Characteristics of MUTYH variants in Japanese colorectal polyposis patients.

PubMed

Takao, Misato; Yamaguchi, Tatsuro; Eguchi, Hidetaka; Tada, Yuhki; Kohda, Masakazu; Koizumi, Koichi; Horiguchi, Shin-Ichiro; Okazaki, Yasushi; Ishida, Hideyuki

2018-06-01

The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer. Since few studies have investigated the genotype-phenotype association in Japanese patients with MUTYH variants, the aim of this study was to clarify the clinicopathological findings in Japanese patients with MUTYH gene variants who were detected by screening causative genes associated with hereditary colorectal polyposis. After obtaining informed consent, genetic testing was performed using target enrichment sequencing of 26 genes, including MUTYH. Of the 31 Japanese patients with suspected hereditary colorectal polyposis, eight MUTYH variants were detected in five patients. MUTYH hotspot variants known for Caucasians, namely p.G396D and p.Y179D, were not among the detected variants.Of five patients, two with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis, while two others had monoallelic MUTYH variants. One patient had the p.P18L and p.G25D variants on the same allele; however, supportive data for considering these two variants 'pathogenic' were lacking. Two patients with biallelic MUTYH variants and two others with monoallelic MUTYH variants were identified among Japanese colorectal polyposis patients. Hotspot variants of the MUTYH gene for Caucasians were not hotspots for Japanese patients.

Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study.

PubMed

Shigekawa, Takashi; Osaki, Akihiko; Sekine, Hiroshi; Sato, Nobuaki; Kanbayashi, Chizuko; Sano, Hiroshi; Takeuchi, Hideki; Ueda, Shigeto; Nakamiya, Noriko; Sugitani, Ikuko; Sugiyama, Michiko; Shimada, Hiroko; Hirokawa, Eiko; Takahashi, Takao; Saeki, Toshiaki

2015-04-10

Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy in Japanese patients with locally advanced prostate cancer.

PubMed

Sakamoto, Masato; Mizowaki, Takashi; Mitsumori, Michihide; Takayama, Kenji; Sasai, Keisuke; Norihisa, Yoshiki; Kamoto, Toshiyuki; Nakamura, Eijiro; Ogawa, Osamu; Hiraoka, Masahiro

2010-12-01

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with locally advanced prostate cancer who initiated salvage hormonal therapy (SHT) at a relatively early phase were evaluated. Between April 1998 and April 2003, 70 Japanese patients with T3N0M0 prostate cancer who received radical 3D-CRT treatment were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were 73 years old, 26.3 ng/ml, and 4 months, respectively. Seventy grays were given in 35 fractions that were confined to the prostate and seminal vesicles. Adjuvant hormonal therapy was not administered after 3D-CRT in any of the cases. The median follow-up period was 64.9 months. The median PSA value at the time of initiation of SHT was 5.0 ng/ml (range 0.1-21.6 ng/ml). Overall, disease-specific, PSA failure-free (based on the Phoenix definition) and SHT-free survival rates at 5 years were 90.3% (95% CI 86.5-94.0), 96.5% (94.0-98.9), 60.5% (48.2-72.7), and 63.5% (57.2-69.8), respectively. Therefore, two-thirds of the patients were still hormone-free at 5 years. PSA control rates in our series of Japanese patients with stage T3N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed higher than expected. This approach involving 3D-CRT combined with NAHT with the initiation of SHT at PSA values of around 5 ng/ml may be one option for Japanese patients with locally advanced prostate cancer, although further prospective study is required to confirm the validity.

Differences in K-ras and mitochondrial DNA mutations and microsatellite instability between colorectal cancers of Vietnamese and Japanese patients.

PubMed

Miwata, Tomohiro; Hiyama, Toru; Quach, Duc Trong; Le, Huy Minh; Hua, Ha Ngoc Thi; Oka, Shiro; Tanaka, Shinji; Arihiro, Koji; Chayama, Kazuaki

2014-11-30

The incidence of early-onset (under 50 years of age) colorectal cancer (CRC) in the Vietnamese has been reported to be quite higher than that in the Japanese. To clarify the differences in genetic alterations between Vietnamese and Japanese CRCs, we investigated mutations in K-ras and mitochondrial DNA (mtDNA) and high-frequency microsatellite instability (MSI-H) in the CRCs of Vietnamese and Japanese patients. We enrolled 60 Vietnamese and 233 Japanese patients with invasive CRCs. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections. K-ras mutations were examined with PCR-single-strand conformation polymorphism analysis. mtDNA mutations and MSI-H were examined with microsatellite analysis using D310 and BAT-26, respectively. K-ras mutations were examined in 60 Vietnamese and 45 Japanese CRCs. The frequency of the mutations in the Vietnamese CRCs was significantly higher than that in the Japanese CRCs (8 of 24 [33%] vs 5 of 45 [11%], p =0.048). MSI-H was examined in 60 Vietnamese and 130 Japanese CRCs. The frequency of MSI-H in the Vietnamese CRCs was also significantly higher than that in the Japanese CRCs (6 of 27 [22%] vs 10 of 130 [8%], p =0.030). mtDNA mutations were examined in 60 Vietnamese and 138 Japanese CRCs. The frequency of mtDNA mutations in the Vietnamese CRCs was significantly higher than that in the Japanese CRCs (19 of 44 [43%] vs 11 of 133 [9%], p <0.001). There were no significant differences in clinicopathologic characteristics, such as age, sex, tumour location, and depth, in terms of tumours with/without each genetic alteration in the CRCs of the Vietnamese and Japanese patients. These results indicate that the developmental pathways of CRCs in the Vietnamese may differ from those of CRCs in the Japanese.

Clinical characteristics and oncological outcomes of testicular cancer patients registered in 2005 and 2008: the first large-scale study from the Cancer Registration Committee of the Japanese Urological Association.

PubMed

Miki, Tsuneharu; Kamoi, Kazumi; Fujimoto, Hiroyuki; Kanayama, Hiro-omi; Ohyama, Chikara; Suzuki, Kazuhiro; Nishiyama, Hiroyuki; Eto, Masatoshi; Naito, Seiji; Fukumori, Tomoharu; Kubota, Yoshinobu; Takahashi, Satoru; Mikami, Kazuya; Homma, Yukio

2014-08-01

To describe the clinical and pathological characteristics and oncological outcomes of testicular cancer diagnosed in Japan, we report the results of the testicular cancer registration carried out by the Japanese Urological Association. Testicular cancer survey was conducted by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. The survey included details such as age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, initial treatment and clinical outcomes. We analyzed 1121 cases of testicular primary germ cell tumor among 1157 registered patients. The median age was 37.0 years. Seminomas and non-seminomatous germ cell tumors accounted for 61.9% and 38.1%, respectively. Measurements of tumor markers were documented in 98.6% of the patients; however, there was an unsatisfactory uniform measurement of human chorionic gonadotropin, which made it difficult to evaluate the International Germ Cell Consensus Classification in all patients. The 1- and 3-year overall survival rates from the entire cohort were 98.3% and 96.8%, respectively. According to the International Germ Cell Consensus Classification, 3-year overall survival rates in the good, intermediate, and poor prognosis group were 99.1%, 100% and 79.9%, respectively. The present report is the first large-scale study of the characteristics and survival of testicular cancer patients in Japan based on multi-institutional registry data, and showed a good prognosis even in an advanced stage. The improved survival attributed substantially to accurate diagnosis and effective multimodal treatment. © 2014 The Japanese Urological Association.

Providing written information increases patient satisfaction: a web-based questionnaire survey of Japanese cancer survivors.

PubMed

Sakai, Hitomi; Katsumata, Noriyuki; Takahashi, Miyako

2017-07-01

The Institute of Medicine (IOM) of the United States recommends that all cancer survivors be provided with a survivorship care plan (SCP), which includes a patient treatment summary and a follow-up care plan. However, SCPs have not been widely adopted in Japan. To provide basic data necessary for implementing SCPs in Japan, we aimed to investigate the forms of clinical and survivorship-related information that Japanese cancer survivors receive from their healthcare providers, and to examine whether written information increases their satisfaction. We performed a cross-sectional online survey of cancer survivors who underwent acute cancer treatment and had at least one follow-up with a physician in the past year. Cancer survivors provided the elements and forms (verbally and/or written) of information they received, as well as the degree of satisfaction with the information provided. Responses were obtained from 545 cancer survivors. Information elements such as surgical procedure (98.3%), surgical outcome (98.1%), and names of administered chemotherapy agents (97.8%) were commonly provided, whereas mental care resources and providers (29.7%), effects on marital relationship and sexual health (35.7%), and effects on fertility (43.4%) were less common. A large proportion of cancer survivors received verbal information only. For 18 of 20 elements, except for effects on fertility and duration of hormonal therapy, satisfaction was significantly higher when both forms of information were provided (P < 0.05). Providing written and verbal explanations of clinical and survivorship-related information can better meet the needs of Japanese cancer survivors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer-updated results.

PubMed

Kimura, Go; Ueda, Takeshi

2017-03-01

A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28-1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18-0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. © The Author 2016. Published by Oxford University Press.

Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

PubMed

Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

2018-01-01

The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Comparison of clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients with colorectal cancer: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

PubMed

Yamaguchi, Tatsuro; Furukawa, Yoichi; Nakamura, Yusuke; Matsubara, Nagahide; Ishikawa, Hideki; Arai, Masami; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Moriya, Yoshihiro; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

2015-02-01

The characteristics of familial colorectal cancer type X are poorly defined. Here we aimed to clarify the differences in clinical features between suspected familial colorectal cancer type X and Lynch syndrome in Japanese patients. We performed germline mutation analyses of mismatch repair genes in 125 patients. Patients who met the Amsterdam Criteria I but lacked mismatch repair gene mutations were diagnosed with suspected familial colorectal cancer type X. We identified 69 patients with Lynch syndrome and 25 with suspected familial colorectal cancer type X. The frequencies of gastric and extracolonic Lynch syndrome-associated cancers were lower with suspected familial colorectal cancer type X than with Lynch syndrome. The number of organs with Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. The cumulative incidence of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. We estimated that the median cancer risk in 60-year-old patients with Lynch syndrome was 89, 36 and 24% for colorectal, endometrial and gastric cancers, respectively. Analyses of family members, including probands, revealed that the median age at diagnosis of extracolonic Lynch syndrome-associated cancer was significantly older with suspected familial colorectal cancer type X than with Lynch syndrome. The frequency of extracolonic Lynch syndrome-associated cancer was significantly lower with suspected familial colorectal cancer type X than with Lynch syndrome. A significant difference in extracolonic Lynch syndrome-associated cancer was evident between suspected familial colorectal cancer type X and Lynch syndrome. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Family history, body mass index and survival in Japanese patients with stomach cancer: a prospective study.

PubMed

Minami, Yuko; Kawai, Masaaki; Fujiya, Tsuneaki; Suzuki, Masaki; Noguchi, Tetsuya; Yamanami, Hideaki; Kakugawa, Yoichiro; Nishino, Yoshikazu

2015-01-15

Family history and nutritional status may affect the long-term prognosis of stomach cancer, but evidence is insufficient and inconsistent. To clarify the prognostic factors of stomach cancer, we conducted a prospective study of 1,033 Japanese patients with histologically confirmed stomach cancer who were admitted to a single hospital between 1997 and 2005. Family history of stomach cancer and pretreatment body mass index (BMI) were assessed using a self-administered questionnaire. Clinical data were retrieved from a hospital-based cancer registry. All patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to family history in parents and siblings and BMI category. During a median follow-up of 5.3 years, 403 all-cause and 279 stomach cancer deaths were documented. Although no association with family history was observed in the patients overall, analysis according to age group found an increased risk of all-cause death associated with a history in first degree relatives (HR = 1.61, 95% CI: 0.93-2.78, p = 0.09) and with a parental history (HR = 1.86, 95% CI: 1.06-3.26) among patients aged under 60 years at diagnosis. BMI was related to all-cause and stomach cancer death among patients aged 60 and over, showing a J-shaped pattern (HR of all-cause death = 2.28 for BMI < 18.5; HR = 1.61 for 25 ≤ vs. ≥ 23.0 to < 25.0 kg/m(2)). A family history of stomach cancer, especially parental history, may affect mortality among younger stomach cancer patients, whereas nutritional status may be a prognostic factor in older patients. © 2014 UICC.

UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients.

PubMed

Onoue, Masahide; Terada, Tomohiro; Kobayashi, Masahiko; Katsura, Toshiya; Matsumoto, Shigemi; Yanagihara, Kazuhiro; Nishimura, Takafumi; Kanai, Masashi; Teramukai, Satoshi; Shimizu, Akira; Fukushima, Masanori; Inui, Ken-ichi

2009-04-01

Gene polymorphisms of the UDP-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) contribute to individual variations in adverse events among patients administered irinotecan, and the distribution of the polymorphisms shows large interethnic differences. Variation in the solute carrier organic anion-transporter family, member 1B1 (SLCO1B1) gene also has a significant effect on the disposition of irinotecan in Asian cancer patients. In the present study, we evaluated the association of genetic polymorphisms of UGT1A1 and SLCO1B1 with irinotecanrelated neutropenia in Japanese cancer patients. One hundred and thirty-five consecutive patients treated with irinotecan were enrolled. Genotypes of UGT1A1 (*60, *28, *6, and *27) and SLCO1B1 (*1b, *5, and haplotype *15) were determined by direct sequencing. Severe neutropenia refers to events observed during the first cycle of irinotecan treatment. Severe neutropenia was observed in 29 patients (22%). Six patients were homozygous and 48 heterozygous for UGT1A1*6. Only 1 patient was homozygous for UGT1A1*28. Homozygosity for UGT1A1*6 was associated with a high risk of severe neutropenia (odds ratio [OR], 7.78; 95% confidence interval [CI], 1.36 to 44.51). No significant association was found between severe neutropenia and other UGT1A1 polymorphisms or SLCO1B1 polymorphisms. These findings suggest that the UGT1A1*6 polymorphism is a potential predictor of severe neutropenia caused by irinotecan in Japanese cancer patients.

Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, Third Edition.

PubMed

Yamazaki, Kentaro; Taniguchi, Hiroya; Yoshino, Takayuki; Akagi, Kiwamu; Ishida, Hideyuki; Ebi, Hiromichi; Nakatani, Kaname; Muro, Kei; Yatabe, Yasushi; Yamaguchi, Kensei; Tsuchihara, Katsuya

2018-06-01

The Japanese Society of Medical Oncology (JSMO) previously published 2 editions of the clinical guidelines: "Japanese guidelines for testing of KRAS gene mutation in colorectal cancer" in 2008 and "Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients" in 2014. These guidelines have contributed to the proper use of KRAS and RAS mutation testing, respectively. Recently, clinical utility, particularly for colorectal cancer (CRC) patients with BRAF V600E mutation or DNA mismatch-repair (MMR) deficiency, has been established. Therefore, the guideline members decided these genetic alterations should also be involved. The aim of this revision is to properly carry out testing for BRAF V600E mutation and MMR deficiency in addition to RAS mutation. The revised guidelines include the basic requirements for testing for these genetic alterations based on recent scientific evidence. Furthermore, because clinical utility of comprehensive genetic testing using next-generation sequencing and somatic gene testing of analyzing circulating tumor DNA has increasingly evolved with recent advancements in testing technology, we noted the current situation and prospects for these testing technologies and their clinical implementation in the revised guidelines. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Evaluating genetic risk for prostate cancer among Japanese and Latinos

PubMed Central

Cheng, Iona; Chen, Gary K.; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy; Shen, Jess; Sheng, Xin; Pooler, Loreall C.; Crenshaw, Andrew T.; Mirel, Daniel B.; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L.; Guy, Michelle; Hamdy, Freddie C.; Kote-Jarai, Zsofia; Neal, David E.; Wilkens, Lynne R.; Monroe, Kristine R.; Stram, Daniel O.; Muir, Kenneth; Eeles, Rosalind A.; Easton, Douglas F.; Kolonel, Laurence N.; Henderson, Brian E.; Le Marchand, Loïc; Haiman, Christopher A.

2012-01-01

Background There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods Our first stage GWAS of prostate cancer included Japanese (cases/controls=1,033/1,042) and Latino (cases/controls=1,043/1,057) from the Multiethnic Cohort. Significant associations from stage 1 (P < 1.0×10−4) were examined in silico in GWAS of prostate cancer (stage 2) in Japanese (cases/controls=1,583/3,386) and Europeans (cases/controls=1,854/1,894). Results No novel stage 1 SNPs outside of known risk regions reached genome-wide significance. For Japanese, in stage 1, the most notable putative novel association was seen with 10 SNPs (P<8.0. x10−6) at chromosome 2q33; however, this was not replicated in stage 2. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR=1.45; P=7.01×10−5 and stage 2: OR=1.58; P =3.05×10−7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele=1.10; P = 2.71×10−25 and OR=1.07; P = 1.02×10−16 for Japanese and Latinos, respectively). Conclusion and Impact Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings demonstrate that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. PMID:22923026

Evaluating genetic risk for prostate cancer among Japanese and Latinos.

PubMed

Cheng, Iona; Chen, Gary K; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy C; Shen, Jess; Sheng, Xin; Pooler, Loreall C; Crenshaw, Andrew T; Mirel, Daniel B; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L; Guy, Michelle; Hamdy, Freddie C; Kote-Jarai, Zsofia; Neal, David E; Wilkens, Lynne R; Monroe, Kristine R; Stram, Daniel O; Muir, Kenneth; Eeles, Rosalind A; Easton, Douglas F; Kolonel, Laurence N; Henderson, Brian E; Le Marchand, Loïc; Haiman, Christopher A

2012-11-01

There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10(-6)) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 10(-16) for Japanese and Latinos, respectively). Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. ©2012 AACR.

Health-related quality of life in Japanese men with localized prostate cancer: assessment with the SF-8.

PubMed

Sugimoto, Mikio; Takegami, Misa; Suzukamo, Yoshimi; Fukuhara, Shunichi; Kakehi, Yoshiyuki

2008-06-01

To evaluate health related quality of life (HRQOL) using the Medical Outcomes Study 8-items Short Form Health Survey (SF-8) questionnaire in Japanese patients with early prostate cancer. A cross-sectional analysis was done in 457 patients with prostate cancer treated with radical prostatectomy, external beam radiotherapy, brachytherapy, androgen deprivation therapy, and watchful waiting or a combination these therapies. General HRQOL was measured using the Japanese version of the SF-8 questionnaire and disease-specific HRQOL was assessed using the Japanese version of the Extended Prostate Cancer Index Composite. The external beam radiotherapy group reported significantly lower values for the physical health component summary score (PCS) in comparison to the radical prostatectomy and brachytherapy groups (P < 0.05). In the analysis of both the PCS and the mental health component summary score (MCS) over time after treatment, higher scores with time were found in the radical prostatectomy group. No significant change over time after androgen deprivation therapy in the PCS was found. In contrast, the MCS was found to deteriorate in the early period, showing a significant increase over time. SF-8 in combination with the Extended Prostate Cancer Index Composite has shown to be a helpful tool in the HRQOL assessment of Japanese patients treated for localized prostate cancer.

Administrators' perspectives on end-of-life care for cancer patients in Japanese long-term care facilities.

PubMed

Fukahori, Hiroki; Miyashita, Mitsunori; Morita, Tatsuya; Ichikawa, Takayuki; Akizuki, Nobuya; Akiyama, Miki; Shirahige, Yutaka; Eguchi, Kenji

2009-10-01

The purpose of this study was to clarify administrators' perspectives on availability of recommended strategies for end-of-life (EOL) care for cancer patients at long-term care (LTC) facilities in Japan. A cross-sectional survey was conducted with administrators at Japanese LTC facilities. Participants were surveyed about their facilities, reasons for hospitalization of cancer patients, and their perspectives on availability of and strategies for EOL care. The 97 responses were divided into medical facility (n = 24) and non-medical facility (n = 73) groups according to physician availability. The most frequent reasons for hospitalization were a sudden change in patient's condition (49.4%), lack of around-the-clock care (43.0%), and inability to palliate symptoms (41.0%). About 50% of administrators believed their facilities could provide EOL care if supported by palliative care experts. There was no significant difference between facility types (P = 0.635). Most administrators (81.2%) regarded unstable cancer patients as difficult to care for. However, many (68.4%) regarded opioids given orally as easy to administer, but regarded continuous subcutaneous infusion/central venous nutrition as difficult. Almost all administrators believed the most useful strategy was transferring patients to hospitals at the request of patients or family members (96.9%), followed by consultation with palliative care experts (88.5%). Although LTC facilities in Japan currently do not provide adequate EOL care for cancer patients, improvement might be possible with support by palliative care teams. Appropriate models are necessary for achieving a good death for cancer patients. Interventions based on these models are necessary for EOL care for cancer patients in LTC facilities.

Evidence-based cancer prevention recommendations for Japanese.

PubMed

Sasazuki, S; Inoue, M; Shimazu, T; Wakai, K; Naito, M; Nagata, C; Tanaka, K; Tsuji, I; Sugawara, Y; Mizoue, T; Matsuo, K; Ito, H; Tamakoshi, A; Sawada, N; Nakayama, T; Kitamura, Y; Sadakane, A; Tsugane, S

2018-06-01

A comprehensive evidence-based cancer prevention recommendation for Japanese was developed. We evaluated the magnitude of the associations of lifestyle factors and infection with cancer through a systematic review of the literature, meta-analysis of published data, and pooled analysis of cohort studies in Japan. Then, we judged the strength of evidence based on the consistency of the associations between exposure and cancer and biological plausibility. Important factors were extracted and summarized as an evidence-based, current cancer prevention recommendation: 'Cancer Prevention Recommendation for Japanese'. The recommendation addresses six important domains related to exposure and cancer, including smoking, alcohol drinking, diet, physical activity, body weight and infection. The next step should focus on the development of effective behavior modification programs and their implementation and dissemination.

Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer.

PubMed

Hatano, Koji; Nishimura, Kazuo; Nakai, Yasutomo; Yoshida, Takahiro; Sato, Mototaka; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Uemura, Motohide; Oka, Daizo; Nakayama, Masashi; Takayama, Hitoshi; Shimizu, Kiyonori; Meguro, Norio; Tanigawa, Tsuyoshi; Yamaguchi, Seiji; Tsujimura, Akira; Nonomura, Norio

2013-08-01

A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.

Tumor development in Japanese patients with Lynch syndrome

PubMed Central

Horiguchi, Shin-ichiro; Yamada, Rin; Takao, Misato; Iijima, Takeru; Wakaume, Rika; Aruga, Tomoyuki; Tabata, Taku; Koizumi, Koichi

2018-01-01

Background Lynch syndrome (LS) patients have a high risk of developing various tumors. This study aimed to clarify the characteristics of tumors developing in LS patients. Methods This is a retrospective review of 55 LS patients treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Results The median age at the diagnosis of the first malignant tumor and first LS-related tumor was 44 (range, 19−65) and 44 (range, 24−66) years, respectively. Of the 55 LS patients with developing malignant tumors, 45 (93.8%) developed an LS-related tumor as the first malignant tumor. Colorectal cancer (CRC) developed in 47 patients (85.4%), followed by endometrial cancer (n = 13, 56.5%) in females and gastric cancer (n = 10, 18.1%). In 6 gastric cancer patients, Helicobacter pylori was detected in resected specimens. Twenty-nine patients (52.7%) developed CRC and extra-colonic tumors; of these, 15 patients (48.3%) had mutations in MLH1, 10 (58.8%) in MSH2, and 4 (57.1%) in MSH6. At the age of 50, the cumulative incidence was 50.9% [95% confidence interval (CI), 36.9−63.3%] for CRC, 17.4% (95% CI, 5.2−35.6%) for endometrial cancer, and 5.5% (95% CI, 1.4−13.8%) for gastric cancer. Eight gastric cancer, one breast cancer patient, five bladder cancer patients, and one prostate cancer patient demonstrated loss of expression of the mismatch repair (MMR) protein; patients with thyroid cancer, spindle cell sarcoma, and giant cell tumors did not demonstrate this. Conclusion Gastric cancer incidence was high in Japanese patients with LS and associated with H. pylori infection. MMR protein deficiency caused the development of malignant tumors in LS patients. PMID:29672549

Japanese Cancer Survivors' Awareness of and Participation in Support Groups.

PubMed

Hatano, Yutaka; Mitsuki, Sachiko; Hosokawa, Toyoshi; Fukui, Kenji

2018-02-01

Cancer survivors face many challenges, and cancer support groups provide a range of support. Several reports have shown the benefits of support groups. However, it is not clear how Japanese cancer survivors use them. This study aimed to examine cancer survivors' awareness of and reasons for participation or non-participation in cancer support groups. We conducted a cross-sectional questionnaire survey with ambulatory patients with cancer across eight designated cancer hospitals. The questionnaire covered patients' demographics, disease characteristics, participation/non-participation in cancer support groups, and reasons for participation/non-participation. In total, 569 questionnaires were distributed, and responses were received from 275 patients with cancer. Of these, 135 patients were aware of support groups and 23 had participated in a group. Patients who were aware of support groups were more likely to be young, female patients. Many patients learned about support groups from hospital notices. Most support group participants expected to receive information about the disease and treatment (91%). They also wanted to hear about other patients' experiences (73%). The most common reasons for non-participation were "no particular reason" (38%) and "family or friends support me" (27%). About half of participating patients were unaware of support groups. Even among patients who were aware, many did not attend a support group. Developing a better understanding of support group use in cancer survivors may enhance provision of adequate care based on individual needs.

Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors: a study from the Japanese Breast Cancer Registry.

PubMed

Kataoka, Akemi; Iwamoto, Takayuki; Tokunaga, Eriko; Tomotaki, Ai; Kumamaru, Hiraku; Miyata, Hiroaki; Niikura, Naoki; Kawai, Masaaki; Anan, Keisei; Hayashi, Naoki; Masuda, Shinobu; Tsugawa, Koichiro; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

2016-11-01

The aim of this study was to investigate whether young age at onset of breast cancer is an independent prognostic factor in patients from the Japanese Breast Cancer Registry, after adjustment of known clinicopathological prognostic factors. Of the 53,670 patients registered between 2004 and 2006 and surveyed after a 5-year follow-up prognosis, 25,898 breast cancer patients (48.3 %), who were obtained prognostic data, were examined. Clinicopathological factors were compared between young adult (YA; <35 years), middle-aged adult (MA; 35-50 years), and older adult (OA; >50 years) patients. Five-year disease-free survival (DFS) and overall survival (OS) rates were studied. YA patients were associated with an advanced TNM stage and aggressive characteristics (e.g. human epidermal growth factor receptor 2 (HER2)-positive or oestrogen receptor (ER)-negative breast cancers) compared to MA and OA patients (P < 0.001). The 5-year DFS and OS rates were 79.4 % and 90.8, 88.5 and 95.0 %, and 87.8 % and 91.6 % for YA, MA, and OA patients, respectively. From the multivariable regression analysis, young age at onset was confirmed as an independent prognostic factor for both DFS (hazard ratio 1.73, 95 % confidence interval 1.42-2.10; P < 0.001) and OS (hazard ratio 1.58, 95 % confidence interval 1.16-2.15; P = 0.004). Young age at onset is an independent negative prognostic factor in breast cancer. Further studies are required to develop new therapeutic strategies for YA breast cancer patients.

Religious care required for Japanese terminally ill patients with cancer from the perspective of bereaved family members.

PubMed

Okamoto, Takuya; Ando, Michiyo; Morita, Tatsuya; Hirai, Kei; Kawamura, Ryo; Mitsunori, Miyashita; Sato, Kazuki; Shima, Yasuo

2010-02-01

The aim of this study was to explore the most suitable religious care for Japanese terminally ill patients with cancer based on the opinions of bereaved family members. A multicenter questionnaire survey on palliative care service was sent to 592 bereaved family members of patients with cancer who were admitted to palliative care units in Japan, and 430 responded by mail. In the section of the questionnaire about religious care, 382 responses were used for quantitative analysis, and 71 responses about religious care for qualitative analysis. In the current study, the 71 responses were grouped into families with and without a religion and were analyzed qualitatively. Families with a religion (N = 28) chose answers such as ''Instrumental care'' such as music or a religious event, ''Freedom of choice of kinds for religious care,'' ''Staff involvement of religious care,'' ''Meeting with a pastoral care workers,'' and ''Burden of offering a different kind of personal religion.'' In contrast, families without a religion (N = 44) chose answers such as ''Instrumental care,'' ''Freedom of choice whether patients receive religious care or not,'' ''Spiritual care,'' ''Not being able to accept religious care,'' and ''Burden of thinking about a religion and nuisance.'' These findings suggest that Japanese bereaved families with a religion generally regard religious care positively and prefer care through their own religion, whereas some families without a religion require religious care but some do not prefer it.

Body mass index influences prostate cancer risk at biopsy in Japanese men.

PubMed

Masuda, Hitoshi; Kagawa, Makoto; Kawakami, Satoru; Numao, Noboru; Matsuoka, Yoh; Yokoyama, Minato; Yamamoto, Shinya; Yonese, Junji; Fukui, Iwao; Kihara, Kazunori

2013-07-01

To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease (Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m(2) ) as follows: <21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9 and ≥30.0. A significant positive association was observed between body mass index and prostate cancer risk at biopsy, with an increased risk observed in men whose body mass index was ≥27.0 compared with the reference group. A significantly increased risk starting at body mass index ≥25.0 was found in high-grade disease. In contrast to our results, there has been no reported increase in the risk of prostate cancer at biopsy in Caucasians within the overweight range (body mass index of 25.0-29.9 based on World Health Organization classification). Japanese men within the overweight body mass index range who have an elevated prostate-specific antigen level also have a significant risk of harboring prostate cancer, especially high-grade disease. Overweight Japanese might be at greater prostate cancer risk at biopsy than overweight Caucasians. © 2012 The Japanese Urological Association.

Digital volumetric measurement of mammographic density and the risk of overlooking cancer in Japanese women.

PubMed

Sawada, Terumasa; Akashi, Sadako; Nakamura, Seigo; Kuwayama, Takashi; Enokido, Katsutoshi; Yoshida, Miwa; Hashimoto, Rikako; Ide, Toshimi; Masuda, Hiroko; Taruno, Kanae; Oyama, Hiroto; Takamaru, Tomoko; Kanada, Yoko; Ikeda, Murasaki; Kosugi, Natsuko; Sato, Hiroki; Nakayama, Sayuka; Ata, Arisa; Tonouchi, Yumi; Sakai, Haruna; Matsunaga, Yuki; Matsutani, Akiko

2017-09-01

Breast density often affects cancer detection via mammography (MMG). Because of this, additional tests are recommended for women with dense breasts. This study aimed to reveal trends in breast density among Japanese women and determine whether differences in breast density differentially affected the detection of abnormalities via MMG. We retrospectively analyzed 397 control women who underwent MMG screening as well as 269 patients who underwent surgery for breast cancer for whom preoperative MMG data were available. VolparaDensity™ (Volpara), a three-dimensional image analysis software with high reproducibility, was used to calculate breast density. Breasts were categorized according to the volumetric density grade (VDG), a measure of the percentage of dense tissue. The associations between age, VDG, and MMG density categories were analyzed. In the control group, 78% of women had dense breasts, while in the breast cancer group, 87% of patients had dense breasts. One of 36 patients with non-dense breasts (2.7%) was classified as category 1 or 2 (C-1 or C-2), indicating that abnormal findings could not be detected by MMG. The proportion of patients with breast cancer who had dense breasts and were classified as C-1 or C-2 was as high as 22.3%. The proportions of Japanese women with dense breasts were high. In addition, the false-negative rate for women with dense breasts was also high. Owing to this, Japanese women with dense breasts may need to commonly undergo additional tests to ensure detection of breast cancer in the screening MMG.

Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer: A post-hoc analysis of the placebo-controlled PREVAIL trial.

PubMed

Kimura, Go; Yonese, Junji; Fukagai, Takashi; Kamba, Tomomi; Nishimura, Kazuo; Nozawa, Masahiro; Mansbach, Hank; Theeuwes, Ad; Beer, Tomasz M; Tombal, Bertrand; Ueda, Takeshi

2016-05-01

To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL. © 2016 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on

Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in Japanese patients with castration-resistant prostate cancer.

PubMed

Mukai, Hirofumi; Takahashi, Shunji; Nozawa, Masahiro; Onozawa, Yusuke; Miyazaki, Jun; Ohno, Keiji; Suzuki, Kazuhiro

2014-04-01

The purpose of the study is to analyze the pharmacokinetic (PK) profile of cabazitaxel and evaluate its safety and tolerability as a 1-h IV infusion every 3 weeks in Japanese patients with castration-resistant prostate cancer (CRPC). Seventeen patients were treated with cabazitaxel at doses of 20 and 25 mg/m(2) for PK analyses. Dose escalation was performed only in the absence of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was the highest dose at which less than 33 % of the patients developed DLT. Cabazitaxel exhibited a triphasic elimination profile with a long terminal half-life of 116 ± 29.0 or 113 ± 28.0 h after IV infusion of 20 or 25 mg/m(2) cabazitaxel, respectively. The major differences in the PK parameters of cabazitaxel and docetaxel were cabazitaxel's fairly high clearance rate, representing approximately half the hepatic flow, and its large volume of distribution at steady-state conditions. No DLT was observed during Cycle 1. Mild-to-moderate hematological adverse events (AEs), including neutropenia, and other AEs typically associated with taxanes were observed; all AEs were manageable. Cabazitaxel at 25 mg/m(2) every 3 weeks was selected as the MTD in Japanese patients. The PK parameters of cabazitaxel in Japanese CRPC patients were comparable with those previously determined in Caucasian subjects. The safety and tolerability of cabazitaxel were also comparable in both ethnic populations.

Clinicopathological importance of anterior prostate cancer in Japanese Men.

PubMed

Sato, Shun; Takahashi, Hiroyuki; Kimura, Takahiro; Egawa, Shin; Furusato, Bungo; Ikegami, Masahiro

2017-03-01

Prostate cancer of transition zone origin or anterior location has been recognized as infrequent, smaller in size and indolent, whereas, our previous report showed that transition zone/anterior cancer was frequently experienced in Japanese men. The current study was conducted to show clinicopathological characteristics of transition zone/anterior cancer. A total of 201 radical prostatectomy specimens were categorized as cancer of anterior or posterior prostate where more than two thirds of the tumor existed in the specific area. Clinicopathological characteristics including Gleason score, pathological stage, lymph node metastasis, extraprostatic extension, surgical incision into the prostate (shown as pT2+), and surgical margin status were compared between anterior and posterior cases. Cases were divided as 83, 73, and 45 of anterior, posterior cancer, and no dominance, respectively. Anterior cancers included significant numbers of high grade tumors (13/83 cases: 15.7%), which was less than posterior cancers (28.8%: 21/73). The cases in pT2+ were significantly more frequent in anterior cases than posterior ones (22.9% vs. 4.1%). No seminal vesicle invasion was shown in anterior cases. Thus, although anterior cancers are less aggressive than posterior cancers, a significant numbers of clinically important cancers were located in the anterior portion in Japanese men. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Safety and pharmacokinetics of ramucirumab in combination with docetaxel in Japanese patients with locally advanced or metastatic breast cancer: a Phase Ib study.

PubMed

Masuda, Norikazu; Iwata, Hiroji; Aogi, Kenjiro; Xu, Yihuan; Ibrahim, Ayman; Gao, Ling; Dalal, Rita; Yoshikawa, Reigetsu; Sasaki, Yasutsuna

2016-12-01

The primary objective of this study was to investigate the safety and tolerability and to confirm the recommended dose of the anti-vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab in combination with docetaxel in Japanese patients with metastatic/locally advanced breast cancer. In this multicenter, single-arm, Phase Ib trial, eligibility criteria included: 20 years or older, Eastern Cooperative Oncology Group performance status of 0/1 and confirmed diagnosis of human epidermal growth factor receptor 2-negative metastatic/locally recurrent inoperable breast adenocarcinoma. Patients received docetaxel (75 mg/m 2 ) followed by ramucirumab (10 mg/kg) on Day 1 of 21-day cycles. Recommended dose was defined as <33% dose-limiting toxicities in dose-limiting toxicity-evaluable patients in Cycle 1. The safety, pharmacokinetics, immunogenicity and antitumor activity were examined. Seven patients were treated. Most adverse events were mild to moderate. Two patients during Cycle 1 experienced a dose-limiting toxicity; one patient each experienced Grade 3 febrile neutropenia and Grade 3 gingivitis. Both dose-limiting toxicities subsequently resolved. No patients discontinued study therapies during Cycle 1. Four serious adverse events were possibly related to ramucirumab in combination with docetaxel. Anti-ramucirumab antibodies were not detected. Pharmacokinetic analysis revealed low total body clearance and long apparent terminal elimination half-life (~7-12 days). Partial response was reported in four patients. The combination of ramucirumab and docetaxel was tolerable in female Japanese patients with breast cancer. Ramucirumab 10 mg/kg in combination with docetaxel (75 mg/m 2 ) was confirmed as the recommended dose among Japanese patients, supporting its use in future studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer.

