 73 lesions, whereas endoscopic mucosal resection was used for six lesions. En bloc resection was performed in all cases. There were no cases of perforation; however, bleeding after ER occurred in five cases (9.3%). ROC curve analysis of bleeding after ER showed that the AUC was 0.843 with a good diagnostic performance. When the cut-off value of RDW was set at 14.4%, sensitivity and specificity were 80% and 85.7%, respectively. There was a bleeding rate of 36.4% (4/11) at an RDW of ≥14.4%, which was significantly higher than that of 2.3% (1/43) at an RDW of <14.4%. CONCLUSION: RDW can be a predictor of bleeding risk after ER for EGC.

An older patient with active ulcerative colitis and coronavirus disease 2019 (COVID-19) pneumonia successfully treated with the combination of anti-TNFα therapy and azathioprine.

Tsukasa Yamakawa, Keisuke Ishigami, Sae Ohwada, Tomoe Kazama, Daisuke Hirayama, Shinji Yoshii, Hiro-O Yamano, Hiroshi Nakase

Clinical journal of gastroenterology 16 ( 2 ) 187 - 192 2023.04 [Domestic journal]

A 77-year-old patient with ulcerative colitis (UC) was transferred to our department because of worsening bloody diarrhea and abdominal pain, which was consistent with a UC flare. Two days after admission, she complained of cough and high fever. The polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive, and a computed tomography showed pneumonia in the left lobe, consistent with coronavirus disease 2019 (COVID-19) pneumonia. However, frequent bloody diarrhea and abdominal pain due to the UC flare persisted; therefore, an additional immunosuppressive agent needed to be considered. We initiated infliximab biosimilar (IFX-BS), and her abdominal symptoms improved. However, they deteriorated after the second IFX-BS infusion. After confirming that the patient was negative for SARS-CoV-2 by PCR, we administered a combination of azathioprine and IFX-BS. The combination treatment improved her intestinal symptoms without worsening COVID-19 pneumonia. She has remained in remission for over a year since her discharge.

Immune-related colitis and pancreatitis treated with infliximab.

Sae Ohwada, Keisuke Ishigami, Yoshihiro Yokoyama, Tomoe Kazama, Yoshiharu Masaki, Mamoru Takahashi, Shinji Yoshii, Hiro-O Yamano, Hirofumi Chiba, Hiroshi Nakase

Clinical journal of gastroenterology 16 ( 1 ) 73 - 80 2023.02 [Domestic journal]

Patients with various cancers benefit from immune checkpoint inhibitors. However, immune checkpoint inhibitor-induced adverse events have also been reported, such as colitis. Prednisolone is the first-line treatment for immune-related adverse events, but second-line therapy for patients refractory to steroids has not been established. Furthermore, the inflammatory cytokine expression pattern in the intestinal mucosa of patients with steroid-refractory immune-related colitis remains unclear. We present the case of a 48-year-old man diagnosed with immune-related colitis and pancreatitis induced by pembrolizumab for advanced lung cancer. First, we administered 50 mg/day of prednisolone, and the patient's abdominal symptoms improved. However, the pancreatic enzyme levels did not return to normal. Furthermore, the patient's diarrhea worsened and hematochezia appeared at a 40 mg/day prednisolone dose. A mucosal cytokine analysis identified a low interleukin-10 messenger RNA level, which has been associated with a poor response to prednisolone. Thus, we administered 5 mg/kg of infliximab; the patient's diarrhea and hematochezia immediately improved, and the pancreatic enzyme levels returned to normal. Infliximab was administered three times every 2 weeks. After, the patient's colitis and pancreatitis did not recur. To our knowledge, this is the first report demonstrating the effectiveness of infliximab for immune-related colitis and pancreatitis.

Endoscopic full-thickness resection using an over-the-scope clip for colon cancer within a diverticulum.

Takakazu Miyake, Shinji Yoshii, Hiroshi Nakase

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 35 ( 1 ) e30-e32 2023.01 [International journal]

Extensive mucosal sloughing of the small intestine and colon in a patient with severe COVID-19.

