Papers - Hirata, Kenro

Multiple immune-related adverse events and anti-tumor efficacy: Real-world data on various solid tumors

Shimozaki K., Sukawa Y., Beppu N., Kurihara I., Suzuki S., Mizuno R., Funakoshi T., Ikemura S., Tsugaru K., Togasaki K., Kawasaki K., Hirata K., Hayashi H., Hamamoto Y., Takaishi H., Kanai T.

Cancer Management and Research (Cancer Management and Research)  12   4585 - 4593 2020

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Purpose: Immune checkpoint inhibitors (ICIs) have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in real-world practice. Patients and Methods: We conducted a retrospective study on patients with recurrent or metastatic non-small-cell lung cancer, malignant melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model and the shared frailty model. Results: Of 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. The median OS was significantly longer in the irAEs than in the no-irAE group (28.1 months vs 12.7 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.33–0.73; P = 0.0004). Moreover, the OS of patients with multiple irAEs was significantly longer than that of patients with a single irAE (42.3 months vs 18.8 months; HR, 0.473; 95% CI, 0.346–0.647; P < 0.0001). Conclusion: Our single-center retrospective study revealed a significant tendency associating the development of multiple irAEs with favorable prognoses.

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Pancreatic fat content may increase the risk of imaging progression in low-risk branch duct intraductal papillary mucinous neoplasm

Kashiwagi K., Minami K., Seino T., Hirata K., Iwasaki E., Inoue N., Iwao Y., Kanai T.

Journal of Digestive Diseases (Journal of Digestive Diseases)  20 ( 10 ) 557 - 562 2019.10

ISSN  17512972

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© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd Objective: To identify risk factors of imaging progression (increase in cyst size or main pancreatic duct size, or a new mural nodule) in low-risk branch duct intraductal papillary mucinous neoplasm (BD-IPMN), including obesity-related factors such as pancreatic fat content. Methods: Our hospital databases were searched for patients who had completed health checkup, including upper abdominal magnetic resonance imaging (MRI) over 48 months (August 2012 to July 2016). Individuals with BD-IPMN without worrisome features and high-risk stigmata who underwent surveillance with at least one follow-up MRI, irrespective of the follow-up period, were included. Pancreatic computed tomography attenuation indexes were defined as the difference between the pancreas and spleen attenuation (P - S) and the pancreas to spleen attenuation ratio (P/S). Results: Among 75 patients diagnosed as having low-risk BD-IPMN, during a median follow-up of 36 months, 11 (15%) had imaging progression in cyst size, including two with worrisome features. A multivariate logistic analysis showed that the initial cyst size and both indexes (P - S, or P/S) were significantly associated with imaging progression in IPMN, respectively (Model 1: odds ratio [OR] 1.188, 95% confidence interval [CI] 1.060-1.331, P = 0.003; OR 0.871, 95% CI 0.776-0.977, P = 0.019; Model 2: OR 1.186, 95% CI 1.064-1.322, P = 0.002; OR 0.002, 95% CI 0.000-0.970, P = 0.049). Conclusions: Pancreatic fat content and initial cyst size were significantly associated with imaging progression in low-risk BD-IPMN. Revisions of international consensus Fukuoka guidelines might be customized based on initial cyst size and pancreatic fat content.

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Unmet needs of cancer patients with chemotherapy-related hand-foot syndrome and targeted therapy-related hand-foot skin reaction: A qualitative study

Komatsu H., Yagasaki K., Hirata K., Hamamoto Y.

European Journal of Oncology Nursing (European Journal of Oncology Nursing)  38   65 - 69 2019.02

ISSN  14623889

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© 2018 Purpose: The objective of this qualitative study was to understand the perceived needs of advanced-stage cancer patients with chemotherapy-related hand-foot syndrome (HFS) and/or targeted therapy-related hand-foot skin reaction (HFSR). Method: Face-to-face interviews were conducted with 20 outpatients with advanced/recurrent cancer and chemotherapy-related HFS and/or targeted therapy-related HFSR using a semi-structured interview guide at Keio University Hospital, Tokyo, Japan. Thematic analysis was used to analyse the data. Results: The unmet needs of cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR was identified through four themes: a sense of helplessness with persistent symptoms, noticeable appearance as a barrier to social participation, decreased willingness to work and continue treatment, and need of individual coping strategies. Conclusion: This study revealed unmet needs of cancer patients with chemotherapy-related HFS and/or targeted therapy-related HFSR that are not often voiced. Health care providers should provide full information in advance and find the best coping strategy for individual patients.