PubMed

Watanabe, Toshiaki; Muro, Kei; Ajioka, Yoichi; Hashiguchi, Yojiro; Ito, Yoshinori; Saito, Yutaka; Hamaguchi, Tetsuya; Ishida, Hideyuki; Ishiguro, Megumi; Ishihara, Soichiro; Kanemitsu, Yukihide; Kawano, Hiroshi; Kinugasa, Yusuke; Kokudo, Norihiro; Murofushi, Keiko; Nakajima, Takako; Oka, Shiro; Sakai, Yoshiharu; Tsuji, Akihito; Uehara, Keisuke; Ueno, Hideki; Yamazaki, Kentaro; Yoshida, Masahiro; Yoshino, Takayuki; Boku, Narikazu; Fujimori, Takahiro; Itabashi, Michio; Koinuma, Nobuo; Morita, Takayuki; Nishimura, Genichi; Sakata, Yuh; Shimada, Yasuhiro; Takahashi, Keiichi; Tanaka, Shinji; Tsuruta, Osamu; Yamaguchi, Toshiharu; Yamaguchi, Naohiko; Tanaka, Toshiaki; Kotake, Kenjiro; Sugihara, Kenichi

2018-02-01

Japanese mortality due to colorectal cancer is on the rise, surpassing 49,000 in 2015. Many new treatment methods have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 for the treatment of colorectal cancer (JSCCR Guidelines 2016) were prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines were prepared by consensus reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches, and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2016.

Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

PubMed Central

Kawakami, Takao; Nagasaka, Keiko; Takami, Sachiko; Wada, Kazuya; Tu, Hsiao-Kun; Otsuji, Makiko; Kyono, Yutaka; Dobashi, Tae; Komatsu, Yasuhiko; Kihara, Makoto; Akimoto, Shingo; Peers, Ian S.; South, Marie C.; Higenbottam, Tim; Fukuoka, Masahiro; Nakata, Koichiro; Ohe, Yuichiro; Kudoh, Shoji; Clausen, Ib Groth; Nishimura, Toshihide; Marko-Varga, György; Kato, Harubumi

2011-01-01

Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control. PMID:21799770

Efficacy and short-term outcomes of preoperative chemoradiotherapy with intermittent oral tegafur-uracil plus leucovorin in Japanese rectal cancer patients: a single center experience retrospective analysis.

PubMed

Nakagawa, Ryosuke; Inoue, Yuji; Ohki, Takeshi; Kaneko, Yuka; Maeda, Fumi; Yamamoto, Masakazu

2017-05-31

Various types of preoperative chemoradiotherapy (CRT) have been established for rectal cancer; thus, Physicians will need to refine the selection of appropriate preoperative CRT for different patients since there are various treatment regimens. Oral tegafur-uracil (UFT) plus leucovorin (LV) is commonly used to treat rectal cancer in Japan. Oral chemotherapy offers patients many potential advantages. Since 2008, we have been performing preoperative CRT with intermittent oral UFT plus LV in locally advanced rectal cancer patients to prevent postoperative local recurrence. Here, in a retrospective analysis, we evaluated the efficacy and short-term outcomes of preoperative CRT with intermittent oral UFT plus LV. We analyzed data from 62 patients with locally advanced rectal cancer, including 31 patients who underwent preoperative CRT between 2009 and 2013 (the CRT group) and 31 patients who were treated with surgery alone between 2001 and 2008 (the non-CRT group). Clinicopathologically, both groups included patients with rectal cancer at clinical tumor stages III-IV or clinical node stages 0-III. In the CRT group, curative operations were performed ≥8 weeks after CRT. Patients were concomitantly treated with 2 cycles of oral UFT (300 mg/m 2 /day, days 1-14 and 29-42) plus LV (75 mg/day, days 1-14 and 29-42) and 45 Gy of radiotherapy. Chemotherapy was repeated every 28 days, followed by a 2-week break. The completion rate of CRT was high at 94% (n = 29/31). The downstaging rate of CRT was 61% (n = 19/31). The pathological complete response rate was 6.5% (n = 2/31). Significant differences were observed in the 3-year local recurrence rate between the two groups (P < 0.05). Preoperative CRT with intermittent oral UFT plus LV appears to be a tolerable and effective treatment for Japanese patients with rectal cancer. A further investigation of a diversification of preoperative CRT for Japanese rectal cancer patients is required.

A Japanese Post-marketing Surveillance of Cetuximab (Erbitux®) in Patients with Metastatic Colorectal Cancer

PubMed Central

Ishiguro, Megumi; Watanabe, Toshiaki; Yamaguchi, Kensei; Satoh, Taroh; Ito, Hideyuki; Seriu, Taku; Sakata, Yuh; Sugihara, Kenichi

2012-01-01

Objective Cetuximab (Erbitux®) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval. Methods All patients to be treated with cetuximab were enrolled by the central enrolment method. Data on treatment status, and incidence and severity of adverse drug reactions were collected. The target number of patients was 1800. Results A total of 2126 patients were enrolled from 637 institutions. Among 2006 patients analysed, 93.2% received cetuximab as third-line or later treatment. The median duration of treatment was 15.3 weeks, and 11.1% of patients received treatment for >48 weeks. The incidence of adverse drug reactions was 89.6%, of which ≥grade 3 was 21.5%. The incidence of infusion reactions was 5.7% (any grade), with 83.3% of them occurring at the first administration. The incidence of skin disorders was 83.7% (any grade), and the time to event varied for each skin disorder. The incidence of interstitial lung diseases was 1.2% (any grade). Diarrhoea and haematotoxicity scarcely occurred with cetuximab alone. Conclusions In this surveillance, the incidence and categories of adverse drug reactions are not distinct from previous reports. Although most patients received cetuximab as third-line or later treatment, treatment was maintained with a median duration of 15 weeks. Cetuximab treatment in practical use is considered to be well tolerated and clinically useful in Japanese patients with metastatic colorectal cancer. PMID:22327124

Panitumumab in Japanese Patients with Unresectable Colorectal Cancer: A Post-marketing Surveillance Study of 3085 Patients†

PubMed Central

Boku, Narikazu; Sugihara, Kenichi; Kitagawa, Yuko; Hatake, Kiyohiko; Gemma, Akihiko; Yamazaki, Naoya; Muro, Kei; Hamaguchi, Tetsuya; Yoshino, Takayuki; Yana, Ikuo; Ueno, Hiroshi; Ohtsu, Atsushi

2014-01-01

Objective Panitumumab was approved in Japan in April 2010 for the treatment of Kirsten rat sarcoma-2 virus oncogene wild-type unresectable and recurrent colorectal cancer. We conducted a post-marketing surveillance study to evaluate the safety and effectiveness of panitumumab. Methods After panitumumab was commercially available in Japan, all patients to be treated with panitumumab were enrolled. Data on baseline characteristics, treatment outcome, and incidence and severity of adverse drug reactions were collected. Results In total, 3091 patients were registered. In the safety analysis set (n = 3085), panitumumab was administered as monotherapy (40.7%) or combination therapy (59.4%). The median treatment duration was 113 days (range: 1–559 days), and 451 (14.6%) patients received panitumumab for ≥10 months. The overall incidence rate of adverse drug reactions was 84.1%, and the most common adverse drug reaction was skin disorders (78.4%). The incidence rates (all grades) of interstitial lung disease, infusion reaction, electrolyte abnormalities and cardiac disorders were 1.3% (mortality rate: 0.6%), 1.5, 19.3 and 0.2%, respectively. The median survival time of patients treated with panitumumab monotherapy as the third-line, or later, therapy was 10.3 months. Conclusion This post-marketing survey in clinical practice confirmed the safety and effectiveness of panitumumab. The benefit/risk balance for panitumumab in Japanese patients with unresectable colorectal cancer remains favorable. PMID:24526771

Good death in Japanese cancer care: a qualitative study.

PubMed

Hirai, Kei; Miyashita, Mitsunori; Morita, Tatsuya; Sanjo, Makiko; Uchitomi, Yosuke

2006-02-01

One of the most important goals of palliative care is achieving a "good death" or a "good dying process." The primary aim of this study was to identify the components of a Japanese "good death" through qualitative interviews with cancer patients, their families, physicians, and nurses. Semistructured interviews were conducted. Thirteen advanced cancer patients, 10 family members of such patients, 20 physicians, and 20 nurses were recruited from five regional cancer institutions in Japan. Content analysis was applied to answers, and 58 attributes were extracted and classified into 17 categories as follows: Freedom from pain or physical/psychological symptoms, Having a good family relationship, Dying in one's favorite place/environment, Having a good relationship with medical staff, Not being a burden to others, Maintaining dignity, Completion of life, Maintaining a sense of control, Fighting against cancer, Maintaining hope, Not prolonging life, Contributing to others, Control of future, Not being aware of death, Appreciating others, Maintaining pride, and Having faith. The most frequently cited category was "Freedom from pain or physical/psychological symptoms" and the least common was "Having faith." This study identified important components of a good death in Japan. A future quantitative survey is planned to clarify the generalizability of these findings as the primary endpoint of palliative care in Japan.

Evaluation of thromboembolic events in cancer patients receiving bevacizumab according to the Japanese Adverse Drug Event Report database.

PubMed

Matsumura, Chikako; Chisaki, Yugo; Sakimoto, Satoko; Sakae, Honoka; Yano, Yoshitaka

2018-01-01

Purpose We aimed to examine the risk factors, time of onset, incidence rates, and outcomes of thromboembolic events induced by bevacizumab in patients with cancer using the Japanese Adverse Drug Event Report (JADER) database of the Pharmaceuticals and Medical Devices Agency. Methods Adverse event data recorded in the JADER database between January 2004 and January 2015 were used. After screening the data using the generic drug name bevacizumab, patient data were classified into two groups by age and five groups by cancer type. The histories of disorders were also categorized. Arterial thromboembolic event and venous thromboembolic event were classified as "favorable" or "unfavorable" outcomes. Results In total, 6076 patients were reported to have developed adverse events during the sample period, of which 233 and 453 developed arterial thromboembolic event and venous thromboembolic event, respectively. Logistic analysis suggested that the presence of cancer was a significant risk factor for both arterial thromboembolic event and venous thromboembolic event. Age (≥70 years), histories of either hypertension or diabetes mellitus were also risk factors for arterial thromboembolic event. Median cumulative times of onset for arterial thromboembolic event and venous thromboembolic event were 60 and 80 days, respectively, and were not significantly different by the log-rank test. By the chi-square test, the rate of unfavorable outcomes was found to be higher after developing arterial thromboembolic event than after venous thromboembolic event. Conclusion Thromboembolism is a leading cause of mortality in patients with cancer. Patients should be monitored for the symptoms of thromboembolic events right from the initial stages of bevacizumab treatment.

Inverse association between yoghurt intake and upper aerodigestive tract cancer risk in a Japanese population.

PubMed

Kawakita, Daisuke; Sato, Fumihito; Hosono, Satoyo; Ito, Hidemi; Oze, Isao; Watanabe, Miki; Hanai, Nobuhiro; Hatooka, Shunzo; Hasegawa, Yasuhisa; Shinoda, Masayuki; Tajima, Kazuo; Murakami, Shingo; Tanaka, Hideo; Matsuo, Keitaro

2012-09-01

Although the combination of tobacco smoking and alcohol drinking account for approximately 80% of upper aerodigestive tract (UADT) cancer risk, the role of dietary factors, including dairy products, in the risk of these cancers remains controversial. We aimed to evaluate the association between dairy product intake and UADT cancer risk in a Japanese population. We conducted a case-control study in 959 patients with UADT cancer and 2877 sex- and age-matched noncancer control subjects who visited the Aichi Cancer Center in Nagoya, Japan. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Associations were assessed by multivariate logistic regression models that considered potential confounders. We found a significant inverse association between yoghurt intake and UADT cancer risk with multivariate-adjusted odds ratios and 95% confidence intervals for <1 time/week, ≥ 1 time/week and <1 time/day, and ≥ 1 time/day consumption of yoghurt of 0.70 (95% confidence interval: 0.54-0.91), 0.67 (0.54-0.84), and 0.73 (0.55-0.95) relative to nonconsumers (P trend=0.005). When stratified by primary tumor site, this association was significant among patients with hypopharyngeal, laryngeal, and esophageal cancer. However, we saw no significant association between milk or butter intake and UADT cancer risk. In this study, we found that a high intake of yoghurt may lower the risk of developing UADT cancer in a Japanese population. Further investigation of this association is warranted.

Health-related quality of life in breast cancer: A cross-cultural survey of German, Japanese, and South Korean patients.

PubMed

Shim, Eun-Jung; Mehnert, Anja; Koyama, Atsuko; Cho, Seong-Jin; Inui, Hiroki; Paik, Nam-Sun; Koch, Uwe

2006-10-01

The aim of this study was to evaluate health-related quality of life (HRQOL) in breast cancer patients across countries, and to cross-culturally examine the impact of psychosocial factors on HRQOL. A total of 413 women with breast cancer from Germany (n = 195), Japan (n = 112), and Korea (n = 106) completed a survey assessing HRQOL and HRQOL-related factors. HRQOL was measured using the Short-Form Health Survey (SF-8). Measures of psychological distress (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised), coping (Dealing with Illness Inventory-German Revised), and social support (Illness-Specific Social Support Scale-German Revised) were included. The effect of the factor country on physical QOL was seen to be significant, but small (P = 0.049, ES = 0.018). The scales of General Health (P = 0.023), Vitality (P = 0.004), and Role Emotional (P = 0.003) differed across countries, with the South Korean patients having lower scores compared to the German and Japanese patients. The nature of the impact of psychosocial factors on HRQOL did not differ greatly across countries except with regard to avoidance, however, the degree to which these factors influence HRQOL did differ greatly. Overall, depression, depressive coping, and problematic support showed a strong detrimental effect on the HRQOL of breast cancer patients. Results from this study suggest that strategies which target an improvement of HRQOL in cancer patients should also consider the patients' cultural and healthcare system contexts. Interventions are needed to improve detrimental psychosocial factors.

Cancer and non-cancer effects in Japanese atomic bomb survivors.

PubMed

Little, M P

2009-06-01

The survivors of the atomic bombings in Hiroshima and Nagasaki are a general population of all ages and sexes and, because of the wide and well characterised range of doses received, have been used by many scientific committees (International Commission on Radiological Protection (ICRP), United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), Biological Effects of Ionizing Radiations (BEIR)) as the basis of population cancer risk estimates following radiation exposure. Leukaemia was the first cancer to be associated with atomic bomb radiation exposure, with preliminary indications of an excess among the survivors within the first five years after the bombings. An excess of solid cancers became apparent approximately ten years after radiation exposure. With increasing follow-up, excess risks of most cancer types have been observed, the major exceptions being chronic lymphocytic leukaemia, and pancreatic, prostate and uterine cancer. For most solid cancer sites a linear dose response is observed, although in the latest follow-up of the mortality data there is evidence (p = 0.10) for an upward curvature in the dose response for all solid cancers. The only cancer sites which exhibit (upward) curvature in the dose response are leukaemia, and non-melanoma skin and bone cancer. For leukaemia the dose response is very markedly upward curving, indeed largely describable as a pure quadratic dose response, particularly in the low dose (0-2 Sv) range. Even 55 years after the bombings over 40% of the Life Span Study cohort remain alive, so continued follow-up of this group is vital for completing our understanding of long-term radiation effects in people. In general, the relative risks per unit dose among the Japanese atomic bomb survivors are greater than those among comparable subsets in studies of medically exposed individuals. Cell sterilisation largely accounts for the discrepancy in relative risks between these two populations, although other

Risk Factors for Oxaliplatin-Induced Hypersensitivity Reactions in Japanese Patients with Advanced Colorectal Cancer

PubMed Central

Seki, Kyoko; Senzaki, Kenzou; Tsuduki, Yasuo; Ioroi, Takeshi; Fujii, Michiko; Yamauchi, Hiroko; Shiraishi, Yukinari; Nakata, Izumi; Nishiguchi, Kohshi; Matsubayashi, Teruhisa; Takakubo, Yoshihide; Okamura, Noboru; Yamamori, Motohiro; Tamura, Takao; Sakaeda, Toshiyuki

2011-01-01

Objective: Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions. Methods: Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP. Results: The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P=0.037), preexisting allergies (P=0.004) and lower level of lactate dehydrogenase (P=0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P=0.043) and lower monocyte count (P=0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P=0.049). Conclusions: Further extensive examination with a large number of patients is needed to establish a patient management strategy. PMID:21448307

Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study.

PubMed

Yamazaki, Naoya; Kiyohara, Yoshio; Uhara, Hisashi; Uehara, Jiro; Fujimoto, Manabu; Takenouchi, Tatsuya; Otsuka, Masaki; Uchi, Hiroshi; Ihn, Hironobu; Minami, Hironobu

2017-06-01

Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8-51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0-71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Significance of common variants on human chromosome 8q24 in relation to the risk of prostate cancer in native Japanese men

PubMed Central

Liu, Miao; Kurosaki, Takayuki; Suzuki, Motofumi; Enomoto, Yutaka; Nishimatsu, Hiroaki; Arai, Tomio; Sawabe, Motoji; Hosoi, Takayuki; Homma, Yukio; Kitamura, Tadaichi

2009-01-01

Background Common variants on human chromosome 8q24, rs1447295 (C/A) and rs6983267 (T/G), have been recently linked to the prevalence of prostate cancer in European and American populations. Here, we evaluated whether the single-nucleotide polymorphisms rs1447295 and rs6983267 were associated with the risk of sporadic prostate cancer as well as latent prostate cancer in a native Japanese population. Results We analyzed genomic DNA samples from 391 sporadic prostate cancer patients, 323 controls who had died from causes unrelated to cancer and 112 Japanese men who were diagnosed as having latent prostate cancer based on autopsy results. The polymorphisms were determined by allelic discrimination using a fluorescent-based TaqMan assay. The A allele of rs1447295 was significantly associated with the risk of sporadic prostate cancer (p = 0.04; age-adjusted OR, 1.34), while the G allele of rs6983267 showed a trend towards being a high-risk allele (p = 0.06; age-adjusted OR, 1.27). No significant difference between these two polymorphisms and the risk of latent prostate cancer was observed in the present Japanese population. Conclusion Known variants on human chromosome 8q24 may be risk factors for sporadic prostate cancer in native Japanese men. PMID:19602258

[Study of the health food information for cancer patients on Japanese websites].

PubMed

Kishimoto, Keiko; Yoshino, Chie; Fukushima, Noriko

2010-08-01

The aim of this paper is to evaluate the reliability of websites providing health food information for cancer patients and, to assess the status to get this information online. We used four common Japanese search engines (Yahoo!, Google, goo, and MSN) to look up websites on Dec. 2, 2008. The search keywords were "health food" and "cancer". The websites for the first 100 hits generated by each search engine were screened and extracted by three conditions. We extracted 64 unique websites by the result of retrieval, of which 54 websites had information about health food factors. The two scales were used to evaluate the quality of the content on 54 websites. On the scale of reliability of information on the Web, the average score was 2.69+/-1.70 (maximum 6) and the median was 2.5. The other scale was matter need to check whether listed to use safely this information. On this scale, the average score was 0.72+/-1.22 (maximum 5) and the median was 0. Three engines showed poor correlation between the ranking and the latter score. But several websites on the top indicated 0 score. Fifty-four websites were extracted with one to four engines and the average number of search engines was 1.9. The two scales were positively correlated with the number of search engines, but these correlations were very poor. Ranking high and extraction by multiple search engines were of minor benefit to pick out more reliable information.

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

PubMed

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

Human papillomavirus genotypes in penile cancers from Japanese patients and HPV-induced NF-κB activation.

PubMed

Senba, Masachika; Mori, Naoki; Wada, Akihiro; Fujita, Shuichi; Yasunami, Michio; Irie, Sumiko; Hayashi, Tomayoshi; Igawa, Tsukasa; Kanetake, Hiroshi; Takahara, Osamu; Toriyama, Kan

2010-03-01

The causal relationship between chronic inflammation and cancer is widely accepted. Numerous investigations have identified nuclear factor-κB (NF-κB) as an important modulator in driving chronic inflammation to cancer. This study aimed to determine the prevalence of human papillomavirus (HPV) in penile cancer in Japanese patients and whether NF-κB is subsequently overexpressed in penile cancer. Thirty-four specimens of penile tissue (16 malignant and 18 benign cases) were examined to determine the association of HPV infection. An in situ hybridization (ISH) method was used to detect and localize HPV-DNA. A sensitive HPV polymerase chain reaction (PCR) procedure was used for the detection of HPV-DNA, and DNA sequencing was used to identify the HPV genotype. HPV-DNA was detected in 37.5 and 75% of cases of penile cancer, using ISH and PCR, respectively. Our efforts to detect HPV genotypes were unsuccessful as HPV-DNA could not be extracted from these materials. Using ISH, a prevalence of 68.2% of HPV infection was found in penile cancer in Kenyan patients in east Africa. In the present study, all 9 HPV-positive cases, (100%) were NF-κB-positive in the nucleus and/or cytoplasm. In contrast, of the 25 HPV-negative cases, 15 (60%) were NF-κB-positive in the nucleus and/or cytoplasm. Therefore, ISH is a method which is able to prove infection of a large quantity of HPV more effectively when compared with PCR. Thus, a large quantity of HPV infection leads to the activity of NF-κB. The most prevalent genotype was the HPV-22 found in 83.3% of the penile cancer cases. In addition, HPV-11 was found in 81.8% of the non-cancer cases. For cases with a high level of infection, the activity of NF-κB increased compared with those with a low level of HPV infection.

Phase Ia/Ib study of the pan-class I PI3K inhibitor pictilisib (GDC-0941) administered as a single agent in Japanese patients with solid tumors and in combination in Japanese patients with non-squamous non-small cell lung cancer.

PubMed

Yamamoto, Noboru; Fujiwara, Yutaka; Tamura, Kenji; Kondo, Shunsuke; Iwasa, Satoru; Tanabe, Yuko; Horiike, Atsushi; Yanagitani, Noriko; Kitazono, Satoru; Inatani, Michiyasu; Tanaka, Jun; Nishio, Makoto

2017-02-01

Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor. This phase Ia/Ib study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of pictilisib in monotherapy or in combination with carboplatin-paclitaxel and bevacizumab (CP + BEV) in Japanese patients with advanced solid tumors or non-squamous non-small cell lung cancer. A standard 3 + 3 dose escalation design was applied. In stage 1, 140, 260, or 340 mg/day of pictilisib was administered once daily to 12 patients with advanced solid tumors. In stage 2, 260 or 340 mg/day of pictilisib was administered in combination with CP + BEV to 7 patients with advanced non-squamous non-small cell lung cancer. In stage 1, 1 of 6 patients in the 340 mg/day cohort exhibited dose limiting toxicity (DLT) of grade 3 maculopapular rash. The maximum plasma concentration and area under the curve of pictilisib were dose-dependent. A reduction in phosphorylated AKT in platelet rich plasma was observed. No patient had an objective anti-tumor response. In stage 2, DLT was observed in 1 of 3 patients in the 260 mg/day cohort (grade 3 febrile neutropenia), and 2 of 4 patients in the 340 mg/day cohort (1 each of grade 3 febrile neutropenia and grade 3 febrile neutropenia/erythema multiforme). Partial responses were observed in 3 out of 7 patients. In conclusion, pictilisib was shown to have good safety and tolerability in Japanese patients with advanced solid tumors. A recommended dose of pictilisib in monotherapy was determined to be 340 mg once daily. For combination with CP + BEV, tolerability up to 260 mg/day was confirmed.

Analysis of Early Death in Japanese Patients With Advanced Non-small-cell Lung Cancer Treated With Nivolumab.

PubMed

Inoue, Takako; Tamiya, Motohiro; Tamiya, Akihiro; Nakahama, Kenji; Taniguchi, Yoshihiko; Shiroyama, Takayuki; Isa, Shin-Ichi; Nishino, Kazumi; Kumagai, Toru; Kunimasa, Kei; Kimura, Madoka; Suzuki, Hidekazu; Hirashima, Tomonori; Atagi, Shinji; Imamura, Fumio

2018-03-01

The increased risk for early death owing to anti-programmed cell death 1 inhibitors is a major disadvantage that requires special management. We evaluated the frequency, causes, and risk factors of early death during nivolumab treatment for non-small cell lung cancer (NSCLC) in a Japanese clinical setting. The medical records of patients with NSCLC who started receiving nivolumab between December 17, 2015 and July 31, 2016 in 3 Japanese institutes were collected. Early death was defined as any death within 3 months from the start of nivolumab treatment, irrespective of its cause. Treatment response was evaluated using the Response Evaluation Criteria In Solid Tumors criteria, version 1.1. A total of 201 patients with NSCLC were enrolled, and 38 (18.9%) died within the first 3 months. Thirty-one (81.6%) patients who experienced early death developed progressive disease, whereas 14 (36.8%) patients who experienced early death demonstrated nivolumab-induced immune-related adverse events, which required corticosteroid intervention, including interstitial lung disease in 7 (18.4%) patients. Multivariate logistic regression demonstrated that an Eastern Cooperative Oncology Group performance status score ≥ 2 (odds ratio [OR], 5.66; 95% confidence interval [CI], 2.01-15.61; P < .001), C-reactive protein-to-albumin ratio > 0.3 (OR, 10.56; 95% CI, 3.61-30.86; P < .001), and the response to prior treatment (OR, 2.07; 95% CI, 1.03-4.14; P = .041) were independent predictors for early death. Disease progression and immune-related adverse events are 2 major causes of early death with nivolumab in patients with NSCLC. An Eastern Cooperative Oncology Group performance status score ≥ 2, pretreatment C-reactive protein-to-albumin ratio > 0.3, and poor response to prior treatment were associated with early death. Copyright © 2017 Elsevier Inc. All rights reserved.

Proteomic alteration in gastic adenocarcinomas from Japanese patients

PubMed Central

Yoshihara, Takahiro; Kadota, Yoshito; Yoshimura, Yoshiyuki; Tatano, Yutaka; Takeuchi, Naohiro; Okitsu, Hiroshi; Umemoto, Atsushi; Yamauchi, Takashi; Itoh, Kohji

2006-01-01

Background Gastric adenocarcinomas comprise one of the common types of cancers in Asian countries including Japan. Comprehensive protein profiling of paired surgical specimens of primary gastric adenocarcinomas and nontumor mucosae derived from Japanese patients was carried out by means of two-dimensional gel electrophoresis (2D-EP) and liquid chromatography-electrospray ionic tandem mass spectrometry (LC-ESI-MS) to establish gastric cancer-specific proteins as putative clinical biomarkers and molecular targets for chemotherapy. Results Relatively common alterations in protein expression were revealed in the tumor tissues. Increases in manganese dismutase and nonhistone chromosomal protein HMG-1 (HMG-1) were observed, while decreases in carbonic anhydrases I and II, glutatione-S-transferase and foveolin precursor (gastrokine-1) (FOV), an 18-kDa stomach-specific protein with putative tumor suppressor activity, were detected. RT-PCR analysis also revealed significant down-regulation of FOV mRNA expression in tumor tissues. Conclusion A possible pathological role for down-regulation of FOV in gastric carcinogenesis was demonstrated. Evaluation of the specific decreases in gene and protein expression of FOV in patients may be utilized as clinical biomarkers for effective diagnosis and assessment of gastric cancer. PMID:17187689

Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome.

PubMed

Tanakaya, Kohji; Yamaguchi, Tatsuro; Ishikawa, Hideki; Hinoi, Takao; Furukawa, Yoichi; Hirata, Keiji; Saida, Yoshihisa; Shimokawa, Mototsugu; Arai, Masami; Matsubara, Nagahide; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

2016-04-01

To elucidate the causes of cancer death in Japanese families with Lynch syndrome (LS). The distributions of cancer deaths in 485 individuals from 67 families with LS (35, 30, and two families with MutL homologue 1 (MLH1), MSH2, and MSH6 gene mutations, respectively), obtained from the Registry of the Japanese Society for Cancer of the Colon and Rectum were analyzed. Among 98 cancer deaths of first-degree relatives of unknown mutation status, 53%, 19%, 13% (among females), 7% (among females) and 5% were due to colorectal, gastric, uterine, ovarian, and hepatobiliary cancer, respectively. The proportion of deaths from extra-colonic cancer was significantly higher in families with MSH2 mutation than in those with MLH1 mutation (p=0.003). In addition to colonic and uterine cancer, management and surveillance targeting gastric, ovarian and hepatobiliary cancer are considered important for Japanese families with LS. Extra-colonic cancer in families with MSH2 mutation might require for more intensive surveillance. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Atezolizumab in Japanese Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer: A Subgroup Analysis of the Phase 3 OAK Study.

PubMed

Hida, Toyoaki; Kaji, Reiko; Satouchi, Miyako; Ikeda, Norihiko; Horiike, Atsushi; Nokihara, Hiroshi; Seto, Takashi; Kawakami, Tomohisa; Nakagawa, Shintaro; Kubo, Toshio

2018-02-01

Atezolizumab, an anti-programmed death-ligand 1 (PD-L1) agent, is effective and well tolerated in patients with pretreated advanced non-small-cell lung cancer (NSCLC). We assessed its efficacy and safety in Japanese patients through subgroup analyses of the phase 3 OAK study (NCT02008227). Key eligibility criteria of this randomized, controlled, open-label, international study include locally advanced/metastatic NSCLC, ≥ 1 prior platinum-based chemotherapy, age ≥ 18 years, measurable disease (Response Evaluation Criteria in Solid Tumors v1.1), and Eastern Cooperative Oncology Group performance status 0 or 1. Atezolizumab 1200 mg or docetaxel 75 mg/m 2 was provided intravenously every 3 weeks. Co-primary end points were overall survival (OS) in the intention-to-treat (ITT) population and those with ≥ 1% PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC; TC1/2/3 or IC1/2/3). Sixty-four ITT patients were Japanese; 19 had TC1/2/3 or IC1/2/3 status. In Japanese ITT patients, median OS in the atezolizumab arm (n = 36) was longer than the docetaxel arm (n = 28; 21.3 months [95% confidence interval (CI), 11.0-not estimable (NE)] versus 17.0 months [95% CI, 12.5-NE], respectively; hazard ratio 0.80 [95% CI, 0.41-1.57]). In the TC1/2/3 or IC1/2/3 population, median OS was 21.3 months (95% CI, 15.0-NE) and NE in the atezolizumab (n = 11) and docetaxel (n = 8) groups, respectively (hazard ratio, 0.81 [95% CI, 0.22-3.05]). Atezolizumab was generally well tolerated, with no treatment-related deaths. Atezolizumab was effective and well tolerated in pretreated Japanese patients with NSCLC. Results are consistent with the primary analysis of OAK. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Clinical safety and efficacy of "filgrastim biosimilar 2" in Japanese patients in a post-marketing surveillance study.

PubMed

Tamura, Kazuo; Hashimoto, Kazue; Nishikawa, Kiyohiro

2018-05-01

We conducted a post-marketing surveillance to evaluate the safety and efficacy of TKN732, approved as "filgrastim biosimilar 2", in Japanese patients who developed neutropenia in the course of cancer chemotherapy or hematopoietic stem cell transplantation. A total of 653 patients were registered during the 2-year enrollment period starting from May 2013, and 627 and 614 patients were eligible for safety and efficacy analyses of the G-CSF biosimilar, respectively. Forty-three adverse drug reactions were reported in 33 patients (5.26%). Back pain was most frequently observed and reported in 20 patients (3.19%), followed by pyrexia (1.28%) and bone pain (0.96%). Risk factors for adverse reactions identified by logistic regression analyses were younger age, presence of past medical history, and lower total dose at the onset of adverse reactions. Among the 576 cancer patients who developed Grade 2-4 neutropenia after chemotherapy, recovery to Grade 1/0 was reported in 553 patients (96%) following filgrastim biosimilar 2 treatment. The median duration of neutrophil counts below 1500/μL was 5 days. In addition, all 11 patients who underwent hematopoietic stem cell transplantation had good responses to filgrastim biosimilar 2. In conclusion, this study showed that filgrastim biosimilar 2 has a similar safety profile and comparable effects to the original G-CSF product in the real world clinical setting. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer—updated results

PubMed Central

Ueda, Takeshi

2017-01-01

Abstract A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28–1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18–0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. PMID:28003320

Clinical characteristics of Japanese patients with severe hypertriglyceridemia.

PubMed

Tada, Hayato; Kawashiri, Masa-Aki; Nakahashi, Takuya; Yagi, Kunimasa; Chujo, Daisuke; Ohbatake, Azusa; Mori, Yukiko; Mori, Shunsuke; Kometani, Mitsuhiro; Fujii, Hiroshi; Nohara, Atsushi; Inazu, Akihiro; Mabuchi, Hiroshi; Yamagishi, Masakazu; Hayashi, Kenshi

2015-01-01

Although of interest, few data exist on the clinical characteristics of Japanese patients with an extremely high triglyceride level (≥ 1000 mg/dL). We assessed the clinical characteristics of Japanese patients with an extremely high triglyceride level. We investigated the presence of coronary artery disease, history of pancreatitis, the presence of fatty liver, and the potential causes of elevated triglyceride in Japanese subjects with an extremely high level of fasting triglyceride (≥ 1000 mg/dL) among 70,368 subjects whose serum triglyceride was measured for any reason at Kanazawa University Hospital from April 2004 to March 2014. We identified 215 (0.31%) subjects (mean age, 46 years; male, 170, mean body mass index, 25 kg/m(2)) with severe hypertriglyceridemia. Among them, 4 (1.9%) subjects were classified as type I, 97 (45.1%) subjects were type IV, and 114 (53.0%) subjects were type V hyperlipidemia, according to Fredrickson's classification. Among 215 subjects, 116 subjects (54.0%) drank alcohol, 58 (27.0%) showed heavy intake (≥ 60 g/d), and 64 (29.8%) subjects had diabetes. In total, 59 (27.4%) subjects had transient severe hypertriglyceridemia caused by corticosteroids (N = 19), antidepressant (N = 18), l-asparaginase and steroids for acute lymphoid leukemia (N = 15), hormone replacement therapy for breast cancer (N = 9), β-blocker (N = 5), hypothyroidism (N = 4), pregnancy (N = 4), and panhypopituitarism (N = 2). As many as 119 (55.3%) subjects exhibited fatty liver. Moreover, 12 (5.6%) and 17 (7.9%) subjects had a history of pancreatitis and coronary artery disease, respectively. A variety of situations can cause severe hypertriglyceridemia. We suggest that potential secondary causes should be carefully assessed for such patients. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics.

PubMed

Yokoyama, A; Muramatsu, T; Omori, T; Yokoyama, T; Matsushita, S; Higuchi, S; Maruyama, K; Ishii, H

2001-03-01

Alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) gene polymorphisms play roles in ethanol metabolism, drinking behavior and esophageal carcinogenesis in Japanese; however, the combined influence of ADH2 and ALDH2 genotypes on other aerodigestive tract cancers have not been investigated. ADH2/ALDH2 genotyping was performed on lymphocyte DNA samples from Japanese alcoholic men (526 cancer-free; 159 with solitary or multiple aerodigestive tract cancers, including 33 oropharyngolaryngeal, 112 esophageal, 38 stomach and 22 multiple primary cancers in two or three organs). After adjustment for age, drinking and smoking habits, and ADH2/ALDH2 genotypes, the presence of either ADH2*1/2*1 or ALDH2*1/2*2 significantly increased the risk for oropharyngolaryngeal cancer [odds ratios (ORs), 6.68 with ADH2*1/2*1 and 18.52 with ALDH2*1/2*2] and esophageal cancer (ORs, 2.64 and 13.50, respectively). For patients with both ADH2*1/2*1 and ALDH2*1/2*2, the risks for oropharyngolaryngeal and esophageal cancers were enhanced in a multiplicative fashion (OR = 121.77 and 40.40, respectively). A positive association with ALDH2*1/2*2 alone was observed for stomach cancer patients who also had oropharyngolaryngeal and/or esophageal cancer (OR = 110.58), but it was not observed for those with stomach cancer alone. Furthermore, in the presence of ALDH2*1/2*2, the risks for multiple intra-esophageal cancers (OR = 3.43) and for esophageal cancer with oropharyngolaryngeal and/or stomach cancer (OR = 3.95) were higher than the risks for solitary intra-esophageal cancer and for esophageal cancer alone, but these tendencies were not observed for ADH2*1/2*1 genotype. Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for oropharyngolaryngeal cancer and 63.9% for esophageal cancer.