Tsukasa Yamakawa, Keisuke Ishigami, Ayumu Takizawa, Yumemi Takada, Sae Ohwada, Yoshihiro Yokoyama, Tomoe Kazama, Daisuke Hirayama, Shinji Yoshii, Hiro-O Yamano, Rina Ohizumi, Naofumi Bunya, Taro Sugawara, Mitsuhiro Tsujiwaki, Shintaro Sugita, Satoshi Takahashi, Eichi Narimatsu, Hiroshi Nakase

DEN open 2 ( 1 ) e42 2022.04 [International journal]

Patients with coronavirus disease 2019 (COVID-19) primarily cause respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. The endoscopic characteristics of the GI tract in COVID-19 patients remain unclear. We herein report a 62-year-old male with severe COVID-19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO). Despite the improvement in his respiratory status, GI bleeding developed. Capsule endoscopy and colonoscopy revealed extensive mucosal sloughing in the lower intestinal tract. Additionally, we performed a comprehensive analysis of the mRNA expression levels of various proinflammatory cytokines in the intestinal mucosal tissues. The results suggested a significant elevation of IL-6, which could be involved in the pathophysiology of the GI involvement in COVID-19. Further investigation with more clinical data, including endoscopic findings and molecular analyses, will contribute to a comprehensive understanding of COVID-19-associated GI injury.

Artificial intelligence-assisted endoscopy changes the definition of mucosal healing in ulcerative colitis.

Hiroshi Nakase, Takehiro Hirano, Kohei Wagatsuma, Tadashi Ichimiya, Tsukasa Yamakawa, Yoshihiro Yokoyama, Yuki Hayashi, Daisuke Hirayama, Tomoe Kazama, Shinji Yoshii, Hiro-O Yamano

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 33 ( 6 ) 903 - 911 2021.09 [International journal]

The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of "mucosal healing (MH)" as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)-assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI-assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, "The road to an exact definition of MH in the treatment of UC has begun only now".

Novel injectable needle-type knife, ProKnife for colorectal endoscopic submucosal dissection.

Shinji Yoshii, Hiro-O Yamano, Hiroshi Nakase

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 33 ( 6 ) e137-e139 2021.09 [International journal]

Lynch症候群を背景とした多発微小大腸癌症例

柴田泰洋, 山野泰穂, 久保俊之, 吉井新二, 赤保内正和, 横山佳浩, 山川司, 風間友江, 山下健太郎, 能正勝彦, 須藤豪太, 山本英一郎, 鈴木拓, 杉田真太郎, 長谷川匡, 永塚真, 菅井有, 仲瀬裕志

日本大腸肛門病学会雑誌 ( (一社)日本大腸肛門病学会 ) 74 ( 5 ) 332 - 332 2021.05

【大腸鋸歯状病変の新展開】分類不能鋸歯状病変を由来としたTraditional serrated adenomaの癌化症例

山川司, 吉井新二, 市原真, 大和田紗恵, 柴田泰洋, 風間友江, 平山大輔, 久保俊之, 能正勝彦, 須藤豪太, 山本英一郎, 鈴木拓, 山野泰穂, 仲瀬裕志

胃と腸 ( (株)医学書院 ) 55 ( 13 ) 1631 - 1638 2020.12

＜文献概要＞患者は40歳代,女性.血便を主訴に近医を受診し,下部消化管内視鏡検査にて上部直腸(Ra)に径約35mmのLST-GMを認めた.本病変は辺縁に平坦部分を伴い複数の分葉構造を呈し,拡大所見では平坦部分は鋸歯状構造を伴ったII型様pitで構成されていたが,既存の分類には合致しない鋸歯状病変と考えられた.病変の大部分を占める中心の隆起部ではIV型pitを主体としcytological dysplasiaを疑った.病理組織像では平坦部の表層部分にわずかに鋸歯状構造は認めるが,深部はうねった管状腺管で腺腫様であり,免疫染色Ki-67では陽性細胞が散在し腺腫や既存の鋸歯状病変にも当てはまらない組織像であった.一方,隆起部では鋸歯状変化を呈するTSA様の領域と,絨毛状の形態をとりtubulovillous adenomaと考えられる領域が混在していた.また,隆起部の粘膜深部に細胞異型,構造異型が強く,腺管が密に増殖した領域があり,同部位でp53,Ki-67がびまん性の陽性を示しtub1相当の腺癌(Tis)と診断した.遺伝子解析では平坦部,隆起部いずれもKRAS変異陽性(G13D)で一連の病変と考えられた.本症例は内視鏡所見や免疫染色,遺伝子解析結果から既存の分類に当てはまらない鋸歯状病変を基盤として発育進展した病変と考え,ここに報告する.

