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高木　諒 (タカギ　リヨウ)

北海道大学病院　医療・ヘルスサイエンス研究開発機構特任助教

研究者基本情報

■ 学位
  • 博士（情報科学）, 2020年06月
■ URL
researchmap URLホームページURL■ ID 各種
研究者番号
  • 10843823
ORCID IDJ-Global ID■ 研究キーワード・分野
研究キーワード
  • 臨床研究
  • 臨床試験
研究分野
  • ライフサイエンス, 衛生学、公衆衛生学分野：実験系を含まない
  • ライフサイエンス, 衛生学、公衆衛生学分野：実験系を含む
  • 自然科学一般, 応用数学、統計数学
  • 情報通信, 統計科学

経歴

■ 経歴
経歴
  • 2024年04月 - 現在
    北海道大学, 北海道大学病院 医療・ヘルスサイエンス研究開発機構, 特任助教
  • 2021年04月 - 2024年03月
    独立行政法人医薬品医療機器総合機構, 新薬審査第五部, 審査専門員
  • 2019年03月 - 2021年03月
    北海道大学, 北海道大学病院 臨床研究開発センター
  • 2016年04月 - 2019年03月
    北海学園大学, 工学部, 非常勤講師

研究活動情報

■ 論文
  • Preoperative brain natriuretic peptide levels are associated with postoperative all-cause mortality in patients with lung cancer
    Shinya Otsuka; Haruhiko Shiiya; Ryo Takagi; Kazufumi Okada; Akihiro Sasaki; Kazuto Ohtaka; Aki Fujiwara-Kuroda; Hideki Ujiie; Masato Aragaki; Tatsuya Kato
    Surgery Today, 2026年05月
    研究論文（学術雑誌）
  • Effect of Skeletal Muscle Mass Loss on Outcomes of Patients With Intraductal Papillary Mucinous Neoplasm.
    Soichiro Oda; Kazumichi Kawakubo; Ryo Takagi; Katsuma Nakajima; Shoya Shiratori; Hiroki Yonemura; Shunichiro Nozawa; Ryo Sugiura; Masatsugu Ohara; Masaki Kuwatani; Naoya Sakamoto
    Pancreas, 2026年03月12日, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVE: To investigate the association between skeletal muscle mass loss and long-term outcomes in patients with intraductal papillary mucinous neoplasm (IPMN). METHODS: This retrospective, single-center cohort study included 700 patients diagnosed with IPMN at Hokkaido University Hospital between April 2011 and April 2023. Skeletal muscle mass was assessed using the psoas muscle index (PMI) measured on a computed tomography scan at the initial visit. The primary outcome was the incidence of pancreatic cancer, and the secondary outcome was overall mortality. Cox proportional hazard models and competing risk analyses were employed to identify independent risk factors. RESULTS: During a median follow-up of 71 months, 27 patients developed pancreatic cancer with an annual incidence rate of 0.63% (95% CI: 0.55-1.86%). Patients with a low PMI had a significantly higher risk of pancreatic cancer than those with a high PMI (adjusted HR: 3.44, 95% CI: 1.62-7.32, P <0.01). Multivariate analysis identified a low PMI and a main pancreatic duct diameter ≥5 mm as independent risk factors for the development of pancreatic cancer. Among the 69 deaths, 61 were comorbidity-related and 8 were pancreatic cancer-related. Low PMI (adjusted HR: 2.57, 95% CI: 1.60-4.12, P <0.01) and a high age-adjusted Charlson Comorbidity Index (aCCI) (adjusted HR: 9.06, 95% CI: 4.63-17.72, P <0.01) were independently associated with all-cause mortality. Competing risk analysis revealed that skeletal muscle mass loss was significantly associated with the incidence of pancreatic cancer in patients with a low aCCI score but not in those with a high aCCI score. CONCLUSIONS: Skeletal muscle mass loss was an independent risk factor for all-cause mortality, and it might be associated with the risk factor for the incidence of pancreatic cancer, particularly IPMN-derived carcinoma in patients with IPMN. Patients with a low PMI and minimal comorbidities might be better to undergo long-term surveillance due to their increased risk of pancreatic cancer.
  • Minimally invasive abdominal and left thoracic approach (MALTA) for Siewert type II esophagogastric junction adenocarcinoma: A retrospective cohort study of perioperative and oncologic outcomes.
    Takeo Nitta; Yuma Ebihara; Ryo Takagi; Hironobu Takano; Saseem Poudel; Hideyuki Wada; Toshiaki Shichinohe; Satoshi Hirano
    Surgical endoscopy, 2025年10月29日, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: The optimal surgical approach for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) remains controversial because of the complex lymphatic spread and anatomical constraints. We previously developed a novel minimally invasive abdominal and left thoracic approach (MALTA) to overcome the limitations of conventional techniques. This study aimed to provide an updated analysis of MALTA with extended follow-up period compared with our initial report. METHOD: A retrospective review was conducted on 16 consecutive patients who underwent MALTA for Siewert type II AEG between 2013 and 2023. The procedure combined laparoscopic gastrectomy and thoracoscopic lower mediastinal esophagectomy with intrathoracic reconstruction, both of which were performed without intraoperative repositioning. Perioperative outcomes, postoperative complications, and survival rates were analyzed. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). The primary outcome was feasibility and safety (R0 resection rate and postoperative complications). Secondary outcomes included OS and DFS. RESULTS: R0 resection was achieved in all patients. The median operative time was 438 min, and median blood loss was 28 mL. Postoperative complications occurred in 31.3% of the patients, including anastomotic leakage (12.5%) and empyema (18.8%). No in-hospital deaths or respiratory complications were reported. The median follow-up duration was 51 months. The 1-, 3-, and 5-year OS rates were 87.5% (95% confidence interval [CI], 61.4-96.9), 67.7% (95% CI, 41.8-85.9), and 60.2% (95% CI, 34.7-81.1), respectively. The DFS rates were 68.8% (95% CI, 43.3-86.4), 56.3% (95% CI, 32.4-77.5), and 42.9% (95% CI, 21.5-67.3), respectively. CONCLUSIONS: MALTA appears to be a feasible, safe, and minimally invasive option for Siewert type II AEG, enabling stable intrathoracic anastomosis without patient repositioning. These results suggest its potential utility in achieving favorable perioperative and survival outcomes.