Population pharmacokinetic-pharmacodynamic modeling and model-based prediction of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer.

PubMed

Fukae, Masato; Shiraishi, Yoshimasa; Hirota, Takeshi; Sasaki, Yuka; Yamahashi, Mika; Takayama, Koichi; Nakanishi, Yoichi; Ieiri, Ichiro

2016-11-01

Docetaxel is used to treat many cancers, and neutropenia is the dose-limiting factor for its clinical use. A population pharmacokinetic-pharmacodynamic (PK-PD) model was introduced to predict the development of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer (NSCLC). Forty-seven advanced or recurrent Japanese patients with NSCLC were enrolled. Patients received 50 or 60 mg/m 2 docetaxel as monotherapy, and blood samples for a PK analysis were collected up to 24 h after its infusion. Laboratory tests including absolute neutrophil count data and demographic information were used in population PK-PD modeling. The model was built by NONMEM 7.2 with a first-order conditional estimation using an interaction method. Based on the final model, a Monte Carlo simulation was performed to assess the impact of covariates on and the predictability of neutropenia. A three-compartment model was employed to describe PK data, and the PK model adequately described the docetaxel concentrations observed. Serum albumin (ALB) was detected as a covariate of clearance (CL): CL (L/h) = 32.5 × (ALB/3.6) 0.965  × (WGHT/70) 3/4 . In population PK-PD modeling, a modified semi-mechanistic myelosuppression model was applied, and characterization of the time course of neutrophil counts was adequate. The covariate selection indicated that α1-acid glycoprotein (AAG) was a predictor of neutropenia. The model-based simulation also showed that ALB and AAG negatively correlated with the development of neutropenia and that the time course of neutrophil counts was predictable. The developed model may facilitate the prediction and care of docetaxel-induced neutropenia.

[Role of Pharmacists in Completion of Adjuvant Cisplatin-Vinorelbine Chemotherapy in Japanese Patients with Non-small Cell Lung Cancer].

PubMed

Morimoto, Yoshihito; Takei, Hidefumi; Tachibana, Keisei; Nakazato, Yoko; Tanaka, Ryota; Nagashima, Yasushi; Watanabe, Kazuhiro; Seki, Reisuke; Shinohara, Takao; Kondo, Haruhiko

2018-01-01

　Adjuvant cisplatin-vinorelbine chemotherapy has been shown to be effective in patients with completely resected non-small cell lung cancer (NSCLC) in several Phase III trials, but not yet in the Japanese population. Pharmacists are expected to assist patients with completion of adjuvant chemotherapy. The aim of this retrospective study was to evaluate the compliance with and safety of adjuvant cisplatin-vinorelbine chemotherapy in Japanese patients and to evaluate the contribution of pharmacists to completion of treatment. Thirty-four patients with NSCLC who received adjuvant cisplatin-vinorelbine chemotherapy at Kyorin University Hospital between January 2006 and June 2015 were reviewed. The treatment schedule comprised cisplatin 80 mg/m 2 on day 1 and vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks. Four 3-week cycles were planned. A pharmacist provided guidance to all patients and monitored them for adverse effects thereafter. The pharmacist intervened with advice to doctors as necessary. The 4 cycles were administered in 67.6% of cases. There were no treatment-related deaths. The main grade 3 or 4 toxicities were neutropenia (76.5%) and anorexia (38.2%). The most common reason for discontinuation and dose reduction was anorexia. There were 56 instances of pharmacist intervention. In total, 96.4% of the pharmacist interventions were implemented by doctors, which included administration of an antiemetic on 15 occasions and hot fomentation for prevention of vasculitis on 7 occasions. Adjuvant cisplatin-vinorelbine chemotherapy was tolerated by most patients but was discontinued because of adverse events in some. Pharmacist intervention aids completion of planned chemotherapy and management of treatment-related adverse events.

Phase II trial of capecitabine plus modified cisplatin (mXP) as first-line therapy in Japanese patients with metastatic gastric cancer (KSCC1104).

PubMed

Satake, Hironaga; Iwatsuki, Masaaki; Uenosono, Yoshikazu; Shiraishi, Takeshi; Tanioka, Hiroaki; Saeki, Hiroshi; Sugimachi, Keishi; Kitagawa, Dai; Shimokawa, Mototsugu; Oki, Eiji; Emi, Yasunori; Kakeji, Yoshihiro; Tsuji, Akihito; Akagi, Yoshito; Natsugoe, Shoji; Baba, Hideo; Maehara, Yoshihiko

2017-01-01

Capecitabine plus cisplatin (XP) is a standard therapy for metastatic gastric cancer (mGC). However, while results from previous phase III trials suggested that the cisplatin dosage should be reduced in Japanese patients, no clinical data exist to support this. Here, we conducted a multicenter study to evaluate the efficacy and safety of modified XP (mXP) in Japanese patients with mGC. Patients with previously untreated mGC received mXP (cisplatin 60 mg/m 2 on day 1 plus capecitabine 1000 mg/m 2 twice daily on days 1-14) every 3 weeks. The primary endpoint was the Response Evaluation Criteria in Solid Tumors-confirmed overall response rate (ORR). A sample size of 40 was planned for a threshold ORR of 30% and an expected value of 50%, with a one-sided α of 0.05 and a beta of approximately 0.2. Forty-two patients were enrolled. One patient did not fulfill the eligibility criteria; therefore, a total of 41 patients were assessed. The results were as follows: complete response in 2 patients, partial response in 16, stable disease in 14, progressive disease in 8, and no evaluation in 1. The confirmed ORR was 43.9% (95% confidence interval 28.7-59.1%). The median progression-free survival and median overall survival were 4.6 and 11.3 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (37.5%), anemia (24.4%), anorexia (24.4%), and nausea (12.2%). First-line chemotherapy with mXP in Japanese patients with mGC did not reach its primary objective. However, it did show a promising response rate and an acceptable tolerability profile.

Applicability of the Proposed Japanese Model for the Classification of Gastric Cancer Location: The "PROTRADIST" Retrospective Study.

PubMed

Marano, Luigi; Petrillo, Marianna; Pezzella, Modestino; Patriti, Alberto; Braccio, Bartolomeo; Esposito, Giuseppe; Grassia, Michele; Romano, Angela; Torelli, Francesco; De Luca, Raffaele; Fabozzi, Alessio; Falco, Giuseppe; Di Martino, Natale

2017-06-01

The extension of lymphadenectomy for surgical treatment of gastric cancer remains discordant among European and Japanese surgeons. Kinami et al. (Kinami S, Fujimura T, Ojima E, et al. PTD classification: proposal for a new classification of gastric cancer location based on physiological lymphatic flow. Int. J. Clin. Oncol. 2008;13:320-329) proposed a new experimental classification, the "Proximal zone, Transitional zone, Distal zone" (PTD) classification, based on the physiological lymphatic flow of gastric cancer site. The aim of the present retrospective study is to assess the applicability of PTD Japanese model in gastric cancer patients of our Western surgical department. Two groups of patients with histologically documented adenocarcinoma of the stomach were retrospectively obtained: In the first group were categorized 89 patients with T1a-T1b tumor invasion; and in the second group were 157 patients with T2-T3 category. The data collected were then categorized according to the PTD classification. In the T1a-T1b group there were no lymph node metastases within the r-GA or r-GEA compartments for tumors located in the P portion, and similarly there were no lymphatic metastases within the l-GEA or p-GA compartments for tumors located in the D portion. On the contrary, in the T2-T3 group the lymph node metastases presented a diffused spreading with no statistical significance between the two classification models. Our results show that the PTD classification based on physiological lymphatic flow of the gastric cancer site is a more physiological and clinical version than the Upper, Medium And Lower classification. It represents a valuable and applicable model of cancer location that could be a guide to a tailored surgical approach in Italian patients with neoplasm confined to submucosa. Nevertheless, in order to confirm our findings, larger and prospective studies are needed.

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

PubMed Central

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-01-01

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing. PMID:29348823

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

PubMed

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-12-22

Pathogenic germline BRCA1 , BRCA2 ( BRCA1/2 ), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1 ), 8 (3.5%; BRCA2 ), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D ), 2 (0.9%; ATM ), 1 (0.4%; MRE11A ), 1 ( FANCC ), and 1 ( GABRA6 ). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2 . Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Risk factors for coronary artery calcification in Japanese patients.

PubMed

Shikada, Tomoki; Washio, Masakazu; Nishizaki, Akiko; Kakino, Takamori; Ooe, Kensuke; Ishibashi, Yuuji; Sagara, Shuuichirou; Morishige, Kunio; Tashiro, Hideki

2015-07-01

Because the prevalence of coronary artery calcification is lower among Japanese than among Western individuals, aspects of the Japanese lifestyle might be related to the development of calcification. We aimed to clarify the relationship between coronary artery calcium scores in Japanese patients and various lifestyle factors among the Japanese population. Study subjects were patients aged ≥20 years who underwent multidetector-row computed tomography. A total of 201 patients agreed to take part in this study and answered a questionnaire regarding lifestyle, medical history, and other factors. Old age, current and former smoking, sedentary work, short sleep time, coronary artery stenosis, treatment with statins, medical history of cerebrovascular disease, medical history of angina pectoris, medical history of ischemic heart disease, and medical history of dyslipidemia were associated with higher odds ratios than the other factors examined, while the Japanese-style breakfast (e.g. boiled rice, miso soup, grilled fish) was associated with lower odds ratios. In this study, smoking, sedentary work, short sleep time, and the Japanese-style breakfast were lifestyle factors related to coronary artery calcification. The lifestyle of Japanese people may be related to coronary calcification. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

ASP8273 tolerability and antitumor activity in TKI-naive Japanese patients with EGFR mutation-positive non-small cell lung cancer.

PubMed

Azuma, Koichi; Nishio, Makoto; Hayashi, Hidetoshi; Kiura, Katsuyuki; Satouchi, Miyako; Sugawara, Shunichi; Hida, Toyoaki; Iwamoto, Yasuo; Inoue, Akira; Takeda, Koji; Ikeda, Satoshi; Nakagawa, Tomoki; Takeda, Kentaro; Asahina, Seitaro; Komatsu, Kanji; Morita, Satoshi; Fukuoka, Masahiro; Nakagawa, Kazuhiko

2018-05-28

Epidermal growth factor receptor (EGFR) activating mutations occur in approximately 50% of East Asian patients with non-small cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitors (TKI). ASP8273 is an orally administered, irreversible EGFR-TKI that inhibits EGFR activating mutations and has demonstrated clinical activity in patients with EGFR mutation-positive NSCLC. EGFR-TKI-naïve Japanese adult patients (≥20 years) with NSCLC harboring EGFR mutations were enrolled in this open-label, single-arm, Phase 2 study (NCT02500927). Patients received ASP8273 300mg once daily until discontinuation criteria were met. The primary endpoint was to determine the safety of ASP8273 300mg; secondary endpoint was antitumor activity defined by RECIST v1.1. Thirty-one patients (12M/19F; median age 64 years [range: 31-82]) with EGFR mutation-positive NSCLC were enrolled; as of 23 February 2016, 25 patients (81%) were still on study. Of the 31 patients, 27 (87%) had an ex19del (n=13, 42%) or a L858R (n=14, 45%) EGFR activating mutation; 2 (7%) had L861Q mutation and 5 (16%) had other EGFR activating mutations, two had an activating mutation and the T790M resistance mutation. The most commonly reported treatment-emergent adverse event was diarrhea [n=24, 77%]. All patients had at least 1 post-baseline scan; 1 patient (3%) achieved a confirmed complete response, 13 (42%) had a confirmed partial response, and 15 (48%) had confirmed stable disease (disease control rate: 94% [n=29/31]) per investigator assessment. Once-daily ASP8273 300 mg was generally well tolerated and demonstrated antitumor activity in TKI-naïve Japanese patients with EGFR mutation-positive NSCLC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prevalence of Lynch syndrome and Lynch-like syndrome among patients with colorectal cancer in a Japanese hospital-based population.

PubMed

Chika, Noriyasu; Eguchi, Hidetaka; Kumamoto, Kensuke; Suzuki, Okihide; Ishibashi, Keiichiro; Tachikawa, Tetsuhiko; Akagi, Kiwamu; Tamaru, Jun-Ichi; Okazaki, Yasushi; Ishida, Hideyuki

2017-02-09

We investigated the prevalence of Lynch syndrome and Lynch-like syndrome among Japanese colorectal cancer patients, as there have been no credible data from Japan. Immunohistochemical analyses for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were carried out in surgically resected, formalin-fixed paraffin-embedded specimens obtained from 1,234 newly diagnosed colorectal cancer patients between March 2005 and April 2014. The presence/absence of the BRAF V600E mutation and hypermethylation of the MLH1 promoter was analyzed where necessary. Genetic testing was finally undertaken in patients suspected as having Lynch syndrome. By the universal screening approach with immunohistochemical analysis for mismatch repair proteins followed by analyses for the BRAF V600E mutation and MLH1 promoter methylation status, 11 (0.9%) of the 1,234 patients were identified as candidates for genetic testing. Out of the 11 patients, 9 (0.7%) were finally diagnosed as having Lynch syndrome; the responsible genes included MLH1 (n = 1), MSH2 (n = 4), EPCAM (n = 1) and MSH6 (n = 3). The remaining two patients (0.2%) were regarded as having Lynch-like syndrome, since biallelic somatic deletion of the relevant mismatch repair genes was detected in the absence of germline mismatch repair alterations. None of the cases was identified as having germline MLH1 epimutation. The prevalence of Lynch syndrome among all newly diagnosed cases of colorectal cancer in Japan is in the same range as that recently reported by studies in Western population. The prevalence of Lynch-like syndrome seems to be extremely low. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Japanese Clinical Practice Guideline for Head and Neck Cancer.

PubMed

Nibu, Ken-Ichi; Hayashi, Ryuichi; Asakage, Takahiro; Ojiri, Hiroya; Kimata, Yoshihiro; Kodaira, Takeshi; Nagao, Toshitaka; Nakashima, Torahiko; Fujii, Takashi; Fujii, Hirofumi; Homma, Akihiro; Matsuura, Kazuto; Monden, Nobuya; Beppu, Takeshi; Hanai, Nobuhiro; Kirita, Tadaaki; Kamei, Yuzuru; Otsuki, Naoki; Kiyota, Naomi; Zenda, Sadamoto; Omura, Ken; Omori, Koichi; Akimoto, Tetsuo; Kawabata, Kazuyoshi; Kishimoto, Seiji; Kitano, Hiroya; Tohnai, Iwai; Nakatsuka, Takashi

2017-08-01

The first revision of "Japanese Clinical Practice Guideline for Head and Neck Cancer" was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification. 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee. A comprehensive literature search was performed for studies published between 2001 and 2012 using PubMed. Qualified studies were analyzed and the results were evaluated, consolidated and codified by all the committee members. Elective neck dissection (ND) does contribute to improvement in survival and should be performed for patients with high-risk tongue cancer. At present, no research has clearly demonstrated the utility of superselective arterial infusion chemotherapy. However, depending on the site and stage of the cancer, combination with radiotherapy may be useful for preserving organ function or improving survival rate. Concurrent CDDP chemotherapy and adjuvant radiotherapy contributes to improvement of survival rate as an adjuvant therapy for advanced squamous cell carcinoma of the head and neck in patients at high risk of recurrence. The anti-EGFR antibody cetuximab (Cmab) has an additive effect with radiotherapy. However, the indication must be carefully considered since this treatment has not been compared with the standard treatment of chemoradiotherapy. Cmab has been shown to have an additive effect with chemotherapy (CDDP/5-FU) in patients with unresectable metastatic or recurrent cancer. Preoperative and postoperative oral care may reduce the risk of postoperative complications such as surgical wound infection and pneumonia in head and neck cancers. Rehabilitation soon after ND for cervical lymph node metastasis is recommended for maintaining and restoring shoulder function. In this article, we described

Perioperative Administration of Traditional Japanese Herbal Medicine Daikenchuto Relieves Postoperative Ileus in Patients Undergoing Surgery for Gastrointestinal Cancer: A Systematic Review and Meta-analysis.

PubMed

Ishizuka, Mitsuru; Shibuya, Norisuke; Nagata, Hitoshi; Takagi, Kazutoshi; Iwasaki, Yoshimi; Hachiya, Hiroyuki; Aoki, Taku; Kubota, Keiichi

2017-11-01

Although it has been widely demonstrated that administration of Daikenchuto (DKT), a traditional Japanese herbal medicine, improves gastrointestinal (GI) motility in patients undergoing abdominal surgery, few studies have investigated the efficacy of perioperative DKT administration for relief of postoperative ileus (PI) in patients undergoing surgery for GI cancer. Therefore, the aim of this study was to investigate whether perioperative administration of DKT relieves PI in patients with GI cancer. We performed a comprehensive electronic search of the literature (Cochrane Library, PubMed, the Web of Science and ICHUSHI) up to December 2016 to identify studies that had shown the efficacy of perioperative DKT administration for relief of PI in patients with GI cancer. To integrate the individual effect of DKT, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I 2 statistics. Seven studies involving a total of 1,134 patients who had undergone GI cancer surgery were included in this meta-analysis. Among 588 patients who received DKT perioperatively, 67 (11.4%) had PI, whereas among 546 patients who did not receive DKT perioperatively, 87 (15.9%) had PI. Perioperative administration of DKT significantly reduced the occurrence of PI (RR=0.58, 95% CI=0.35-0.97, p=0.04, I 2 =48%) in comparison to patients who did not receive DKT or received placebo. The result of this meta-analysis suggests that perioperative administration of DKT relieves PI in patients undergoing surgery for GI cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Automatic Estimation of Volumetric Breast Density Using Artificial Neural Network-Based Calibration of Full-Field Digital Mammography: Feasibility on Japanese Women With and Without Breast Cancer.

PubMed

Wang, Jeff; Kato, Fumi; Yamashita, Hiroko; Baba, Motoi; Cui, Yi; Li, Ruijiang; Oyama-Manabe, Noriko; Shirato, Hiroki

2017-04-01

Breast cancer is the most common invasive cancer among women and its incidence is increasing. Risk assessment is valuable and recent methods are incorporating novel biomarkers such as mammographic density. Artificial neural networks (ANN) are adaptive algorithms capable of performing pattern-to-pattern learning and are well suited for medical applications. They are potentially useful for calibrating full-field digital mammography (FFDM) for quantitative analysis. This study uses ANN modeling to estimate volumetric breast density (VBD) from FFDM on Japanese women with and without breast cancer. ANN calibration of VBD was performed using phantom data for one FFDM system. Mammograms of 46 Japanese women diagnosed with invasive carcinoma and 53 with negative findings were analyzed using ANN models learned. ANN-estimated VBD was validated against phantom data, compared intra-patient, with qualitative composition scoring, with MRI VBD, and inter-patient with classical risk factors of breast cancer as well as cancer status. Phantom validations reached an R 2 of 0.993. Intra-patient validations ranged from R 2 of 0.789 with VBD to 0.908 with breast volume. ANN VBD agreed well with BI-RADS scoring and MRI VBD with R 2 ranging from 0.665 with VBD to 0.852 with breast volume. VBD was significantly higher in women with cancer. Associations with age, BMI, menopause, and cancer status previously reported were also confirmed. ANN modeling appears to produce reasonable measures of mammographic density validated with phantoms, with existing measures of breast density, and with classical biomarkers of breast cancer. FFDM VBD is significantly higher in Japanese women with cancer.

Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small cell lung cancer: AURA3 trial.

PubMed

Akamatsu, Hiroaki; Katakami, Nobuyuki; Okamoto, Isamu; Kato, Terufumi; Kim, Young Hak; Imamura, Fumio; Shinkai, Masaharu; Hodge, Rachel A; Uchida, Hirohiko; Hida, Toyoaki

2018-04-26

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase 3 study comparing the efficacy of osimertinib (80 mg/day) with platinum-based therapy plus pemetrexed (500 mg/m 2 ) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary endpoint was progression-free survival (PFS) based on investigator assessment. PFS improvement was clinically meaningful in the osimertinib group (n=41) versus the platinum-pemetrexed group (n=22; hazard ratio 0.27, 95% confidence interval 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in five patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR mutant and T790M NSCLC whose disease has progressed following first-line EGFR-TKI treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Japanese Encephalitis Virus in Meningitis Patients, Japan

PubMed Central

Ito, Mikako; Takao, Shinichi; Shimazu, Yukie; Fukuda, Shinji; Miyazaki, Kazuo; Kurane, Ichiro; Takasaki, Tomohiko

2005-01-01

Cerebrospinal fluid specimens from 57 patients diagnosed with meningitis were tested for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified. Two products had highest homology with Nakayama strain and 2 with Ishikawa strain. Results suggest that Japanese encephalitis virus causes some aseptic meningitis in Japan. PMID:15757569

Characteristics and prognosis of Japanese colorectal cancer patients: The BioBank Japan Project.

PubMed

Tamakoshi, Akiko; Nakamura, Koshi; Ukawa, Shigekazu; Okada, Emiko; Hirata, Makoto; Nagai, Akiko; Matsuda, Koichi; Kamatani, Yoichiro; Muto, Kaori; Kiyohara, Yutaka; Yamagata, Zentaro; Ninomiya, Toshiharu; Kubo, Michiaki; Nakamura, Yusuke

2017-03-01

Colorectal cancer is the third most common cancer worldwide, and in Japan, it is estimated that about 10% of men and 8% of women will be diagnosed with colorectal cancer during their lifetime. We focused on 5864 participants (3699 men and 2165 women) who had colorectal cancer and were registered with BioBank Japan (BBJ) between April 2003 and March 2008. Characteristics of colon and rectal cancer patients were calculated separately. Among the enrolled patients registered in BBJ within 90 days after diagnosis, we also calculated the 5-year cumulative and relative survival rates, and estimated the effect of lifestyle factors on all-cause mortality. Our participants included younger men than those in the Patient Survey and the Cancer Registry Japan. In more than 95% of cases the histological type was adenocarcinoma both in colon and rectal cancer. Rectal cancer patients tended to eat more meat and less green leafy vegetables compared with colon cancer patients. The 5-year cumulative survival rate was 73.0% (95% CI; 70.1%-75.7%) and the 5-year relative survival rate was 80.6% (77.4%-83.6%), respectively, for colon cancer. For rectal cancer, the rates were 73.3% (69.1%-77.0%) and 80.9% (76.3%-85.0%), in the same order. Lifestyle factors such as consuming less green leafy vegetables, being underweight, smoking, not consuming alcoholic beverages and being physically inactive were found to be related to poor survival. We described lifestyle characteristics of colorectal cancer patients in BBJ and examined the impacts on subsequent all-cause mortality. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chronological changes in lung cancer surgery in a single Japanese institution

PubMed Central

Nakamura, Haruhiko; Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Saji, Hisashi

2017-01-01

Background The aim of this study was to evaluate the chronological changes in epidemiological factors and surgical outcomes in patients with lung cancer who underwent surgery in a single Japanese institution. Patients and methods A clinicopathological database of patients with lung cancer who underwent surgery with curative intent from January 1974 to December 2014 was reviewed. The chronological changes in various factors, including patient’s age, sex, histological type, tumor size, pathological stage (p-stage), surgical method, operative time, intraoperative blood loss, 30-day mortality, and postoperative overall survival (OS), were evaluated. Results A total of 1,616 patients were included. The numbers of resected patients, females, adenocarcinomas, p-stage IA patients, and age at the time of surgery increased with time, but tumor size decreased (all P<0.0001). Concerning surgical methods, the number of sublobar resections increased, but that of pneumonectomies decreased (P<0.0001). The mean operative time, intraoperative blood loss, and the postoperative 30-day mortality rate decreased (all P<0.0001). When the patients were divided into two groups (1974–2004 and 2005–2014), the 5-year OS rates for all patients and for p-stage IA patients improved from 44% to 79% and from 73% to 89%, respectively (all P<0.0001). The best 5-year OS rate was obtained for sublobar resection (73%), followed by lobectomy (60%), combined resection (22%), and pneumonectomy (21%; P<0.0001). Conclusion Changes in epidemiological factors, a trend toward less invasive surgery, and a remarkably improved postoperative OS were confirmed, which demonstrated the increasingly important role of surgery in therapeutic strategies for lung cancer. PMID:28331339

[Everolimus plus exemestane in postmenopausal patients with estrogen-receptor-positive advanced breast cancer - Japanese subgroup analysis of BOLERO -2].

PubMed

Ito, Yoshinori; Masuda, Norikazu; Iwata, Hiroji; Mukai, Hirofumi; Horiguchi, Jun; Tokuda, Yutaka; Kuroi, Katsumasa; Mori, Asuka; Ohno, Nobutsugu; Noguchi, Shinzaburo

2015-01-01

In a phase 3, double-blind, randomized, international study (the BOLERO-2), the addition of mTOR inhibitor everolimus to exemestane was evaluated in postmenopausal women with estrogen-receptor-positive (ER⁺) advanced/recurrent breast cancer that was refractory to any nonsteroidal aromatase inhibitor (NSAI). This report presents the safety and updated (18- month) efficacy results from the Japanese subset (n=106) of BOLERO-2. After a median follow-up of 18 months, the median progression-free survival time was 8.5 months with everolimus plus exemestane compared to 4.2 months with placebo plus exemestane. The most common adverse events (AEs) with everolimus plus exemestane were stomatitis, rash, dysgeusia, and non-infectious lung disease. The AEs reported with the combination therapy were mostly of grade 1 or 2 and manageable with appropriate intervention. In conclusion, this combination could be a useful addition to the armamentarium of treatments for Japanese postmenopausal women with ER⁺ advanced/recurrent breast cancer progressing on NSAIs.

Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case-control study in Japanese women.

PubMed

Mizoo, Taeko; Taira, Naruto; Nishiyama, Keiko; Nogami, Tomohiro; Iwamoto, Takayuki; Motoki, Takayuki; Shien, Tadahiko; Matsuoka, Junji; Doihara, Hiroyoshi; Ishihara, Setsuko; Kawai, Hiroshi; Kawasaki, Kensuke; Ishibe, Youichi; Ogasawara, Yutaka; Komoike, Yoshifumi; Miyoshi, Shinichiro

2013-12-01

Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk. A case-control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses. High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR=1.37 [95% CI: 1.11-1.70]), rs3757318 (OR=1.33[1.05-1.69]), and rs3803662 (OR=1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers. In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers.

Development of the Japanese version of an information aid to provide accurate information on prognosis to patients with advanced non-small-cell lung cancer receiving chemotherapy: a pilot study.

PubMed

Nakano, Kikuo; Kitahara, Yoshihiro; Mito, Mineyo; Seno, Misato; Sunada, Shoji

2018-02-27

Without explicit prognostic information, patients may overestimate their life expectancy and make poor choices at the end of life. We sought to design the Japanese version of an information aid (IA) to provide accurate information on prognosis to patients with advanced non-small-cell lung cancer (NSCLC) and to assess the effects of the IA on hope, psychosocial status, and perception of curability. We developed the Japanese version of an IA, which provided information on survival and cure rates as well as numerical survival estimates for patients with metastatic NSCLC receiving first-line chemotherapy. We then assessed the pre- and post-intervention effects of the IA on hope, anxiety, and perception of curability and treatment benefits. A total of 20 (95%) of 21 patients (65% male; median age, 72 years) completed the IA pilot test. Based on the results, scores on the Distress and Impact Thermometer screening tool for adjustment disorders and major depression tended to decrease (from 4.5 to 2.5; P = 0.204), whereas no significant changes were seen in scores for anxiety on the Japanese version of the Support Team Assessment Schedule or in scores on the Hearth Hope Index (from 41.9 to 41.5; p = 0.204). The majority of the patients (16/20, 80%) had high expectations regarding the curative effects of chemotherapy. The Japanese version of the IA appeared to help patients with NSCLC maintain hope, and did not increase their anxiety when they were given explicit prognostic information; however, the IA did not appear to help such patients understand the goal of chemotherapy. Further research is needed to test the findings in a larger sample and measure the outcomes of explicit prognostic information on hope, psychological status, and perception of curability.

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cancer understanding among Japanese students based on a nationwide survey.

PubMed

Sugisaki, Koshu; Ueda, Seiji; Monobe, Hirofumi; Yako-Suketomo, Hiroko; Eto, Takashi; Watanabe, Masaki; Mori, Ryoichi

2014-11-01

The objective of this study was to determine cancer understanding among Japanese primary and secondary school students. The study design was a cross-sectional nationwide survey using a self-administered questionnaire. The prefecture with the lowest student population was set to 1, and that with the highest student population was set to 18 for elementary schools and 19 for junior high and high schools based on the ratio of the student population. In this way, 213 elementary schools, 222 junior high schools, and 208 high schools were selected from all 47 prefectures in Japan, and questionnaires were sent to each school. The questionnaire listed the names of 15 cancers and asked respondents to choose one answer from three: "Never heard of," "Heard of/Don't understand," or "Heard of/Understand." Response rates for schools were 44.1 % (n = 94) for elementary schools, 46.4 % (n = 103) for junior high schools, and 55.8 % (n = 116) for high schools. A total of 8,876 questionnaires were used for the analysis. Our survey suggests that the most commonly understood types of cancer differed by grade, with lung cancer the most commonly understood in elementary school, leukemia in junior high schools, and breast cancer in high schools. Girls tended to demonstrate greater cancer understanding than boys, with particularly large differences by gender in rates of understanding of breast and uterine cancer at each assessed grade level. Here, we examined Japanese primary and secondary school students. Marked differences in cancer recognition by grade and gender suggest that educational efforts are needed at various grade levels and gender-specific cancer education. Further, more than 50 % of students at any school level were not familiar with most cancers. It suggests that cancer education is deficient.

[Change of creatinine clearance rate in accordance with aging in Japanese patients with head and neck cancer].

PubMed

Nishimura, Goshi; Horiuchi, Choichi; Yoshida, Takafumi; Kawakami, Mariko; Yabuki, Kenichiro; Taguchi, Takahide; Nagao, Junichi; Kondo, Norio; Masuda, Yoko; Matsuda, Hideki; Mikami, Yasukazu; Tsukuda, Mamoru

2006-04-01

Most of the head and neck tumors are squamous cell carcinomas (SCCs), which are relatively sensitive to chemotherapeutic agents. Cis-platinum (CDDP), 5-fluorouracil and taxanes are widely used worldwide for SCCs, and CDDP is the most common agent. Renal toxicity is a well-known adverse effect of CDDP, and adequate pre and post-hydration or combined administration of neutralizing agents is performed during CDDP injection. Before the CDDP administration, we have to evaluate renal function of the patients using creatinine clearance rate (Ccr). In Japan, CDDP at the dose of 60-70 mg/m(2)/day is administered in cases with over 65 ml/min/1.73 m(2) of Ccr, whereas in cases under 60 ml/min/1.73 m(2), we use other drugs, e.g., carboplatin, to prevent the renal dysfunction followed by chemotherapy. In other countries, the dose of CDDP is 70-100 mg/m(2)/day, and the discrepancy is based on the poor renal function of Japanese. We calculated Ccrs of 107 head and neck cancer patients since January, 2004 to August, 2005, and evaluated renal function before any treatment. Ccr was decreased in proportion to aging. At the age of fifties, 43.5% of the patients indicated lower Ccr than 65 ml/min/1.73 m(2): sixties, 45.7%; seventies, 50.0%; and eighties, 85.7%. In the United States, the average glomerular filtration rate of over 70 year-old healthy people is estimated as 75 ml/min/ 1.73 m(2), and it is considered sufficient kidney function for the administration of CDDP at the dose of 70-100 mg/ m(2)/day. The incident rate of end-stage renal disease is 1.3 times higher in the United States than in Japan. The incident rate of diabetes, which is the main cause of renal dysfunction, is almost the same in both countries. Though the reason is unclear, it is the fact that the renal function of Japanese decreases quickly in accordance with aging.

[Clinical features of idiopathic restless legs syndrome in Japanese patients].

PubMed

Kume, Akito; Kume, Hideaki

2010-06-01

Little is known about the diagnosis and management of restless legs syndrome (RLS) in Japanese neurology clinics. To validate the diagnostic criteria of the International RLS Study Group (IRLSSG) and the treatment algorithm of the Mayo Clinic in a Japanese neurology clinic setting and to clarify the features of Japanese patients with idiopathic RLS. Patients with RLS symptoms were examined by a neurologist and the assessment included neurological examination, tests for periodic limb movements (PLM) and dopaminergic response, and the clinical diagnosis was made according to IRLSSG diagnostic criteria. Patients diagnosed with idiopathic RLS were treated with dopaminergic agents and the efficacy was evaluated. The study subjects were 151 Japanese patients who presented with RLS symptoms. Idiopathic RLS was diagnosed in 113 patients, secondary RLS in 16 and RLS mimics in 22. The cause of RLS mimics was either myelopathy, radiculopathy or neuropathy in 11 patients. The mean age of patients with idiopathic RLS was 50.1 (SD 20.0) years, 63% were woman, 97% had daily RLS, 31% had family history (40% of the early-onset subgroup), 86% reported unpleasant sensations in the lower legs, 43% had PLM in the daytime suggested immobilization test, 81% suffered from insomnia, 49% had limitations of work and activities, 71% reported impaired mood, 27% had consulted physicians about their symptoms, 4% had been diagnosed with RLS, 73% improved after dopaminergic treatments, and 33% experienced complete remission. The clinical features of Japanese patients with idiopathic RLS were identical to those reported in western countries, which suggests that IRLSSG diagnostic criteria and Mayo Clinic treatment algorism are valid in Japanese neurology clinics. Both patients and physicians were not fully aware of RLS in this country. Neurological examination was important in excluding RLS mimics and making a diagnosis of RLS.

Phase I dose-finding study of monotherapy with atezolizumab, an engineered immunoglobulin monoclonal antibody targeting PD-L1, in Japanese patients with advanced solid tumors.

PubMed

Mizugaki, Hidenori; Yamamoto, Noboru; Murakami, Haruyasu; Kenmotsu, Hirotsugu; Fujiwara, Yutaka; Ishida, Yoshimasa; Kawakami, Tomohisa; Takahashi, Toshiaki

2016-10-01

Background Atezolizumab is an engineered immunoglobulin monoclonal antibody that targets the programmed death-1/programmed death-ligand 1 pathway. Methods In this phase I dose-finding study, we assessed the safety, feasibility, pharmacokinetics (PK), and exploratory anti-tumor activity of atezolizumab monotherapy up to 20 mg/kg in Japanese patients with advanced solid tumors who had failed standard therapy or for whom there is no standard therapy. Results Six patients were enrolled and received intravenous atezolizumab every 3 weeks (q3w) at doses of 10 or 20 mg/kg. Tumor types were non-small cell lung cancer (n = 3), melanoma (n = 1), pancreatic cancer (n = 1), and thymic cancer (n = 1). No dose-limiting toxicities were observed. All adverse events (AEs) were grade 1 or 2 in severity. No discontinuations or deaths due to AEs were observed. As of the data cutoff, no partial responses were observed; however, stable disease was observed in all six patients. The maximum mean serum atezolizumab concentration was 220 μg/mL (SD ± 21.9), with 10-mg/kg dosing and 536 μg/mL (SD ± 49.4) with 20-mg/kg dosing. Three patients were still on treatment, and three of the six had achieved a progression-free survival of >12 months. Conclusions Atezolizumab was well tolerated in Japanese patients at doses up to 20 mg/kg q3w. The safety profile and Cycle 1 serum atezolizumab concentrations were similar to those previously observed in non-Japanese patients. These data support the participation of Japanese patients in ongoing pivotal global studies of atezolizumab.

Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

PubMed

Okubo, Sumiko; Nishiuma, Shinichi; Kobayashi, Noriko; Taketsuna, Masanori; Taniai, Hisashi

2012-11-01

Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

Validation of the Japanese disease severity classification and the GAP model in Japanese patients with idiopathic pulmonary fibrosis.