分類不能鋸歯状病変を伴ったtraditional serrated adenoma癌化症例

山川司, 吉井新二, 市原真, 秋田浩太朗, 大和田紗恵, 横山佳浩, 柴田泰洋, 風間友江, 赤保内正和, 久保俊之, 仲地耕平, 能正勝彦, 山下健太郎, 須藤豪太, 山本英一郎, 鈴木拓, 山野泰穂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 62 ( Suppl.2 ) 2150 - 2150 2020.10

分類不能鋸歯状病変を伴ったtraditional serrated adenoma癌化症例

山川司, 吉井新二, 市原真, 秋田浩太朗, 大和田紗恵, 横山佳浩, 柴田泰洋, 風間友江, 赤保内正和, 久保俊之, 仲地耕平, 能正勝彦, 山下健太郎, 須藤豪太, 山本英一郎, 鈴木拓, 山野泰穂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 62 ( Suppl.2 ) 2150 - 2150 2020.10

SSA/P由来が示唆された横行結腸SM癌の一例

久保俊之, 山野泰穂, 中村友哉, 柴田泰洋, 山川司, 風間友江, 赤保内正和, 吉井新二, 山下健太郎, 須藤豪太, 山本英一郎, 鈴木拓, 永塚真, 菅井有, 杉田真太朗, 長谷川匡, 遠藤高夫, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 62 ( Suppl.1 ) 1327 - 1327 2020.08

横行結腸に発生したcytological dysplasiaを伴う分類困難な鋸歯状病変の1例

秋田浩太朗, 山野泰穂, 柴田泰洋, 久保俊之, 吉井新二, 横山佳浩, 風間友江, 三橋慧, 能正勝彦, 山下健太郎, 須藤豪太, 山本英一郎, 鈴木拓, 寺井琴美, 辻脇光洋, 長谷川匡, 永塚真, 菅井有, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 62 ( Suppl.1 ) 1265 - 1265 2020.08

Superficially serrated adenoma(SuSA)の発がんが観察された微小大腸癌の1例

柴田泰洋, 山野泰穂, 久保俊之, 吉井新二, 山下健太郎, 須藤豪太, 山本英一郎, 鈴木拓, 寺井琴美, 長谷川匡, 永塚真, 菅井有, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 62 ( Suppl.1 ) 1265 - 1265 2020.08

Acute progressing hepatic angiosarcoma: An autopsy case report.

Masaki Inoue, Mio Matsumoto, Yusuke Sakuhara, Yasunari Takakuwa, Shinji Yoshii, Nobuaki Akakura, Naoya Sakamoto

Radiology case reports 15 ( 8 ) 1403 - 1407 2020.08 [International journal]

A man in his 50s presented with pitting edema of both lower legs and abdominal distension as his chief complaint. His personal medical history and family history were unremarkable, except that he was a heavy drinker consuming 66 g of alcohol per day and a heavy smoker. Blood tests upon admission showed slight hepatic dysfunction, thrombocytopenia, jaundice, hypoalbuminemia, and decreased coagulability. Tumor marker tests showed elevated levels of CA19-9 and PIVKA-II. Contrast-enhanced computed tomography revealed enhancement of multiple masses predominantly in the right lobe of the liver in the early phase, followed by diffuse enhancement of the entire liver in the delayed phase. Hepatic arteriography demonstrated large hemangioma-like lesions corresponding to the masses revealed by computed tomography. That findings seemed to be cotton wool appearance. On magnetic resonance images, there were multiple mass-like lesions that showed homogeneous or heterogeneous low signal intensity on T1-weighted images, and clearly high signal intensity on T2-weighted images. The findings were atypical and no definite diagnosis could be made. Hepatic failure then rapidly worsened, and the patient died on hospital day 20. Autopsy led to the diagnosis of hepatic angiosarcoma.

Lynch症候群に合併した多発微小大腸癌の1例

柴田泰洋, 山野泰穂, 久保俊之, 吉井新二, 山下健太郎, 須藤豪太, 山本英一郎, 鈴木拓, 寺井琴美, 長谷川匡, 永塚真, 菅井有, 仲瀬裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 117 ( 臨増総会 ) A319 - A319 2020.07

Lynch症候群に合併した多発微小大腸癌の1例

柴田泰洋, 山野泰穂, 久保俊之, 吉井新二, 山下健太郎, 須藤豪太, 山本英一郎, 鈴木拓, 寺井琴美, 長谷川匡, 永塚真, 菅井有, 仲瀬裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 117 ( 臨増総会 ) A319 - A319 2020.07

Continuous Anticoagulation and Cold Snare Polypectomy Versus Heparin Bridging and Hot Snare Polypectomy in Patients on Anticoagulants With Subcentimeter Polyps: A Randomized Controlled Trial.