  • Reproducibility of glycocheck measurements in patients under general anesthesia with muscle relaxants: A prospective observational study
    Takayuki Toki; Kazuyuki Mizunoya; Takashi Soejima; Yasunori Yagi; Naoko Nakamine; Yusuke Itosu; Ryo Takagi; Isao Yokota; Yuji Morimoto
    Journal of Clinical Monitoring and Computing, 2025年07月10日
    研究論文（学術雑誌）
  • A feasibility pilot study comparing tablets and smartphones for an app-based speed training program in older people: an open-label, randomized controlled PROBE trial
    Yuki Takakura; Mika Otsuki; Ryo Takagi; Kiyohiro Houkin
    Cognitive Processing, Springer Science and Business Media LLC, 2025年03月06日
    研究論文（学術雑誌）
  • Validity and Utility of a Risk Prediction Model for Wound Infection After Lower Third Molar Surgery.
    Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Keisuke Okamoto; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
    Oral diseases, 2025年01月10日, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVES: To externally validate a clinical prediction model for surgical site infection (SSI) after lower third molar (L3M) surgery and evaluate its clinical usefulness. METHODS: We conducted a retrospective cohort study of patients who underwent L3M surgery at Hokkaido University Hospital. The study was designed to evaluate the historical and methodological transportability. Clinical usefulness was evaluated using decision curve analysis on the data of the non-antibiotic-treated patients. RESULTS: We obtained 2543 validation cohorts from April 2020 to March 2023, and 640 non-antibiotic cohorts from July 2010 to September 2023. The incidences of SSI after L3M surgery were 5.3% (135/2543) and 7.7% (49/640) in the validation and non-antibiotic cohorts, respectively. The discrimination ability of the prediction model was acceptable for the external validation cohort (c-statistic: 0.67; 95% CI: 0.62-0.71) and adequate for the non-antibiotic cohort (c-statistic: 0.72; 95% CI: 0.63-0.79). In both cohorts, the model showed excellent calibration between the observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds. CONCLUSION: A simple risk prediction model for SSI after L3M surgery demonstrated clinical transportability and usefulness. This model may help surgeons/clinicians determine the appropriateness of prophylactic antibiotics administration for patients in L3M surgery.
  • A multicenter, prospective, phase II trial of second-line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to an anti-EGFR antibody: HGCSG1801.
    Hiroshi Nakatsumi; Yoshito Komatsu; Kazuaki Harada; Yasuyuki Kawamoto; Satoshi Yuki; Kentaro Sawada; Atsushi Ishiguro; Susumu Sogabe; Takayuki Ando; Yusuke Sasaki; Ayumu Yoshikawa; Michio Nakamura; Masayoshi Dazai; Miki Tateyama; Osamu Muto; Masahito Kotaka; Tamotsu Sagawa; Tetsuhito Muranaka; Kazuteru Hatanaka; Ryo Takagi; Yu Sakata
    International journal of cancer, 155, 12, 2223, 2231, 2024年12月15日, ［国際誌］
    英語, 研究論文（学術雑誌）, Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open-label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin-based chemotherapy plus an anti-EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6-month PFS rate was 58.8% (90% confidence interval [CI], 45.7%-72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5-11.0 months) and 18.8 months (95% CI, 12.9-26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0-36.0%) and disease control rate was 88.4% (95% CI, 74.9-96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin-based chemotherapy plus an anti-EGFR agent.
  • Reply to Accurate Risk Prediction Model for Surgical Site Infection After Lower Third Molar Surgery.
    Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
    Oral diseases, 2024年11月03日, ［国際誌］
    英語
  • Development of a risk prediction model for surgical site infection after lower third molar surgery.
    Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
    Oral diseases, 30, 5, 3202, 3211, 2024年07月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: There is little evidence regarding risk prediction for surgical site infection (SSI) after lower third molar (L3M) surgery. METHODS: We conducted a nested case-control study to develop a multivariable logistic model for predicting the risk of SSI after L3M surgery. Data were obtained from Hokkaido University Hospital from April 2013 to March 2020. Multiple imputation was applied for the missing values. We conducted decision tree (DT) analysis to evaluate the combinations of factors affecting SSI risk. RESULTS: We identified 648 patients. The final model retained the available distal space (Pell & Gregory II [p = 0.05], Pell & Gregory III [p < 0.01]), depth (Pell & Gregory B [p < 0.01], Pell & Gregory C [p < 0.01]), surgeon's experience (3-10 years [p = 0.25], <3 years [p < 0.01]), and simultaneous extraction of both L3M [p < 0.01]; the concordance-statistic was 0.72. The DT analysis demonstrated that patients with Pell and Gregory B or C and simultaneous extraction of both L3M had the highest risk of SSI. CONCLUSIONS: We developed a model for predicting SSI after L3M surgery with adequate predictive metrics in a single center. This model will make the SSI risk prediction more accessible.
  • Surveillance esophagogastroduodenoscopy using linked color imaging and narrow-band imaging: A multicenter randomized controlled trial.
    Marina Kubo; Shoko Ono; Osamu Dohi; Hayato Fukui; Takuto Hikichi; Tsunetaka Kato; Momoko Tsuda; Mio Matsumoto; Sosuke Kato; Rieko Mukai; Nobuaki Yagi; Ryo Takagi; Naoya Sakamoto; Mototsugu Kato
    Journal of gastroenterology and hepatology, 39, 6, 1065, 1072, 2024年06月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND AND AIM: There has been no report on a direct comparison between linked color imaging (LCI) and second-generation narrow-band imaging (2G-NBI) for surveillance of epithelial neoplasms in the upper gastrointestinal tract (UGIT). The aim of this study was to verify the superiority of LCI to 2G-NBI for surveillance esophagogastroduodenoscopy and to clarify how each endoscopic system should be used. METHODS: This study was conducted as an open-label, two-arm-parallel (1:1), multicenter, randomized controlled trial at six institutions. Patients aged 20-85 years with a treatment history of epithelial neoplasms in the UGIT were recruited. Patients were assigned to a 2G-NBI group and an LCI group, and esophagogastroduodenoscopy was performed with primary image-enhanced endoscopy followed by white light imaging (WLI). The primary endpoint was the detection rate of one or more epithelial neoplasms in the primary image-enhanced endoscopy. A WLI-detected epithelial neoplasm was defined as a lesion that was detected in only WLI. RESULTS: A total of 372 patients in the 2G-NBI group and 378 patients in the LCI group were analyzed. Epithelial neoplasms in the UGIT were detected by 2G-NBI in 18 patients (4.6%) and were detected by LCI in 20 patients (5.3%) (P = 0.87). WLI-detected epithelial neoplasms were in 11 patients in the 2G-NBI group (3.0%) and in 1 patient in the LCI group (0.27%) (P = 0.003). CONCLUSIONS: Linked color imaging did not show superiority to 2G-NBI for the detection of epithelial neoplasms. Also, the percentage of WLI-detected epithelial neoplasms in primary NBI was significantly higher than that in primary LCI.