PubMed

Kondoh, Shun; Chiba, Hirofumi; Nishikiori, Hirotaka; Umeda, Yasuaki; Kuronuma, Koji; Otsuka, Mitsuo; Yamada, Gen; Ohnishi, Hirofumi; Mori, Mitsuru; Kondoh, Yasuhiro; Taniguchi, Hiroyuki; Homma, Sakae; Takahashi, Hiroki

2016-09-01

The clinical course of idiopathic pulmonary fibrosis (IPF) shows great inter-individual differences. It is important to standardize the severity classification to accurately evaluate each patient׳s prognosis. In Japan, an original severity classification (the Japanese disease severity classification, JSC) is used. In the United States, the new multidimensional index and staging system (the GAP model) has been proposed. The objective of this study was to evaluate the model performance for the prediction of mortality risk of the JSC and GAP models using a large cohort of Japanese patients with IPF. This is a retrospective cohort study including 326 patients with IPF in the Hokkaido prefecture from 2003 to 2007. We obtained the survival curves of each stage of the GAP and JSC models to perform a comparison. In the GAP model, the prognostic value for mortality risk of Japanese patients was also evaluated. In the JSC, patient prognoses were roughly divided into two groups, mild cases (Stages I and II) and severe cases (Stages III and IV). In the GAP model, there was no significant difference in survival between Stages II and III, and the mortality rates in the patients classified into the GAP Stages I and II were underestimated. It is difficult to predict accurate prognosis of IPF using the JSC and the GAP models. A re-examination of the variables from the two models is required, as well as an evaluation of the prognostic value to revise the severity classification for Japanese patients with IPF. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Costs associated with febrile neutropenia in Japanese patients with primary breast cancer: post-hoc analysis of a randomized clinical trial.

PubMed

Miyake, Osamu; Murata, Kyoko; Tanaka, Shiro; Ishiguro, Hiroshi; Toi, Masakazu; Tamura, Kazuo; Kawakami, Koji

2018-05-01

Febrile neutropenia (FN), a decrease in blood neutrophils accompanied by fever, is a major adverse event (AE) associated with cancer chemotherapy. We aimed to estimate the direct medical costs associated with FN management in breast cancer patients within a clinical trial with pegfilgrastim, a pegylated form of recombinant granulocyte colony-stimulating factor (G-CSF). We obtained data from 346 Japanese breast cancer patients in a randomized, placebo-controlled clinical trial comparing FN incidence due to TC adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) between pegfilgrastim-treated and placebo groups. We estimated mean costs for chemotherapy drugs, drugs for all AEs and FN, and hospitalization for all AEs and FN. We also calculated mean costs associated with drugs and hospitalization for FN specifically for patients who developed FN in the placebo group. For the pegfilgrastim and placebo groups, the total cost during the first cycle of chemotherapy was ¥189 135 and ¥98 106. This difference is associated with prophylactic use of pegfilgrastim. Our analysis clarified in the placebo group that FN incidents of 119/173 (68.6%), the mean drug cost related to all AEs and hospitalization caused by the first cycle of chemotherapy were ¥14 411and ¥11 180, respectively. The cost of each for FN treatment was ¥16 429 for the placebo group. The mean treatment cost for patients who developed FN in placebo group, was ¥11 145 for drugs and ¥28 420 for drugs and hospitalization. Pegfilgrastim reduced the costs incurred for both drugs and hospitalization for AEs as well as FN, although the total medical cost during the chemotherapy increased. Our study constitutes baseline data for further health economic evaluations of pegfilgrastim.

Primary Gleason Grade 4 Impact on Biochemical Recurrence After Permanent Interstitial Brachytherapy in Japanese Patients With Low- or Intermediate-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uesugi, Tatsuya; Saika, Takashi, E-mail: saika@cc.okayama-u.ac.jp; Edamura, Kohei

2012-02-01

Purpose: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on National Comprehensive Cancer Network (NCCN) guidelines. Methods and Materials: From January 2004 to December 2009, 414 consecutive Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the NCCN guidelines were treated with PPB. The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factorsmore » associated with BCR. Results: Median follow-up was 36.5 months. The 2-, 3-, 4-, and 5-year BCR-free rates using the Phoenix definition were 98.3%, 96.0%, 91.6%, and 87.0%, respectively. On univariate analysis, the Gleason score, especially primary Gleason grade 4 in biopsy specimens, was a strong predicting factor (p < 0.0001), while age, initial prostate-specific antigen (PSA) level, T stage, and minimal dose delivered to 90% of the prostate volume (D90) were insignificant. Multivariate analysis indicated that a primary Gleason grade 4 was the most powerful prognostic factor associated with BCR (hazard ratio = 6.576, 95% confidence interval, 2.597-16.468, p < 0.0001). Conclusions: A primary Gleason grade 4 carried a worse BCR prognosis than the primary grade 3 in patients treated with PPB. Therefore, the indication for PPB in patients with a Gleason sum of 4 + 3 deserves careful and thoughtful consideration.« less

Phase I study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer.

PubMed

Daga, Haruko; Takeda, Koji; Okada, Hideaki; Miyazaki, Masaki; Ueda, Shinya; Kaneda, Hiroyasu; Okamoto, Isamu; Yoh, Kiyotaka; Goto, Koichi; Konishi, Koichi; Sarashina, Akiko; Tanaka, Tetsuya; Kaiser, Rolf; Nakagawa, Kazuhiko

2015-12-01

This open-label, phase I, dose-escalation part of a phase I/II study evaluated the safety, pharmacokinetics, and preliminary efficacy of nintedanib, a triple angiokinase inhibitor, combined with pemetrexed in Japanese patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. A fixed dose of pemetrexed (500 mg/m(2) iv) was administered on Day 1 of each 21-day cycle followed by oral nintedanib twice daily (bid) on days 2-21, starting at 100 mg bid and escalating to 200 mg bid in 50-mg intervals, using a standard 3 + 3 design. After ≥4 cycles of combination therapy, patients could continue nintedanib monotherapy until disease progression or undue adverse events (AEs). Primary endpoints were maximum tolerated dose (MTD), defined as the highest dose at which the incidence of dose-limiting toxicities (DLTs) was <33.3 % during the first treatment course, and AEs (CTCAE v3.0). DLTs were primarily defined as grade ≥3 non-hematologic or grade 4 hematologic AEs. Eighteen patients were included in the analysis. DLTs were experienced by 2/9 patients receiving 200 mg bid, 1/6 receiving 150 mg bid, and 0/3 receiving the lowest dose. The MTD of nintedanib plus pemetrexed was 200 mg bid. The most common drug-related AEs were elevated liver enzymes and gastrointestinal AEs. Two patients achieved partial response, and 10 had stable disease. Nintedanib plus pemetrexed had a manageable safety profile and showed promising signs of efficacy in previously treated Japanese patients with advanced NSCLC. As in Caucasian patients, the MTD of nintedanib was 200 mg bid. Clinical trial information NCT00979576.

Does remnant gastric cancer really differ from primary gastric cancer? A systematic review of the literature by the Task Force of Japanese Gastric Cancer Association.

PubMed

Shimada, Hideaki; Fukagawa, Takeo; Haga, Yoshio; Oba, Koji

2016-04-01

Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords "remnant," "stomach," and "cancer," revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course.

RSPO fusion transcripts in colorectal cancer in Japanese population.

PubMed

Shinmura, Kazuya; Kahyo, Tomoaki; Kato, Hisami; Igarashi, Hisaki; Matsuura, Shun; Nakamura, Satoki; Kurachi, Kiyotaka; Nakamura, Toshio; Ogawa, Hiroshi; Funai, Kazuhito; Tanahashi, Masayuki; Niwa, Hiroshi; Sugimura, Haruhiko

2014-08-01

R-spondin (RSPO) gene fusions have recently been discovered in a subset of human colorectal cancer (CRC) in the U.S. population; however, whether the fusion is recurrent in CRC arising in patients from the other demographic areas and whether it is specific for CRC remain uncertain. In this study, we examined 75 primary CRCs and 121 primary lung cancers in the Japanese population for EIF3E-RSPO2 and PTPRK-RSPO3 fusion transcripts using RT-PCR and subsequent sequencing analyses. Although the expression of EIF3E-RSPO2 and PTPRK-RSPO3 was not detected in any of the lung carcinomas, RSPO fusions were detected in three (4%) of the 75 CRCs. Two CRCs contained EIF3E-RSPO2 fusion transcripts, and another CRC contained PTPRK-RSPO3 fusion transcripts. Interestingly, in one of the two EIF3E-RSPO2 fusion-positive CRCs, a novel fusion variant form of EIF3E-RSPO2 was identified: exon 1 of EIF3E was connected to exon 2 of RSPO2 by a 351-bp insertion. A quantitative RT-PCR analysis revealed that RSPO mRNA expression was upregulated in the three CRCs containing RSPO fusion transcripts, while it was downregulated in nearly all of the other CRCs. An immunohistochemical analysis and a mutational analysis revealed that the RSPO fusion-containing CRC had a CDX2 cell lineage, was positive for mismatch repair protein expression, and had the wild-type APC allele. Finally, the forced expression of RSPO fusion proteins were shown to endow colorectal cells with an increased growth ability. These results suggest that the expression of RSPO fusion transcripts is related to a subset of CRCs arising in the Japanese population.

Interleukin-10 -1082 gene polymorphism and susceptibility to cervical cancer among Japanese women.

PubMed

Matsumoto, Koji; Oki, Akinori; Satoh, Toyomi; Okada, Satoshi; Minaguchi, Takeo; Onuki, Mamiko; Ochi, Hiroyuki; Nakao, Sari; Sakurai, Manabu; Abe, Azusa; Hamada, Hiromi; Yoshikawa, Hiroyuki

2010-11-01

Polymorphisms in cytokine genes can influence immune responses to human papillomavirus infection, possibly modifying risks of cervical cancer. Using an amplification refractory mutation system-polymerase chain reaction method, we analyzed a single nucleotide polymorphism (A/G) at position -1082 in interleukin-10 promoter region in 440 Japanese women: 173 women with normal cytology, 163 women with cervical intraepithelial neoplasia and 104 women with invasive cervical cancer. The carrier frequency of interleukin-10 -1082 G alleles associated with higher interleukin-10 production increased with disease severity: 9.8% for normal cytology; 19.6% for cervical intraepithelial neoplasia; 29.8% for invasive cervical cancer (P for trend < 0.001). Among cytologically normal women, human papillomavirus infections were more common in those who were positive for an interleukin-10 -1082 G allele (P = 0.04). In conclusion, our data suggest that interleukin-10 -1082 gene polymorphism may serve as a marker of genetic susceptibility to cervical cancer among Japanese women.

Cross-cultural comparison of breast cancer patients' Quality of Life in the Netherlands and Japan.

PubMed

Fischer, M J; Inoue, K; Matsuda, A; Kroep, J R; Nagai, S; Tozuka, K; Momiyama, M; Weijl, N I; Langemeijer-Bosman, D; Ramai, S R S; Nortier, J W R; Putter, H; Yamaoka, K; Kubota, K; Kobayashi, K; Kaptein, A A

2017-11-01

Cultural differences are hypothesized to influence patients' Quality of Life (QoL) reports. However, there is a lack of empirical cross-cultural studies comparing QoL of patients with cancer. This study aims to compare QoL of women with breast cancer in the Netherlands and Japan, and to investigate the association of QoL with sociodemographic, clinical, and psychological variables (illness perceptions). Dutch (n = 116) and Japanese (n = 148) women with early breast cancer undergoing chemotherapy completed the EORTC QLQ-C30 and Brief Illness Perception Questionnaire immediately before their second cycle of chemotherapy. Dutch women reported poorer Physical, Role, Emotional, and Cognitive functioning than Japanese women. Additionally, illness perceptions were significantly different in Japan and the Netherlands, but these did not vary across treatment type. In Japan, QoL of women receiving AC-chemotherapy was better than that of women receiving FEC-chemotherapy, whereas in the Netherlands, QoL did not vary as a function of chemotherapy. Illness perceptions about symptom severity, adverse consequences, and emotional representations were negatively related to most domains of patients' QoL in both countries. Adding illness perceptions as covariates to the ANOVA analyses rendered the effects of country and treatment type on QoL non-significant. Comparing Dutch and Japanese women with early breast cancer revealed important differences in treatment modalities and illness perceptions which both appear to influence QoL. Perceptions about cancer have been found to vary across cultures, and our study suggests that these perceptions should be considered when performing cross-cultural studies focusing on patient-reported outcomes.

A novel deletion in the splice donor site of MLH1 exon 6 in a Japanese colon cancer patient with Lynch syndrome.

PubMed

Yamaguchi, Junya; Sato, Yuri; Kita, Mizuho; Nomura, Sachio; Yamamoto, Noriko; Kato, Yo; Ishikawa, Yuichi; Arai, Masami

2015-10-01

Lynch syndrome is an autosomal dominantly inherited disease that is characterized by a predisposition to cancers, mainly colorectal cancer. Germline mutations of DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2 have been described in patients with Lynch syndrome. Here, we report deletion of 2 bp in the splice donor site of the MLH1 exon 6 (c.545+4_545+5delCA) in a 48-year-old Japanese woman with Lynch syndrome. RT-PCR direct sequencing analysis revealed that this mutation led to an increase in the level of an MLH1 transcript in which exon 6 was skipped, and may cause a frameshift (p.E153FfsX8). Therefore, this mutation appears to be pathogenic and is responsible for Lynch syndrome. Additionally, analysis of the patient's tumor cells indicated microsatellite instability high phenotype and loss of the MLH1 and PMS2 proteins. To our knowledge, this is a germline splice site mutation of MLH1 that has not been reported previously. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mitochondrial haplogroups associated with Japanese centenarians, Alzheimer's patients, Parkinson's patients, type 2 diabetic patients and healthy non-obese young males.

PubMed

Takasaki, Shigeru

2009-07-01

The relationships between five classes of Japanese people (i.e., 96 centenarians, 96 Alzheimer's disease (AD) patients, 96 Parkinson's disease (PD) patients, 96 type 2 diabetic (T2D) patients, and 96 healthy non-obese young males) and their mitochondrial single nucleotide polymorphism (mtSNP) frequencies at individual mtDNA positions of the entire mitochondrial genome were examined using the radial basis function (RBF) network and the modified method. New findings of mitochondrial haplogroups were obtained for individual classes. The five classes of people were associated with the following haplogroups: Japanese centenarians-M7b2, D4b2a, and B5b; Japanese AD patients-G2a, B4c1, and N9b1; Japanese PD patients-M7b2, B4e, and B5b; Japanese T2D patients-B5b, M8a1, G, D4, and F1; and Japanese healthy non-obese young males- D4g and D4b1b. From the points of common haplogroups among the five classes, the centenarians have the common haplogroups M7b2 and B5b with the PD patients and common haplogroup B5b with the T2D patients. In addition, the 112 Japanese semi-supercentenarians (over 105 years old) recently reported were also examined by the method proposed. The results obtained were the haplogroups D4a, B4c1a, M7b2, F1, M1, and B5b. These results are different from the previously reported haplogroup classifications. As the proposed analysis method can predict a person's mtSNP constitution and the probabilities of becoming a centenarian, AD patient, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.

[Cancer Survivorship: the patient and medical care staff - how will society deal with cancer ?].

PubMed

Honda, Mayumi

2011-07-01

Instead of being preoccupied with treatment effectiveness, rates of survival, and asking how much longer will I live?, let us think in terms of how will I live my life the way I want to live it? In recent years, a new way of thinking called Cancer Survivorship has emerged in the United States, and has been drawing attention in Japan. Cancer Survivorship is a concept developed by a cancer patient support group in the United States in 1986, focusing on the experience of living with, through, and beyond cancer. Opposing society's narrow view of cancer patients as victims handed out a death sentence, Cancer Survivorship focuses on living life to the fullest from the time of cancer diagnosis until the moment of death,and works as a movement appealing to society to allow cancer survivors the right to live as they wish. This way of thinking has spread globally, and in Italy, a movement aimed at protecting cancer survivors' freedom to do paid work has unfolded. Even in Japan, with an increase in the number of cancer patients and an improved five-year survival rate, patient support groups have been emerging with the Cancer Survivorship mentality. However, Japanese society still has not given the movement sufficient recognition, and the question now is if cancer patients, even those in the terminal stage, can seize their lives and be someone who lives in the present.

Psychosocial factors affecting the therapeutic decision-making and postoperative mood states in Japanese breast cancer patients who underwent various types of surgery: body image and sexuality.

PubMed

Adachi, Keiichiro; Ueno, Tokumi; Fujioka, Toshio; Fujitomi, Yutaka; Ueo, Hiroaki

2007-06-01

We conducted an empirical study to clarify how psychosocial factors (e.g. body image and sexuality) influence therapeutic decision-making and to identify the factors that affect post-operative mood states in Japanese women who underwent various types of surgery. One hundred and two patients who had undergone surgical treatment for breast cancer participated in this study. Twenty-five patients had undergone mastectomy, 67 breast conserving treatment and 11 skin-sparing mastectomy and immediate breast reconstruction. The participants were evaluated based on a battery of questionnaires including value estimates of decision-making factors, a shortened version of the Profile of Mood States and self-efficacy. The patients regarded the possibility of cure and recurrence of cancer as well as the physician's support as important, regardless of the treatments they had chosen. The patients that had immediate breast reconstruction placed significantly more importance on their body image and sexuality (i.e. physical appearance, attractiveness to partner and self-evaluation of femininity and sexuality) than the mastectomy patients. After surgery, the former group tended to have a more negative mood on the shortened version of the Profile of Mood States than the latter group. Degree of self-efficacy had a marked influence on the patients' mood after surgery. This study suggests the importance of discussing body image and sexuality that has tended to be disregarded in therapeutic decision-making situations in breast cancer patients in Japan. Self-efficacy is a crucial variable for improving mood after treatment.

Willingness of Japanese patients with breast cancer to have genetic testing of BRCA without burden of expenses.

PubMed

Nakagomi, Hiroshi; Sakamoto, Ikuko; Hirotsu, Yosuke; Amemiya, Kenji; Mochizuki, Hitoshi; Inoue, Masayuki; Nakagomi, Satoko; Kubota, Takeo; Omata, Masao

2016-07-01

Genetic analysis for individuals who are at risk for hereditary breast and ovarian cancer syndrome (HBOC) has becoming widely accepted. The poor introduction of the genetic testing of BRCA in Japan compared with western countries could be due to insufficient recognition of its importance, prejudice against a heredity disease, especially in non-urban districts, and its high cost. There is few available data regarding the acceptance or willingness to have genetic testing among Japanese who are at risk and living outside Tokyo. Of 670 patients seen and detailed family history taken at our hospital, located non-urban, 30 (4 %) gave the family history of breast cancer in more than 2 members within the second degree relatives ("stronger" family history group), 92 (14 %) in 1 member ("weaker" group), and 548 (82 %) in none of members ("sporadic" group). Then, we selected 107 (24 from "stronger", 50 from "weaker", 33 from "sporadic" family history group) to see if they are willing to receive cost-free genetic testing of BRCA 1 and BRCA2. Ninety-two of 107 (86 %) patients agreed and 15 (14 %) refused. The rate of refusal for BRCA testing was higher in "stronger family history group" (6/24, 25 %) compared to "weaker" (7/50, 14 %) or "sporadic" (2/33, 6 %) (p = 0.04), respectively. These data indicate that the currently available preventive measures and/or counseling system may not be sufficient enough to convince the high risk population to receive the genetic testing or to overcome the prejudice in non-urban area in Japan, even if served free.

Toward freedom from cancer pain in Japan.

PubMed

Otsuka, Kuniko; Yasuhara, Hajime

2007-01-01

Life expectancy in Japan is highest in the world. Cancer is the leading cause of mortality in Japan, accounting for about 30 percent of all deaths. Many Japanese cancer patients experience severe pain although they and their families hope to be pain free at the end of their lives. Toward that end, the consumption of morphine in Japan has increased markedly since 1989. The amount of morphine hydrochloride and morphine sulfate consumed in 2001 was 6.1 times that used in Japan in 1989. However, the amount of morphine consumed in Japan is still less than in other developed nations, and was only one-sixth of the amount used in Australia in 2001. As a result, many Japanese cancer patients experience potentially manageable cancer pain, largely because the amount of the drug used by doctors is insufficient for pain control. An increasing number of Japanese doctors now understand that their patients' quality of life is most important in end-of-life care and how to use the three step analgesic ladder of the World Health Organization (WHO). However, other doctors do not understand these issues sufficiently causing some patients to die without good pain control. Both the general population and some medical professionals misunderstand and have prejudice against the use of morphine. Patients often do not participate in decision making about medical treatment because of remaining paternalism in the relationship between Japanese doctors and patients. Thus, cancer pain management in Japan is not as effective as it can be and not all Japanese cancer patients receive appropriate management for their cancer pain. To improve outcomes for Japanese patients, it is necessary for health professional and social work students and practicing professionals to receive contemporary education including an introduction to palliative care and ethics.

Construction of a model for predicting creatinine clearance in Japanese patients treated with Cisplatin therapy.

PubMed

Yajima, Airi; Uesawa, Yoshihiro; Ogawa, Chiaki; Yatabe, Megumi; Kondo, Naoki; Saito, Shinichiro; Suzuki, Yoshihiko; Atsuda, Kouichiro; Kagaya, Hajime

2015-05-01

There exist various useful predictive models, such as the Cockcroft-Gault model, for estimating creatinine clearance (CLcr). However, the prediction of renal function is difficult in patients with cancer treated with cisplatin. Therefore, we attempted to construct a new model for predicting CLcr in such patients. Japanese patients with head and neck cancer who had received cisplatin-based chemotherapy were used as subjects. A multiple regression equation was constructed as a model for predicting CLcr values based on background and laboratory data. A model for predicting CLcr, which included body surface area, serum creatinine and albumin, was constructed. The model exhibited good performance prior to cisplatin therapy. In addition, it performed better than previously reported models after cisplatin therapy. The predictive model constructed in the present study displayed excellent potential and was useful for estimating the renal function of patients treated with cisplatin therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Information-seeking experiences and decision-making roles of Japanese women with breast cancer.

PubMed

Nakashima, Mitsuyo; Kuroki, Syoji; Shinkoda, Harumi; Suetsugu, Yoshiko; Shimada, Kazuo; Kaku, Tsunehisa

2012-06-01

To investigate the information-seeking experiences and decision-making roles of Japanese women with breast cancer, to examine the relationship between information-seeking experiences and decision-making roles, and to explore the factors that influenced taking a more active role than the preferred role during the treatment decision-making process. In a cross-sectional study, women with breast cancer were retrospectively administered the Control Preferences Scale and the Information-Seeking Experience Scale. The Chi-Square test was used to compare differences among individual variables in decision-making roles and information-seeking experiences. Logistic regression analysis was used to explore the factors that influenced taking a more active role than the preferred role. One hundred and four patients with breast cancer participated in the investigation. Eighty-five patients (78%) perceived themselves as having knowledge of breast cancer and most patients (92%) sought information on breast cancer. The preferred roles in decision-making that they reported having before treatment were 18% active, 69% collaborative and 13% passive. The actual roles they perceived having experienced were 27% active, 43% collaborative and 30% passive. Although there was concordance of preferred and actual role for only 59% of the women, most patients reported that they were satisfied with their decision-making. Many women with breast cancer reported negative experiences with information seeking, including wanting more information (49%), expending a lot of effort to obtain the information needed (53%), not having enough time to obtain needed information (55%), frustration during the search for information (44%), concerns about the quality of the information (45%) and difficulty understanding the information received (49%). This study revealed that having a more active actual role than the initial preferred role was associated with emotional expression to the physician, having undergone

Anti-Tribbles Homolog 2 Autoantibodies in Japanese Patients with Narcolepsy

PubMed Central

Toyoda, Hiromi; Tanaka, Susumu; Miyagawa, Taku; Honda, Yutaka; Tokunaga, Katsushi; Honda, Makoto

2010-01-01

Study Objectives: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy. The association with human leukocyte antigen (HLA)-DQB1*0602 and T-cell receptor alpha locus suggests that autoimmunity plays a role in narcolepsy. A recent study reported an increased prevalence of autoantibodies against Tribbles homolog 2 (TRIB2) in patients with narcolepsy. To replicate this finding, we examined anti-TRIB2 autoantibodies in Japanese patients with narcolepsy. Design: We examined anti-TRIB2 autoantibodies against a full-length [35S]-labeled TRIB2 antigen in Japanese patients with narcolepsy-cataplexy (n = 88), narcolepsy without cataplexy (n = 18), and idiopathic hypersomnia with long sleep time (n = 11). The results were compared to Japanese healthy controls (n = 87). Thirty-seven healthy control subjects were positive for HLA-DRB1*1501-DQB1*0602. We also examined autoantibodies against another Tribbles homolog, TRIB3, as an experimental control. Measurements and Results: Autoantibodies against TRIB2 were found in 26.1% of patients with narcolepsy-cataplexy, a significantly higher prevalence than the 2.3% in healthy controls. We found that anti-TRIB3 autoantibodies were rare in patients with narcolepsy and showed no association with anti-TRIB2 indices. No significant correlation was found between anti-TRIB2 positivity and clinical information. Conclusions: We confirmed the higher prevalence and specificity of anti-TRIB2 autoantibodies in Japanese patients with narcolepsy-cataplexy. This suggests a subgroup within narcolepsy-cataplexy might be affected by an anti-TRIB2 autoantibody-mediated autoimmune mechanism. Citation: Toyoda H; Tanaka S; Miyagawa T; Honda Y; Tokunaga K; Honda M. Anti-Tribbles homolog 2 autoantibodies in Japanese patients with narcolepsy. SLEEP 2010;33(7):875-878. PMID:20614847

The serum vaspin levels are reduced in Japanese chronic hemodialysis patients.

PubMed

Inoue, Junko; Wada, Jun; Teshigawara, Sanae; Hida, Kazuyuki; Nakatsuka, Atsuko; Takatori, Yuji; Kojo, Shoichirou; Akagi, Shigeru; Nakao, Kazushi; Miyatake, Nobuyuki; McDonald, John F; Makino, Hirofumi

2012-12-03

Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine identified in genetically obese rats that correlates with insulin resistance and obesity in humans. Recently, we found that 7% of the Japanese population with the minor allele sequence (A) of rs77060950 exhibit higher levels of serum vaspin. We therefore evaluated the serum vaspin levels in Japanese chronic hemodialysis patients. Healthy Japanese control volunteers (control; n = 95, 49.9 ± 6.91 years) and Japanese patients undergoing hemodialysis therapy (HD; n = 138, 51.4 ± 10.5 years) were enrolled in this study, and serum samples were subjected to the human vaspin RIA system. The measurement of the serum vaspin levels demonstrated that a fraction of control subjects (n = 5) and HD patients (n = 11) exhibited much higher levels (> 10 ng/ml; Vaspin High group), while the rest of the population exhibited lower levels (< 3 ng/ml; Vaspin Low group). By comparing the patients in the Vaspin Low group, the serum vaspin levels were found to be significantly higher in the control subjects (0.87 ± 0.24 ng/ml) than in the HD patients (0.32 ± 0.15 ng/ml) (p < 0.0001). In the stepwise regression analyses, the serum creatinine and triglyceride levels were found to be independently and significantly associated with the vaspin concentrations in all subjects. The creatinine levels are negatively correlated with the serum vaspin levels and were significantly reduced in the Japanese HD patients in the Vaspin Low group.

Validation of the Japanese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module.

PubMed

Tsuji, Naoko; Kakee, Naoko; Ishida, Yasushi; Asami, Keiko; Tabuchi, Ken; Nakadate, Hisaya; Iwai, Tsuyako; Maeda, Miho; Okamura, Jun; Kazama, Takuro; Terao, Yoko; Ohyama, Wataru; Yuza, Yuki; Kaneko, Takashi; Manabe, Atsushi; Kobayashi, Kyoko; Kamibeppu, Kiyoko; Matsushima, Eisuke

2011-04-10

The PedsQL 3.0 Cancer Module is a widely used instrument to measure pediatric cancer specific health-related quality of life (HRQOL) for children aged 2 to 18 years. We developed the Japanese version of the PedsQL Cancer Module and investigated its reliability and validity among Japanese children and their parents. Participants were 212 children with cancer and 253 of their parents. Reliability was determined by internal consistency using Cronbach's coefficient alpha and test-retest reliability using intra-class correlation coefficient (ICC). Validity was assessed through factor validity, convergent and discriminant validity, concurrent validity, and clinical validity. Factor validity was examined by exploratory factor analysis. Convergent and discriminant validity were examined by multitrait scaling analysis. Concurrent validity was assessed using Spearman's correlation coefficients between the Cancer Module and Generic Core Scales, and the comparison of the scores of child self-reports with those of other self-rating depression scales for children. Clinical validity was assessed by comparing the on- and off- treatment scores using Kruskal-Wallis and Mann-Whitney U tests. Cronbach's coefficient alpha was over 0.70 for the total scale and over 0.60 for each subscale by age except for the 'pain and hurt' subscale for children aged 5 to 7 years. For test-retest reliability, the ICC exceeded 0.70 for the total scale for each age. Exploratory factor analysis demonstrated sufficient factorial validity. Multitrait scaling analysis showed high success rates. Strong correlations were found between the reports by children and their parents, and the scores of the Cancer Module and the Generic Core Scales except for 'treatment anxiety' subscales for child reports. The Depression Self-Rating Scale for Children (DSRS-C) scores were significantly correlated with emotional domains and the total score of the cancer module. Children who had been off treatment over 12 months

Replication of prostate cancer risk loci in a Japanese case-control association study.

PubMed

Yamada, Hiroki; Penney, Kathryn L; Takahashi, Hiroyuki; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin; Freedman, Matthew L

2009-10-07

Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.

Attitudes towards cross-border reproductive care among infertile Japanese patients.

PubMed

Hibino, Yuri; Shimazono, Yosuke; Kambayashi, Yasuhiro; Hitomi, Yoshiaki; Nakamura, Hiroyuki

2013-11-01

The attitudes towards cross-border reproductive care (CBRC) held by infertile Japanese patients have not been explored. The objective of the present study was to examine interest levels, preferred destinations, motivations, and sources of information related to CBRC. Our findings provide a general outline of CBRC and the future of reproduction and assisted reproductive technology (ART) in Japan. The study used a cross-sectional design. Data were collected from 2,007 infertile Japanese patients from 65 accredited ART clinics in Japan (response rate, 27.4 %) via anonymous questionnaires. Most of the infertile Japanese patients who responded denied using CBRC. However, by group, 171 (8.5 %) patients in non-donor in vitro fertilization, 150 (7.5 %) in egg donation, 145 (7.2 %) in pre-implantation genetic diagnosis, and 129 (6.4 %) in surrogacy said that, depending on the situation, they might travel abroad in the future. Older respondents were more likely to express an intention to travel overseas for egg donation in the future. The most popular destination for CBRC was the United States. Popular reasons for interest in CBRC among those considering or planning using this approach to third-party reproduction were that egg donation or surrogacy was unavailable or that obtaining ethical approval takes too long in Japan, whereas these processes are legal and affordable overseas. However, high cost was the most common reason for hesitancy regarding CBRC. Among the participants who were considering or planning to travel abroad for this purpose, TV, medical agencies, print media, and message boards on websites were popular sources of information, whereas doctors, friends, and patient self-help groups were not. Although CBRC among infertile Japanese patients is not at present common, the demand for and use of this approach may increase in the future in the context of the increasingly aging population. Lack of regulation and unavailability of third-party reproduction is a

Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.

PubMed

Kato, Haruo; Furuya, Yosuke; Miyazawa, Yoshiyuki; Miyao, Takeshi; Syuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

2016-11-01

Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS. An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The Japanese Guidelines for Breast Cancer Screening.

PubMed

Hamashima, Chisato; Hamashima C, Chisato; Hattori, Masakazu; Honjo, Satoshi; Kasahara, Yoshio; Katayama, Takafumi; Nakai, Masahiro; Nakayama, Tomio; Morita, Takako; Ohta, Koji; Ohnuki, Koji; Sagawa, Motoyasu; Saito, Hiroshi; Sasaki, Seiju; Shimada, Tomoyuki; Sobue, Tomotaka; Suto, Akihiko

2016-05-01

The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women. The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated. Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validation of a Japanese version of the Scoliosis Research Society-22 Patient Questionnaire among idiopathic scoliosis patients in Japan.

PubMed

Hashimoto, Hideki; Sase, Takeshi; Arai, Yasuhisa; Maruyama, Toru; Isobe, Keijirou; Shouno, Yasuhiro

2007-02-15

A cross-sectional observational study to determine the response distribution, internal consistency, and construct, concurrent, and discriminative validities of The Scoliosis Research Society-22 (SRS-22) Patient Questionnaire translated into Japanese as compared with the other language versions. To validate the Japanese version of SRS22. The SRS-22 was translated into several languages but yet not into Japanese. The Japanese SRS-22 and Medical Outcomes Study Short Form 36 were simultaneously administered to 114 adolescent idiopathic scoliosis patients. Exploratory factor analysis revealed a 4-factor structure, though several items were not loaded as theoretically expected. The originally constructed Japanese SRS-22 subscales and the English version showed similar response distribution. Internal consistency was fair but lower than that of the English version. The concurrent validity of the translated version, except for the self-image subscale, was supported using Medical Outcomes Study Short Form 36 subscales as a reference. The function scale differed significantly by curve angle magnitude and treatment status. The self-image score was the highest in patients under observation when curve angle was < 40 degrees, while postsurgical patients marked the highest scores when the angle > or = 40 degrees, respectively. The Japanese SRS-22 is valid and may be useful for clinical evaluation of Japanese scoliosis patients, though the self-image subscale may need further assessment.

Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology.

PubMed

Nawa, Toru; Kato, Jun; Kawamoto, Hirofumi; Okada, Hiroyuki; Yamamoto, Hiroshi; Kohno, Hiroyuki; Endo, Hisayuki; Shiratori, Yasushi

2008-03-01

Recently, the clinical and biological differences between right- and left-sided colon cancers have been widely debated. However, close analyses of these clinical differences, based on large-scale studies, have been scarcely reported. A total of 3552 consecutive Japanese colorectal cancer cases were examined and the clinical differences between right- and left-sided colon cancer cases were investigated. The proportion of right-sided colon cancer was relatively high in patients aged less than 40 years (33%) and more than 80 years (43%). The proportion of right-sided colon cancer in patients aged 40-59 years was relatively low (male 22% and female 29%). In male patients the proportion increased in the 70-79 years age group (30%), while in female patients the proportion increased in the 60-69 years age group (39%). Right-sided colon cancer was more likely to be detected at an advanced stage (T1 stage; left 22%, right 15%) (P < 0.01) with severe symptoms. Polypoid-type early cancer was dominant in the left colon (left 59%; right 40%) (P < 0.01), while the proportion of flat-type early cancer in the right colon was significantly higher than that in the left colon (left 25%; right 44%) (P < 0.01). Specific age distribution of right-sided colon cancer was observed and the difference between male and female patients was highlighted. Other clinical features also differed between right- and left-sided colon cancer, suggesting that different mechanisms may be at work during right and left colon carcinogenesis.

[Quality of life in patients with Japanese cedar pollinosis: using the SF-8 health status questionnaire (Japanese version)].

PubMed

Fujii, Tsukasa; Ogino, Satoshi; Arimoto, Hiroe; Irifune, Morihiro; Iwata, Nobuko; Ookawachi, Ichiro; Kikumori, Hiroshi; Seo, Ritsu; Takeda, Mariko; Tamaki, Akiko; Baba, Kenji; Nose, Michihiro

2006-10-01

The number of patients with Japanese cedar pollinosis (JCP) is increasing, and now, has extended up to about 15% of the Japanese. It is reported that the QOL is an important outcome in the JCP treatment. This study aimed to evaluate the QOL in patients with JCP by means of the SF-8 Health Survey (Japanese Version), a new, even shorter generic health survey. 411 patients with JCP who visited 10 ENT clinics in Osaka from March 14 to March 26 (peak pollen season) were questioned, and 204 patients without any treatments in this season were engaged in this study as subjects. In this study, the QOL scores were evaluated using the SF-8. This is an 8-item version of the SF-36 that yields a comparable 8-dimension health profile and comparable estimates of summary scores for the physical and mental components of health. The QOL score depressed in the patients with JCP compared with healthy subjects (Japanese national norms). Both Mental Component Score (MCS) and Physical Component Score (PCS) scores decreased more in females than in males. In females, MCS were significantly lower than national norms. The older the patients were, the lower PCS scores were showed. The severity of nasal symptoms influenced the PCS scores. These results showed the tendency similar to the early studies using SF-36 questionnaire. The sensitivity of SF-8 in the individual is not better than that of other specific QOL questionnaires, but SF-8 can be answered in a short time compared with other questionnaires including SF-36. We suggested that SF-8 become a useful questionnaire in the future.