Takeuchi Y, Mabe K, Shimodate Y, Yoshii S, Yamada S, Iwatate M, Kawamura T, Hotta K, Nagaike K, Ikezawa N, Yamasaki T, Komeda Y, Asai S, Abe Y, Akamatsu T, Sakakibara Y, Ikehara H, Kinjo Y, Ohta T, Kitamura Y, Shono T, Inoue T, Ohda Y, Kobayashi N, Tanuma T, Sato R, Sakamoto T, Harada N, Chino A, Ishikawa H, Nojima M, Uraoka T, Madowazu, Study Group

Annals of internal medicine 171 ( 4 ) 229 - 237 2019.07 [Refereed] [International journal]

BACKGROUND: Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP). OBJECTIVE: To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps. DESIGN: Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355). SETTING: 30 Japanese institutions. PATIENTS: Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp. INTERVENTION: Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy. MEASUREMENTS: The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP). RESULTS: A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group. LIMITATION: An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously. CONCLUSION: Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP. PRIMARY FUNDING SOURCE: Japanese Gastroenterological Association.

Concise Commentary: Caution, Not Cauterization-Management of Post-ESD Colorectal Hemorrhage.

Yoshii S

Digestive diseases and sciences 64 ( 3 ) 888 - 889 2019.03 [Refereed] [International journal]

Usefulness of transabdominal ultrasonography for assessing ulcerative colitis: a prospective, multicenter study.

Kinoshita K, Katsurada T, Nishida M, Omotehara S, Onishi R, Mabe K, Onodera A, Sato M, Eto K, Suya M, Maemoto A, Hasegawa T, Yamamoto J, Mitsumori D, Yoshii S, Ono K, Sakamoto N

Journal of gastroenterology 54 ( 6 ) 521 - 529 2018.12 [Refereed] [Domestic journal]

BACKGROUND: Transabdominal ultrasonography (US) has been reported to be a useful tool for evaluating ulcerative colitis (UC) although with less well-established data than for Crohn's disease. This prospective multicenter study aimed to establish the usefulness of US compared with colonoscopy (CS) for assessing disease extent and activity of UC. METHODS: Altogether, 173 patients with UC were prospectively enrolled, among whom 156 were eligible for this study. All patients underwent US and CS within 2 days at five facilities. We divided the colon into six segments and examined each segment and the rectum using US and CS. US severity was graded 1-4 regarding bowel wall thickness, stratification, and ulceration. CS severity was also graded 1-4 according to Matts' endoscopic classification. Concordance between US and CS grades for all colonic segments was analyzed using kappa statistics. US and CS findings were also compared with the clinical disease activity index (CAI) and histological grade using Spearman's correlation coefficient. RESULTS: There was moderate concordance between US and CS grades in all colonic segments (weighted κ = 0.55, p < 0.001). Concordance was rated moderate for each colonic segment but only slight for the rectum. The US grade was significantly correlated with the CAI score (r = 0.40, p < 0.001) and histological grade (r = 0.35, p < 0.001). CONCLUSIONS: This prospective multicenter study showed moderate concordance between US and CS for assessing the disease activity of UC. Hence, US may be used more generally for evaluating UC in daily clinical practice.

Cold snare polypectomy technique is a procedure with a low bleeding risk

Shinji Yoshii, Mio Matsumoto

Digestive Endoscopy ( Blackwell Publishing ) 30 51 - 52 2018.04 [Refereed] [International journal]

Endoscopic management of colorectal tumors less than 10 mm in size: Current status and future perspectives in Japan from a questionnaire survey.

Toshio Uraoka, Shiro Oka, Shin Ichihara, Mineo Iwatate, Naoto Tamai, Takuji Kawamura, Yoji Takeuchi, Yuichi Mori, Shinji Yoshii, Shinichi Hashimoto, Shiaw Hooi Ho, Han-Mo Chiu

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 30 Suppl 1 36 - 40 2018.04 [Refereed] [International journal]

Safety of Cold Polypectomy for Colorectal Polyps in Patients on Antithrombotic Medication

Mio Matsumoto, Shinji Yoshii, Taku Shigesawa, Masayoshi Dazai, Manabu Onodera, Mototsugu Kato, Naoya Sakamoto

Digestion ( S. Karger AG ) 97 ( 1 ) 76 - 81 2018.03 [Refereed] [International journal]

Background: The cold polypectomy (CP) technique has been increasingly used in recent years. However, there have been few studies about post-polypectomy bleeding (PPB) in patients who underwent CP and who were on antithrombotic drugs. The objective of this study was to determine the safety of CP in patients on antithrombotic medication. Methods: The subjects were patients who underwent CP in our hospital between April 2014 and March 2016. PPB rates were examined in relation to the use of antithrombotic medication. Results: CP was performed to remove 2,466 polyps in 1,003 patients. There were 549 polyps (22.3%) in186 patients in the antithrombotic group and 1,917 polyps (77.7%) in 817 patients in the non-Antithrombotic group. PPB occurred in 0.55% (3/549) of patients in the antithrombotic group and in 0.10% (2/1,917) of patients in the non-Antithrombotic group, showing no significant difference (p = 0.07). Patients in the antithrombotic group in whom PPB occurred included 1 aspirin user with 1 polyp and 1 aspirin plus clopidogrel user with 2 polyps. No PPB occurred in patients on other antithrombotic agents or receiving heparin bridging. There was no significant difference between PPB rates in patients with small polyps (6-9 mm) in the antithrombotic and non-Antithrombotic groups, but there was a significant difference between PPB rates in the 2 groups for patients with diminutive group (1-5 mm). Conclusion: CP is a safe procedure even in patients on antithrombotic medication.