  • Sentinel node restoration by vascularized lymph node transfer in mice.
    Erika G Kusajima; Yuhei Yamamoto; Kosuke Ishikawa; Takahiro Miura; Emi Funayama; Masayuki Osawa; Ryo Takagi; Taku Maeda
    Microsurgery, 44, 1, e30981, 2024年01月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Recent reports have indicated that vascularized lymph node transfer (VLNT) may improve the impaired immunity in lymphedema but there has been no report concerning anti-cancer immunity. In the early tumor immune response, dendritic cells (DCs) participate in tumor recognition and antigen presentation in local lymphatics. Here, we investigated the impact of VLNT on DC dynamics against cancer in mouse models. METHODS: Forty-seven 8-week-old C57BL/6 N male mice were divided into three surgical groups: a VLNT model in which a vascularized inguinal lymph node (LN) flap was transferred into the ipsilateral fossa after a popliteal LN was removed; a LN dissection (LND) model in which the popliteal LN was dissected; and a control model in which a skin incision was made at the popliteal fossa and an ipsilateral inguinal LN was removed. Postoperative lymphatic flows were observed by indocyanine green lymphography and B16-F10-luc2 mouse melanoma were implanted into the ipsilateral footpad. The proportion of DCs in the transplanted nodes was measured by CD11c immunohistochemistry using digital imaging analysis 4 days after cancer implantation. Metastases to the lungs and LNs were quantitatively evaluated by luciferase assay 4 weeks after cancer implantation. RESULTS: After VLNT, lymphatic reconnection was observed in 59.2% of mice. The proportion of DCs was significantly higher in the VLNT group with lymphatic reconnection (8.6% ± 1.0%) than in the naïve LN (4.3% ± 0.4%) (p < .001). The tumor burden of lung metastases was significantly less in the VLNT group with lymphatic reconnection compared with the LND group (p = .049). CONCLUSIONS: Metastasis decreased in mice with reconnected lymphatics after VLNT. A possible explanation was that lymphatic restoration may have contributed to the tumor immune response by allowing DC migration to LNs.
  • A validation study for wide-range remote assessment of cognitive functions in the healthy older Japanese population: a pilot randomised crossover trial.
    Yuki Takakura; Mika Otsuki; Ryo Takagi; Kiyohiro Houkin
    BMC geriatrics, 23, 1, 575, 575, 2023年09月19日, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: The assessment of a wide range of cognitive functions using video teleconference (VTC) systems cannot be applied in practice yet. We aimed to determine the feasibility and reliability of previously unvalidated remote cognitive function tests in Japan using common information and communication technology (ICT) devices, software, and VTC systems compared with face-to-face (FTF) assessment. METHODS: The sample consisted of 26 participants from senior citizens clubs and an employment service centre in Sapporo Japan, including 11 females and 15 males (age averaged 78.6 ± 6.8 years). Tests included the RCPM, Story recall, 10/36 spatial recall, selective reminding test, SDMT, PASAT, FAB, TMT-A, TMT-B, visual cancellation task, digit span, tapping span. The experimental design was a counterbalanced crossover randomised controlled trial. Intraclass correlations (ICCs), paired-samples t-tests, Cohen's Kappa (κ) coefficients, and Wilcoxon signed-rank test were calculated to compare the scores between VTC and FTF assessments. RESULTS: All ICCs were significant and ranged from 0.47 (RCPM time) to 0.92 (RCPM score and PASAT), with a mean ICC of 0.75. Digit span using Cohen's Kappa (κ) coefficient was significant, but the tapping span was not. Paired samples t-test showed statistically significant differences in SDMT, RCPM time, and cancellation time. CONCLUSIONS: The results suggest that remote video conference-based neuropsychological tests even using familiar devices and software may be able to assess a wide range of cognitive functions in the Japanese older population. As for the processing speed tasks, we need to create our own standards for the remote condition. For the tapping span, we should consider increasing the number of trials.
  • Characteristics and usefulness of transabdominal ultrasonography in immune-mediated colitis.
    Kensuke Sakurai; Takehiko Katsurada; Mutsumi Nishida; Satomi Omotehara; Shinya Fukushima; Shinsuke Otagiri; Kazunori Nagashima; Reizo Onishi; Ryo Takagi; Yoshito Komatsu; Naoya Sakamoto
    Intestinal research, 21, 1, 126, 136, 2023年01月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND/AIMS: The usefulness of ultrasonography (US) in diseases of the gastrointestinal tract has been reported recently. This prospective study aimed to determine the features of US findings in immune-mediated colitis (IMC), an adverse event induced by immune checkpoint inhibitor, and examine the correlation between US findings, colonoscopy (CS) findings, and severity of colitis. METHODS: We studied patients examined using CS and US upon suspicion of IMC in Hokkaido University Hospital between April 2018 and February 2021. Endoscopic findings of IMC were assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). The severity of US findings in IMC was evaluated using US grade, which is the ultrasonographic grading scale in ulcerative colitis. Bowel wall thickness and the intensity of the color Doppler signal were also analyzed. Severity of colitis was evaluated using Common Terminology Criteria for Adverse Events (CTCAE) grade version 5. RESULTS: Fourteen patients with IMC were enrolled. The US findings were bowel wall thickening, loss of stratification, ulceration and increased blood flow signal. The US grade was moderately correlated with the UCEIS (r=0.687, p=0.009) and CTCAE grade (r=0.628, p=0.035). Bowel wall thickness and UCEIS (r=0.628, p=0.020), as well as color Doppler signal grade and CTCAE grade (r=0.724, p=0.008), were significantly correlated. CONCLUSIONS: US findings in IMC were mainly similar to those of ulcerative colitis, but there were some findings that were characteristic only of IMC. Significant correlation was found between US findings, CS findings, and severity of colitis. Hence, US could be useful for the evaluation of IMC.
  • Comparison of Access Route for Endovascular Treatment by Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRA and Contrast-Enhanced MRA.