Alcohol and aldehyde dehydrogenase gene polymorphisms influence susceptibility to esophageal cancer in Japanese alcoholics.

PubMed

Yokoyama, A; Muramatsu, T; Omori, T; Matsushita, S; Yoshimizu, H; Higuchi, S; Yokoyama, T; Maruyama, K; Ishii, H

1999-11-01

Studies have consistently demonstrated that inactive aldehyde dehydrogenase-2 (ALDH2), encoded by ALDH2*1/2*2, is closely associated with alcohol-related carcinogenesis. Recently, the contributions of alcohol dehydrogenase-2 (ADH2) polymorphism to alcoholism, esophageal cancer, and the flushing response have also been described. To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs). This study also tested 82 of the alcoholics with esophageal cancer to determine whether cancer susceptibility is associated with patients' responses to simple questions about current or former flushing after drinking a glass of beer. The frequencies of ADH2*1/2*1 and ALDH2*1/2*2 were significantly higher in alcoholics with, than in those without, esophageal cancer (0.473 vs. 0.289 and 0.560 vs. 0.099, respectively). After adjustment for drinking and smoking, the analysis showed significantly increased cancer risk for alcoholics with either ADH2*1/2*I (OR = 2.03) or ALDH2*1/2*2 (OR = 12.76). For those having ADH2*1/2*1 combined with ALDH2*1/2*2, the esophageal cancer risk was enhanced in a multiplicative fashion (OR = 27.66). Responses to flushing questions showed that only 47.8% of the ALDH2*1/2*2 heterozygotes with ADH2*1/ 2*1, compared with 92.3% of those with ALDH2*1/2*2 and the ADH2*2 allele, reported current or former flushing. Genotyping showed that for alcoholics who reported ever flushing, the questionnaire was 71.4% correct in identifying ALDH2*1/2*2 and 87.9% correct in identifying ALDH2*1/2*1. Japanese alcoholics can be divided into cancer susceptibility groups on the basis of their combined ADH2 and ALDH2 genotypes. The flushing questionnaire can predict high risk ALDH2*1/2*2 fairly accurately in persons with ADH2*2 allele, but a reliable

Quality assurance manual of endoscopic screening for gastric cancer in Japanese communities.

PubMed

Hamashima, Chisato; Fukao, Akira

2016-09-02

The Japanese government introduced endoscopic screening for gastric cancer in 2015 as a public policy based on the Japanese guidelines on gastric cancer screening. To provide appropriate endoscopic screening for gastric cancer in Japanese communities, we developed a quality assurance manual of endoscopic screening and recommend 10 strategies with their brief descriptions as follows: (i) Formulation of a committee responsible for implementing and managing endoscopic screening, and for deciding the suitable implementation methods in consideration of the local context; (ii) Development of an interpretation system that leads to a final judgement to standardize endoscopic examination and improve its accuracy; (iii) Preparation of management and reporting systems for adverse effects by the committee for safety management; (iv) Obtaining informed consent before operation following adequate explanations regarding the benefits and harms of endoscopic screening; (v) Avoidance of frequent screenings to reduce false-positive results and overdiagnosis. As a reference, the target age group is ≥50 years, and the screening interval is 2 years; (vi) Keeping the biopsy rate within 10% as post-biopsy bleeding may occur. Before endoscopic screening, any history of antithrombotic drug usage should be checked; (vii) Nonadministration of sedation in endoscopic screening for safety management; (viii) Adherence to proper endoscopic cleaning and disinfection to reduce infection; (ix) Use of a checklist to achieve optimal program preparation when municipal governments introduce endoscopic screening; (x) Identification of the aims and roles by referring to a checklist if primary care physicians decide to participate in endoscopic screening. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer.

PubMed

Yamada, Rin; Yamaguchi, Tatsuro; Iijima, Takeru; Wakaume, Rika; Takao, Misato; Koizumi, Koichi; Hishima, Tsunekazu; Horiguchi, Shin-Ichiro

2018-06-01

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50-45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

PubMed

Araki, K; Noguchi, Y; Hirouchi, T; Yoshikawa, E; Kataoka, S; Silverni, L; Miyazawa, H; Kuzuhara, H; Suzuki, C; Shimada, Y; Hamasato, S; Maeda, N; Shimamura, Y; Ogawa, Y; Ohtsuki, Y; Fujimoto, S

2000-12-01

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Population Pharmacokinetics of Hydroxychloroquine in Japanese Patients With Cutaneous or Systemic Lupus Erythematosus.

PubMed

Morita, Shigemichi; Takahashi, Toshiya; Yoshida, Yasushi; Yokota, Naohisa

2016-04-01

Hydroxychloroquine (HCQ) is an effective treatment for patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) and has been used for these patients in more than 70 nations. However, in Japan, HCQ has not been approved for CLE or SLE. To establish an appropriate therapeutic regimen and to clarify the pharmacokinetics (PK) of HCQ in Japanese patients with CLE with or without SLE (CLE/SLE), a population pharmacokinetic (PopPK) analysis was performed. In a clinical study of Japanese patients with a diagnosis of CLE irrespective of the presence of SLE, blood and plasma drug concentration-time data receiving multiple oral doses of HCQ sulfate (200-400 mg daily) were analyzed using nonlinear mixed-effects model software. The blood and plasma concentrations of HCQ were analyzed using a high-performance liquid chromatography tandem mass spectrometry method. Model evaluation and validation were performed using goodness-of-fit (GOF) plots, visual predictive check, and a bootstrap. The PopPKs of HCQ in the blood and plasma of 90 Japanese patients with CLE/SLE were well described by a 1-compartment model with first-order absorption and absorption lag time. Body weight was a significant (P < 0.001) covariate of oral clearance of HCQ. The final model was assessed using GOF plots, a bootstrap, and visual predictive check, and this model was appropriate. Simulations based on the final model suggested that the recommended daily doses of HCQ sulfate (200-400 mg) based on the ideal body weight in Japanese patients with CLE/SLE were in the similar concentration ranges. The PopPK models derived from both blood and plasma HCQ concentrations of Japanese patients with CLE/SLE were developed and validated. Based on this study, the dosage regimens of HCQ sulfate for Japanese patients with CLE/SLE should be calculated using the individual ideal body weight.

Measuring perceived effects of drinking an extract of basidiomycetes Agaricus blazei murill: a survey of Japanese consumers with cancer

PubMed Central

Talcott, James A; Clark, Jack A; Lee, Insu P

2007-01-01

Background To survey cancer patients who consume an extract of the Basidiomycetes Agaricus blazei Murill mushroom (Sen-Sei-Ro) to measure their self-assessment of its effects and to develop an instrument for use in future randomized trials. Methods We designed, translated and mailed a survey to 2,346 Japanese consumers of Sen-Sei-Ro self-designated as cancer patients. The survey assessed consumer demographics, cancer history, Sen-Sei-Ro consumption, and its perceived effects. We performed exploratory psychometric analyses to identify distinct, multi-item scales that could summarize perceptions of effects. Results We received completed questionnaires from 782 (33%) of the sampled Sen-Sei-Ro consumers with a cancer history. Respondents represented a broad range of cancer patients familiar with Sen-Sei-Ro. Nearly all had begun consumption after their cancer diagnosis. These consumers expressed consistently positive views, though not extremely so, with more benefit reported for more abstract benefits such as emotional and physical well-being than relief of specific symptoms. We identified two conceptually and empirically distinct and internally consistent summary scales measuring Sen-Sei-Ro consumers' perceptions of its effects, Relief of Symptoms and Functional Well-being (Cronbach's alpha: Relief of Symptoms, α = .74; Functional Well-Being, α = .91). Conclusion Respondents to our survey of Sen-Sei-Ro consumers with cancer reported favorable perceived effects from its use. Our instrument, when further validated, may be a useful outcome in trials assessing this and other complementary and alternative medicine (CAM) substances in cancer patients. PMID:17967191

Characteristics associated with empathic behavior in Japanese oncologists.

PubMed

Kondo, Kyoko; Fujimori, Maiko; Shirai, Yuki; Yamada, Yu; Ogawa, Asao; Hizawa, Nobuyuki; Uchitomi, Yosuke

2013-11-01

Oncologists must have empathy when breaking bad news to patients who have incurable advanced cancer, and the level of empathy often depends on various individual characteristics. This study aimed to clarify the relationship between these characteristics and empathic behavior in Japanese oncologists. We videotaped consultations in which oncologists conveyed news of incurable advanced cancer to simulated patients. Oncologists' empathetic behaviors were coded, and regression analysis was performed to determine the existence of any relationships with factors such as age, sex, and specialism. Sixty oncologists participated. In a multivariate model, only age was related to the empathy score (r=0.406, p=0.033); younger oncologists scored higher than did older oncologists. We found that empathic behaviors were more frequent in younger oncologists. This information could be useful in determining the best approach for implementing future empathy and communication training programs for experienced oncologists in Japanese medical institutions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Congenital abnormalities in Japanese patients with Menkes disease.

PubMed

Gu, Yan-Hong; Kodama, Hiroko; Kato, Tadaaki

2012-10-01

Menkes disease (MNK) is an X-linked recessive disorder. Incidence of live-born infants with MNK is 2.8 per million live births in Japan. The aim of this study was to observe congenital malformations (CMs) in MNK patients. Subjects comprised 35 Japanese male patients with classical MNK who received copper histidine treatment. Patient clinical data were obtained anonymously from medical records or medical record summaries by pediatrician's retrospective review through a survey. We observed 21 different CMs in 14 patients. Eight of these had a single CM, while six had multiple CMs. The most frequent CM was higher arched palate with other CMs found in five patients. There was no relationship between CMs and mutations in the ATP7A gene. Using Mann-Whitney U tests, age at death was also significantly lower in MNK patients with CMs (P<0.05), compared to those without CMs, even though there was no significant difference of age onset, age at diagnosis and age at start of treatment with copper histidine between both groups of patients. Sudden death occurred in three MNK patients with CMs only: two with congenital heart disease, and one with microphallus. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Genome-Wide Association Study of Breast Cancer in the Japanese Population

PubMed Central

Low, Siew-Kee; Takahashi, Atsushi; Ashikawa, Kyota; Inazawa, Johji; Miki, Yoshio; Kubo, Michiaki; Nakamura, Yusuke; Katagiri, Toyomasa

2013-01-01

Breast cancer is the most common malignancy among women in worldwide including Japan. Several studies have identified common genetic variants to be associated with the risk of breast cancer. Due to the complex linkage disequilibrium structure and various environmental exposures in different populations, it is essential to identify variants associated with breast cancer in each population, which subsequently facilitate the better understanding of mammary carcinogenesis. In this study, we conducted a genome-wide association study (GWAS) as well as whole-genome imputation with 2,642 cases and 2,099 unaffected female controls. We further examined 13 suggestive loci (P<1.0×10−5) using an independent sample set of 2,885 cases and 3,395 controls and successfully validated two previously-reported loci, rs2981578 (combined P-value of 1.31×10−12, OR = 1.23; 95% CI = 1.16–.30) on chromosome 10q26 (FGFR2), rs3803662 (combined P-value of 2.79×10−11, OR = 1.21; 95% CI = 1.15–.28) and rs12922061 (combined P-value of 3.97×10−10, OR = 1.23; 95% CI = 1.15–.31) on chromosome 16q12 (TOX3-LOC643714). Weighted genetic risk score on the basis of three significantly associated variants and two previously reported breast cancer associated loci in East Asian population revealed that individuals who carry the most risk alleles in category 5 have 2.2 times higher risk of developing breast cancer in the Japanese population than those who carry the least risk alleles in reference category 1. Although we could not identify additional loci associated with breast cancer, our study utilized one of the largest sample sizes reported to date, and provided genetic status that represent the Japanese population. Further local and international collaborative study is essential to identify additional genetic variants that could lead to a better, accurate prediction for breast cancer. PMID:24143190

Epidermal growth factor receptor gene amplification in surgical resected Japanese lung cancer.

PubMed

Sasaki, Hidefumi; Shimizu, Shigeki; Okuda, Katsuhiro; Kawano, Osamu; Yukiue, Haruhiro; Yano, Motoki; Fujii, Yoshitaka

2009-06-01

To evaluate the epidermal growth factor receptor (EGFR) protein expression and increased copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC), we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR increased copy number and EGFR protein expression statuses in 109 surgically treated NSCLC cases. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR increased copy number was defined as Cappuzzo et al. criteria. FISH positive was found from 36/109 (33.0%) lung cancer patients, including 30 high polysomy cases and 6 gene amplification cases. FISH-positive cases were significantly correlated with worse prognosis (log-rank test p=0.0097). Within EGFR-mutant patients (n=55), FISH-positive cases were also correlated with poor prognosis (p=0.0255). FISH-negative tumors were found to be more frequently well-differentiated histology. Smoking status (never smoker vs. smoker, p=0.1510), and gender (p=0.5248) did not correlated with FISH positive. EGFR IHC results were correlated with FISH results (p=0.004), but not correlated with prognosis (p=0.2815). Although EGFR FISH-positive rate did not correlated with EGFR mutation (p=0.1973), EGFR polysomy or amplification cases were correlated with EGFR mutations (p=0.0023). In conclusion, the EGFR FISH-positive rate in Japanese patients with NSCLC was similar to rates in Western populations, unlike the higher frequencies of EGFR mutation in East Asians. A high EGFR gene copy number might have shorter survival in NSCLC.

Social disclosure about lymphoedema symptoms: A qualitative study among Japanese breast cancer survivors.

PubMed

Tsuchiya, Miyako; Horn, Sandra; Ingham, Roger

2015-01-01

Disclosing illness-related problems is the first step in help-seeking. The aim of this qualitative study was to explore Japanese breast cancer (BC) survivors' decision-making about disclosure of lymphoedema symptoms to people in their social networks. A total of ten women participated in group discussions in Japan. A dual analytic approach, thematic analysis and conceptual analysis, was applied to the transcripts. Two themes (perceived responsibility of social roles within the family and unsupportive reactions to BC from others) affected participants' decision-making. Support programs for Japanese BC survivors who feel unable to disclose lymphoedema symptoms to family members are suggested.

Cancer in patients with schizophrenia: What is the next step?

PubMed

Chou, Frank H-C; Tsai, Kuan-Yi; Wu, Hung-Chi; Shen, Shih-Pei

2016-11-01

People with schizophrenia, who constitute approximately 0.3-1% of the general population, have a nearly 20% shorter life expectancy than the general population. The incidence of varied types of cancers in patients with schizophrenia is controversial. The majority of previous research has demonstrated that patients who have schizophrenia and cancer have early mortality compared to the general population with cancer. The causes of early mortality in patients with schizophrenia and cancer might be attributed to a lower cancer screening rate and lack of effective treatment, including: (i) patient factors, such as poor lifestyle, passive attitude toward treatment, or comorbidity; (ii) physician factors, such as physician bias, which may decrease the delivery of care for individuals with mental disorders; and (iii) hospital administration factors, such as stigma and discrimination. Additional studies on patients with schizophrenia and cancer are warranted and should include the following: a comprehensive review of previous studies; a focus on differentiating the specific types of cancer; and methods for improvement. To decrease the early mortality of patients with schizophrenia, the following measures are proposed: (i) enhance early detection and early treatment, such as increasing the cancer screening rate for patients with schizophrenia; (ii) provide effective, timely treatment and rehabilitation; (iii) improve patients' psychiatric symptoms and cognitive impairment; (iv) promote healthy behavior in the general population and emphasize healthy lifestyles in vulnerable populations; and (v) remove the stigma of schizophrenia. To reduce disparities in physical health, public health strategies and welfare policies must continue to focus on this group of patients. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Treatment of delirium with risperidone in cancer patients.

PubMed

Kishi, Yasuhiro; Kato, Masashi; Okuyama, Toru; Thurber, Steven

2012-08-01

Antipsychotic medications have frequently been regarded as the treatment of choice for delirium. This study examined the clinical efficacy of risperidone for the treatment of delirium in cancer patients, combined with a repeated assessment of underlying medical severity levels. The study included consecutive referrals of 29 delirious cancer patients (mean age, 68.9 ± 12.5 years; male, 69%) to the psychiatric consultation service. Risperidone was given orally once per day (mean dosage, 1.4 ± 1.3 mg/day). Study participants were assessed using quantitative standardized scales of cognitive function, delirium, and physical impairment at baseline and at the end of the study (seventh day). Risperidone with routine clinical management was effective for the treatment of delirium: 48% of the patients responded and 38% achieved remission. The reduction of delirium severity occurred in 79% of the patients. Changes in delirium severity were unrelated to age, gender, general cognitive dysfunction, or to severity of attendant medical conditions. In addition to changes in agitation and perceptional disturbances, risperidone was also effective for other specific delirium symptoms. Risperidone with routine clinical management is effective in the treatment of delirium in advanced cancer patients, independent of changes in the underlying medical condition. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

PubMed

Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Uchida, Toshiki; Suzuki, Tatsuya; Kobayashi, Yukio; Mori, Masakazu; Terui, Yasuhito; Yokoyama, Masahiro; Hotta, Tomomitsu

2013-01-01

As CD20 has become an established target for treating B-cell malignancies, there is interest in developing anti-CD20 antibodies with different functional activity from rituximab that might translate into improved efficacy. Obinutuzumab (GA101) is a glycoengineered, humanized type II anti-CD20 monoclonal antibody that has demonstrated superior activity to type I antibodies in preclinical studies and is currently being investigated in phase III trials. In this phase I dose-escalating study in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the primary endpoint was to characterize the safety of GA101; secondary endpoints were efficacy, pharmacokinetics and pharmacodynamics. Patients received up to nine doses of GA101 with up to 52 weeks' follow up. Most adverse events were grade 1 or 2 infusion-related reactions, and 10 grade 3/4 adverse events occurred. No dose-limiting toxicities were observed and the maximum tolerated dose was not identified. Out of 12 patients, 7 responded (end-of-treatment response rate 58%), with 2 complete responses and 5 partial responses. Responses were observed from low to high doses, and no dose-efficacy relationship was observed. B-cell depletion occurred in all patients after the first infusion and was maintained for the duration of treatment. Serum levels of GA101 increased in a dose-dependent fashion, although there was inter-patient variability. This phase I study demonstrated that GA101 has an acceptable safety profile and offers encouraging activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. © 2012 Japanese Cancer Association.

[Possible role of genetic factors on reduced risk for gastric cancer among duodenal ulcer patients].

PubMed

Matsuda, Koichi; Tanikawa, Chizu; Nakamura, Yusuke

2013-08-01

Although H. pylori causes both gastric cancer and peptic ulcer, duodenal ulcer patients were known to have low risk for gastric cancer. Recently the association of PSCA and ABO with duodenal ulcer were identified by GWAS in the Japanese population. A T-allele of SNP rs2294008 in the PSCA promoter creates the upstream translational initiation codon and affects the protein localization from cytoplasm to cell surface. A T-allele of SNP rs2294008 increased gastric cancer risk but reduced duodenal ulcer risk. In addition, blood type O was shown to increase risk for duodenal ulcer, while blood type A was associated with gastric cancer risk in the Caucasian population. Our finding would partially explain low risk of gastric cancer among duodenal ulcer patients.

The effect of exemestane, anastrozole, and tamoxifen on lipid profiles in Japanese postmenopausal early breast cancer patients: final results of National Surgical Adjuvant Study BC 04, the TEAM Japan sub-study.

PubMed

Hozumi, Y; Suemasu, K; Takei, H; Aihara, T; Takehara, M; Saito, T; Ohsumi, S; Masuda, N; Ohashi, Y

2011-08-01

In this Tamoxifen Exemestane Adjuvant Multinational Japan sub-study, we evaluated the time course of changes in serum lipids in postmenopausal women with hormone-sensitive early breast cancer treated with exemestane, anastrozole, or tamoxifen for postoperative adjuvant therapy. A total of 154 breast cancer patients were assigned to receive exemestane, anastrozole, or tamoxifen in this randomized open-label study. Serum lipid parameters including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during 1 year of treatment. TC and LDL-C rapidly decreased in patients treated with tamoxifen at 3 months. Compared with anastrozole and exemestane patients, TC and LDL-C were significantly lower at all assessment time points in tamoxifen patients (P < 0.05). TG increased in tamoxifen patients; it was significantly higher compared with exemestane patients at all assessment time points (P < 0.05). HDL-C slightly decreased in exemestane patients; it was significantly lower compared with anastrozole patients at 3 months and 1 year (P = 0.0179 and 0.0013, respectively). Changes of lipid profiles in Japanese postmenopausal women treated with tamoxifen were relatively favorable, while exemestane and anastrozole had no clinically significant effect on the serum lipids.

A potential protective effect in multilingual patients with semantic dementia: two case reports of patients speaking Taiwanese and Japanese.

PubMed

Liu, Yi-Chien; Yip, Ping-Keung; Fan, Yu-Ming; Meguro, Kenichi

2012-03-01

Several reports have suggested that multilingualism has a protective effect against semantic dementia. Here, we provide further evidence for this effect. The patient was a 75-year-old right-handed Taiwanese woman who had retired after working as a tailor. She was able to speak Taiwanese, Japanese and Mandarin Chinese fluently until 5 years ago. She gradually developed symptoms of profound anomia and difficulty with word-finding. Her mother tongue was Taiwanese and she had learned Japanese as her first symbolized language. She had used Mandarin Chinese for most of her life, but depended on Japanese to read and write (such as reading a newspaper and keeping accounts). However, she could now speak only very simple Taiwanese and Japanese, and could recognize only simple Japanese characters. SECOND: The patient was a 62-year-old right-handed man who had worked as an ironworker. He could speak Taiwanese and Mandarin Chinese fluently until 5 years ago. His mother tongue was Taiwanese. After 5 years of language deterioration, he was unable to communicate with his family members or recognize any characters, including numbers. SPECT RESULTS: Brain perfusion ECD SPECT (Tc-99m-ethyl cysteinate dimer single-photon emission computed tomography) showed less perfusion in the multilingual patient (Case #1) than in the bilingual patient (Case #2). Neuropsychological tests also demonstrated a slower rate of degeneration in the multilingual patient. We speculate that reading and writing in Japanese had a greater impact on the semantic system in Case #1. Thus, this patient showed relatively less degeneration or functional inactivity, as shown by perfusion in the frontal lobe, and this might be due to the persistent activation involved in multilingualism.

Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis.

PubMed

Hosono, Satoyo; Terasawa, Teruhiko; Katayama, Takafumi; Sasaki, Seiju; Hoshi, Keika; Hamashima, Chisato

2018-04-01

The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were carried out to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan. Ovid Medline and Ichushi-Web databases were searched from inception through to May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis. The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% confidence interval [CI], 0.18-1.96%; I 2 = 99%) for conventional cytology and 0.04% (95% CI, 0.00-0.35%; I 2 = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on four direct and nine comparative studies, showed no significant difference (summary odds ratio = 3.5 × 10 -2 favoring LBC [95% CI, 6.9 × 10 -4 -1.7]; I 2 = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests. In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Clinical features, anti-cancer treatments and outcomes of lung cancer patients with combined pulmonary fibrosis and emphysema.

PubMed

Minegishi, Yuji; Kokuho, Nariaki; Miura, Yukiko; Matsumoto, Masaru; Miyanaga, Akihiko; Noro, Rintaro; Saito, Yoshinobu; Seike, Masahiro; Kubota, Kaoru; Azuma, Arata; Kida, Kouzui; Gemma, Akihiko

2014-08-01

Combined pulmonary fibrosis and emphysema (CPFE) patients may be at significantly increased risk of lung cancer compared with either isolated emphysema or pulmonary fibrosis patients. Acute exacerbation (AE) of interstitial lung disease caused by anticancer treatment is the most common lethal complication in Japanese lung cancer patients. Nevertheless, the clinical significance of CPFE compared with isolated idiopathic interstitial pneumonias (IIPs) in patients with lung cancer is not well understood. A total of 1536 patients with lung cancer at Nippon Medical School Hospital between March 1998 and October 2011 were retrospectively reviewed. Patients with IIPs were categorized into two groups: (i) CPFE; IIP patients with definite emphysema and (ii) non-CPFE; isolated IIP patients without definite emphysema. The clinical features, anti-cancer treatments and outcomes of the CPFE group were compared with those of the non-CPFE group. CPFE and isolated IIPs were identified in 88 (5.7%) and 63 (4.1%) patients respectively, with lung cancer. AE associated with initial treatment occurred in 22 (25.0%) patients in the CPFE group and in 8 (12.7%) patients in the non-CPFE group, irrespective of treatment modality. Median overall survival (OS) of the CPFE group was 23.7 months and that of the non-CPFE group was 20.3 months (P=0.627). Chemotherapy was performed in a total of 83 patients. AE associated with chemotherapy for advanced lung cancer occurred in 6 (13.6%) patients in the CPFE group and 5 (12.8%) patients in the non-CPFE group. Median OS of the CPFE group was 14.9 months and that of the non-CPFE group was 21.6 months (P=0.679). CPFE was not an independent risk factor for AE and was not an independent prognosis factor in lung cancer patients with IIPs. Therefore, great care must be exercised with CPFE as well as IIP patients when performing anticancer treatment for patients with lung cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation.

PubMed

Tanigawa, Takahiko; Kaneko, Masato; Hashizume, Kensei; Kajikawa, Mariko; Ueda, Hitoshi; Tajiri, Masahiro; Paolini, John F; Mueck, Wolfgang

2013-01-01

The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.

Therapeutic approaches for patients with coexisting familial adenomatous polyposis and colorectal cancer.

PubMed

Inoue, Yasuhiro; Ishida, Hideyuki; Ueno, Hideki; Kobayashi, Hirotoshi; Yamaguchi, Tatsuro; Konishi, Tsuyoshi; Tomita, Naohiro; Matsubara, Nagahide; Ishida, Fumio; Hinoi, Takao; Kanemitsu, Yukihide; Watanabe, Toshiaki; Sugihara, Kenichi

2016-09-01

Colorectal cancer is a major cause of death in patients with familial adenomatous polyposis. Despite evidence for prophylactic colectomy, there is no ideal therapy for patients with coexisting familial adenomatous polyposis and colorectal cancer. We evaluated the correlation between surgery for familial adenomatous polyposis and multimodal treatment for colorectal cancer, and clarified prognosis of Japanese patients with familial adenomatous polyposis and colorectal cancer. We retrospectively reviewed data from 303 patients who underwent colorectal surgery for familial adenomatous polyposis between 2000 and 2012. Overall, 172 patients had colorectal cancer. The most common procedure for familial adenomatous polyposis was restorative proctocolectomy with ileal pouch anal anastomosis, irrespective of colorectal cancer. Partial colectomy was more frequent in patients with than without colorectal cancer (8.7% and 0%, respectively). Ileal pouch anal anastomosis was frequently (60.6%) performed in patients with Stage I-III colorectal cancer. Overall, 12 of 20 patients with Stage IV colorectal cancer underwent metastasectomy; six patients simultaneously and six metachronously. There were fewer cases of ileal pouch anal anastomosis, but more total colectomy with ileorectal anastomosis was performed metachronously, compared with simultaneous metastasectomy (P = 0.006). More cytotoxic (P = 0.006) and molecular (P = 0.03) agents were administered to the ileorectal anastomosis/partial colectomy patients, compared with total proctocolectomy/ileal pouch anal anastomosis patients. A 5-year overall survival was 100% in Stage 0/I, 89.8% in Stage II, 87.9% in Stage III and 48.4% in Stage IV. In patients with familial adenomatous polyposis and colorectal cancer, primary surgery, metastasectomy and chemotherapy could be compatible with standard surgical approaches for familial adenomatous polyposis . However, modifying surgical procedures for familial adenomatous polyposis might help

Effect of a decision aid with patient narratives in reducing decisional conflict in choice for surgery among early-stage breast cancer patients: A three-arm randomized controlled trial.

PubMed

Osaka, Wakako; Nakayama, Kazuhiro

2017-03-01

We aimed to evaluate the effect of a decision aid (DA) with patient narratives on decisional conflict in surgery choice for Japanese women with early-stage breast cancer. Two hundred ten women with early-stage breast cancer were randomly assigned to an intervention or control group. Groups 1 and 2 received standard information and a DA, with or without patient narratives, and Group 3 received standard information (control) before surgery choice. At baseline, post-intervention (Time 2), and 1 month after surgery (Time 3), we evaluated decisional conflict as the primary outcome using a decisional conflict scale (DCS). Sidak corrections for multiple comparisons in analysis of covariate were used to compare Time 2 and Time 3 DCS mean scores between each pair of groups. At Time 3, decisional conflict was significantly reduced for Group 1 vs control (P=0.021, Cohen's d =0.26) and Group 2 vs control (P=0.008, Cohen's d=0.40). The DAs with and without patient narratives are equivalently effective at reducing postoperative decisional conflict in Japanese women with early-stage breast cancer. The DAs with and without patient narratives can be used in clinical practice for women with early-stage breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pharmacologic study (JP28927) of alectinib in Japanese patients with ALK+ non-small-cell lung cancer with or without prior crizotinib therapy.

PubMed

Hida, Toyoaki; Nakagawa, Kazuhiko; Seto, Takashi; Satouchi, Miyako; Nishio, Makoto; Hotta, Katsuyuki; Takahashi, Toshiaki; Ohe, Yuichiro; Takeda, Koji; Tatsuno, Masahiro; Asakawa, Takashi; Shimada, Tadashi; Tanaka, Tomohiro; Tamura, Tomohide

2016-11-01

We report pharmacokinetics, efficacy and safety data for a new 150-mg alectinib capsule in ALK+ non-small-cell lung cancer in a multicenter, open-label pharmacologic study (JP28927). Eligible patients (≥20 years, locally advanced/metastatic ALK+ disease, ALK inhibitor-naïve and -pretreated [including crizotinib refractory]) were randomized 1:1 to receive one of two sequences of alectinib 300 mg twice daily (comprising different schedules of 20/40-mg and 150-mg capsules) until investigator-determined lack of clinical benefit. Co-primary endpoints were: bioequivalence of alectinib 20/40 mg vs 150 mg; food effect with 150 mg; and safety. Thirty-five patients were enrolled; median treatment duration was 13.1 months (range 1.1-15.0). Under fasting conditions, exposure of the two formulations was similar; mean AUC last  ± standard deviation 3230 ± 914 h·ng/mL vs 3710 ± 1040 h·ng/mL, respectively, for 150-mg vs 20/40-mg capsules. Food effect with 150 mg alectinib was negligible. Treatment-related adverse events in >20% of patients were constipation (31.4%), dysgeusia (25.7%), and decreased white blood cell and neutrophil count (22.9% each). No treatment-related grade 4/5 events occurred. Median time to response was 1.2 months (95% CI 1.1-2.1). For the full analysis set (n = 35) and crizotinib-failure subpopulations (n = 23), the overall response rate was 70.0% (95% CI 50.6-85.3) and 65.0% (95% CI 40.8-84.6), and median progression-free survival was 13.9 months (95% CI 11.1-not reached) and 12.9 months (95% CI 3.9-not reached), respectively. The 150-mg capsule had a similar exposure profile to 20/40-mg capsules. Alectinib demonstrated promising efficacy and was well tolerated. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Impact of depression on health utility value in cancer patients.

PubMed

Fujisawa, Daisuke; Inoguchi, Hironobu; Shimoda, Haruki; Yoshiuchi, Kazuhiro; Inoue, Shinichiro; Ogawa, Asao; Okuyama, Toru; Akechi, Tatsuo; Mimura, Masaru; Shimizu, Ken; Uchitomi, Yosuke

2016-05-01

The quality-adjusted life year, which is usually calculated from the health utility value, is now a standard measurement used in political decision-making in health. Although depression is the leading cause of decrement in health utility in general population, impact of comorbid depression among cancer patients has not been studied sufficiently. Therefore, this study aimed to measure the impact of depression on cancer patients' health utility score, according to the severity of depression. Impact of depression severity (measured by the Patient Health Questionnaire) on health utility score (measured by the EuroQoL-5 scale) was evaluated in a sample of 328 Japanese cancer patients, controlling for performance status, symptom burden, and demographic variables. The patients with depression had significantly lower health utility value than those without depression (mean decrement = 0.14). Decrements in health utility of 0.13, 0.18, and 0.19 were observed for mild, moderate, and moderately severe to severe level of depression, respectively. The difference was significant between groups. Depression severity was a significant predictor for health utility (standardized coefficient beta = -0.25), which was comparable with physical symptom burden and performance status. Participants' age, gender, cancer stage, and comorbid illness were not significant. The model explained 37.9% of the variance. Even mild level of depression caused clinically meaningful decrement in health utility value in cancer patients, which was comparable with decrements due to major physical complications of cancer. Influence of depression should be carefully investigated when interpreting the quality-adjusted life year among cancer patients. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

[Depression screening test for patients with metastatic gastric and colorectal cancer].

PubMed

Ina, Kenji; Sugiyama, Akemi; Yuasa, Shu; Koga, Chiaki; Yamazaki, Emiko; Katayama, Yoshiko; Nagaoka, Masatoshi; Nagao, Seiji

2010-06-01

The prevalence of depression has been reported to be higher in cancer patients, especially those of advanced stage, compared to normal controls. However, depression is often under-recognized in clinical oncology settings. And this psychological problem is not routinely assessed even in patients with inoperable metastatic cancer who often have psychological disorders. Psychological distress including depression, is affected by physical, psychosocial, and clinical factors. In order to detect psychiatric problems at the early stage, we assessed the mental conditions of 47 inpatients with metastatic gastric and colorectal cancerusing the Japanese version of Zung's Self Rating Depression Scale(SDS)and analyzed the relationships between these factors and SDS scores. While SDS scores of our patients did not differ according to their gender, age, performance status (PS), ortypes of patients' character, they were significantly higher in Group B(cancer patients with palliative care alone), compared to Group A(those receiving chemotherapy)(p<0. 001). As the disease in the four identical patients progressed to the terminal stage, their scores were significantly increased, respectively(p<0. 05). These results suggest that psychological intervention should be more critical for terminally ill patients without any indication of chemotherapy.

Time-Dependent Changes in Psychosocial Distress in Japanese Patients with Implantable Cardioverter Defibrillators.

PubMed

Saito, Nao; Taru, Chiemi; Miyawaki, Ikuko

2016-12-02

This prospective study clarified changes in the mood states of Japanese patients with implantable cardioverter defibrillators as well as factors related to the mood states. Using a longitudinal repeated-measure design, 29 patients with implantable cardioverter defibrillators completed the Profile of Mood States-Short Form Japanese Version questionnaire before discharge and 1, 4, 7, and 13 months after implantation. One month after discharge, the mood states of the patients with implantable cardioverter defibrillators improved. From 7 to 13 months after discharge, moods deteriorated; 13 months after discharge, moods were equivalent to those at the time of discharge. No relationship with defibrillation experience was detected in this study, but employment, age, sex, and lack of experience of syncopal attack were factors related to poor mood states for patients with implantable cardioverter defibrillators. Therefore, Japanese patients with implantable cardioverter defibrillators with any factor deteriorating their mood state should be monitored so that their mood state does not deteriorate again between six months and one year after implantation.

Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients with schizophrenia.

PubMed

Fujino, Haruo; Sumiyoshi, Chika; Sumiyoshi, Tomiki; Yasuda, Yuka; Yamamori, Hidenaga; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Higuchi, Arisa; Hibi, Yumiko; Matsuura, Yukako; Hashimoto, Ryota; Takeda, Masatoshi; Imura, Osamu

2014-07-01

Patients with schizophrenia have been reported to perform worse than non-schizophrenic populations on neuropsychological tests, which may be affected by cultural factors. The aim of this study was to examine the performance of a sizable number of patients with schizophrenia on the Japanese version of the Wechsler Adult Intelligence Scale-III (WAIS-III) compared with healthy controls. Performance on the WAIS-III was evaluated in 157 Japanese patients with schizophrenia and in 264 healthy control subjects. All IQ scores and four indices from the WAIS-III were impaired for patients with schizophrenia compared with healthy controls. Processing Speed was markedly disturbed, approximately 2 SD below that of the healthy control group. Among the 13 subtests, Comprehension (z = -1.70, d = 1.55), Digit Symbol Coding (z = -1.84, d = 1.88), and Symbol Search (z = -1.85, d = 1.77) were profoundly impaired relative to the healthy controls. These results indicate that the pattern and degree of impairment, as evaluated by the WAIS-III, in Japanese patients are similar to those previously reported in English-speaking patients and that the deficits of some neuropsychological domains relevant to functional outcomes are universally characteristic of schizophrenia. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Thymidylate synthase (TS) gene expression in primary lung cancer patients: a large-scale study in Japanese population.