Two Cases of Chronic Gastritis with non-Helicobacter pylori Helicobacter Infection

Satoka Shiratori, Katsuhiro Mabe, Shinji Yoshii, Yasunari Takakuwa, Masaaki Sato, Masahiko Nakamura, Takahiko Kudo, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 55 ( 14 ) 1865 - 1869 2016 [Refereed] [Domestic journal]

Two men, 48 and 54 years of age, were referred for medical checkups without any particular symptoms. Upper gastrointestinal endoscopy showed a normal gastric body, but white marbled appearance in the lesser curvature of the gastric angle and antrum. Biopsy specimens revealed relatively long and tightly coiled organisms. The two patients were diagnosed as having non-Helicobacter pylori helicobacter (NHPH) infection according to the findings of pathological and quantitative reverse transcription-polymerase chain reaction (qRTPCR) analyses. After triple therapy (amoxicillin, clarithromycin, and rabeprazole), endoscopy showed an improvement of the white marbled lesions and biopsy specimens showed no NHPH. The white marbled appearance limited to the gastric angle and antrum may be a potential characteristic finding of NHPH-infected gastritis.

Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway

Miki Ito, Shinichi Kanno, Katsuhiko Nosho, Yasutaka Sukawa, Kei Mitsuhashi, Hiroyoshi Kurihara, Hisayoshi Igarashi, Taiga Takahashi, Mami Tachibana, Hiroaki Takahashi, Shinji Yoshii, Toshinao Takenouchi, Tadashi Hasegawa, Kenji Okita, Koichi Hirata, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki Yamamoto, Yasuhisa Shinomura

INTERNATIONAL JOURNAL OF CANCER ( WILEY-BLACKWELL ) 137 ( 6 ) 1258 - 1268 2015.09 [Refereed] [International journal]

Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions (p=0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p=0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p<0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the colorectal continuum concept. What's new? Changes in the microbial community in the human gut may contribute to colorectal cancer (CRC). Of particular interest are changes in populations of Fusobacterium nucleatum, which previous work has shown to be abundant in CRC tissues. In this study, F. nucleatum was detected in CRCs, as well as in premalignant lesions with elevated CpG island methylator phenotype status. In sessile serrated adenomas, F. nucleatum increased steadily from the sigmoid colon to the cecum, supporting the existence of a colorectal continuum. F. nucleatum may become increasingly abundant with histological grade and may influence CRC progression.

Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer

Hisayoshi Igarashi, Hiroyoshi Kurihara, Kei Mitsuhashi, Miki Ito, Hiroyuki Okuda, Shinichi Kanno, Takafumi Naito, Shinji Yoshii, Hiroaki Takahashi, Takaya Kusumi, Tadashi Hasegawa, Yasutaka Sukawa, Yasushi Adachi, Kenji Okita, Koichi Hirata, Yu Imamura, Yoshifumi Baba, Kohzoh Imai, Hiromu Suzuki, Hiroyuki Yamamoto, Katsuhiko Nosho, Yasuhisa Shinomura

ANNALS OF SURGICAL ONCOLOGY ( SPRINGER ) 22 ( 8 ) 2640 - 2648 2015.08 [Refereed] [International journal]

Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC. We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated. KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027). High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.

Clinicopathological and Molecular Characteristics of Serrated Lesions in Japanese Elderly Patients

Katsuhiko Nosho, Hisayoshi Igarashi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Shinji Yoshii, Masashi Mikami, Hiroaki Takahashi, Takaya Kusumi, Masao Hosokawa, Yasutaka Sukawa, Yasushi Adachi, Tadashi Hasegawa, Kenji Okita, Koichi Hirata, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki Yamamoto, Yasuhisa Shinomura

DIGESTION ( KARGER ) 91 ( 1 ) 57 - 63 2015 [Refereed] [International journal]