    Satoshi Kobayashi; Toshiya Osanai; Taku Sugiyama; Noriyuki Fujima; Ryo Takagi; Isao Yokota; Akiyoshi Hamaguchi; Toshitaka Nakamura; Kazutoshi Hida; Miki Fujimura
    Journal of neuroendovascular therapy, 17, 6, 120, 124, 2023年, ［国内誌］
    英語, 研究論文（学術雑誌）, OBJECTIVE: In endovascular treatment, it is important to evaluate the access route for placing a catheter into the common carotid artery (CCA) promptly and safely prior to the procedure. We examined whether non-contrast MRA using time-spatial labeling inversion pulse (Time-SLIP) can be used in patients prior to endovascular thrombectomy for acute ischemic stroke. We compared Time-SLIP MRA to contrast-enhanced (CE) MRA and evaluated the efficacy in the evaluation of access routes. METHODS: We retrospectively reviewed 31 patients admitted between October 2018 and December 2018 for cerebral infarction at our hospital. Blood vessels were imaged from the aortic arch to the CCA. A radiologist blindly evaluated quality score, stenosis, shape of the aorta, and degree of tortuosity. RESULTS: There were no "non-diagnostic" images. The sensitivity, specificity, positive predictive value, and negative predictive value for stenosis were 83%, 96%, 83%, and 96%, respectively. The sensitivity for the aorta type classification was 100%. The sensitivity for mild tortuosity was 93%, for moderate was 100%, and for severe was 100%. CONCLUSION: Time-SLIP MRA can be an alternative to CE MRA in access route assessment for patients with cerebral infarction who are not eligible for acute thrombectomy therapy.
  • Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome.
    Rika Saito; Yasuyuki Kawamoto; Mutsumi Nishida; Takahito Iwai; Yasuka Kikuchi; Isao Yokota; Ryo Takagi; Takahiro Yamamura; Ken Ito; Kazuaki Harada; Satoshi Yuki; Yoshito Komatsu; Naoya Sakamoto
    International journal of clinical oncology, 27, 11, 1780, 1790, 2022年11月, ［国内誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early. METHODS: In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT. RESULTS: Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase  ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32-0.41). The change in rate of LSM by SWE was correlated with an SV increase  ≥ 30% (r = 0.40). CONCLUSIONS: The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.
  • Association Between Vitamin A Intake and Disease Severity in Early-Onset Heterotopic Ossification of the Posterior Longitudinal Ligament of the Spine.
    Tsutomu Endo; Shiro Imagama; Satoshi Kato; Takashi Kaito; Hiroaki Sakai; Shiro Ikegawa; Yoshiharu Kawaguchi; Masahiro Kanayama; Yuichiro Hisada; Yoshinao Koike; Kei Ando; Kazuyoshi Kobayashi; Itaru Oda; Kazufumi Okada; Ryo Takagi; Norimasa Iwasaki; Masahiko Takahata
    Global spine journal, 12, 8, 1770, 1780, 2022年10月, ［国際誌］
    英語, 研究論文（学術雑誌）, STUDY DESIGN: A sex- and age-matched case-control study and a cross-sectional study. OBJECTIVE: In our previous study, patients with early-onset (<50 years of age) ossification of the posterior longitudinal ligament (OPLL) had distinct features such as morbid obesity, a high prevalence of lifestyle-related diseases, and diffuse ossified lesions mainly affecting the thoracic spine. Our goals were to determine whether early-onset OPLL patients have unbalanced dietary habits and to identify nutritional factors associated with OPLL exacerbation. METHODS: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan. RESULTS: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level. CONCLUSIONS: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.
  • Predictors of the development of nab-paclitaxel-induced peripheral neuropathy in breast cancer patients: post hoc analysis of a prospective, phase II, self-controlled clinical trial.
    Yuko Kanbayashi; Koichi Sakaguchi; Takeshi Ishikawa; Yusuke Tabuchi; Ryo Takagi; Isao Yokota; Norito Katoh; Koichi Takayama; Tetsuya Taguchi
    Medical oncology (Northwood, London, England), 39, 10, 153, 153, 2022年07月19日, ［国際誌］
    英語, 研究論文（学術雑誌）, In a previous study, we showed that cryotherapy and compression therapy have comparable efficacy in preventing nab-paclitaxel-induced peripheral neuropathy. However, even with cryotherapy or compression therapy, there were patients with National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade ≥ 2 and/or Patient Neurotoxicity Questionnaire (PNQ) grade ≥ D peripheral neuropathies. Therefore, this post hoc analysis was performed to identify predictors of nab-paclitaxel-induced peripheral neuropathy. The clinical data in this post hoc analysis were the data of 38 breast cancer patients receiving chemotherapy with nanoparticle albumin-bound paclitaxel (nab-PTX) at our outpatient chemotherapy center from August 2017 to March 2019. The number of patients was analyzed assuming that there were data for 76 hands. Variables related to the development of nab-PTX-induced peripheral neuropathy were used for regression analysis. Multivariate-ordered logistic regression analysis was performed to identify predictors for the development of nab-PTX-induced peripheral neuropathy. Significant factors included smoking history [odds ratio (OR) 4.64, 95% confidence interval (CI) 1.60-13.5; P = 0.0048] with neuropathy evaluated by CTCAE, body mass index (BMI) (OR 1.13, 95% CI 1.01-1.26; P = 0.039) with neuropathy evaluated by PNQ (sensory), and smoking history (OR 3.80, 95% CI 1.40-10.30; P = 0.0087) and age (OR 1.06, 95% CI 1.01-1.11; P = 0.012) with neuropathy evaluated by PNQ (motor). In conclusion, smoking history, BMI and age were identified as significant predictors of the development of nab-PTX-induced-peripheral neuropathy.
  • Evaluation of the strategies to reduce third-generation oral cephalosporins in dentistry at a Japanese academic hospital: An interrupted time series analysis.
    Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
    Journal of clinical pharmacy and therapeutics, 47, 7, 1010, 1019, 2022年07月, ［国際誌］
    英語, 研究論文（学術雑誌）, WHAT IS KNOWN AND OBJECTIVE: Third-generation oral cephalosporins, especially cefcapene-pivoxil (CFPN-PI), have been used frequently in the Japanese dental field. In December 2014 and April 2016, the newly published clinical guidelines recommended the use of amoxicillin (AMPC). Thus, it is important to evaluate the impact of these guidelines on the prescription profiles of prophylactic antibiotics, clinical outcomes and cost-effectiveness of antibiotics. METHODS: We conducted a retrospective study to analyse an interrupted time series analysis from April 2013 to March 2020 at the Department of Dentistry of Hokkaido University Hospital. A segmented regression model was used to estimate the changes in the incidence of infectious complications following tooth extraction. Prescribed antibiotic data were evaluated via days of therapy (DOT). Antibiotic costs were calculated in terms of the Japanese yen (JPY). RESULTS AND DISCUSSION: We identified 17,825 eligible patients. The incidence rates of infectious complications (SSI + dry socket) and SSI after tooth extraction were 3.2% and 2.2%, respectively, during the entire period. The extraction of impacted third molars corresponded to 5.0% and 3.4%, respectively. However, their incidence rates were not significantly different during this period. The use of prophylactic antibiotics and antibiotic cost showed consistent trends following the implementation of guidelines. The mean DOT of CFPN-PI decreased (ranging from 4893.6 DOTs/1000 patients [March 2013 to November 2014] to 3856.4 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3856.4 DOTs/1000 patients [December 2014 to March 2016] to 2293.9 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). In contrast, the mean DOT of AMPC was found to be increased (ranging from 1379.7 DOTs/1000 patients [March 2013 to November 2014] to 3236.3 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3236.3 DOTs/1000 patients [December 2014 to March 2016] to 4597.8 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). The mean monthly cost was decreased (ranging from 905.3 JPY [March 2013 to November 2014] to 788.7 JPY [December 2014 to March 2016]; p = 0.003, and from 788.7 JPY [December 2014 to March 2016] to 614.0 JPY [April 2016 to March 2020]; p < 0.001). WHAT IS NEW AND CONCLUSION: After December 2014, prophylactic antibiotics were switched from CFPN-PI to AMPC, and the incidence rate of infectious complications was not significantly different over time. However, changing antibiotics is useful from a cost-effectiveness perspective.
  • Clinical features and significance of leukopenia occurring immediately after endovascular surgery.
    Takashi Soejima; Kazuyuki Mizunoya; Yuki Izumi; Takeshi Yokoyama; Ryo Takagi; Yuji Morimoto
    Journal of anesthesia, 36, 1, 144, 151, 2022年02月, ［国内誌］
    英語, 研究論文（学術雑誌）, PURPOSE: Inflammation after stent graft surgery is known as postimplantation syndrome (PIS) and it causes leukocytosis. However, we have experienced leukopenia in the very early postoperative phase of endovascular surgery at our institution. We investigated leukopenia, an under-recognized phenomenon that occurred after transcatheter aortic valve implantation (TAVI), endovascular aortic repair (EVAR), and thoracic endovascular aortic repair (TEVAR). METHODS: Records of patients who underwent TAVI, EVAR, and TEVAR between March 2018 and February 2019 were retrospectively reviewed. Primary outcomes were the decline rate of white blood cell count (DR-WBC) in the immediate postoperative period and its differences among surgical procedures. The secondary endpoint was the relationship between DR-WBC and infectious complications. Furthermore, the incidence of PIS and its differences among the procedures and associations with DR-WBC were evaluated. RESULTS: A total of 108 patients (TAVI 41, EVAR 37, TEVAR 30) were included. DR-WBC immediately after surgery was higher in the TAVI group when compared with other groups (TAVI, 43.1 ± 22.6%; EVAR, 27.6 ± 17.3%; TEVAR, 25.4 ± 27.4%; P < 0.01). DR-WBC was not significantly different regardless of postoperative infection (P = 0.45) or PIS (P = 0.62). The incidence rate of PIS was higher in the EVAR group compared with the TAVI group, and was not associated with DR-WBC. CONCLUSIONS: Leukopenia was a common phenomenon immediately after endovascular surgery, especially TAVI. It resolved a day after surgery and was not associated with PIS or infectious complications. Therefore, it seems to be a transient abnormal hematological finding and a self-limiting condition.
  • Transabdominal Ultrasonography for Preoperative Diagnosis of Lymph Node Metastasis in Colon Cancer: A Retrospective Cohort Study.
    Ken Imaizumi; Shigenori Homma; Mutsumi Nishida; Takeshi Soyama; Ryosuke Shimura; Yusuke Kudo; Satomi Omotehara; Isao Yokota; Ryo Takagi; Hiroki Matsui; Yoichi Miyaoka; Nobuki Ichikawa; Tadashi Yoshida; Norihiko Takahashi; Akinobu Taketomi
    Cancer diagnosis & prognosis, 2, 2, 173, 183, 2022年, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND/AIM: Although computed tomography (CT) is the standard modality for diagnosing lymph node metastasis (LNM), transabdominal ultrasonography (US) can be useful due to its high spatial resolution and use of Doppler signals to precisely analyse lymph nodes. This study aimed to evaluate the accuracy of US for lymph node assessment, establish US-based diagnostic criteria for LNM, and compare the capability of US with that of CT for the diagnosis of LNM. PATIENTS AND METHODS: This retrospective, single-institution, cohort study included patients who underwent radical surgery for clinical stage 0-III colon cancer, between March 2012 and February 2019. RESULTS: Overall, 34.9% (66/189) of patients had pathological LNM. The optimal US diagnostic criteria were 1) short axis ≥7 mm and short/long ratio ≥0.75 and 2) at least two of the following: the absence of hilar echoes, expansive appearance, or peripheral/mixed vascularity by the colour Doppler and/or contrast-enhanced method. Compared to CT, US showed a higher diagnostic sensitivity (54.5% vs. 43.9%; p=0.296), higher concordance with the number of pathological LNM (correlation coefficient: US, 0.42; CT, 0.27) and pathological N diagnosis (weighted ĸ: US, 0.35; CT, 0.18), and higher sensitivity for advanced LNM, including multiple LNMs (47.4% vs. 18.4%; p=0.014) and N2 stage (27.8% vs. 5.6%; p=0.177). CONCLUSION: US has higher sensitivity than CT for diagnosing LNM in colon cancer, along with a more accurate preoperative diagnosis of the N stage. Additionally, US may be more helpful than CT alone for preoperatively deciding the appropriateness of neoadjuvant treatment in colon cancer with advanced LNM.
  • Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies.