PubMed

Tanaka, F; Wada, H; Fukui, Y; Fukushima, M

2011-08-01

Previous small-sized studies showed lower thymidylate synthase (TS) expression in adenocarcinoma of the lung, which may explain higher antitumor activity of TS-inhibiting agents such as pemetrexed. To quantitatively measure TS gene expression in a large-scale Japanese population (n = 2621) with primary lung cancer, laser-captured microdissected sections were cut from primary tumors, surrounding normal lung tissues and involved nodes. TS gene expression level in primary tumor was significantly higher than that in normal lung tissue (mean TS/β-actin, 3.4 and 1.0, respectively; P < 0.01), and TS gene expression level was further higher in involved node (mean TS/β-actin, 7.7; P < 0.01). Analyses of TS gene expression levels in primary tumor according to histologic cell type revealed that small-cell carcinoma showed highest TS expression (mean TS/β-actin, 13.8) and that squamous cell carcinoma showed higher TS expression as compared with adenocarcinoma (mean TS/β-actin, 4.3 and 2.3, respectively; P < 0.01); TS gene expression was significantly increased along with a decrease in the grade of tumor cell differentiation. There was no significant difference in TS gene expression according to any other patient characteristics including tumor progression. Lower TS expression in adenocarcinoma of the lung was confirmed in a large-scale study.

Genetic variants within obesity-related genes are associated with tumor recurrence in patients with stages II/III colon cancer.

PubMed

Sebio, Ana; Gerger, Armin; Matsusaka, Satoshi; Yang, Dongyun; Zhang, Wu; Stremitzer, Stefan; Stintzing, Sebastian; Sunakawa, Yu; Yamauchi, Shinichi; Ning, Yan; Fujimoto, Yoshiya; Ueno, Masashi; Lenz, Heinz-Josef

2015-01-01

Obesity is an established risk factor for colorectal cancer (CRC) incidence and it is also linked to CRC recurrence and survival. Polymorphisms located in obesity-related genes are associated with an increased risk of developing several cancer types including CRC. We evaluated whether single-nucleotide polymorphisms in obesity-related genes may predict tumor recurrence in colon cancer patients. Genotypes were obtained from germline DNA from 207 patients with stage II or III colon cancer at the Norris Comprehensive Cancer Center. Nine polymorphisms in eight obesity-related genes (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA, and DSCR1) were evaluated. The primary endpoint of the study was the 3-year recurrence rate. Positive associations were also tested in an independent Japanese cohort of 350 stage III CRC patients. In univariate analysis, for PPARrs1801282, patients with a CC genotype had significantly lower recurrence probability (29 ± 4% SE) compared with patients with a CG genotype (48 ± 8% SE) [hazard ratio (HR): 1.77; 95% confidence interval (CI), 1.01-3.10; P = 0.040]. For DSCR1rs6517239, patients with an AA genotype had higher recurrence probability than patients carrying at least one allele G (37 ± 4% SE vs. 15 ± 6% SE) (HR: 0.51; 95% CI, 0.27-0.94; P = 0.027). This association was stronger in the patients bearing a left-sided tumor (HR: 0.34; 95% CI, 0.13-0.88; P = 0.018). In the Japanese cohort, no associations were found. This hypothesis-generating study suggests a potential influence of polymorphisms within obesity-related genes in the recurrence probability of colon cancer. These interesting results should be evaluated further.

Coffee consumption and risk of colorectal cancer in a population-based prospective cohort of Japanese men and women.

PubMed

Lee, Kyung-Jae; Inoue, Manami; Otani, Tetsuya; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro

2007-09-15

We prospectively examined the association between coffee consumption and the risk of developing colorectal cancer in a large population-based cohort study (the JPHC Study) of Japanese men and women. Data were analyzed from a population-based cohort of 96,162 subjects (46,023 men and 50,139 women). A total of 1,163 incident colorectal cancers were identified during the follow-up period, including 763 cases of colon cancer and 400 of rectal cancer. We observed a significant inverse association between coffee consumption and the risk of developing invasive colon cancer among women. Compared with those who almost never consumed coffee, women who regularly consumed 3 or more cups of coffee per day had a RR of 0.44 (95% CI = 0.19-1.04; p for trend = 0.04) after adjustment for potential confounding factors. However, no significant association was found for rectal cancer in women. In men, no significant decrease was observed in any colorectal cancer site. Further, additional analyses on the association of green tea consumption with colorectal cancer risk found no significant association in men or women. These findings suggest that coffee consumption may lower the risk of colon cancer among Japanese women. (c) 2007 Wiley-Liss, Inc.

Sentinel lymph node navigation surgery for gastric cancer: Does it really benefit the patient?

PubMed

Tani, Tohru; Sonoda, Hiromichi; Tani, Masaji

2016-03-14

Sentinel lymph node (SLN) navigation surgery is accepted as a standard treatment procedure for malignant melanoma and breast cancer. However, the benefit of reduced lymphadenectomy based on SLN examination remains unclear in cases of gastric cancer. Here, we review previous studies to determine whether SLN navigation surgery is beneficial for gastric cancer patients. Recently, a large-scale prospective study from the Japanese Society of Sentinel Node Navigation Surgery reported that the endoscopic dual tracer method, using a dye and radioisotope for SLN biopsy, was safe and effective when applied to cases of superficial and relatively small gastric cancers. SLN mapping with SLN basin dissection was preferred for early gastric cancer since it is minimally invasive. However, previous studies reported that limited gastrectomy and lymphadenectomy may not improve the patient's postoperative quality of life (QOL). As a result, the benefit of SLN navigation surgery for gastric cancer patients, in terms of their QOL, is limited. Thus, endoscopic and laparoscopic limited gastrectomy combined with SLN navigation surgery has the potential to become the standard minimally invasive surgery in early gastric cancer.

Association between shift work and the risk of death from biliary tract cancer in Japanese men.

PubMed

Lin, Yingsong; Nishiyama, Takeshi; Kurosawa, Michiko; Tamakoshi, Akiko; Kubo, Tatsuhiko; Fujino, Yoshihisa; Kikuchi, Shogo

2015-10-21

There is increasing evidence suggesting that shift work involving night work may increase cancer risk. We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46,395 men recruited, 22,224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths.

Association of Clinical Features with Human Leukocyte Antigen in Japanese Patients with Ulcerative Colitis.

PubMed

Iwamoto, Taku; Yashima, Kazuo; Morio, Keiko; Ueda, Naoki; Ikebuchi, Yuichiro; Kawaguchi, Koichiro; Harada, Kenichi; Isomoto, Hajime

2018-03-01

The human leukocyte antigen (HLA) region has been found to be involved in the pathogenesis of inflammatory bowel disease (IBD), which is classified into ulcerative colitis (UC) and Crohn's disease (CD), by genome-wide association studies. The aim of this study was to confirm whether HLA-alleles confer susceptibility to UC and to determine whether HLA-allel1es are associated with the clinical phenotypes in Japanese patients with UC. In this study, HLA typing was performed by PCR-sequence-specific oligonucleotides (PCR-SSO) to confirm the correlation between UC and HLA alleles (for HLA-A, B, DRB1) in 45 Japanese UC patients. In addition, whether the HLA alleles are related to patient and clinical background characteristics was examined. Overall, 62.2%, and 66.7% of the 45 UC patients had HLA-B*52 and HLA-DRB1*15, respectively. These allele frequencies were significantly higher than in previously reported Japanese control persons ( P < 0.0001). The frequencies of extraintestinal manifestations [odds ratio (OR) = 0.12, P = 0.039] and a history of colectomy (OR = 0.18, P = 0.046) were lower in HLA-B*52-positive UC patients than in HLA-B*52 negative UC patients. The white blood cell (WBC) count was significantly higher in HLA-DRB1*15-positive patients (9430 ± 4592/μL) than in HLA-DRB1*15-negative patients (6729 ± 2160/μL). Thus, HLA-B*52 and DRB1*15 appear to be associated with disease features and severity in Japanese UC patients. These results indicate that HLA-B*52 and DRB1*15 are not only associated with overall UC susceptibility, but also with the clinical phenotypes in Japanese patients.

A double-blind, randomized comparative study to investigate the morphine to hydromorphone conversion ratio in Japanese cancer patients

PubMed Central

Inoue, Satoshi; Saito, Yoji; Tsuneto, Satoru; Aruga, Etsuko; Ogata, Takeshi; Uemori, Mitsutoshi

2018-01-01

Abstract Objective To confirm the morphine to hydromorphone conversion ratio for hydromorphone (DS-7113b) immediate-release tablets in cancer patients who achieved pain control with oral morphine. Methods This was a multicenter, active-controlled, randomized, double-blind, parallel-group, comparative study (July 2013 to December 2014) at 39 Japanese sites. Seventy-one patients (aged >20 years) who had achieved pain control with morphine 60 mg/day and 90 mg/day were randomly allocated 1:1 to hydromorphone immediate-release tablets at a dose converted at a hydromorphone:morphine ratio of 1:5 or 1:8, respectively, and treated for up to 5 days. The efficacy was evaluated as the pain control ratio. Results The pain control ratio in the full analysis set was 83.3% (25/30) in the conversion ratio 1:5 group and 95.0% (38/40) in the conversion ratio 1:8 group, and both groups demonstrated highly successful pain control. The incidence of adverse events was 46.7% (14/30) in the conversion ratio 1:5 group and 58.5% (24/41) in the 1:8 group; the difference was not clinically relevant. Frequently observed adverse events (incidence ≥5%) were nausea, vomiting, diarrhea, somnolence and dyspnea. Conclusions A high pain control ratio was maintained by a switch at either conversion ratio, and no notable difference was observed in the incidence of adverse events. A switch from morphine to hydromorphone is effective at a dose converted at ratios of 1:5 and 1:8. PMID:29635632

Xeroderma pigmentosum complementation group F: Report of a case and review of Japanese patients.

PubMed

Tofuku, Yukari; Nobeyama, Yoshimasa; Kamide, Ryoichi; Moriwaki, Shinichi; Nakagawa, Hidemi

2015-09-01

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors. Among XP, XP-F presents relatively uniquely in Japanese. To clarify the characteristics of this group, we describe a case of XP-F and review Japanese cases previously reported. A 50-year-old Japanese woman was referred to us with multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities. She had experienced bulla formation with approximately 10 min of sunlight exposure during her elementary school years. Her parents had been first cousins, and her mother and sister had photosensitivity. She showed no neurological or developmental abnormalities. Ultraviolet (UV) irradiation testing revealed normal levels for minimal erythema dose with UV-A and UV-B. Sensitivity to UV-C and DNA repair ability in the patient's fibroblasts were indicated between that in normal individuals and that in an XP-A patient. Complementation assay revealed that transfection of the XPF gene led most efficient DNA repair compared with the other XP genes. Therefore, the patient was diagnosed with XP-F. Twenty-three cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case. Our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years). This suggests that cutaneous malignant tumors could occur in the age range of 30-50 years in XP-F patients. © 2015 Japanese Dermatological Association.

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients.

PubMed

Kaihan, Ahmad Baseer; Yasuda, Yoshinari; Katsuno, Takayuki; Kato, Sawako; Imaizumi, Takahiro; Ozeki, Takaya; Hishida, Manabu; Nagata, Takanobu; Ando, Masahiko; Tsuboi, Naotake; Maruyama, Shoichi

2017-12-01

The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

The Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer.

PubMed

Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao

2017-01-01

The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1-11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS-JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Cost-effectiveness analysis of prophylactic cervical cancer vaccination in Japanese women.

PubMed

Konno, Ryo; Sasagawa, Toshiyuki; Fukuda, Takashi; Van Kriekinge, Georges; Demarteau, Nadia

2010-04-01

The incidence of cervical cancer (CC) is high in Japan and is further increasing among women younger than 30 years. This burden could be reduced by the implementation of a CC vaccine, but its cost-effectiveness is unknown. We quantified the clinical impact and assessed the cost-effectiveness of adding CC vaccination at age 12 to the current screening in place in Japan with a lifetime Markov model adapted to the Japanese setting. Transition probabilities and utility values were obtained from public databases. Direct costs for treatment and screening were estimated using Japanese medical fees. Annual costs and benefits were discounted at 3%. Sensitivity analyses were conducted on the age at vaccination, the vaccine characteristics, the discount rates, the proportion of human papillomavirus types 16/18 in cancer, and the screening coverage. Vaccinating a 12-year-old cohort was predicted to reduce CC incidence and deaths from CC by 73%. These clinical effects were associated with an incremental cost-effectiveness ratio of yen1.8 million per quality-adjusted life year gained. The incremental cost-effectiveness ratio of vaccinating all 10- to 45-year-old women was yen2.8 million per quality-adjusted life year, still below the threshold value. The implementation of a CC vaccination in Japan could reduce the CC burden in a very cost-effective manner for women up to 45 years.

Relationship between ABO blood group and clinicopathological factors and their effect on the survival of Japanese patients with esophageal squamous cell carcinoma.

PubMed

Shiratori, Fumiaki; Shimada, Hideaki; Yajima, Satoshi; Suzuki, Takashi; Oshima, Yoko; Nanami, Tatsuki; Ito, Masaaki; Kaneko, Hironori

2017-08-01

Several studies have evaluated the association between ABO blood group and the prognosis of various types of cancer; however, little is known about the relationship between ABO blood group and esophageal squamous cell carcinoma (SCC). We investigated how ABO blood group and clinicopathological characteristics are related to the survival of Japanese patients with esophageal SCC. We reviewed the medical records of 181 patients who underwent surgery for esophageal SCC between June, 2004 and December, 2015 and analyzed the association between ABO blood group and clinicopathological factors. Clinicopathological factors were also evaluated by univariate and multivariate analyses for possible association with survival. The prevalence of each blood group was as follows: A, 35.5%; B, 22.4%; O, 32.8%; and AB, 8.2%. The 5-year overall survival of all patients was 37.1%. Patients with non-type B blood had significantly worse 5-year overall survival than those with type B blood (30.2 vs. 58.8%, P < 0.05). ABO blood groups were associated with the survival of Japanese patients with esophageal SCC. Patients with non-B blood groups had significantly worse overall survival than those with the B blood group.

Trust in One’s Physician: The Role of Ethnic Match, Autonomy, Acculturation, and Religiosity Among Japanese and Japanese Americans

PubMed Central

Tarn, Derjung M.; Meredith, Lisa S.; Kagawa-Singer, Marjorie; Matsumura, Shinji; Bito, Seiji; Oye, Robert K.; Liu, Honghu; Kahn, Katherine L.; Fukuhara, Shunichi; Wenger, Neil S.

2005-01-01

PURPOSE Trust is a cornerstone of the physician-patient relationship. We investigated the relation of patient characteristics, religiosity, acculturation, physician ethnicity, and insurance-mandated physician change to levels of trust in Japanese American and Japanese patients. METHODS A self-administered, cross-sectional questionnaire in English and Japanese (completed in the language of their choice) was given to community-based samples of 539 English-speaking Japanese Americans, 340 Japanese-speaking Japanese Americans, and 304 Japanese living in Japan. RESULTS Eighty-seven percent of English-speaking Japanese Americans, 93% of Japanese-speaking Japanese Americans, and 58% of Japanese living in Japan responded to trust items and reported mean trust scores of 83, 80, and 68, respectively, on a scale ranging from 0 to 100. In multivariate analyses, English-speaking and Japanese-speaking Japanese American respondents reported more trust than Japanese respondents living in Japan (P values <.001). Greater religiosity (P <.001), less desire for autonomy (P <.001), and physician-patient relationships of longer duration (P <.001) were related to increased trust. Among Japanese Americans, more acculturated respondents reported more trust (P <.001), and Japanese physicians were trusted more than physicians of another ethnicity. Among respondents prompted to change physicians because of insurance coverage, the 48% who did not want to switch reported less trust in their current physician than in their former physician (mean score of 82 vs 89, P <.001). CONCLUSIONS Religiosity, autonomy preference, and acculturation were strongly related to trust in one’s physician among the Japanese American and Japanese samples studied and may provide avenues to enhance the physician-patient relationship. The strong relationship of trust with patient-physician ethnic match and the loss of trust when patients, in retrospect, report leaving a preferred physician suggest unintended

Salient Features and Outline of the Joint Japanese Guidelines for Safe Handling of Cancer Chemotherapy Drugs

PubMed Central

Kanda, Kiyoko; Hirai, Kazue; Iino, Keiko; Nomura, Hisanaga; Yasui, Hisateru; Kano, Taro; Ichikawa, Chisato; Hiura, Sumiko; Morita, Tomoko; Mitsuma, Ayako; Komatsu, Hiroko

2017-01-01

The purpose of this paper is to introduce the outline and describe the salient features of the “Joint Guidelines for Safe Handling of Cancer Chemotherapy Drugs” (hereinafter, “Guideline”), which were published in July 2015. The purpose of this Guideline is to provide guidance to protect against occupational exposure to hazardous drugs (HDs) to all medical personnel involved in cancer chemotherapy, including physicians, pharmacists, and nurses and home health-care providers. The Guideline was developed according to the Medical Information Network Distribution Service guidance for developing clinical practice guidelines, with reference to five authoritative guidelines used worldwide. PubMed, Cumulative Index to Nursing and Allied Health Literature, Ichushi-Web, and Cochrane Central Register of Controlled Trials were used for a systematic search of the literature. Eight clinical questions (CQs) were eventually established, and the strength of recommendation for each CQ is presented based on 867 references. The salient features of the Guideline are that it was jointly developed by three societies (Japanese Society of Cancer Nursing, Japanese Society of Medical Oncology, and Japanese Society of Pharmaceutical Oncology), contains descriptions including the definition of HDs and the concept of hierarchy of controls, and addresses exposure control measures during handling of chemotherapy drugs. Our future task is to collect additional evidence for the recommended exposure control measures and to assess whether publication of the Guideline has led to adherence of measures to prevent occupational exposure. PMID:28966958

Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone.

PubMed

Miura, Yukiko; Saito, Takefumi; Tanaka, Toru; Takoi, Hiroyuki; Yatagai, Yohei; Inomata, Minoru; Nei, Takahito; Saito, Yoshinobu; Gemma, Akihiko; Azuma, Arata

2018-01-01

Idiopathic pulmonary fibrosis (IPF) is a disease with a worse prognosis than some types of cancer. In patients with IPF, lung cancer is critical because of the associated high mortality rate from its progression and fatal complications from anticancer treatments. Therefore, preventing lung cancer in patients with IPF is primordial. Pirfenidone is an anti-fibrotic agent that reduces the decline in forced vital capacity. This study aimed to assess the effect of pirfenidone in the development of lung cancer in patients with IPF. Data from 261 patients with IPF with and without pirfenidone were retrospectively reviewed, and the incidence of lung cancer was analyzed. In the pirfenidone group, the incidence of lung cancer was significantly lower than in the non-pirfenidone group (2.4% vs. 22.0%, P < 0.0001). Multivariate Cox proportional hazards regression analysis demonstrated that pirfenidone decreased the risk of lung cancer (hazard ratio, 0.11; 95% confidence interval, 0.03 to 0.46; P = 0.003), whereas coexisting emphysema increased the incidence of lung cancer (hazard ratio, 3.22; 95% confidence interval, 1.35 to 7.70; P = 0.009). Pirfenidone might correlate with a decreased risk of lung cancer in patients with IPF. However, no definite conclusion can be drawn from this retrospective study, and a multicenter, prospective cohort study is still warranted to confirm the effect of pirfenidone on lung cancer in patients with IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Applying Japanese management tips to patient accounts.

PubMed

Groenevelt, C J

1990-04-01

"Just in time," a Japanese management philosophy that has been applied successfully in manufacturing operations, also can be used to improve management of patient accounts departments. Under its principles, healthcare organizations would develop standardized procedures; involve workers in decision making; set up training and education programs aimed at creating a multi-skilled pool of workers; establish smooth production schedules; and foster cooperation and commitment to the philosophy throughout the organization.

Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer.

PubMed

Shitara, Kohei; Muro, Kei; Shimada, Yasuhiro; Hironaka, Shuichi; Sugimoto, Naotoshi; Komatsu, Yoshito; Nishina, Tomohiro; Yamaguchi, Kensei; Segawa, Yoshihiko; Omuro, Yasushi; Tamura, Takao; Doi, Toshihiko; Yukisawa, Seigo; Yasui, Hirofumi; Nagashima, Fumio; Gotoh, Masahiro; Esaki, Taito; Emig, Michael; Chandrawansa, Kumari; Liepa, Astra M; Wilke, Hansjochen; Ichimiya, Yukako; Ohtsu, Atsushi

2016-07-01

We evaluated the safety and efficacy of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients previously treated for advanced gastric or gastroesophageal junction adenocarcinoma in Japanese and Western subgroups from the RAINBOW trial. Patients received ramucirumab at 8 mg/kg or placebo (days 1 and 15) plus paclitaxel at 80 mg/m(2) (days 1, 8, and 15 of a 28-day cycle). End points were compared between treatment arms within Japanese (N = 140) and Western (N = 398) populations. The incidence of adverse events of grade 3 or higher was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 83.8 % vs 52.1 %; Western population, 79.1 % vs 61.9 %). Neutropenia was the commonest adverse event of grade 3 or higher, with a higher incidence for ramucirumab plus paclitaxel (Japanese population, 66.2 % vs 25.4 %; Western population, 32.1 % vs 14.7 %). The incidence of febrile neutropenia was low and was similar between treatment arms in both populations. The overall survival hazard ratio was 0.88 (95 % confidence interval, 0.60-1.28) in the Japanese population and 0.73 (95 % confidence interval, 0.58-0.91) in the Western population. The progression-free survival hazard ratio was 0.50 (95 % confidence interval, 0.35-0.73) in the Japanese population and 0.63 (95 % confidence interval, 0.51-0.79) in the Western population. The objective response rate was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 41.2 % vs 19.4 %; Western population, 26.8 % vs 13.0 %), as was the 6-month survival rate (Japanese population, 94.1 % vs 71.4 %; Western population, 66.0 % vs 49.0 %). Safety profiles of the ramucirumab plus paclitaxel arm were similar between populations, though there was a higher incidence of neutropenia in Japanese patients. Progression-free survival and objective response rate improvements were observed for ramucirumab plus paclitaxel in both populations. CLINICALTRIALS. NCT

Breastfeeding and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

PubMed

Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Tsuji, Ichiro; Tamakoshi, Akiko; Wakai, Kenji; Matsuo, Keitaro; Ito, Hidemi; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

2012-02-01

We reviewed epidemiological studies on breastfeeding and breast cancer among Japanese women. This report is part of a series of articles written by our research group, whose aim was to evaluate the existing evidence concerning the association between health-related lifestyles and cancer. Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented by manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility. Three cohort studies and five case-control studies were identified. Cohort studies failed to find a significant inverse association between breastfeeding and the risk of breast cancer. Most of the case-control studies observed a statistically significant or non-significant risk reduction for women who ever had breastfed or for women with a longer duration of breastfeeding. Experimental studies have supported the biological plausibility of a protective effect of breastfeeding on breast cancer risk. We conclude that breastfeeding possibly decreases the risk of breast cancer among Japanese women.

Association between SCO2 mutation and extreme myopia in Japanese patients.

PubMed

Wakazono, Tomotaka; Miyake, Masahiro; Yamashiro, Kenji; Yoshikawa, Munemitsu; Yoshimura, Nagahisa

2016-07-01

To investigate the role of SCO2 in extreme myopia of Japanese patients. In total, 101 Japanese patients with extreme myopia (axial length of ≥30 mm) OU at the Kyoto University Hospital were included in this study. Exon 2 of SCO2 was sequenced by conventional Sanger sequencing. The detected variants were assessed using in silico prediction programs: SIFT, PolyPhen-2 and MutationTaster. To determine the frequency of the mutations in normal subjects, we referred to the 1000 Genomes Project data and the Human Genetic Variation Database (HGVD) in the Human Genetic Variation Browser. The average age of the participants was 62.9 ± 12.7 years. There were 31 males (30.7 %) and 70 females. Axial lengths were 31.76 ± 1.17 mm OD and 31.40 ± 1.07 mm OS, and 176 eyes (87.6 %) out of 201 eyes had myopic maculopathy of grade 2 or more. Among the 101 extremely myopic patients, one mutation (c.290 C > T;p.Ala97Val) in SCO2 was detected. This mutation was not found in the 1000 Genomes Project data or HGVD data. Variant type of the mutation was nonsynonymous. Although the SIFT prediction score was 0.350, the PolyPhen-2 probability was 0.846, thus predicting its pathogenicity to be possibly damaging. MutationTaster PhyloP was 1.268, suggesting that the mutation is conserved. We identified one novel possibility of an extreme myopia-causing mutation in SCO2. No other disease-causing mutation was found in 101 extremely myopic Japanese patients, suggesting that SCO2 plays a limited role in Japanese extreme myopia. Further investigation is required for better understanding of extreme myopia.

Nras and Kras mutation in Japanese lung cancer patients: Genotyping analysis using LightCycler.

PubMed

Sasaki, Hidefumi; Okuda, Katsuhiro; Kawano, Osamu; Endo, Katsuhiko; Yukiue, Haruhiro; Yokoyama, Tomoki; Yano, Motoki; Fujii, Yoshitaka

2007-09-01

Activating mutations of Ras gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. Many studies have showed that the Kras gene is activated by point mutations in approximately 15-20% of non-small cell lung cancers (NSCLCs), however, there are only a few reports on Nras mutations in NSCLC. We have genotyped Nras mutation status (n=195) and Kras mutation status (n=190) in surgically treated lung adenocarcinoma cases. The presence or absence of Nras and Kras mutations was analyzed by real-time quantitative polymerase chain reaction (PCR) with mutation-specific sensor and anchor probes. EGFR mutation status at kinase domain has already been reported. Nras mutation was found in 1 of 195 patients. This mutation was a G-to-T transversion, involving the substitution of the normal glycine (GGT) with cystein (TGT) and thought to be a somatic mutation. The patient was male and a smoker. Kras mutant patients (11.1%; 21/190) had a significantly worse prognosis than wild-type patients (p=0.0013). Eighty-two EGFR mutations at kinase domain had exclusively Nras or Kras mutations. Although Nras gene mutation might be one of the mechanisms of oncogenesis of lung adenocarcinoma, this was a very rare event. Further studies are needed to confirm the mechanisms of Nras mutations for the sensitivity of molecular target therapy for lung cancer.

Hla-B genotype in Japanese patients with Crohn's disease.

PubMed

Kinouchi, Yoshitaka; Matsumoto, Keisuke; Negoro, Kenichi; Takagi, Sho; Takahashi, Seiichi; Hiwatashi, Nobuo; Shimosegawa, Tooru

2003-10-01

The HLA-B gene is one of the susceptibility genes for inflammatory bowel disease. Previous association studies of HLA-B showed several associated alleles and haplotypes of HLA-B in patients with ulcerative colitis, and among the associated alleles HLA-B*52 is well known to be strongly associated with ulcerative colitis in Japanese patients. However, there are no convincing reports about HLA-B including the B*52 allele in patients with Crohn's disease. The purpose of this study was to determine if HLA-B, especially the B*52 allele, confers susceptibility to Crohn's disease or determines the disease phenotype of Crohn's disease. A total of 195 patients with Crohn's disease (49 ileitis, 106 ileocolitis, 34 colitis, 6 uncertain) and 185 healthy controls were studied in this case-controlled study. All patients and healthy controls were Japanese. Genotyping of the HLA-B gene was performed by a polymerase chain reaction, sequence-specific primer that can classify the gene into 23 allele groups. Allele frequencies were compared between patients with Crohn's disease and healthy controls with chi-squared test using a 2 x 2 contingency table. P value was corrected by the number of allele groups (n = 23) observed in the Japanese population or the number of clinical subgroups. Corrected P values of <0.05 were considered to be statistically significant. Before the correction for multiple testing, B*4001 and B*44 were associated with patients with Crohn's disease, positively and negatively, respectively. However, after the correction there were no significant differences in any HLA-B alleles between patients with Crohn's disease and healthy controls. In the subgroup analysis according to clinical phenotypes (disease location, anal lesion, age at diagnosis, need for surgery), none of the HLA-B alleles except B*52 showed any disease phenotype-genotype associations. The allele frequency of B*52 in the colitis type (16.2 percent; corrected P = 0.011) was significantly higher than

Awareness and behavior of oncologists and support measures in medical institutions related to ongoing employment of cancer patients in Japan.

PubMed

Wada, Koji; Ohtsu, Mayumi; Aizawa, Yoshiharu; Tanaka, Hiroshi; Tagaya, Nobumi; Takahashi, Miyako

2012-04-01

Improved outcomes of cancer treatment allow patients to undergo treatment while working. However, support from oncologists and medical institutions is essential for patients to continue working. This study aimed to clarify oncologists' awareness and behavior regarding patients who work during treatment, support in medical institutions and their association. A questionnaire was mailed to all 453 diplomates and faculty of the subspecialty board of medical oncology in the Japanese Society of Medical Oncology and all 1016 surgeons certified by the Japanese Board of Cancer Therapy living in the Kanto area. The questionnaire assessed demographics, oncologist awareness and behavior regarding patient employment and support measures at their medical institutions. Logistic regression analysis was used to examine the association of awareness and behavior of oncologists with support measures at their institutions. A total of 668 individuals participated. The overall response rate was 45.5%. Only 53.6% of respondents advised patients to tell their supervisors about prospects for treatment and ask for understanding. For medical institutions, 28.8% had a nurse-involved counseling program and adjustments in radiation therapy (28.0%) and chemotherapy (41.9%) schedules to accommodate patients' work. There was a significant correlation between awareness and behavior of oncologists and medical institutions' measures to support employed cancer patients. There is room for improvement in awareness and behavior of oncologists and support in medical institutions for cancer patients continuing to work. Oncologists could support working patients by exerting influence on their medical institutions. Conversely, proactive development of support measures by medical institutions could alter the awareness and behavior of oncologists.

Congruence between Preferred and Actual Participation Roles Increases Satisfaction with Treatment Decision Making among Japanese Women with Breast Cancer

PubMed

Yamauchi, Keiko; Nakao, Motoyuki; Nakashima, Mitsuyo; Ishihara, Yoko

2017-04-01

Objective: This study investigated the correlation between participation in the treatment decision-making process and satisfaction with the process among Japanese women with breast cancer. The influence of sociodemographic and clinical characteristics on satisfaction with the treatment decision-making process was also examined. Methods: We conducted a cross-sectional, self-administered internet survey of 650 Japanese women with breast cancer in March 2016. Decisional role (active, collaborative, passive) in the treatment decision-making was elicited using the Japanese version of the Control Preference Scale. Satisfaction with the decision-making process was assessed. Result: About half of the participants preferred to play a collaborative role, while half of the participants perceived that they played an active role. Satisfaction among the participants who made their treatment choice collaboratively with their physicians was significantly higher than that of participants who made the choice by themselves or entrusted their physicians to make the decision. However, two-way ANOVA demonstrated that satisfaction level was associated with the congruence between the participants’ preferred and actual decisional roles, but not with the actual decisional roles that they played. This association had no interaction with sociodemographic and clinical status, except for education level. A majority of the participants who participated in the roles they preferred in choosing their treatment option indicated that they would participate in the same role if they were to face a similar decision-making situation in the future. Conclusion: Regardless of their role played in the cancer treatment decision-making process, and irrespective of their sociodemographic and clinical status, Japanese women with breast cancer are more satisfied with the treatment decision-making process when their participation in the process matches their preferred role in the process. Creative Commons

Congruence between Preferred and Actual Participation Roles Increases Satisfaction with Treatment Decision Making among Japanese Women with Breast Cancer

PubMed Central

Yamauchi, Keiko; Nakao, Motoyuki; Nakashima, Mitsuyo; Ishihara, Yoko

2017-01-01

Objective: This study investigated the correlation between participation in the treatment decision-making process and satisfaction with the process among Japanese women with breast cancer. The influence of sociodemographic and clinical characteristics on satisfaction with the treatment decision-making process was also examined. Methods: We conducted a cross-sectional, self-administered internet survey of 650 Japanese women with breast cancer in March 2016. Decisional role (active, collaborative, passive) in the treatment decision-making was elicited using the Japanese version of the Control Preference Scale. Satisfaction with the decision-making process was assessed. Result: About half of the participants preferred to play a collaborative role, while half of the participants perceived that they played an active role. Satisfaction among the participants who made their treatment choice collaboratively with their physicians was significantly higher than that of participants who made the choice by themselves or entrusted their physicians to make the decision. However, two-way ANOVA demonstrated that satisfaction level was associated with the congruence between the participants’ preferred and actual decisional roles, but not with the actual decisional roles that they played. This association had no interaction with sociodemographic and clinical status, except for education level. A majority of the participants who participated in the roles they preferred in choosing their treatment option indicated that they would participate in the same role if they were to face a similar decision-making situation in the future. Conclusion: Regardless of their role played in the cancer treatment decision-making process, and irrespective of their sociodemographic and clinical status, Japanese women with breast cancer are more satisfied with the treatment decision-making process when their participation in the process matches their preferred role in the process. PMID:28545197

Benefits of peer support in online Japanese breast cancer communities: differences between lurkers and posters.

PubMed

Setoyama, Yoko; Yamazaki, Yoshihiko; Namayama, Kazuhiro

2011-12-29

Web 2.0 has improved interactions among peers on the Internet, especially for the many online patient communities that have emerged over the past decades. Online communities are said to be particularly beneficial peer support resources for patients with breast cancer. However, most studies of online patient communities have focused on those members who post actively (posters), even though there are many members who participate without posting (lurkers). In addition, little attention has been paid to the usage of online communities among non-English-speaking patients. The present study explored the differences in peer support received by lurkers and posters in online breast cancer communities. It also examined the effects of such support on both groups' mental health. We conducted an exploratory, descriptive, cross-sectional, Web-based survey among members of four Japanese online breast cancer communities. In an online questionnaire, we asked questions regarding sociodemographics, disease-related characteristics, mental health, participation in online communities, and peer support received from those communities. Of the 465 people who accessed the questionnaire, 253 completed it. Of the respondents, 113/220 (51.4%) were lurkers. There was no significant difference between lurkers and posters with regard to sociodemographic variables. About half of the posters had been given a diagnosis of breast cancer less than a year previously, which was a significantly shorter period than that of the lurkers (P = .02). The 5 support functions extracted by factor analysis were the same for both posters and lurkers. These were emotional support/helper therapy, emotional expression, conflict, advice, and insight/universality. When the support scores were calculated, insight/universality scored highest for both posters and lurkers, with scores that were not significantly different between the two groups. Among the 5 support scores, emotional support/helper therapy and emotional

[Cancer and Malnutrition].

PubMed

Tsuzuki, Norimasa; Higashiguchi, Takashi; Ito, Akihiro; Ohara, Hiroshi; Futamura, Akihiko

2015-07-01

A Japanese proverb says that a balanced diet leads to a healthy body. However, the relation between healthy life and nutrition has not been established precisely and quantitatively. Cancer cachexia, which is malnutrition in cancer patients, has been studied extensively. Appropriate nutrition support can prevent the progression of malnutrition in cancer patients and advance the tolerance for anticancer therapy. In refractory cachexia (terminally cancer patients), we will judge the necessity of reduction of nutrition support, what it is called "gear-change", because the support is burden for the body. It is important to restrict the quantity of nutrition and to give medical treatment to retain bodily function in these patients.

FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema.