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Early administration of systemic chemotherapy should be considered for scirrhous gastric cancer: A case report

Aoki Y, Hamamoto Y, Ugamura A, Togasaki K, Suzuki T, Kawasaki K, Hirata K, Kasuga A, Sukawa Y, Kanai T, Takaishi H.

Mol Clin Oncol 10 ( 1 ) 113 - 117 2019

Research paper (scientific journal), Joint Work, Accepted

集学的治療を要する頸部食道がん

平田　賢郎

内科 123 ( 4 ) 549 - 550 2019

Research paper (scientific journal), Single Work

Inhibiting xCT improves 5-fluorouracil resistance of gastric cancer induced by CD44 variant 9 expression

Miyoshi S., Tsugawa H., Matsuzaki J., Hirata K., Mori H., Saya H., Kanai T., Suzuki H.

Anticancer Research (Anticancer Research)  38 ( 11 ) 6163 - 6170 2018.11

ISSN  02507005

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© 2018 International Institute of Anticancer Research.All right reserved. Background/Aim: Cancer stem cells (CSCs) play a critical role in resistance to chemotherapy. CD44 is a cell surface marker of CSCs. CD44 variant 9 (CD44v9) interacts with a cystine-glutamate antiporter (xCT) and is an unfavorable predictive factor in gastric cancer. We investigated the impact of CD44v9 expression on 5-fluorouracil (5-FU) resistance and the efficacy of the xCT inhibitor, sulfasalazine (SASP), in improving drug resistance. Materials and Methods: The human gastric cancer cell line MKN28 was transfected with pRc/CMV plasmids encoding human CD44 or CD44v9, which were used for in vitro and in vivo experiments. Results: CD44v9 expression results in 5-FU resistance by increasing intracellular glutathione and suppressing the drug-induced production of reactive oxygen species (ROS). SASP improved the drug sensitivity of CD44v9-expressing cells. Conclusion: Inhibition of xCT improved the clinical efficacy of chemotherapy against gastric cancer. CD44v9 expression can be a novel biomarker to predict resistance against 5-FU in gastric cancer.

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Post-progression survival following second-line chemotherapy in patients with advanced pancreatic cancer previously treated with gemcitabine: a meta-analysis

Kasuga A., Hamamoto Y., Takeuchi A., Okano N., Togasaki K., Aoki Y., Suzuki T., Kawasaki K., Hirata K., Sukawa Y., Kanai T., Takaishi H.

Investigational New Drugs (Investigational New Drugs)  36 ( 5 ) 939 - 948 2018.10

ISSN  01676997

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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Background Post-progression survival (PPS) could be a confounding element in interpreting data from clinical trials of second-line chemotherapy in patients with advanced pancreatic cancer (PC) previously treated with gemcitabine (GEM) because a recent meta-analysis of oxaliplatin combination therapy showed statistical heterogeneity for overall survival (OS) but not for progression-free survival (PFS). This study aimed to improve the understanding of the impact of PPS on OS in this setting. Methods Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. We evaluated relationships between OS and PFS, PPS, and other variables. Results Totally, 17 RCTs with 3253 patients were identified. Median OS was strongly and moderately associated with median PPS and PFS, respectively (r = 0.913; p < 0.001 and 0.780; p < 0.001, respectively). The proportion of patients with good performance status was significantly associated with both PPS and PFS (r = 0.574, p < 0.001 and 0.492, p < 0.001, respectively). The induction rate of subsequent chemotherapy was related to the duration of PPS and OS (r = 0.640, p < 0.001 and 0.647, p < 0.001, respectively). Median PPS and OS were significantly longer in recent trials than those in older trials (3.55 versus 2.78 months, p < 0.001 and 6.29 versus 5.02 months, p < 0.001). Conclusions Median PPS was strongly correlated with median OS. Given the recently increased opportunity for subsequent chemotherapy and supportive care, PPS may serve as an important element to clarify problems in this setting.

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免疫チェックポイント阻害薬の自己免疫疾患関連副作用(irAE)としての腸炎

下嵜啓太郎、平田賢郎

IBD Research 12 ( 4 ) 247 - 253 2018

Research paper (scientific journal), Joint Work

再発食道癌の治療　化学療法・化学放射線療法

下嵜啓太郎、平田賢郎、浜本康夫

日本臨床 76 ( 8 ) 417 - 423 2018

Research paper (scientific journal), Joint Work

【免疫チェックポイント療法の新潮流】消化器癌治療における位置付けと今後の展望

津軽開、平田賢郎、浜本康夫

医薬ジャーナル 54 ( 8 ) 1849 - 1852 2018

Research paper (scientific journal), Joint Work

Complications and outcomes of routine endoscopy in the very elderly

Miyanaga R, Hosoe N, Naganuma M, Hirata K, Fukuhara S, Nakazato Y, Ojiro K, Iwasaki E, Yahagi N, Ogata H, Kanai T.