    Hiroshi Nakatsumi; Yoshito Komatsu; Tetsuhito Muranaka; Satoshi Yuki; Yasuyuki Kawamoto; Kazuaki Harada; Masayoshi Dazai; Miki Tateyama; Yusuke Sasaki; Takuto Miyagishima; Yasushi Tsuji; Masaki Katagiri; Michio Nakamura; Susumu Sogabe; Kazuteru Hatanaka; Takashi Meguro; Tomoe Kobayashi; Atsushi Ishiguro; Osamu Muto; Yoshiaki Shindo; Masahito Kotaka; Takayuki Ando; Ryo Takagi; Naoya Sakamoto; Yu Sakata
    Frontiers in oncology, 12, 939425, 939425, 2022年, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies. METHODS: FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi. DISCUSSION: There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.
  • Crohn's Disease Activity Evaluation by Transabdominal Ultrasonography: Correlation with Double-Balloon Endoscopy.
    Kana Yamanashi; Takehiko Katsurada; Mutsumi Nishida; Reizo Onishi; Satomi Omotehara; Shinsuke Otagiri; Kensuke Sakurai; Kazunori Nagashima; Kenji Kinoshita; Ryo Takagi; Naoya Sakamoto
    Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 40, 12, 2595, 2605, 2021年12月, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVES: Transabdominal ultrasonography (US) has been reported as a useful tool for evaluating Crohn's disease (CD) activity. Endoscopic findings and Crohn's disease activity index (CDAI) are currently considered the gold standard for assessing CD activity. We assessed the correlation between US and double-balloon endoscopy (DBE), and CDAI for evaluating CD activity. METHODS: We analyzed patients with CD undergoing US and DBE within 10 days between the procedures. The intestine was divided into four segments and analyzed by the US scoring system (US-CD) and the simple endoscopic score for Crohn's disease (SES-CD). CDAI was compared with US-CD and SES-CD. Spearman's rank correlation coefficient was used for statistical analysis. RESULTS: Twenty-five patients with CD (11 women, 14 men; mean age 35.4 ± 14.9 years, range 16-65 years) were enrolled. Twenty-four patients received antitumor necrosis factor inhibitor therapy. CDAI was 128.1 (range 36-227). A significant moderate correlation was found between the US-CD and SES-CD in all segments (ρ = .64, P < .01). The US-CD showed a strong correlation with CDAI (ρ = .78, P < .01), whereas the SES-CD showed a moderate correlation (ρ = .55, P < .05). CONCLUSIONS: US-CD and SES-CD showed a moderate correlation for assessing CD activity. US-CD showed a stronger correlation with CDAI than SES-CD, suggesting that US could more accurately evaluate the disease activity.
  • Acute Oral Calcium Suppresses Food Intake Through Enhanced Peptide-YY Secretion Mediated by the Calcium-Sensing Receptor in Rats.
    Akiho Igarashi; Shono Ogasawara; Ryo Takagi; Kazufumi Okada; Yoichi M Ito; Hiroshi Hara; Tohru Hira
    The Journal of nutrition, 151, 5, 1320, 1328, 2021年05月11日, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Dietary calcium has been proposed to reduce appetite in human studies. Postprandial satiety is mainly controlled by gut hormones. However, the effect of calcium on appetite and the role of gut hormones remain unclear. OBJECTIVES: We examined whether oral administration of calcium reduces food intake in rats and investigated the underlying mechanism. METHODS: Male Sprague Dawley rats (8-12 wk old) were used after an overnight fastifffng. In a series of 2 trials with 1-wk interval between challenges, food intake was measured 0.5-24 h after oral gavage of a vehicle (saline containing 1.5% carboxymethyl cellulose) as the control treatment, or the vehicle containing various calcium compounds [calcium chloride (CaCl2), calcium carbonate, calcium lactate, in a random order] at 150 mg calcium/kg dose. A conditional taste aversion test was conducted. In separate experiments, plasma calcium and gut hormone concentrations were measured 15 or 30 min after oral administration of the calcium compounds. In anesthetized rats, portal peptide-YY (PYY) concentrations were measured after intraluminal administration of a liquid meal with or without additional calcium. RESULTS: Oral CaCl2 reduced food intake acutely (30 min, ∼20%, P < 0.05) compared with control rats, without taste aversion. Plasma PYY concentration was higher (100%, P < 0.05) in CaCl2-preloaded rats than in control rats, 15 min after administration. In anesthetized rats, luminal meal + CaCl2 induced a 4-fold higher increase in plasma PYY than the control treatment did. Oral administration of a calcium-sensing receptor (CaSR) agonist suppressed food intake (∼30%, P < 0.05), but CaCl2 and CaSR agonist did not suppress food intake under treatment with a PYY receptor antagonist. Furthermore, the CaSR antagonist attenuated the effect of CaCl2 on food intake. CONCLUSIONS: CaCl2 suppresses food intake partly by increasing CaSR-mediated PYY secretion in rats. Our findings could at least partially explain the satiating effect of calcium.
  • Primary 12α-Hydroxylated Bile Acids Lower Hepatic Iron Concentration in Rats.
    Shota Hori; Minako Satake; Ohji Kohmoto; Ryo Takagi; Kazufumi Okada; Satoru Fukiya; Atsushi Yokota; Satoshi Ishizuka
    The Journal of nutrition, 151, 3, 523, 530, 2021年03月11日, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Primary 12α-hydroxylated bile acids (12αOH BAs) enhance intestinal iron uptake due to their ability ex vivo to chelate iron. However, no information is available on their role in vivo, especially in the liver. OBJECTIVES: To investigate the effects and mechanisms of primary 12αOH BAs on hepatic iron concentration in vivo. METHODS: Male Wistar King A Hokkaido male rats (WKAH/HkmSlc) rats aged 4-5 weeks were fed a control diet or a diet with cholic acid (CA; 0.5 g/kg diet), the primary 12αOH BA, for 2 weeks (Study 1) or 13 weeks (Study 2). In Study 3, rats fed the same diets were given drinking water either alone or containing vancomycin (200 mg/L) for 6 weeks. The variables measured included food intake (Studies 1-3), bile acid profiles (Studies 1 and 3), hepatic iron concentration (Studies 1-3), fecal iron excretion (Studies 1 and 2), iron-related liver gene expression (Studies 2 and 3), and plasma iron-related factors (Studies 2 and 3). RESULTS: In Study 1, CA feed reduced the hepatic iron concentration (-16%; P = 0.005) without changing food intake or fecal iron excretion. In Study 2, we found a significant increase in the aortic plasma concentration of lipocalin 2 (LCN2; +65%; P < 0.001), an iron-trafficking protein. In Study 3, we observed no effect of vancomycin treatment on the CA-induced reduction of hepatic iron concentration (-32%; P < 0.001), accompanied by increased plasma LCN2 concentration (+72%; P = 0.003), in the CA-fed rats despite a drastic reduction in the secondary 12αOH BA concentration (-94%; P < 0.001) in the aortic plasma. CONCLUSIONS: Primary 12αOH BAs reduced the hepatic iron concentration in rats. LCN2 may be responsible for the hepatic iron-lowering effect of primary 12αOH BAs by transporting iron out of the liver.