PubMed

Nemoto-Hasebe, I; Akiyama, M; Nomura, T; Sandilands, A; McLean, W H I; Shimizu, H

2009-12-01

Mutations in the gene encoding filaggrin (FLG) have been shown to predispose to atopic eczema (AE). Further to establish population genetics of FLG mutations in the Japanese population and to elucidate effects of FLG mutations to filaggrin biosynthesis in skin of patients with AE. We searched for FLG mutations in 19 newly recruited Japanese patients with AE. We then screened 137 Japanese patients with AE and 134 Japanese control individuals for a novel mutation identified in the present study. In addition, we evaluated FLG mRNA expression by real-time reverse transcription-polymerase chain reaction and profilaggrin/filaggrin protein expression by immunohistochemical staining in the epidermis of the patients carrying the novel mutation. We identified a novel FLG nonsense mutation c.12069A>T (p.Lys4021X) in one patient with AE. Upon further screening, p.Lys4021X was identified in four patients with AE (2.9% of all the patients with AE). In total, there are at least eight FLG variants in the Japanese population. Here we show that about 27% of patients in our Japanese AE case series carry one or more of these eight FLG mutations and these variants are also carried by 3.7% of Japanese general control individuals. There is a significant statistical association between the eight FLG mutations and AE (chi(2) P = 6.50 x 10(-8)). Interestingly, the present nonsense mutation is in the C-terminal incomplete filaggrin repeat and is the mutation nearest the C-terminal among previously reported FLG mutations. Immunohistochemical staining for filaggrin revealed that this nonsense mutation leads to remarkable reduction of filaggrin protein expression in the patients' epidermis. We clearly demonstrated that FLG mutations are significantly associated with AE in the Japanese population. The present results further support the hypothesis that the C-terminal region is essential for proper processing of profilaggrin to filaggrin.

Dietary patterns and breast cancer risk in a prospective Japanese study.

PubMed

Kojima, Reiji; Okada, Emiko; Ukawa, Shigekazu; Mori, Mitsuru; Wakai, Kenji; Date, Chigusa; Iso, Hiroyasu; Tamakoshi, Akiko

2017-01-01

The association between dietary patterns and breast cancer has been inconsistent. This study examined associations between dietary patterns and risk of developing breast cancer among 23,172 women from the Japan Collaborative Cohort Study, including 119 incidences of breast cancer diagnosed during a median 16.9-year follow-up period. Factor analysis was conducted to obtain dietary patterns, and Cox proportional models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) for breast cancer morbidity. Three dietary patterns were identified: ''vegetable pattern'' (vegetables, potatoes, seaweed, tofu, fruits, fresh fish, eggs, and miso soup); ''animal food pattern'' (meat, deep-fried foods, fried vegetables, fish paste and salt-preserved fish); and "dairy product pattern'' (milk, dairy products, fruits, coffee and tea). After adjusting for potential confounders, the vegetable and dairy product patterns were not significantly associated with risk of breast cancer. However, the animal food pattern was significantly associated with a decreased risk of breast cancer morbidity among premenopausal women by HR 0.47 for the 2nd tertile (95 % CI 0.22-1.00) and HR 0.42 for the 3rd tertile (95 % CI 0.18-0.93), compared with the bottom tertile (p for trend 0.04). We found no significant association between the vegetable and dairy product dietary patterns and breast cancer risk; however, an animal product diet may reduce risk of breast cancer among premenopausal Japanese women.

Patterns of Radiotherapy Practice for Pancreatic Cancer in Japan: Results of the Japanese Radiation Oncology Study Group (JROSG) Survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.j; Ito, Yoshinori; Karasawa, Katsuyuki

2010-07-01

Purpose: To determine the patterns of radiotherapy practice for pancreatic cancer in Japan. Methods and Materials: A questionnaire-based national survey of radiotherapy for pancreatic cancer treated between 2000 and 2006 was conducted by the Japanese Radiation Oncology Study Group (JROSG). Detailed information on 870 patients from 34 radiation oncology institutions was accumulated. Results: The median age of all patients was 64 years (range, 36-88), and 80.2% of the patients had good performance status. More than 85% of patients had clinical Stage T3-T4 disease, and 68.9% of patients had unresectable disease at diagnosis. Concerning radiotherapy (RT), 49.8% of patients were treatedmore » with radical external beam RT (EBRT) (median dose, 50.4 Gy), 44.4% of patients were treated with intraoperative RT (median dose, 25 Gy) with or without EBRT (median dose, 45 Gy), and 5.9% of patients were treated with postoperative radiotherapy (median dose, 50 Gy). The treatment field consisted of the primary tumor (bed) only in 55.6% of the patients. Computed tomography-based treatment planning and conformal RT was used in 93.1% and 83.1% of the patients treated with EBRT, respectively. Chemotherapy was used for 691 patients (79.4%; before RT for 66 patients; during RT for 531; and after RT for 364). Gemcitabine was the most frequently used drug, followed by 5-fluorouracil. Conclusion: This study describes the general patterns of RT practice for pancreatic cancer in Japan. Most patients had advanced unresectable disease, and radical EBRT, as well as intraoperative RT with or without EBRT, was frequently used. Chemotherapy with gemcitabine was commonly used in conjunction with RT during the survey period.« less

Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.

PubMed

Teranishi, Hideto; Koga, Yuhki; Nishio, Hisanori; Kato, Wakako; Ono, Hiroaki; Kanno, Shunsuke; Nakashima, Kentaro; Takada, Hidetoshi

2017-07-01

Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged ≥13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered. The detection rates for extended-spectrum β-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p = 0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p < 0.01; respectively). Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Screening for major depressive episodes in Japanese patients with epilepsy: validation and translation of the Japanese version of Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

PubMed

Tadokoro, Yukari; Oshima, Tomohiro; Fukuchi, Toshihiko; Kanner, Andres M; Kanemoto, Kousuke

2012-09-01

We validated and translated into Japanese the English version of the screening instrument Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to identify major depressive episodes in patients with epilepsy. A total of 159 Japanese subjects with epilepsy underwent a psychiatric structured interview with the Japanese version of the Mini International Neuropsychiatric Interview (M.I.N.I.-J) followed by completion of the Japanese version of NDDI-E (NDDI-E-J). Twelve participants met the M.I.N.I.-J criteria of current major depressive episode. Participants had no difficulties completing the NDDI-E-J. Its Cronbach's alpha coefficient was 0.83 and a cut-off score greater than 16 provided a sensitivity of 0.92, a specificity of 0.89, and a negative predictive value of 0.99. The NDDI-E-J appears to be useful for primary care clinicians to screen for major depressive episodes in epilepsy patients. Routine use of this brief and self-administered instrument in busy clinical settings will likely improve management of depression in Japanese individuals with epilepsy. Copyright © 2012 Elsevier Inc. All rights reserved.

Usefulness of esophagogastroduodenoscopy and 18F-fluorodeoxyglucose positron-emission tomography in detecting synchronous multiple primary cancers with oral cancer.

PubMed

Ishibashi-Kanno, Naomi; Yamagata, Kenji; Uchida, Fumihiko; Hasegawa, Shogo; Yanagawa, Toru; Bukawa, Hiroki

2017-12-01

The purpose of this study is to compare the value of screening for synchronous multiple primary cancers in other organs by esophagogastroduodenoscopy (EGD) or 18 F-fluorodeoxyglucose positron-emission tomography (PET-CT) in patients newly diagnosed with oral cancer. We retrospectively examined consecutive Japanese patients who were diagnosed with oral squamous cell carcinoma (OSCC) and were screened for synchronous multiple primary cancers in other organs by EGD and/or PET-CT between January 2010 and December 2015 at our institution. The study included 190 patients (106 males and 84 females) from 36 to 93 years of age (median age 68.8 years). The patients were screened by EGD, PET-CT, or both before beginning treatment for OSCC. Of 190 Japanese patients with OSCC, 15 had multiple primary cancers: 13 patients had double cancer and two had triple cancers. The sites of the 17 multiple primary cancers were gastric (6), esophageal (4), and lung (3), and ovarian, colon, liver, and thyroid (1 each). All of the gastric and esophageal cancers were found by EGD and were not detected by PET-CT. For three patients, the detection of multiple cancers affected the treatment modality or order of treatment selected for the OSCC. In two cases, the oral cancer and multiple primary cancer(s) in another organ were resected simultaneously by joint surgical teams. PET-CT for oral cancer patients is an effective supporting diagnostic tool. However, the ability of PET-CT has some limitations. Especially for early detection of the upper gastrointestinal cancers, it is necessary to be supplemented by EGD.

Azathioprine Intolerance in Japanese Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis

PubMed Central

Morishita, Michiko; Watanabe, Haruki; Yan, Minglu; Zeggar, Sonia; Hiramatsu, Sumie; Ohashi, Keiji; Miyawaki, Yoshia; Katsuyama, Eri; Katsuyama, Takayuki; Takano Narazaki, Mariko; Toyota Tatebe, Noriko; Sunahori Watanabe, Katsue; Kawabata, Tomoko; Sada, Ken-Ei; Wada, Jun

2017-01-01

Objective To assess the safety of azathioprine (AZA) in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods We retrospectively enrolled 67 consecutive AAV patients who had initiated AZA treatment from January 2006 to August 2014 at Okayama University Hospital. We evaluated the development of severe adverse events (AEs), AZA discontinuation due to total AEs (severe AEs included) within 1 year, and AZA-associated risk factors. Results The patients' median age was 70 years old. Forty-nine women and 18 men participated at the initiation of the study. Fifty-eight (87%) patients experienced AEs, and 36 experienced severe AEs (21 hepatic and 11 cytopenic severe AEs). Thirty-one (46%) patients discontinued treatment because of AEs. Abnormal hepatic laboratory test results at the treatment initiation were more frequent in patients with hepatic severe AEs and were associated with treatment discontinuation. The leukocyte and neutrophil counts at the treatment initiation were lower in the patients who discontinued treatment because of cytopenic AEs than in those who continued treatment. Only two patients experienced flare-ups during treatment. Conclusion The AE-associated AZA discontinuation rate in Japanese AAV patients was relatively high. AZA use warrants caution in patients with abnormal hepatic laboratory test results or low leukocyte or neutrophil counts. PMID:28674351

Alcohol drinking and esophageal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

PubMed

Oze, Isao; Matsuo, Keitaro; Wakai, Kenji; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Tsuji, Ichiro; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

2011-05-01

Although alcohol drinking is considered as an important risk factor for esophageal cancer, the magnitude of the association might be varied among geographic areas. Therefore, we reviewed epidemiologic studies on the association between alcohol drinking and esophageal cancer among the Japanese population. Original data were obtained from MEDLINE, searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. We identified four cohort studies and nine case-control studies. All cohort studies and case-control studies showed strong positive associations between esophageal cancer and alcohol drinking. All cohort studies and six case-control studies showed that alcohol drinking had the dose- or frequency-response relationships with esophageal cancer. In addition, four case-control studies showed that acetaldehyde dehydrogenase Glu504Lys polymorphism had strong effect modification with alcohol drinking. We conclude that there is convincing evidence that alcohol drinking increases the risk of esophageal cancer in the Japanese population.

Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

PubMed Central

Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm

2015-01-01

Purpose To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. Patients and methods This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. Results The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum. Conclusion These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional

Novel USH2A mutations in Japanese Usher syndrome type 2 patients: marked differences in the mutation spectrum between the Japanese and other populations.

PubMed

Nakanishi, Hiroshi; Ohtsubo, Masafumi; Iwasaki, Satoshi; Hotta, Yoshihiro; Usami, Shin-Ichi; Mizuta, Kunihiro; Mineta, Hiroyuki; Minoshima, Shinsei

2011-07-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A. In a recent mutation screening of USH2A in Japanese USH2 patients, we identified 11 novel mutations in 10 patients and found the possible frequent mutation c.8559-2A>G in 4 of 10 patients. To obtain a more precise mutation spectrum, we analyzed further nine Japanese patients in this study. We identified nine mutations, of which eight were novel. This result indicates that the mutation spectrum for USH2A among Japanese patients largely differs from Caucasian, Jewish and Palestinian patients. Meanwhile, we did not find the c.8559-2A>G in this study. Haplotype analysis of the c.8559-2G (mutated) alleles using 23 single nucleotide polymorphisms surrounding the mutation revealed an identical haplotype pattern of at least 635 kb in length, strongly suggesting that the mutation originated from a common ancestor. The fact that all patients carrying c.8559-2A>G came from western Japan suggests that the mutation is mainly distributed in that area; indeed, most of the patients involved in this study came from eastern Japan, which contributed to the absence of c.8559-2A>G.

The influence of personality and perceived stress on the development of breast cancer: 20-year follow-up of 29,098 Japanese women

PubMed Central

Sawada, Takayuki; Nishiyama, Takeshi; Kikuchi, Norimasa; Wang, Chaochen; Lin, Yingsong; Mori, Mitsuru; Tanno, Kozo; Tamakoshi, Akiko; Kikuchi, Shogo

2016-01-01

Breast cancer is the most common cancer in women. However, it remains unproven whether psychological factors have an influence on breast cancer incidence. In our earlier study, subjects possessing two personality traits, decisiveness and “ikigai” (a Japanese word meaning something that makes one’s life worth living), showed a significantly lower risk of developing breast cancer, although no psychological factors have been convincingly demonstrated to have an influence on breast cancer development in other studies. Therefore, we conducted this follow-up analysis to confirm the association between breast cancer incidence and psychological traits, using the final dataset of a large-scale prospective cohort study in Japan. We identified 209 cases of incident breast cancer out of a maximum 21-year follow-up of 29,098 Japanese women. Cox proportional hazard regression analysis, adjusted for the same potential confounders used in our previous study, did not reveal any significant relationships between breast cancer incidence and four psychological traits: having “ikigai”, decisiveness, ease of anger arousal, and perceived stress. Our finding is consistent with previous studies, and suggests that the psychological traits are unlikely to be an important risk factor for breast cancer. PMID:27586560

The influence of personality and perceived stress on the development of breast cancer: 20-year follow-up of 29,098 Japanese women.

PubMed

Sawada, Takayuki; Nishiyama, Takeshi; Kikuchi, Norimasa; Wang, Chaochen; Lin, Yingsong; Mori, Mitsuru; Tanno, Kozo; Tamakoshi, Akiko; Kikuchi, Shogo

2016-09-02

Breast cancer is the most common cancer in women. However, it remains unproven whether psychological factors have an influence on breast cancer incidence. In our earlier study, subjects possessing two personality traits, decisiveness and "ikigai" (a Japanese word meaning something that makes one's life worth living), showed a significantly lower risk of developing breast cancer, although no psychological factors have been convincingly demonstrated to have an influence on breast cancer development in other studies. Therefore, we conducted this follow-up analysis to confirm the association between breast cancer incidence and psychological traits, using the final dataset of a large-scale prospective cohort study in Japan. We identified 209 cases of incident breast cancer out of a maximum 21-year follow-up of 29,098 Japanese women. Cox proportional hazard regression analysis, adjusted for the same potential confounders used in our previous study, did not reveal any significant relationships between breast cancer incidence and four psychological traits: having "ikigai", decisiveness, ease of anger arousal, and perceived stress. Our finding is consistent with previous studies, and suggests that the psychological traits are unlikely to be an important risk factor for breast cancer.

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts.

PubMed

Schneider, Uwe; Walsh, Linda

2015-08-01

Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin's disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for

Study abroad experience is related to Japanese doctors' behavior to see foreign patients.

PubMed

Tamamaki, Kinko; Nishio, Hisahide

2013-04-17

Globalization in Japan involves increases in the number of foreign residents. While there are some English-speaking Japanese doctors that are willing to see foreign patients, many are reluctant to do so. In this study, we attempted to clarify the factors that encourage Japanese doctors to see foreign patients. We conducted a questionnaire survey among medical doctors in Kobe City, Japan. The questionnaire was distributed to 172 doctors, and we received 139 responses. Statistical analysis showed a significant correlation between the frequency of seeing foreign patients and having the experience of studying abroad (p<0.05), confirming our hypothesis. There was also a significant correlation between having the experience of studying abroad and the doctors' self-evaluations of their English ability (p<0.05). There was no significant correlation found, however, between the frequency of seeing foreign patients and that of reading English research articles. These data suggested that the experience of living abroad rather than the exposure to English research articles was more highly correlated with seeing greater numbers of foreign patients. In conclusion, greater exposure to colloquial English was one of the determinants of the doctors' greater willingness to see foreign patients. In the Japanese medical education curriculum, therefore, it would be necessary to offer alternatives to studying abroad for those students who do not have such opportunities.

Pediatric Cancer Patients' Important End-of-Life Issues, Including Quality of Life: A Survey of Pediatric Oncologists and Nurses in Japan.

PubMed

Nagoya, Yuko; Miyashita, Mitsunori; Shiwaku, Hitoshi

2017-05-01

Research into the key themes and concepts of quality of life (QOL) relevant to the end-of-life (EOL) care of pediatric cancer patients in the Japanese context is imperative. This study aimed at identifying the key items and constructive concepts of QOL at EOL of pediatric cancer patients. In 2015, pediatricians and nurses were recruited from 163 pediatric oncology treatment facilities in Japan. The questionnaire was developed on the basis of a previous qualitative study. Items that were rated as "very important" or "important" by at least 80% of the respondents were considered as "common and important" QOL items. Exploratory factor analysis was performed to conceptualize QOL of the pediatric cancer patients during EOL care. A total of 157 pediatricians and 270 nurses participated in this study. Fifty-five items were refined to 35 "common and important" QOL items. On factor analysis, 12 domains (containing 29 items) were identified: playing and learning; fulfilling wishes; spending time with family; receiving relief from physical and psychological suffering; making many wonderful memories; having a good relationship with the medical staff; having a peaceful death in the presence of family; spending time with a minimum of medical treatment; living one's life as usual; spending time in a calm hospital environment; being oneself; and having a close family. Although the respondents in this study were medical care providers rather than the patients or their family members, findings should help medical staff provide better palliative care to Japanese pediatric cancer patients.

Moraxella osloensis: an unusual cause of central venous catheter infection in a cancer patient

PubMed Central

Hadano, Yoshiro; Ito, Kenta; Suzuki, Jun; Kawamura, Ichiro; Kurai, Hanako; Ohkusu, Kiyofumi

2012-01-01

Moraxella osloensis is a rare causative organism of infections in humans, with most cases reported in cancer patients. We report the case of a 67-year-old Japanese man with advanced cancer of the pancreatic head and multiple liver metastases who developed fever with chills. Blood culture was found to be positive for Gram-negative bacilli that were aerobic, oxidase-positive, and catalase-positive. M. osloensis was identified by 16 rRNA gene sequencing. Prompt control of the infection was achieved by treatment with cefepime for 14 days, without the need for removal of the central venous catheter. PMID:23109812

Moraxella osloensis: an unusual cause of central venous catheter infection in a cancer patient.

PubMed

Hadano, Yoshiro; Ito, Kenta; Suzuki, Jun; Kawamura, Ichiro; Kurai, Hanako; Ohkusu, Kiyofumi

2012-01-01

Moraxella osloensis is a rare causative organism of infections in humans, with most cases reported in cancer patients. We report the case of a 67-year-old Japanese man with advanced cancer of the pancreatic head and multiple liver metastases who developed fever with chills. Blood culture was found to be positive for Gram-negative bacilli that were aerobic, oxidase-positive, and catalase-positive. M. osloensis was identified by 16 rRNA gene sequencing. Prompt control of the infection was achieved by treatment with cefepime for 14 days, without the need for removal of the central venous catheter.

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study.

PubMed

Kitagawa, Mayumi; Tashiro, Kunio

2005-09-01

To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson's disease (PD). A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively. In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist. Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.

Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer.

PubMed

Inoue, Kenichi; Kuroi, Katsumasa; Shimizu, Satoru; Rai, Yoshiaki; Aogi, Kenjiro; Masuda, Norikazu; Nakayama, Takahiro; Iwata, Hiroji; Nishimura, Yuichiro; Armour, Alison; Sasaki, Yasutsuna

2015-12-01

Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients. In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles. The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9). The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.

[Interindividual variation of pharmacokinetic disposition of and clinical responses to opioid analgesics in cancer pain patients].

PubMed

Naito, Takafumi; Kawakami, Junichi

2015-01-01

Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. In our study, the impact of genetic variants and pharmacokinetics on clinical responses to oxycodone were evaluated in Japanese populations. (2) Opioid switching improves the opioid tolerance related to the balance between analgesia and adverse effects. Some patients have difficulty in obtaining better opioid tolerance in recommended conversion ratios. The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual variations in clinical responses to fentanyl in cancer patients. However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.

Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls.

PubMed

Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm

2015-01-01

To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum. These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional benefit in disease management of COPD in Japan.

Revision concepts and distinctive points of the new Japanese classification for biliary tract cancers in comparison with the 7(th) edition of the Union for International Cancer Control and the American Joint Committee on Cancer staging system.

PubMed

Ohtsuka, Masayuki; Miyakawa, Shuichi; Nagino, Masato; Takada, Tadahiro; Miyazaki, Masaru

2015-03-01

The 3(rd) English edition of the Japanese classification of the biliary tract cancers (JC) is now available in this journal. The primary aim of this revision is to provide all clinicians and researchers with a common language of cancer staging at an international level. On the other hand, there are several important issues that should be solved for the optimization of the staging system. Revision concepts and major revision points of the 3(rd) English edition of the JC were reviewed. Furthermore, comparing with the 7(th) edition of staging system developed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), distinctive points in the JC was discussed. In this edition of the JC, the same stage groupings as those in the UICC/AJCC staging system were basically adopted. T, N, and M categories were also identical in principle with those in the UICC/AJCC staging system, although slight modifications were proposed as the "Japanese rules". As distinctive points, perihilar cholangiocarcinomas and ampullary region carcinomas were clearly defined. Intraepithelial tumor was discriminated from invasive carcinoma at ductal resection margins. Classifications of site-specific surgical margin status remained in this edition. Histological classification was based on that in the former editions of the JC, but adopted some parts of the World Health Organization classification. The JC now share its staging system of the biliary tact carcinomas with the UICC/AJCC staging system. Future validation of the "Japanese rules" could provide important evidence to make globally standardized staging system. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Male Breast Cancer Incidence and Mortality Risk in the Japanese Atomic Bomb Survivors - Differences in Excess Relative and Absolute Risk from Female Breast Cancer.

PubMed

Little, Mark P; McElvenny, Damien M

2017-02-01

There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the United Kingdom, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. We compare radiation-associated excess relative and absolute risks of male and female breast cancers. Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. We observed significant (p ≤ 0.01) dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are elevations by factors of approximately 15 and 5, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data, there are elevations by factors of approximately 20 and 10, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least a factor of 5 that of many other malignancies. There is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding. Citation: Little MP, McElvenny DM. 2017. Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors - differences in excess relative and absolute risk from female breast cancer. Environ Health

Cancer--Living with Cancer - Multiple Languages

MedlinePlus

... français) Haitian Creole (Kreyol ayisyen) Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Nepali (नेपाली) Polish (polski) ... Families - हिन्दी (Hindi) PDF American Cancer Society Japanese (日本語) Expand Section Cancer Related Fatigue - 日本語 (Japanese) ...

N-acetyltransferase 2 polymorphism and breast cancer risk with smoking: a case control study in Japanese women.

PubMed

Hara, Akio; Taira, Naruto; Mizoo, Taeko; Nishiyama, Keiko; Nogami, Tomohiro; Iwamoto, Takayuki; Motoki, Takayuki; Shien, Tadahiko; Matsuoka, Junji; Doihara, Hiroyoshi; Ishihara, Setsuko; Kawai, Hiroshi; Kawasaki, Kensuke; Ishibe, Youichi; Ogasawara, Yutaka; Miyoshi, Shinichiro

2017-03-01

Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia. We conducted a case-control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype. In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38-3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype. Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.

Development and validation of the Japanese version of the Decisional Conflict Scale to investigate the value of pharmacists' information: a before and after study.

PubMed

Kawaguchi, Takashi; Azuma, Kanako; Yamaguchi, Takuhiro; Soeda, Hiroshi; Sekine, Yusuke; Koinuma, Masayoshi; Takeuchi, Hironori; Akashi, Takao; Unezaki, Sakae

2013-04-17

The information provided in patient-centered care and shared decision-making influences patients' concerns and adherence to treatment. In the decision-making process, patients experience decisional conflict. The Decisional Conflict Scale (DCS) is a 16-item, self-administered questionnaire consisting of 5 subscales developed to assess patients' decisional conflict. This study aimed to develop the Japanese version of the DCS and to clarify the influence of the information provided by pharmacists' on decisional conflict among patients with cancer. We developed the Japanese version of the DCS by using the forward-backward translation method. One hundred patients who were recommended a new chemotherapy regimen were recruited. The psychometric properties of the Japanese DCS, including internal consistency, convergent validity, discriminant validity, and construct validity, were examined. We assessed the decisional conflict of patients before and after the pharmacists' provision of information. Ninety-four patients, predominately female, with an average age of 58.1 years were sampled. The scores on the 5 subscales of the DCS showed high internal consistency (Cronbach's alpha = 0.84-0.96). Multi-trait scaling analysis and cluster analysis showed strong validity. The mean total DCS score decreased significantly from 40.2 to 31.7 after patients received information from the pharmacists (p < 0.001, paired t-test). Scores on all 5 subscales, namely, uncertainty, informed, values clarity, support, and effective decision, also significantly improved (p < 0.001 for all categories, paired t-test). The psychometric properties of the Japanese version of the DCS are considered appropriate for it to be administered to patients with cancer. Pharmacists' provision of information was able to decrease decisional conflict among patients with cancer who were recommended a new chemotherapy regimen.

Assessing medical decision making capacity among cancer patients: Preliminary clinical experience of using a competency assessment instrument.

PubMed

Akechi, Tatsuo; Okuyama, Toru; Uchida, Megumi; Sugano, Koji; Kubota, Yosuke; Ito, Yoshinori; Sakamoto, Nobuhiro; Kizawa, Yoshiyuki

2015-12-01

This study investigates the usefulness of the Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory (SICIATRI) for cancer patients, which is a structured interview that assesses a patient's competency in clinical practice. The SICIATRI, originally developed to measure patients' competency to give informed consent, were administered referred cancer patients who needed for assessing medical decision making capacity. The usefulness of the SICIATRI was investigated retrospectively. Recommendation for modification of the SICIATRI for cancer patients if applicable were made by the research team. Among the 433 cancer patients referred for psychiatric consultation, 12 were administered the SICIATRI and all of the administration were conducted without big problems. All patients were 60 years or older. The most common purpose for competency evaluation was to analyze patients' understanding of the anti-cancer treatment proposed by oncologists, followed by their refusal of the treatment. Half of the patients (n = 6) were diagnosed with delirium and three among them were judged as having the most impaired status of a patient's competency. Two patients (17%) were diagnosed with major depression and another two (17%) were mental retardation and each one patient was diagnosed with dementia and past history of alcohol dependence. Among 6 patients without delirium 5 subjects including a dementia patient were judged as fully competent. Total of 5 small potential modifications of the SICIATRI for its use with Japanese cancer patients were recommended. Our experience suggests that the SICIATRI is a useful instrument for psycho-oncology clinical practice.

Development of a questionnaire to evaluate asthma control in Japanese asthma patients.

PubMed

Tohda, Yuji; Hozawa, Soichiro; Tanaka, Hiroshi

2018-01-01

The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients. A total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated. The intra-class correlation coefficients (ICCs) were within the range of 0.55-0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were -0.78, -0.78, and 0.77, respectively, showing a significant correlation (p < 0.0001). The JACS questionnaire was validated in terms of reliability and validity. It will be necessary to evaluate the therapeutic efficacy measured by the JACS questionnaire and calculate cutoff values for the asthma control status in a higher number of patients. UMIN000016589. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Factors Affecting Professional Autonomy of Japanese Nurses Caring for Culturally and Linguistically Diverse Patients in a Hospital Setting in Japan.

PubMed

Kuwano, Noriko; Fukuda, Hiromi; Murashima, Sachiyo

2016-11-01

The study aimed to analyze the professional autonomy of Japanese nurses when caring for non-Japanese patients and to identify its contributing factors. A descriptive cross-sectional design was used. Participants included 238 clinical nurses working at 27 hospitals in Japan. The Intercultural Sensitivity Scale (Chen and Starosta), and the Scale for Professional Autonomy in Nursing (Kikuchi and Harada) were used to measure intercultural sensitivity and professional autonomy. Stepwise multiple regression analysis was used to identify the most significant factors affecting professional autonomy. Professional autonomy of Japanese nurses caring for non-Japanese patients was significantly lower than when caring for Japanese patients (142.84 vs. 172.85; p < .001). Contributing factors were intercultural sensitivity (p < .001), length of nurse experience (p < .05), and availability of interpretation service (p < .05). Incorporating transcultural nursing content into training programs in schools and hospitals could enhance professional autonomy of Japanese nurses by promoting intercultural sensitivity. © The Author(s) 2015.

Negotiating end-of-life decision making: a comparison of Japanese and U.S. residents' approaches.

PubMed

Gabbay, Baback B; Matsumura, Shinji; Etzioni, Shiri; Asch, Steven M; Rosenfeld, Kenneth E; Shiojiri, Toshiaki; Balingit, Peter P; Lorenz, Karl A

2005-07-01

To compare Japanese and U.S. resident physicians' attitudes, clinical experiences, and emotional responses regarding making disclosures to patients facing incurable illnesses. From September 2003 to June 2004, the authors used a ten-item self-administered anonymous questionnaire in a cross-sectional survey of 103 internal medicine residents at two U.S. sites in Los Angeles, California, and 244 general medical practice residents at five Japanese sites in Central Honshu, Kyushu, Okinawa, Japan. The Japanese residents were more likely to favor including the family in disclosing diagnosis (95% versus 45%, p<.001) and prognosis (95% versus 51%, p<.001) of metastatic gastric cancer. Of residents who favored diagnostic or prognostic disclosure to both the patient and family, Japanese residents were more likely to prefer discussion with the family first. Trainees in Japan expressed greater uncertainty about ethical practices related to disclosure of diagnosis or prognosis. Many Japanese and U.S. residents indicated that they had deceived a patient at the request of a family (76% versus 18 %, p<.001), or provided nonbeneficial care (56% versus 72%, p<.05), and many expressed guilt about these behaviors. The residents' approaches to end-of-life decision making reflect known cultural preferences related to the role of patients and their families. Although Japanese trainees were more likely to endorse the role of the family, they expressed greater uncertainty about their approach. Difficulty and uncertainty in end-of-life decision making were common among both the Japanese and U.S. residents. Both groups would benefit from ethical training to negotiate diverse, changing norms regarding end-of-life decision making.

Psychological and behavioral mechanisms influencing the use of complementary and alternative medicine (CAM) in cancer patients.

PubMed

Hirai, K; Komura, K; Tokoro, A; Kuromaru, T; Ohshima, A; Ito, T; Sumiyoshi, Y; Hyodo, I

2008-01-01

This study explored the psychological and behavioral mechanisms of complementary and alternative medicine (CAM) use in Japanese cancer patients using two applied behavioral models, the transtheoretical model (TTM), and theory of planned behavior (TPB). Questionnaires were distributed to 1100 patients at three cancer treatment facilities in Japan and data on 521 cancer patients were used in the final analysis. The questionnaire included items based on TTM and TPB variables, as well as three psychological batteries. According to the TTM, 88 patients (17%) were in precontemplation, 226 (43%) in contemplation, 33 (6%) in preparation, 71 (14%) in action, and 103 (20%) in maintenance. The model derived from structural equation modeling revealed that the stage of CAM use was significantly affected by the pros, cons, expectation from family, norms of medical staff, use of chemotherapy, period from diagnosis, and place of treatment. The primary factor for the stage of CAM use was the expectation from family. The findings revealed the existence of a number of psychologically induced potential CAM users, and psychological variables including positive attitude for CAM use and perceived family expectation greatly influence CAM use in cancer patients.

Cancer articles in weekly magazines: useful media to deliver cancer information to the public?

PubMed

Nagata, Masayoshi; Takita, Morihito; Kishi, Yukiko; Kodama, Yuko; Matsumura, Tomoko; Murashige, Naoko; Homma, Yukio; Kami, Masahiro

2013-04-01

Japanese weekly magazines, which have a circulation of over 2 700 000, play important roles in communicating with the public. They offer a wide range of information, entertainment, gossip, politics and economics, and often include articles on cancer. However, cancer articles in magazines have not been systematically analyzed. We investigated cancer-related articles and advertisements in six major Japanese weekly magazines to demonstrate trends in public interest regarding cancer. The total number of articles assessed from July 2009 to December 2010 was 36 914, of which 696 (1.9%) were cancer articles. The total number of advertisements was 21 718, of which 340 (1.6%) were related to cancer. The number of cancer articles demonstrated an upward trend during the study period. Articles focused on lung (n = 145) and urogenital cancer (n = 122). The most common content comprised therapies and diagnosis (n = 340) and case reports on individual patients (n = 160). After a famous Japanese comedian revealed his prostate cancer diagnosis, the number of articles on prostate cancer increased from 2.0 to 6.6 per month. Immunotherapy including some dubious folk therapies was the most frequently reported cancer therapy in articles and advertisements (30.4%). A small group of oncologists were repeatedly referred to in comment sources; 35.6% of comments were presented by only five doctors. Cancer articles in weekly magazines are common paper media for providing cancer information to the public. However, the information provided might place emphasis on unestablished treatments or biased opinions.

The role of family nutritional support in Japanese patients with type 2 diabetes mellitus.

PubMed

Watanabe, Koin; Kurose, Takeshi; Kitatani, Naomi; Yabe, Daisuke; Hishizawa, Masahiro; Hyo, Takanori; Seino, Yutaka

2010-01-01

We investigated the role of family support in glycemic control by nutritional self-care behavior of Japanese patients with type 2 diabetes. One hundred twelve Japanese out-patients with type 2 diabetes were recruited for the study at Kansai Electric Power Hospital. Interviews were conducted and HbA1c and triglyceride levels were measured. HbA1c levels were significantly related to family nutritional support. Patients under 60 years old with family nutritional support showed significantly lower HbA1c than patients without family support (p<0.05). Female patients with family support showed significantly lower HbA1c than those without family support (p<0.05). In addition, male patients with family support showed significantly lower triglyceride levels than those without family support (p<0.05). In male patients, those who were supported by cooking or buying light meals showed significantly lower HbA1c than those who were supported by advice or encouragement (p<0.05). The frequency of support (every day, 2-3 days, 1 week) showed similar outcomes in glycemic control. Patients who appreciate the support and follow the advice showed lower HbA1c (6.88 +/- 0.22%) than (7.43 +/- 0.23%) patients who appreciate the advice but sometimes feel emotional barriers. Family nutritional support is useful in improving metabolic outcome of diabetic patients. Self-care practice in disease management should be carefully adjusted to the family setting of type 2 diabetic patients. Emotional barriers to family support may affect the metabolic consequences, especially in the Japanese elderly.

Benefits of Peer Support in Online Japanese Breast Cancer Communities: Differences Between Lurkers and Posters

PubMed Central

Yamazaki, Yoshihiko; Namayama, Kazuhiro

2011-01-01

Background Web 2.0 has improved interactions among peers on the Internet, especially for the many online patient communities that have emerged over the past decades. Online communities are said to be particularly beneficial peer support resources for patients with breast cancer. However, most studies of online patient communities have focused on those members who post actively (posters), even though there are many members who participate without posting (lurkers). In addition, little attention has been paid to the usage of online communities among non-English-speaking patients. Objective The present study explored the differences in peer support received by lurkers and posters in online breast cancer communities. It also examined the effects of such support on both groups’ mental health. Methods We conducted an exploratory, descriptive, cross-sectional, Web-based survey among members of four Japanese online breast cancer communities. In an online questionnaire, we asked questions regarding sociodemographics, disease-related characteristics, mental health, participation in online communities, and peer support received from those communities. Results Of the 465 people who accessed the questionnaire, 253 completed it. Of the respondents, 113/220 (51.4%) were lurkers. There was no significant difference between lurkers and posters with regard to sociodemographic variables. About half of the posters had been given a diagnosis of breast cancer less than a year previously, which was a significantly shorter period than that of the lurkers (P = .02). The 5 support functions extracted by factor analysis were the same for both posters and lurkers. These were emotional support/helper therapy, emotional expression, conflict, advice, and insight/universality. When the support scores were calculated, insight/universality scored highest for both posters and lurkers, with scores that were not significantly different between the two groups. Among the 5 support scores, emotional

Effects of Anma massage therapy (Japanese massage) for gynecological cancer survivors: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Cancer patients and survivors regularly feel anxious about cancer recurrence or death, even after the conclusion of medical treatment, and they are often highly physiologically and psychologically stressed. Massage therapy is one of the most widely used complementary and alternative therapies used in the hope of alleviating such stress and physical and psychological complaints and to improve health-related quality of life. This randomized phase III, two-armed, parallel group, clinical trial was designed after obtaining positive findings in a preliminary study. The primary objective is to verify the effects of continuous Japanese massage therapy, referred to as Anma therapy, for cancer survivors. The secondary objective is to confirm the immediate effects of a single Anma massage session for cancer survivors. Methods/Design Sixty cancer survivors older than 20 years of age who have had histologically confirmed uterine cervical, endometrial, ovarian, fallopian tube or peritoneal cancer in the past, but with no recurrence for more than 3 years since receiving standard medical treatment, are being recruited by gynecologists in medical facilities. In the coordinating office, they are randomly allocated to two groups (n = 30 each): an Anma massage group receiving a 40-min Anma massage session once weekly over a 2-month intervention period (total of eight Anma massage sessions) and a control group being followed by medical doctors and receiving no Anma massage sessions. The primary end point is the severity of physical subjective symptoms that cancer survivors report in daily life, assessed using a Visual Analogue Scale. Secondary end points are urine and saliva analyses, psychological condition and health-related quality-of-life scores as determined on the basis of a self-report questionnaire. Discussion Using the evidence-based findings of this trial, medical professionals should be able to explain the benefits conferred by Anma massage to cancer survivors

Male Breast Cancer Incidence and Mortality Risk in the Japanese Atomic Bomb Survivors – Differences in Excess Relative and Absolute Risk from Female Breast Cancer

PubMed Central

Little, Mark P.; McElvenny, Damien M.