Endosc Int Open 6 ( 2 ) E224 - E229 2018

Research paper (scientific journal), Joint Work, Accepted,  ISSN  2364-3722

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BACKGROUND AND STUDY AIMS:  In Japan, the elderly population has been increasing annually. The number of elderly patients for whom esophagogastroduodenoscopy (EGD) and colonoscopy (CS) is indicated also has been rising. The aim of this study was to evaluate the safety and efficacy of routine endoscopy in a cohort of octogenarians aged 85 years and older - defined by the World Health Organization as the very elderly. PATIENTS AND METHODS:  A total of 5,586 patients underwent EGDs, and 2,484 patients underwent CSs performed at the Keio University Hospital from January to September 2014. One hundred eighty-five EGDs and 70 of the CS were performed in the very elderly. Six hundred nine EGDs and 262 CS were performed on younger patients (aged forties). Statistical analysis was performed by univariate and multivariate analyses. RESULTS:  On univariate analysis, the rate of adverse events (AEs) in the very elderly was significantly higher compared to the younger group (6.3 % vs. 1.1 %; P  < 0.01). Moreover, the very elderly cohort received substantial therapeutic intervention as compared to the younger (16.9 % vs. 6.9 %; P  < 0.01). On multivariate analysis, independent risk factors of AEs included: very elderly patients (odds ratio (OR) 3.30, 95 % confidence interval (CI) 1.05 - 10.35), inpatients (OR 3.22, 95 % CI 1.34 - 7.74), and use of pethidine hydrochloride prescription (OR 3.44, 95 % CI 1.51 - 7.81). CONCLUSIONS:  Routine endoscopy in the very elderly incurs a significant risk of AEs, particularly when combined with pethidine hydrochloride prescription.

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C型慢性肝炎/代償性肝硬変患者に対するオムビタスビル/パリダプレビル/リトナビル併用療法およびソフォスブビル/レジパスビル併用療法における治療前因子、治療効果、副作用についての検討

済生会医学・福祉共同研究    62 - 66 2018

Research paper (bulletin of university, research institution), Joint Work

Inter‑evaluator heterogeneity of clinical diagnosis for locally advanced esophageal squamous cell carcinoma.

Kenro Hirata

Esophagus  2017

Research paper (scientific journal)

Benefit of rebiopsy for deciding treatment strategy in rectal cancer: A case report.

Kenro Hirata

Oncol Lett 14 ( 3 ) 3697 - 3700 2017

Research paper (scientific journal)

Positive relationship between subsequent chemotherapy and overall survival in pancreatic cancer: meta-analysis of postprogression survival for first-line chemotherapy.

Kenro Hirata

Cancer Chemother Pharmacol 79 ( 3 ) 595 - 602 2017

Research paper (scientific journal)

Soft palatal melanosis, a simple predictor for neoplasia in the upper aerodigestive tract in Japanese alcoholic men

Kenro Hirata

Cancer Sci 108 ( 5 ) 1058 - 1064 2017

Research paper (scientific journal), Joint Work

主な抗がん薬と使用上の注意点 血管新生阻害薬

平田賢郎、青木優、浜本康夫、高石官均

腎と透析 83 ( 5 ) 737 - 739 2017

Research paper (scientific journal), Joint Work

C型慢性肝炎患者(セログループI)に対するダクルインザ・スンベプラ併用療法における治療前因子及び治療効果の検討

済生会医学・福祉共同研究  2017

Research paper (bulletin of university, research institution), Joint Work

Presence of columnar-lined esophagus is negatively associated with the presence of esophageal varices in Japanese alcoholic men.

Yokoyama A, Hirata K, Nakamura R, Omori T, Mizukami T, Aida J, Maruyama K, Yokoyama T.

World J Gastroenterol 23 ( 39 ) 7150 - 7159 2017

Research paper (scientific journal), Joint Work, Accepted

Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study.

Kenro Hirata

United European Gastroenterology Journal 4 ( 3 ) 380 - 387 2016

Research paper (scientific journal)