  • Reliability of an ultrasonographical scoring system for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation.
    Takahito Iwai; Mutsumi Nishida; Junichi Sugita; Yusuke Kudo; Rika Takasugi; Isao Yokota; Ryo Takagi; Hitoshi Shibuya; Shuichiro Takahashi; Takanori Teshima
    Journal of medical ultrasonics (2001), 48, 1, 45, 52, 2021年01月, ［国内誌］
    英語, 研究論文（学術雑誌）, PURPOSE: Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a fatal complication after hematopoietic stem cell transplantation. We previously reported the usefulness of an ultrasonographical (US) scoring system, the Hokkaido US-based scoring system consisting of ten parameters (HokUS-10): (1) hepatomegaly in the left lobe and (2) right lobe, (3) dilatation of the main portal vein (PV), (4) hepatofugal flow in the main PV, (5) decreased velocity of the PV, (6) dilatation of the para-umbilical vein (PUV), (7) appearance of blood flow signal in the PUV, (8) gallbladder (GB) wall thickening, (9) ascites, and (10) increased resistive index of the hepatic artery, for the diagnosis of SOS/VOD. However, the reliability of this system among operators remains elusive. Therefore, we prospectively evaluated the reliability of HokUS-10. METHODS: Twenty-four healthy volunteers and 40 patients with liver dysfunction were enrolled. Inter- and intra-operator reliabilities were analyzed using three sonographers. RESULTS: The median concordance rate of HokUS-10 among three sonographers and intra-operator in 24 volunteers was 92% (95% CI: 73-98%) and 98% (95% CI: 92-100%), respectively. In all 64 cases, in terms of the reliability between two sonographers for three representative US parameters (amount of ascites, GB wall thickening, and appearance of PUV blood flow signal), the median concordance rate was more than 98% (95% CI: 86-106%). CONCLUSION: The inter- and intra-reliabilities of HokUS-10 were excellent. Thus, US might be a reliable tool for SOS/VOD diagnosis.
  • Second primary malignancy after rituximab-containing immunochemotherapy for diffuse large B cell lymphoma.
    Yoshiaki Chinen; Kazuna Tanba; Ryo Takagi; Hitoji Uchiyama; Nobuhiko Uoshima; Kazuho Shimura; Shin-Ichi Fuchida; Miki Kiyota; Mitsushige Nakao; Taku Tsukamoto; Yuji Shimura; Tsutomu Kobayashi; Shigeo Horiike; Katsuya Wada; Chihiro Shimazaki; Hiroto Kaneko; Yutaka Kobayashi; Masafumi Taniwaki; Isao Yokota; Junya Kuroda
    Leukemia & lymphoma, 61, 14, 3378, 3386, 2020年12月, ［国際誌］
    英語, 研究論文（学術雑誌）, Extended post-therapy long-term survival of patients with diffuse large B cell lymphoma (DLBCL) may also lead to an increase of late adverse events. We retrospectively investigated the frequency and clinical manifestation of second primary malignancy (SPM) after rituximab-containing immunochemotherapy in patients with DLBCL treated at seven institutes belonging to the Kyoto Clinical Hematology Study Group (KOTOSG) from the perspective of the existence of past or synchronous cancer history. In a median follow-up period of 899 days, 69 SPMs were observed in 58 of 809 patients. The most frequent SPM was gastric cancer, followed by lung cancer and colorectal cancer. The cumulative incidence of SPM increased steadily over time and was not significantly influenced by the presence or absence of past or synchronous cancer history. Our study suggests the need for careful attention to SPM in patients with DLBCL in daily practice.
  • SOS/VOD評価における超音波検査スコアHokUS-3の検者再現性に関する検討
    岩井 孝仁; 西田 睦; 工藤 悠輔; 高杉 莉佳; 横田 勲; 高木 諒; 渋谷 斉; 高橋 秀一郎; 杉田 純一; 豊嶋 崇徳
    超音波医学, 47, Suppl., S344, S344, (公社)日本超音波医学会, 2020年11月
    日本語
  • Analysis of the optimal psoas muscle mass index cut-off values, as measured by computed tomography, for the diagnosis of loss of skeletal muscle mass in Japanese people.
    Masatsugu Ohara; Goki Suda; Megumi Kimura; Osamu Maehara; Tomoe Shimazaki; Taku Shigesawa; Kazuharu Suzuki; Akihisa Nakamura; Naoki Kawagishi; Masato Nakai; Takuya Sho; Mitsuteru Natsuizaka; Kenichi Morikawa; Koji Ogawa; Tomoe Kobayashi; Minoru Uebayashi; Ryo Takagi; Isao Yokota; Tsuyoshi Shimamura; Naoya Sakamoto
    Hepatology research : the official journal of the Japan Society of Hepatology, 50, 6, 715, 725, 2020年06月, ［国際誌］
    英語, 研究論文（学術雑誌）, UNLABELLED: This study aimed to determine the optimal psoas muscle mass index (PMI) cut-off values for diagnosis of skeletal muscle mass loss. METHODS: We evaluated PMI in two groups of normal controls: a medical check-up group and a liver donation candidate group. We analyzed two novel PMI cut-off values, one based on the mean - two standard deviations (2SD) and one based on the lower 5%. Skeletal muscle mass index (SMI) evaluations using computed tomography (sliceOmatic; TomoVision) and bioelectrical impedance analysis and PMI evaluation were undertaken simultaneously. We analyzed the correlation between our PMI cut-off values and the Japan Society of Hepatology-defined SMI cut-off values. The prevalence of skeletal muscle mass loss in patients with liver disease was assessed using the novel PMI cut-off values. RESULTS: In 504 normal controls aged ≤50 years, the PMI cut-off values based on mean -2SD and the lower 5% were set at 3.30 cm2 /m2 for men and 1.69 cm2 /m2 for women and 3.74 cm2 /m2 for men and 2.29 cm2 /m2 for women, respectively. The PMI cut-off values based on the lower 5% alone showed that skeletal muscle mass loss increased with age. Furthermore, they correlated well with Japan Society of Hepatology-defined SMI (sliceOmatic) cut-off values and showed a significantly higher prevalence of skeletal muscle mass loss in patients with liver cirrhosis than those without liver cirrhosis. CONCLUSIONS: We propose the following PMI cut-off values: 3.74 cm2 /m2 for male individuals and 2.29 cm2 /m2 for female individuals. These cut-off values can facilitate accurate diagnosis and management of sarcopenia in patients with chronic liver disease.