Background: The population in Japan is aging more rapidly than in any other country. However, no studies have determined the characteristics of the large population of elderly patients with colorectal tumors. Therefore, we examined the clinicopathological and molecular features of these tumors in elderly patients. Methods: In total, 1,627 colorectal tumors (393 serrated lesions, 277 non-serrated adenomas and 957 colorectal cancers) were acquired from patients. Tumor specimens were analyzed for BRAF and KRAS mutations, CpG island methylator phenotype-specific promoters (CACNA1G, CDKN2A, IGF2 and RUNX3), IGFBP7, MGMT, MLH1 and RASSF2 methylation, microsatellite instability (MSI) and microRNA-31 (miR-31). Results: The frequency of elderly patients (aged >= 75 years) with sessile serrated adenomas (SSAs) with cytological dysplasia was higher than that of those with other serrated lesions and non-serrated adenomas (p < 0.0001). In elderly patients, all SSAs were located in the proximal colon (particularly the cecum to ascending colon). High miR-31 expression, MLH1 methylation and MSI-high status were more frequently detected in SSAs from elderly patients than in those from non-elderly patients. In contrast, no significant differences were found between older age of onset and high-grade dysplasia for traditional serrated adenomas or non-serrated adenomas in any of these molecular alterations. Conclusion: In elderly patients, all SSAs were located in the proximal colon. Furthermore, cytological dysplasia and molecular alterations were more frequently detected in elderly patients with SSAs than in non-elderly patients. Thus, careful colonoscopic examinations of the proximal colon are necessary for elderly patients because SSAs in those patients may exhibit malignant potential. (C) 2015 S. Karger AG, Basel

MicroRNA-31 expression in relation to BRAF mutation, CpG island methylation and colorectal continuum in serrated lesions

Miki Ito, Kei Mitsuhashi, Hisayoshi Igarashi, Katsuhiko Nosho, Takafumi Naito, Shinji Yoshii, Hiroaki Takahashi, Masahiro Fujita, Yasutaka Sukawa, Eiichiro Yamamoto, Taiga Takahashi, Yasushi Adachi, Masanori Nojima, Yasushi Sasaki, Takashi Tokino, Yoshifumi Baba, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki Yamamoto, Yasuhisa Shinomura

INTERNATIONAL JOURNAL OF CANCER ( WILEY-BLACKWELL ) 135 ( 11 ) 2507 - 2515 2014.12 [Refereed] [International journal]

The CpG island methylator phenotype (CIMP) is a distinct form of epigenomic instability. Many CIMP-high colorectal cancers (CRCs) with BRAF mutation are considered to arise from serrated pathway. We recently reported that microRNA-31 (miR-31) is associated with BRAF mutation in colorectal tumors. Emerging new approaches have revealed gradual changes in BRAF mutation and CIMP-high throughout the colorectum in CRCs. Here, we attempted to identify a possible association between miR-31 and epigenetic features in serrated pathway, and hypothesized that miR-31 supports the "colorectal continuum" concept. We evaluated miR-31 expression, BRAF mutation and epigenetic features including CIMP status in 381 serrated lesions and 222 non-serrated adenomas and examined associations between them and tumor location (rectum; sigmoid, descending, transverse and ascending colon and cecum). A significant association was observed between high miR-31 expression and CIMP-high status in serrated lesions with BRAF mutation (p=0.0001). In contrast, miR-31 was slightly but insignificantly associated with CIMP status in the cases with wild-type BRAF. miR-31 expression in sessile serrated adenomas (SSAs) with cytological dysplasia was higher than that in SSAs, whereas, no significant difference was observed between traditional serrated adenomas (TSAs) and TSAs with high-grade dysplasia. The frequency of miR-31, BRAF mutation CIMP-high and MLH1 methylation increased gradually from the rectum to cecum in serrated lesions. In conclusion, miR-31 expression was associated with CIMP-high status in serrated lesions with BRAF mutation. Our data also suggested that miR-31 plays an important role in SSA evolution and may be a molecule supporting the colorectal continuum.

Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review

Hideki Ueno, Kazuo Hase, Yojiro Hashiguchi, Hideyuki Shimazaki, Shinji Yoshii, Shin-ei Kudo, Masafumi Tanaka, Yoshito Akagi, Takeshi Suto, Shinji Nagata, Keiji Matsuda, Koji Komori, Kazuhiko Yoshimatsu, Yasuhiko Tomita, Shozo Yokoyama, Eiji Shinto, Takahiro Nakamura, Kenichi Sugihara

JOURNAL OF GASTROENTEROLOGY ( SPRINGER JAPAN KK ) 49 ( 9 ) 1314 - 1323 2014.09 [Refereed] [Domestic journal]

Background Novel risk factors for lymph node metastasis (LNM) in T1 colorectal cancer (CRC) have been recently proposed, but most have not been implemented because of the lack of validation. Here we determined the value of poorly differentiated clusters (PDCs) in a multi-institutional cohort of T1 CRC cases. Methods A pathology review involving 30 institutions was conducted for 3556 T1 CRCs. PDC was defined as malignant clusters comprising >= 5 cells and lacking a glandular formation. The ability to identify LNM risk was compared using Akaike's information criterion (AIC). Results PDC was observed in 1401 tumors (39.4 %), including 94 (17.8 %) with <1000 mu m submucosal invasion and 1307 (43.2 %) with >= 1000 mu m submucosal invasion (P<0.0001). The incidence of LNM was higher in PDC-positive tumors (17.4 %) than in PDC-negative tumors (6.9 %; P<0.0001), and PDCs had an adverse impact on LNM irrespective of the degree of submucosal invasion. Grade 3, vascular invasion, budding, and submucosal invasion depth were also significant factors (all, P<0.0001). AIC of risk factor to identify LNM risk was most favorable for vascular invasion (2273.4), followed by PDC (2357.4); submucosal invasion depth (2429.1) was the most unfavorable. Interinstitutional judgment disparities were smaller in PDC (kappa, 0.51) than vascular invasion (0.33) or tumor grade (0.48). Conclusions PDC is a promising new parameter with good ability to identify LNM risk. Use of its appropriate judgment criteria will enable us determine whether an observational policy can be safely applied following local tumor excision in T1 CRC cases.

IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

Takafumi Naito, Katsuhiko Nosho, Miki Ito, Hisayoshi Igarashi, Kei Mitsuhashi, Shinji Yoshii, Hironori Aoki, Masafumi Nomura, Yasutaka Sukawa, Eiichiro Yamamoto, Yasushi Adachi, Hiroaki Takahashi, Masao Hosokawa, Masahiro Fujita, Toshinao Takenouchi, Reo Maruyama, Hiromu Suzuki, Yoshifumi Baba, Kohzoh Imai, Hiroyuki Yamamoto, Shuji Ogino, Yasuhisa Shinomura

WORLD JOURNAL OF GASTROENTEROLOGY ( BAISHIDENG PUBLISHING GROUP INC ) 20 ( 29 ) 10050 - 10061 2014.08 [Refereed] [International journal]

AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions. METHODS: To accurately analyze the association between the histological types and molecular features of each type of serrated lesion, we consecutively collected 1386 formalin-fixed paraffin-embedded tissue specimens that comprised all histological types [hyperplastic polyps (HPs, n = 121), sessile serrated adenomas (SSAs, n = 132), traditional serrated adenomas (TSAs, n = 111), non-serrated adenomas (n = 195), and colorectal cancers (CRCs, n = 827)]. We evaluated the methylation levels of IGF2 DMR0 and long interspersed nucleotide element-1 (LINE-1) in HPs (n = 115), SSAs (n = 120), SSAs with cytological dysplasia (n = 10), TSAs (n = 91), TSAs with high-grade dysplasia (HGD) (n = 15), non-serrated adenomas (n = 80), non-serrated adenomas with HGD (n = 105), and CRCs (n = 794). For the accurate quantification of the relative methylation levels (scale 0%-100%) of IGF2 DMR0 and LINE-1, we used bisulfite pyrosequencing method. Tumor specimens were analyzed for microsatellite instability, KRAS (codons 12 and 13), BRAF (V600E), and PIK3CA (exons 9 and 20) mutations; MLH1 and MGMT methylation; and IGF2 expression by immunohistochemistry. RESULTS: The distribution of the IGF2 DMR0 methylation level in 351 serrated lesions and 185 non-serrated adenomas (with or without HGD) was as follows: mean 61.7, median 62.5, SD 18.0, range 5.0-99.0, interquartile range 49.5-74.4. The IGF2 DMR0 methylation level was divided into quartiles (Q1 >= 74.5, Q2 62.6-74.4, Q3 49.6-62.5, Q4 <= 49.5) for further analysis. With regard to the histological type, the IGF2 DMR0 methylation levels of SSAs (mean +/- SD, 73.1 +/- 12.3) were significantly higher than those of HPs (61.9 +/- 20.5), TSAs (61.6 +/- 19.6), and non-serrated adenomas (59.0 +/- 15.8) (P < 0.0001). The IGF2 DMR0 methylation level was inversely correlated with the IGF2 expression level (r = -0.21, P = 0.0051). IGF2 DMR0 hypomethylation was less frequently detected in SSAs compared with HPs, TSAs, and non-serrated adenomas (P < 0.0001). Multivariate logistic regression analysis also showed that IGF2 DMR0 hypomethylation was inversely associated with SSAs (P < 0.0001). The methylation levels of IGF2 DMR0 and LINE-1 in TSAs with HGD (50.2 +/- 18.7 and 55.7 +/- 5.4, respectively) were significantly lower than those in TSAs (61.6 +/- 19.6 and 58.8 +/- 4.7, respectively) (IGF2 DMR0, P = 0.038; LINE-1, P = 0.024). CONCLUSION: IGF2 DMR0 hypomethylation may be an infrequent epigenetic alteration in the SSA pathway. Hypomethylation of IGF2 DMR0 and LINE-1 may play a role in TSA pathway progression. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Association of microRNA-31 with BRAF mutation, colorectal cancer survival and serrated pathway