  • Comparison of the efficacy of cryotherapy and compression therapy for preventing nanoparticle albumin-bound paclitaxel-induced peripheral neuropathy: A prospective self-controlled trial.
    Yuko Kanbayashi; Koichi Sakaguchi; Takeshi Ishikawa; Yoshimi Ouchi; Katsuhiko Nakatsukasa; Yusuke Tabuchi; Fuminao Kanehisa; Minako Hiramatsu; Ryo Takagi; Isao Yokota; Norito Katoh; Tetsuya Taguchi
    Breast (Edinburgh, Scotland), 49, 219, 224, 2020年02月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Recently, the efficacy of cryotherapy and compression therapy to prevent taxane-induced peripheral neuropathy has been reported. We prospectively compared the efficacy of cryotherapy using a frozen glove (FG) and compression therapy using a surgical glove (SG) to prevent nanoparticle albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy. PATIENTS AND METHODS: Breast cancer patients who received 260 mg/m2 of nab-PTX were eligible to participate in this trial. Patients wore a FG on one hand (60 min) without changing and two SGs of the same size (i.e., one size smaller than the size that best fit their hand) on the other hand (90 min) during chemotherapy. Peripheral neuropathy was evaluated at each treatment cycle using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, the Patient Neurotoxicity Questionnaire (PNQ), and the Functional Assessment of Cancer Therapy-Taxane subscale. Temperatures at each fingertip in both groups were measured thermographically. RESULTS: Between August 2017 and March 2019, 43 patients were enrolled and 38 were evaluated. No cases showed discordance of peripheral neuropathy between each gloved group in cases of CTCAE ≥ grade 2. In cases of PNQ ≥ grade D, using the Nam equivalence test, the upper test (P = 0.0329) and lower test (P = 0.0052) both showed negative results in comparisons between each gloved group. Fingertip temperature was significantly lower in the FG group than in the SG group after treatment (P < 0.0001). CONCLUSIONS: It seems to be no difference in incidence of nab-PTX-induced peripheral neuropathy using either cryotherapy or compression therapy.
  • Effects of dapagliflozin and/or insulin glargine on beta cell mass and hepatic steatosis in db/db mice.
    Kazuno Omori; Akinobu Nakamura; Hideaki Miyoshi; Kiyohiko Takahashi; Naoyuki Kitao; Hiroshi Nomoto; Hiraku Kameda; Kyu Yong Cho; Ryo Takagi; Kanako C Hatanaka; Yasuo Terauchi; Tatsuya Atsumi
    Metabolism: clinical and experimental, 98, 27, 36, 2019年09月, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVE: To explore the beneficial effects of dapagliflozin and/or insulin glargine on the pancreatic beta cell mass and hepatic steatosis in db/db mice. METHODS: Six-week-old db/db mice were assigned to one of four groups: untreated (Placebo), treated with dapagliflozin (Dapa), treated with insulin glargine (Gla), or treated with dapagliflozin and insulin glargine (Dapa+Gla). After 8 weeks of treatment, we determined glucose tolerance, beta cell mass, hepatic lipid content and gene expression. RESULTS: Glucose tolerance was significantly ameliorated in the three treated groups to the same degree compared with the Placebo group. Immunohistochemical analysis revealed that the pancreatic beta cell mass was significantly maintained in the Dapa and Dapa+Gla groups, but not in the Gla group, compared with the Placebo group (Placebo 2.25 ± 1.44 mg, Dapa 5.01 ± 1.63 mg, Gla 3.79 ± 0.96 mg, Dapa+Gla 5.19 ± 1.78 mg). However, the triglyceride content of the liver was markedly elevated in the Gla group compared with that in the other three groups (Placebo 24.1 ± 11.5 mg, Dapa 30.6 ± 12.9 mg, Gla 128 ± 49.7 mg, Dapa+Gla 54.4 ± 14.1 mg per gram liver). The expression levels of genes related to fatty acid synthesis and lipid storage were significantly upregulated in the Gla group. CONCLUSIONS: Our results showed that beta cell mass was sustained and hepatic steatosis was prevented, after 8 weeks of treatment with either dapagliflozin or dapagliflozin plus insulin glargine, but not with insulin glargine alone, in db/db mice.
  • Comparison of the average surviving fraction model with the integral biologically effective dose model for an optimal irradiation scheme.
    Ryo Takagi; Yuriko Komiya; Kenneth L Sutherland; Hiroki Shirato; Hiroyuki Date; Masahiro Mizuta
    Journal of radiation research, 59, suppl_1, i32-i39, 2018年03月01日, ［国際誌］
    英語, 研究論文（学術雑誌）, In this paper, we compare two radiation effect models: the average surviving fraction (ASF) model and the integral biologically effective dose (IBED) model for deriving the optimal irradiation scheme and show the superiority of ASF. Minimizing the effect on an organ at risk (OAR) is important in radiotherapy. The biologically effective dose (BED) model is widely used to estimate the effect on the tumor or on the OAR, for a fixed value of dose. However, this is not always appropriate because the dose is not a single value but is distributed. The IBED and ASF models are proposed under the assumption that the irradiation is distributed. Although the IBED and ASF models are essentially equivalent for deriving the optimal irradiation scheme in the case of uniform distribution, they are not equivalent in the case of non-uniform distribution. We evaluate the differences between them for two types of cancers: high α/β ratio cancer (e.g. lung) and low α/β ratio cancer (e.g. prostate), and for various distributions i.e. various dose-volume histograms. When we adopt the IBED model, the optimal number of fractions for low α/β ratio cancers is reasonable, but for high α/β ratio cancers or for some DVHs it is extremely large. However, for the ASF model, the results keep within the range used in clinical practice for both low and high α/β ratio cancers and for most DVHs. These results indicate that the ASF model is more robust for constructing the optimal irradiation regimen than the IBED model.
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