Katsuhiko Nosho, Hisayoshi Igarashi, Masanori Nojima, Miki Ito, Reo Maruyama, Shinji Yoshii, Takafumi Naito, Yasutaka Sukawa, Masashi Mikami, Wakana Sumioka, Eiichiro Yamamoto, Sei Kurokawa, Yasushi Adachi, Hiroaki Takahashi, Hiroyuki Okuda, Takaya Kusumi, Masao Hosokawa, Masahiro Fujita, Tadashi Hasegawa, Kenji Okita, Koichi Hirata, Hiromu Suzuki, Hiroyuki Yamamoto, Yasuhisa Shinomura

CARCINOGENESIS ( OXFORD UNIV PRESS ) 35 ( 4 ) 776 - 783 2014.04 [Refereed] [International journal]

High miR-31 expression was associated with BRAF mutation and unfavourable survival in CRCs. Moreover, miR-31 inhibitor exhibited antitumour effect in colon cancer cell line, suggesting that miR-31 may be a useful biomarker and therapeutic target in CRC.BRAF is an important gene in colorectal cancers (CRCs) that is associated with molecular characterization and resistance to targeted therapy. Although microRNAs (miRNAs) are useful biomarkers of various cancers, the association between miRNA and BRAF in CRCs is undefined. Therefore, this study was conducted to identify a relationship between specific miRNA molecules and BRAF mutation in CRCs and serrated lesions. miRNA array was used for the measurement of 760 miRNAs in 29 CRCs. To assess the identified miRNAs, quantitative reverse transcriptionPCR was performed on 721 CRCs, 381 serrated lesions and 251 non-serrated adenomas. Moreover, proliferation and invasion assays were conducted using cell lines. miRNA array analysis revealed that microRNA-31 (miR-31)-5p was the most up-regulated miRNA in CRCs with mutated BRAF (V600E) compared with CRCs possessing wild-type BRAF (including cases with KRAS mutation). High miR-31 expression was associated with BRAF and KRAS mutations and proximal location (P < 0.0001). High miR-31 expression was related to cancer-specific mortality [multivariate hazard ratio 2.06, 95% confidence interval: 1.363.09, P 0.0008]. Functional analysis demonstrated that miR-31 inhibitor decreased cell invasion and proliferation. With regard to serrated lesions, high miR-31 expression was less frequently detected in hyperplastic polyps compared with other serrated lesions. In conclusion, associations were identified between miR-31, BRAF and prognosis in CRC. Transfection of miR-31 inhibitor had an antitumour effect. Thus, miR-31 may be a promising diagnostic biomarker and therapeutic target in colon cancers. Moreover, high miR-31 expression in serrated lesions suggested that miR-31 may be a key molecule in serrated pathway.

Submucosal hematoma is a highly suggestive finding for amyloid light-chain amyloidosis: Two case reports.

Yoshii S, Mabe K, Nosho K, Yamamoto H, Yasui H, Okuda H, Suzuki A, Fujita M, Sato T

World journal of gastrointestinal endoscopy ( BAISHIDENG PUBLISHING GROUP INC ) 4 ( 9 ) 434 - 437 2012.09 [Refereed] [International journal]

The clinical and endoscopic features of amyloid lightchain (AL) amyloidosis are diverse and mimic various other diseases. Endoscopically, few reports on submucosal hematomas of the gastrointestinal (GI) tract are available in the literature. Here, we report two cases of AL amyloidosis presenting as submucosal hematomas in the absence of clinical disease elsewhere in the body. The 2 cases were referred to our hospital because of hematochezia. The endoscopic findings in both cases were similar in submucosal hematoma formation. However, the clinical courses differed. In the first case, there was no evidence of systemic amyloidosis and the disease was conservatively managed. In the second case, the disease progressed to systemic amyloidosis and the patient died within a short time. We conclude that the endoscopic detection of a submucosal hematoma in the setting of GI bleeding should raise suspicion of AL amyloidosis. Referral to a hematologist should be done immediately for treatment while the involvement is limited to the GI tract. (C) 2012 Baishideng. All rights reserved.

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