2016-01-01

Background: There are well-known associations of ionizing radiation with female breast cancer, and emerging evidence also for male breast cancer. In the United Kingdom, female breast cancer following occupational radiation exposure is among that set of cancers eligible for state compensation and consideration is currently being given to an extension to include male breast cancer. Objectives: We compare radiation-associated excess relative and absolute risks of male and female breast cancers. Methods: Breast cancer incidence and mortality data in the Japanese atomic-bomb survivors were analyzed using relative and absolute risk models via Poisson regression. Results: We observed significant (p ≤ 0.01) dose-related excess risk for male breast cancer incidence and mortality. For incidence and mortality data, there are elevations by factors of approximately 15 and 5, respectively, of relative risk for male compared with female breast cancer incidence, the former borderline significant (p = 0.050). In contrast, for incidence and mortality data, there are elevations by factors of approximately 20 and 10, respectively, of female absolute risk compared with male, both statistically significant (p < 0.001). There are no indications of differences between the sexes in age/time-since-exposure/age-at-exposure modifications to the relative or absolute excess risk. The probability of causation of male breast cancer following radiation exposure exceeds by at least a factor of 5 that of many other malignancies. Conclusions: There is evidence of much higher radiation-associated relative risk for male than for female breast cancer, although absolute excess risks for males are much less than for females. However, the small number of male cases and deaths suggests a degree of caution in interpretation of this finding. Citation: Little MP, McElvenny DM. 2017. Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors – differences in excess relative and

Red meat intake may increase the risk of colon cancer in Japanese, a population with relatively low red meat consumption.

PubMed

Takachi, Ribeka; Tsubono, Yoshitaka; Baba, Keisuke; Inoue, Manami; Sasazuki, Shizuka; Iwasaki, Motoki; Tsugane, Shoichiro

2011-01-01

Asian populations have changed from traditional to Westernized diets, with increased red meat intake. They are suggested to be particularly susceptible to the adverse effects of red meat on the development of colorectal cancers, however, few prospective studies of this putative link have been conducted. We examined associations between the consumption of red and processed meat and the risk of subsite-specific colorectal cancer by gender in a large Japanese cohort. During 1995-1998, a validated food frequency questionnaire was administered to 80,658 men and women aged 45-74 years. During 758,116 person-years of follow-up until the end of 2006, 1,145 cases of colorectal cancer were identified. Higher consumption of red meat was significantly associated with a higher risk of colon cancer among women [multivariate hazard ratios (95%CIs) for the highest versus lowest quintiles (HR): 1.48 (1.01, 2.17; trend p=0.03)], as was higher consumption of total meat among men [HR=1.44 (1.06, 1.98; trend p=0.07)]. By site, these positive associations were found for the risk of proximal colon cancer among women and for distal colon cancer among men. No association was found between the consumption of processed meat and risk of either colon or rectal cancer. In conclusion, red meat intake may modestly increase the risk of colon cancer in middle-aged Japanese, although the highest quintile of red meat consumption could be considered moderate by Western standards.

The Japan Lung Cancer Society–Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer

PubMed Central

Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao

2017-01-01

The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1–11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS–JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established. PMID:27609192

Assessment of Japanese stimulant control law offenders using the Addiction Severity Index--Japanese version: comparison with patients in treatment settings.

PubMed

Watanabe, Takashi; Ogai, Yasukazu; Koga, Takehiro; Senoo, Eiichi; Nakamura, Kazuhiko; Mori, Norio; Ikeda, Kazutaka

2009-12-01

The present study assessed problems in Japanese prisoners (inmates) who abused methamphetamine. Fifty-two male inmates were assessed in 2005-2007 using the Addiction Severity Index-Japanese version and compared with 55 male methamphetamine abusers in hospitals and recovery centers. The chi(2) and Mann-Whitney-Wilcoxon tests showed that the inmates had a significantly lower education level, more frequently had full-time jobs, had more experience living with a sexual partner, and more frequently had a history of juvenile delinquency and criminal records than patients. Although psychiatric symptoms, such as depression, anxiety, and hallucinations, were not common among inmates, suicidal behavior and trouble controlling violence were common in both groups.

Application of the COOP/WONCA charts to aged patients with chronic obstructive pulmonary disease: a comparison between Japanese and Chinese populations

PubMed Central

2013-01-01

Background The prevalence of chronic obstructive pulmonary disease (COPD) is similar in Japan and China and is increasing due to high rates of smoking in these countries. Reducing COPD is an important public health issue. The goals of this study were to verify the reliability and validity of the Japanese version of the COOP/WONCA charts, a tool for measuring health status, and to examine the qualitative differences in health status between Japanese and Chinese patients with COPD and between these patients and healthy subjects. Methods From 2008 to 2011, we examined the factors affecting the health status of Japanese and Chinese populations living in six cities. Participants were patients with COPD staged according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (140 Japanese, 201 Chinese) and healthy subjects (243 Japanese, 199 Chinese), all 50 to 79 years old. Health status was measured by using the COOP/WONCA charts, and basic information such as smoking status and medical history was reported by the participants. Results The Japanese and Chinese versions of the COOP/WONCA charts were shown to be reliable and valid by test-retest, comparison with the SF-36 and respiratory symptoms, and correlation of results obtained from patients and their physicians. Stepwise multiple regression analyses demonstrated that “Physical fitness”, “Daily activities”, and “Social activities” were predicted by COPD status and/or respiratory symptoms; “Feelings” by nationality and respiratory symptoms; “Pain” by sex and respiratory symptoms; and “Overall health” by nationality. When the COOP/WONCA scores were stratified by nationality, age, sex, and COPD status, the difference of each score between the patients and healthy subjects was larger for the Chinese subjects than for the Japanese. The physical, psychosocial activities, and pain scores increased significantly as COPD status worsened in Chinese subjects, whereas these scores

Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples.

PubMed

Kiura, Katsuyuki; Yoh, Kiyotaka; Katakami, Nobuyuki; Nogami, Naoyuki; Kasahara, Kazuo; Takahashi, Toshiaki; Okamoto, Isamu; Cantarini, Mireille; Hodge, Rachel; Uchida, Hirohiko

2018-04-01

Osimertinib is a potent, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for EGFR-TKI sensitizing (EGFRm) and T790M resistance mutations. The primary objective of the cytology cohort in the AURA study was to investigate safety and efficacy of osimertinib in pretreated Japanese patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC), with screening EGFR T790M mutation status determined from cytology samples. The cytology cohort was included in the Phase I dose expansion component of the AURA study. Patients were enrolled based on a positive result of T790M by using cytology samples, and received osimertinib 80 mg in tablet form once daily until disease progression or until clinical benefit was no longer observed at the discretion of the investigator. Primary endpoint for efficacy was objective response rate (ORR) by investigator assessment. Twenty-eight Japanese patients were enrolled into the cytology cohort. At data cut-off (February 1, 2016), 12 (43%) were on treatment. Investigator-assessed ORR was 75% (95% confidence interval [CI] 55, 89) and median duration of response was 9.7 months (95% CI 3.8, not calculable [NC]). Median progression-free survival was 8.3 months (95% CI 4.2, NC) and disease control rate was 96% (95% CI 82, 100). The most common all-causality adverse events were paronychia (46%), dry skin (46%), diarrhea (36%) and rash (36%). Osimertinib provided clinical benefit with a manageable safety profile in patients with pretreated EGFR T790M mutation-positive NSCLC whose screening EGFR T790M mutation-positive status was determined from cytology samples. (ClinicalTrials.gov number NCT01802632). © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Risk Assessment Among Prostate Cancer Patients Receiving Primary Androgen Deprivation Therapy

PubMed Central

Cooperberg, Matthew R.; Hinotsu, Shiro; Namiki, Mikio; Ito, Kazuto; Broering, Jeanette; Carroll, Peter R.; Akaza, Hideyuki

2009-01-01

Purpose Prostate cancer epidemiology has been marked overall by a downward risk migration over time. However, in some populations, both in the United States and abroad, many men are still diagnosed with high-risk and/or advanced disease. Primary androgen deprivation therapy (PADT) is frequently offered to these patients, and disease risk prediction is not well-established in this context. We compared risk features between large disease registries from the United States and Japan, and aimed to build and validate a risk prediction model applicable to PADT patients. Methods Data were analyzed from 13,740 men in the United States community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and 19,265 men in the Japan Study Group of Prostate Cancer (J-CaP) database, a national Japanese registry of men receiving androgen deprivation therapy. Risk distribution was compared between the two datasets using three well-described multivariable instruments. A novel instrument (Japan Cancer of the Prostate Risk Assessment [J-CAPRA]) was designed and validated to be specifically applicable to PADT patients, and more relevant to high-risk patients than existing instruments. Results J-CaP patients are more likely than CaPSURE patients to be diagnosed with high-risk features; 43% of J-CaP versus 5% of CaPSURE patients had locally advanced or metastatic disease that could not be stratified with the standard risk assessment tools. J-CAPRA—scored 0 to 12 based on Gleason score, prostate-specific antigen level, and clinical stage—predicts progression-free survival among PADT patients in J-CaP with a c-index of 0.71, and cancer-specific survival among PADT patients in CaPSURE with a c-index of 0.84. Conclusion The novel J-CAPRA is the first risk instrument developed and validated for patients undergoing PADT. It is applicable to those with both localized and advanced disease, and performs well in diverse populations. PMID:19667269

A prospective cohort study of shift work and the risk of death from pancreatic cancer in Japanese men.

PubMed

Lin, Yingsong; Ueda, Junko; Yagyu, Kiyoko; Kurosawa, Michiko; Tamakoshi, Akiko; Kikuchi, Shogo

2013-07-01

There is mounting evidence that shift work involving night work increases cancer risk. We examined the relationship between working rotating shifts and the risk of death from pancreatic cancer on the basis of data from the Japanese Collaborative Cohort Study (JACC Study). The present analysis was restricted to 22,224 men who were 40-65 years of age at baseline (1988-1990) and who reported working full time or were self-employed in the JACC Study. The subjects were followed through 31 December 2009. Information on occupation and lifestyle factors was collected using a self-administered questionnaire. The Cox proportional hazards model was used to estimate the relative risk (RR) and 95% confidence interval (CI) for the risk of death from pancreatic cancer in relation to shift work. During the follow-up period, 127 pancreatic cancer deaths were observed. Overall, we found no statistically significant increase in the risk of death from pancreatic cancer associated with rotating shift work. As compared to day-shift workers, the RRs were 0.83 (95% CI 0.43-1.60) for rotating shift workers and 0.61 (95% CI 0.22-1.60) for fixed night-shift workers, after adjustment for potential confounding factors. The multivariable-adjusted RR was 1.34 (95% CI 0.66-2.75) among rotating shift workers in the analysis restricted to men who reported working full time at baseline. Our data did not support the hypothesis that shift work is significantly associated with the risk of death from pancreatic cancer in this cohort of Japanese men.

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneider, Uwe, E-mail: uwe.schneider@uzh.ch; Walsh, Linda

Purpose: Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend themore » risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Methods: Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. Results: It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin’s disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. Conclusions: The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained

Helicobacter pylori dupA gene is not associated with clinical outcomes in the Japanese population.

PubMed

Nguyen, L T; Uchida, T; Tsukamoto, Y; Kuroda, A; Okimoto, T; Kodama, M; Murakami, K; Fujioka, T; Moriyama, M

2010-08-01

The dupA gene of Helicobacter pylori was suggested to be a risk factor for duodenal ulcer but protective against gastric cancer. The present study aimed to re-examine the role of dupA in H. pylori-infected Japanese patients. We found that dupA status was not associated with any gastroduodenal disease, histological score of chronic gastritis or with the extent of interleukin-8 production from gastric cell lines. These results indicate that dupA is unlikely to be a virulence factor of H. pylori in the Japanese population.

Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

PubMed

Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

2012-01-01

The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PubMed

Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

2017-09-01

Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and

Views of Japanese patients on the advantages and disadvantages of hemodialysis and peritoneal dialysis.

PubMed

Nakamura-Taira, Nanako; Muranaka, Yoshimi; Miwa, Masako; Kin, Seikon; Hirai, Kei

2013-08-01

The preference for dialysis modalities is not well understood in Japan. This study explored the subjective views of Japanese patients undergoing dialysis regarding their treatments. The participants were receiving in-center hemodialysis (CHD) or continuous ambulatory peritoneal dialysis (CAPD). In Study 1, 34 participants (17 CHD and 17 CAPD) were interviewed about the advantages and disadvantages of dialysis modalities. In Study 2, 454 dialysis patients (437 CHD and 17 CAPD) rated the advantages and disadvantages of CHD and CAPD in a cross-sectional survey. Interviews showed that professional care and dialysis-free days were considered as advantages of CHD, while independence, less hospital visits, and flexibility were considered as advantages of CAPD. Disadvantages of CHD included restriction of food and fluids and unpleasant symptoms after each dialysis session. Catheter care was an additional disadvantage of CAPD. Survey showed that the highly ranked advantages were professional care in CHD and less frequent hospital visits in CAPD, while the highly ranked disadvantages were concerns about emergency and time restrictions in CHD, and catheter care and difficulty in soaking in a bath in CAPD. The total scores of advantages and disadvantages showed that CHD patients subjectively rated their own modality better CHD over CAPD, while CAPD patients had the opposite opinion. The results of this study indicate that the factors affecting the decision-making process of Japanese patients are unique to Japanese culture, namely considering the trouble caused to the people around patients (e.g., families, spouses, and/or caregivers).

The impact of breast cancer on employment among Japanese women.

PubMed

Saito, Nobue; Takahashi, Miyako; Sairenchi, Toshimi; Muto, Takashi

2014-01-01

Breast cancer (BC) is a cancer that affects working age women in Japan. The aim of this study was to examine the impact that BC has on the work-related life of Japanese women and identify factors that correlate with job resignation. A cross-sectional Internet survey of cancer survivors in Japan was conducted from December 2011 to February 2012. The questionnaire included questions regarding demographic characteristics, impact of cancer diagnosis and treatment on job resignation and consultation behavior of respondents regarding work-related issues. This study reports results obtained from 105 respondents with BC. The mean age of respondents at diagnosis was 42.5 ± 6.4 years, and the median time since diagnosis was 40 months. Thirty-one respondents (29.5%) lost their jobs, and 12 could not find another job after BC diagnosis. Nearly half of the respondents (47.6%) reported a decrease in personal income after diagnosis. Multiple logistic regression analysis revealed that contract or part time workers were significantly more likely to lose their jobs compared with regular, full time workers (odds ratio, 2.52; 95% confidence interval, 1.39 to 4.55; p<0.001). Seventy-nine respondents (75.2%) consulted someone regarding work-related issues. The most frequently consulted person was the boss at the workplace. Our findings suggest that women with BC experience various job-related problems. In order to create a supportive work environment for BC survivors, focus should be placed on facilitating communication and coordination between BC survivors, healthcare providers and coworkers.

Demographic and lifestyle factors and survival among patients with esophageal and gastric cancer: The Biobank Japan Project.

PubMed

Okada, Emiko; Ukawa, Shigekazu; Nakamura, Koshi; Hirata, Makoto; Nagai, Akiko; Matsuda, Koichi; Ninomiya, Toshiharu; Kiyohara, Yutaka; Muto, Kaori; Kamatani, Yoichiro; Yamagata, Zentaro; Kubo, Michiaki; Nakamura, Yusuke; Tamakoshi, Akiko

2017-03-01

Several studies have evaluated associations between the characteristics of patients with esophageal and gastric cancer and survival, but these associations remain unclear. We described the distribution of demographic and lifestyle factors among patients with esophageal and gastric cancer in Japan, and investigated their potential effects on survival. Between 2003 and 2007, 24- to 95-year-old Japanese patients with esophageal and gastric cancer were enrolled in the BioBank Japan Project. The analysis included 365 patients with esophageal squamous cell carcinoma (ESCC) and 1574 patients with gastric cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using medical institution-stratified Cox proportional hazards models. During follow-up, 213 patients with ESCC (median follow-up, 4.4 years) and 603 patients with gastric cancer (median follow-up, 6.1 years) died. Among patients with ESCC, the mortality risk was higher in ever drinkers versus never drinkers (multivariable HR = 2.37, 95% CI: 1.24, 4.53). Among patients with gastric cancer, the mortality risk was higher in underweight patients versus patients of normal weight (multivariable HR = 1.66, 95% CI: 1.34, 2.05). Compared to patients with gastric cancer with no physical exercise habit, those who exercised ≥3 times/week had a lower mortality risk (multivariate HR = 0.75, 95% CI = 0.61, 0.93). However, lack of stage in many cases was a limitation. Among patients with ESCC, alcohol drinkers have a poor prognosis. Patients with gastric cancer who are underweight also have a poor prognosis, whereas patients with physical exercise habits have a good prognosis. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

A primary tumor of mixed histological type is a novel poor prognostic factor for patients undergoing resection of liver metastasis from gastric cancer.

PubMed

Ikari, Naoki; Taniguchi, Kiyoaki; Serizawa, Akiko; Yamada, Takuji; Yamamoto, Masakazu; Furukawa, Toru

2017-05-01

Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer. We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014. The median overall survival of the patients was 28 months. The 5-year survival rate was 33.9%. Primary tumors of a mixed histological type, and residual tumors during the course of treatment were identified as significant independent poor prognostic factors. Histological evaluation of primary tumors may aid to identify patients suitable for undergoing surgical resection of liver metastasis from gastric cancer. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Smoking prevalence and beliefs on smoking cessation among members of the Japanese Cancer Association in 2006 and 2010.

PubMed

Kumiko, Saika; Tomotaka, Sobue; Masakazu, Nakamura; Akira, Oshima; Keiji, Wakabayashi; Nobuyuki, Hamajima; Yumiko, Mochizuki; Rie, Yamaguchi; Kazuo, Tajima

2012-08-01

Smoking is a significant contributing factor to disease-related deaths worldwide. Members of the Japanese Cancer Association (JCA) can play a leading role in helping people to live tobacco-free through social action. In 2010, this study assessed smoking prevalence among JCA members and their attitudes toward smoking, smoking cessation, and their responsibilities. Results of the 2010 survey were compared with those of a 2006 survey. Final response rates were 60.8% in the 2006 survey and 47.4% in the 2010 survey, and the current smoking rates were 9.0% and 5.3%, respectively. Regarding concern by current smokers over smoking cessation, the percentage of smokers who were ready to quit smoking within the next month increased from 4.9% to 6.3% between 2006 and 2010. Most JCA members agreed with antismoking actions such as smoking bans in all workplaces, public places, or while walking in the street, regulation restricting the sale and distribution of tobacco to children, tobacco education at school, use of tobacco tax for health, provision of information on tobacco, and smoking cessation support. Approximately 30% of responders disagreed on actions to raise the price of tobacco, regulations restricting the sale of tobacco, health warnings on tobacco packaging, bans on tobacco advertisement, and antismoking campaigns. Barriers to smoking cessation interventions identified were physician's time required to provide interventions, resistance of patients to smoking cessation advice, and lack of education on tobacco control. Not only antismoking actions but also support of smokers by health professionals through adequate education on smoking cessation treatment is needed in the future. © 2012 Japanese Cancer Association.

Assessment of Japanese Stimulant Control Law Offenders Using the Addiction Severity Index—Japanese Version: Comparison with Patients in Treatment Settings

PubMed Central

Watanabe, Takashi; Ogai, Yasukazu; Koga, Takehiro; Senoo, Eiichi; Nakamura, Kazuhiko; Mori, Norio; Ikeda, Kazutaka

2009-01-01

The present study assessed problems in Japanese prisoners (inmates) who abused methamphetamine. Fifty-two male inmates were assessed in 2005–2007 using the Addiction Severity Index-Japanese version and compared with 55 male methamphetamine abusers in hospitals and recovery centers. The χ2 and Mann-Whitney-Wilcoxon tests showed that the inmates had a significantly lower education level, more frequently had full-time jobs, had more experience living with a sexual partner, and more frequently had a history of juvenile delinquency and criminal records than patients. Although psychiatric symptoms, such as depression, anxiety, and hallucinations, were not common among inmates, suicidal behavior and trouble controlling violence were common in both groups. PMID:20049245

Assertions of Japanese Websites for and Against Cancer Screening: a Text Mining Analysis

PubMed

Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

2017-04-01

Background: Cancer screening rates are lower in Japan than in Western countries such as the United States and the United Kingdom. While health professionals publish pro-cancer-screening messages online to encourage proactive seeking for screening, anti-screening activists use the same medium to warn readers against following guidelines. Contents of pro- and anti-cancer-screening sites may contribute to readers’ acceptance of one or the other position. We aimed to use a text-mining method to examine frequently appearing contents on sites for and against cancer screening. Methods: We conducted online searches in December 2016 using two major search engines in Japan (Google Japan and Yahoo! Japan). Targeted websites were classified as “pro”, “anti”, or “neutral” depending on their claims, with the author(s) classified as “health professional”, “mass media”, or “layperson”. Text-mining analyses were conducted, and statistical analysis was performed using the chi-square test. Results: Of the 169 websites analyzed, the top-three most frequently appearing content topics in pro sites were reducing mortality via cancer screening, benefits of early detection, and recommendations for obtaining detailed examination. The top three most frequent in anti-sites were harm from radiation exposure, non-efficacy of cancer screening, and lack of necessity of early detection. Anti-sites also frequently referred to a well-known Japanese radiologist, Makoto Kondo, who rejects the standard forms of cancer care. Conclusion: Our findings should enable authors of pro-cancer-screening sites to write to counter misleading anti-cancer-screening messages and facilitate dissemination of accurate information. Creative Commons Attribution License

Validity and reliability of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Japanese patients with bipolar disorder.

PubMed

Toyoshima, Kuniyoshi; Fujii, Yutaka; Mitsui, Nobuyuki; Kako, Yuki; Asakura, Satoshi; Martinez-Aran, Anabel; Vieta, Eduard; Kusumi, Ichiro

2017-08-01

In Japan, there are currently no reliable rating scales for the evaluation of subjective cognitive impairment in patients with bipolar disorder. We studied the relationship between the Japanese version of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and objective cognitive assessments in patients with bipolar disorder. We further assessed the reliability and validity of the COBRA. Forty-one patients, aged 16-64, in a remission period of bipolar disorder were recruited from Hokkaido University Hospital in Sapporo, Japan. The COBRA (Japanese version) and Frankfurt Complaint Questionnaire (FCQ), the gold standard in subjective cognitive assessment, were administered. A battery of neuropsychological tests was employed to measure objective cognitive impairment. Correlations among the COBRA, FCQ, and neuropsychological tests were determined using Spearman's correlation coefficient. The Japanese version of the COBRA had high internal consistency, good retest reliability, and concurrent validity-as indicated by a strong correlation with the FCQ. A significant correlation was also observed between the COBRA and objective cognitive measurements of processing speed. These findings are the first to demonstrate that the Japanese version of the COBRA may be clinically useful as a subjective cognitive impairment rating scale in Japanese patients with bipolar disorder. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Risk factors for parastomal hernia in Japanese patients with permanent colostomy.

PubMed

Funahashi, Kimihiko; Suzuki, Takayuki; Nagashima, Yasuo; Matsuda, Satoshi; Koike, Junichi; Shiokawa, Hiroyuki; Ushigome, Mitsunori; Arai, Kenichiro; Kaneko, Tomoaki; Kurihara, Akiharu; Kaneko, Hironori

2014-08-01

Although the definitive risk factors for parastomal hernia development remain unclear, potential contributing factors have been reported from Western countries. The aim of this study was to identify the risk factors for parastomal hernia in Japanese patients with permanent colostomies. All patients who received abdominoperineal resection or total pelvic exenteration at our institution between December 2004 and December 2011 were reviewed. Patient-related, operation-related and postoperative variables were evaluated, in both univariate and multivariate analyses, to identify the risk factors for parastomal hernia formation. Of the 80 patients who underwent colostomy, 22 (27.5 %) developed a parastomal hernia during a median follow-up period of 953 days (range 15-2792 days). Hernia development was significantly associated with increasing patient age and body mass index, a laparoscopic surgical approach and the transperitoneal route of colostomy formation. In the multivariate analysis, the body mass index (p = 0.022), the laparoscopic approach (p = 0.043) and transperitoneal stoma creation (p = 0.021) retained statistical significance. Our findings in Japanese ostomates match those from Western countries: a higher body mass index, the use of a laparoscopic approach and a transperitoneal colostomy are significant independent risk factors for parastomal hernia formation. The precise role of the stoma creation route remains unclear.

Macrovascular Complications and Prevalence of Urgency Incontinence in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

PubMed

Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Kanzaki, Sayaka; Maruyama, Koutatsu; Tanaka, Keiko; Ueda, Teruhisa; Senba, Hidenori; Torisu, Masamoto; Minami, Hisaka; Onji, Morikazu; Tanigawa, Takeshi; Matsuura, Bunzo; Hiasa, Yoichi; Miyake, Yoshihiro

2017-01-01

Objective Macrovascular diseases and urgency incontinence are common among Japanese patients with type 2 diabetes mellitus. However, little evidence exists regarding the association between stroke and urgency incontinence among patients with type 2 diabetes mellitus. We examined the associations between macrovascular complications and urgency incontinence among Japanese patients with type 2 diabetes mellitus. Methods The study subjects were 818 Japanese patients with type 2 diabetes mellitus. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate?" We adjusted our analyses for sex, age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, glycated hemoglobin, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy. Results The prevalence of urgency incontinence was 9.2%. Stroke was independently positively associated with urgency incontinence, with an adjusted odds ratio of 2.34 (95% confidence interval: 1.03-4.95). The associations between ischemic heart disease or peripheral artery disease and the prevalence of urgency incontinence were not significant. Conclusion In Japanese patients with type 2 diabetes mellitus, stroke, but not ischemic heart diseases or peripheral artery disease, was independently positively associated with urgency incontinence.

Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R.

1994-09-01

Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 genemore » region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.« less

Cross-cultural comparison of the Scoliosis Research Society Outcomes Instrument between American and Japanese idiopathic scoliosis patients: are there differences?

PubMed

Watanabe, Kei; Lenke, Lawrence G; Bridwell, Keith H; Hasegawa, Kazuhiro; Hirano, Toru; Endo, Naoto; Cheh, Gene; Kim, Yongjung J; Hensley, Marsha; Stobbs, Georgia; Koester, Linda

2007-11-15

A comparative study. To report a preliminary evaluation of the Scoliosis Research Society Outcomes Instrument (SRS-24) and determine whether differences in baseline scores exist between American and Japanese patients with idiopathic scoliosis. Because the SRS outcomes instrument was primarily introduced for the American population, baseline scores in the Japanese population might differ from the American population. A comparative study using the SRS instrument between American and Japanese patients with idiopathic scoliosis has not been reported. Two comparable groups of 100 idiopathic scoliosis patients before spinal fusion were separated into American (A) and Japanese (J). There were no statistically significant differences between the groups for gender (A: 9 men/91 women vs. J: 13 men/87 women), age (A: 15.0 +/- 2.4 vs. J: 14.9 +/- 3.8), main curve location (A: 77 thoracic/23 lumbar, J: 76 thoracic/24 lumbar), main curve Cobb angle (A: 50.5 +/- 5.2 vs. J: 51.1 +/- 8.7), and thoracic kyphosis (A: 20.9 +/- 14.3 vs. J: 19.9 +/- 12.1) (P > 0.05, for all comparisons). Patients were evaluated using the first section of the SRS-24 which was divided into 4 domains: total pain, general self-image, general function, and activity. SRS-24 scores were statistical compared in individual domains and questions using the Mann-Whitney U test. American patients had significantly lower scores in pain (P < 0.0001, A: 3.7 +/- 0.8 vs. J: 4.3 +/- 0.4), function (P < 0.01, A: 3.9 +/- 0.6 vs. J: 4.2 +/- 0.5), and activity (P < 0.0001, A: 4.5 +/- 0.8 vs. J: 4.9 +/- 0.3) domains compared with Japanese patients. Japanese patients had significantly lower scores in the self-image (P < 0.0001, A: 4.0 +/- 0.7 vs. J: 3.5 +/- 0.5) domain. With regard to individual questions, there were significant differences in the scores between the 2 groups for all questions except 5 and 13 (P < 0.05, for all comparisons). SRS-24 scores in the Japanese idiopathic scoliosis population differed from that of the

Adverse drug event profile associated with pregabalin among patients with and without cancer: analysis of a spontaneous reporting database.

PubMed

Kose, Eiji

2018-03-25

Pregabalin is used for the relief of neuropathic pain in patients with and without cancer. However, no report has examined whether there is a difference in the adverse drug event (ADE) profile of pregabalin in each context. We aimed to establish whether pregabalin's ADE profile was different between patients with and without cancer. This study was based on the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database. Reports obtained from the JADER database were analysed from April 2004 to December 2016 for ADEs, using reporting odds ratios (RORs), a method of disproportionality analysis. We evaluated the association between the RORs and ADEs of pregabalin and compared the age, dosage and time at which ADEs occurred in patients with and without cancer. The primary outcome was RORs. Secondary outcomes were expression age and time-to-onset of ADE among patients with and without cancer. In total, 426 216 reports from the JADER database were analysed. The major side effects associated with pregabalin among both patient groups were interstitial pneumonia, renal failure, liver failure, altered consciousness, heart failure and rhabdomyolysis. The pregabalin dose was significantly higher in patients with cancer than in those without cancer. Furthermore, the times to reporting of interstitial pneumonia, altered consciousness and liver failure were significantly shorter in patients with cancer than in those without cancer. The ADE profiles of pregabalin were broadly similar among patients with and without cancer, but time-to-onset and type of some ADEs may be different. © 2018 John Wiley & Sons Ltd.

Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer.

PubMed

Satoh, Taroh; Yamada, Yasuhide; Muro, Kei; Hayashi, Hidetoshi; Shimada, Yasuhiro; Takahari, Daisuke; Taku, Keisei; Nakajima, Takako Eguchi; Shi, Xiaojin; Brown, Kathryn H; Boku, Narikazu

2012-02-01

The primary objective of this Phase I study was to assess the safety and tolerability of the vascular endothelial growth factor signalling inhibitor cediranib in combination with cisplatin plus an oral fluoropyrimidine, in Japanese patients with previously untreated advanced gastric cancer. Patients received continuous, once-daily oral doses of cediranib 20 mg in combination with either cisplatin (60 mg/m(2) iv day 1) plus S-1 (40-60 mg bid, days 1-21) every 5 weeks for a maximum of eight cycles [Arm A]; or cisplatin (80 mg/m(2) iv, day 1) plus capecitabine (1,000 mg/m(2) bid, days 1-14) every 3 weeks for a maximum of six cycles [Arm B]. In both arms, the assessment period for dose-limiting toxicities (DLTs) was the first 21 days of cycle 1. Fourteen patients (Arm A, n = 6; Arm B, n = 8) were enrolled and received at least one dose of cediranib. One patient in each arm experienced a DLT (Arm A; decreased appetite, grade 3; Arm B, decreased appetite, fatigue and hyponatraemia, all grade 3). Overall, the most common adverse events were decreased appetite, fatigue and nausea (all n = 13 [92.9%]). Preliminary efficacy evaluation showed one confirmed (Arm A) and three unconfirmed (Arm A, n = 1; Arm B, n = 2) partial responses that were ongoing at data cut-off. Cediranib 20 mg/day in combination with cisplatin and S-1 or capecitabine was tolerable, with no new toxicities identified, and showed preliminary evidence of antitumour activity.

Insulin, insulin-like growth factor-I and breast cancer risk in Japanese women.

PubMed

Hirose, Kaoru; Toyama, Tatsuya; Iwata, Hiroji; Takezaki, Toshiro; Hamajima, Nobuyuki; Tajima, Kazuo

2003-01-01

To evaluate the effects of glucose metabolism related factors, such as insulin and insulin-like growth-factors (IGFs), on breast cancer development among Japanese women, we conducted a case-referent study comparing 187 women presenting with operable breast cancer and 190 women of the same age having no breast cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were determined by multiple logistic regression analysis. In the present study, no association in risk was observed with increasing levels of IGF-I or IGF binding protein-3 (IGFBP-3), before or after adjustment these factors. However, a suggestion of a positive association of an increased breast cancer risk was evident in postmenopausal women with elevated plasma insulin levels, particularly those with BMI>23.07. The OR for plasma insulin in the top tertile was 4.48 (95%CI:1.07-18.7) compared to the bottom tertile. For C-peptide, there was a similar positive association, with a corresponding OR of 2.28. In addition, we observed strong links between plasma insulin, C-peptide levels and estrogen receptor (ER) negative breast cancer, with ORs of 2.79(95%CI:1.09-7.16), and 2.52 (95%CI:0.91-6.97) respectively, for the top versus bottom tertiles. In conclusion, the present study suggested that plasma insulin level is a predictor of postmenopausal breast cancer in obese women and ER negative breast cancer. Additional studies are needed to clarify the role of glucose metabolism pathways in breast cancer development and interaction of IGF systems.

Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study.

PubMed

Yamanaka, Hisashi; Tanaka, Yoshiya; Takeuchi, Tsutomu; Sugiyama, Naonobu; Yuasa, Hirotoshi; Toyoizumi, Shigeyuki; Morishima, Yosuke; Hirose, Tomohiro; Zwillich, Samuel

2016-01-28

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study. A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9 %) experienced adverse events; the majority of which (97.8 %) were of mild or moderate severity. The two most common treatment-emergent adverse events were nasopharyngitis (n = 293, 60.3 %) and herpes zoster (n = 94, 19.3 %). For all tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib

Comparison of Practices, Knowledge, Confidence, and Attitude toward Oral Cancer among Oral Health Professionals between Japan and Australia.

PubMed

Haresaku, Satoru; Makino, Michiko; Sugiyama, Seiichi; Naito, Toru; Mariño, Rodrigo Jose

2018-04-01

The purpose of this study was to investigate the practices, knowledge, confidence, and attitude toward oral cancer among Japanese oral health professionals (J-OHPs) and to identify Japanese-specific problems in oral cancer practices by comparing them between Japan and Australia. A questionnaire survey regarding oral cancer practices among Australian oral health professionals (Au-OHPs) was conducted in Australia in 2014-2015. The questionnaire was translated into Japanese, and a Web-based questionnaire survey was conducted among 131 Japanese dentists (J-Dentists) and 131 dental hygienists (J-DHs) in 2016. To compare the J-OHPs' findings with the Au-OHPs', the data of Australian dentists (Au-dentists) and Australian dental hygienists (Au-DHs) were extracted from the Australian survey. Those findings were then compared via a statistical analysis. Eighty-two J-Dentists, 55 J-DHs, 214 Au-Dentists, and 45 Au-DHs participated in this study. Only 34.1 % of J-Dentists and 36.4 % of J-DHs performed oral cancer screenings on their patients; J-OHPs were significantly less likely to perform them than Au-OHPs. The level of knowledge and confidence regarding oral cancer among JOHPs were significantly lower than among Au-OHPs. About 90 % of J-OHPs felt that they needed additional training in oral cancer practices. Less than 40 % of J-OHPs performed oral cancer screenings in their patients. The low level of knowledge and confidence regarding oral cancer among JOHPs may contribute to their low performance of oral cancer practices. Therefore, further education and training programs for oral cancer practices should be provided to Japanese OHPs for the prevention and early detection of oral cancer.

Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

PubMed

Yamazaki, Naoya; Uhara, Hisashi; Wada, Hidefumi; Matsuda, Kenji; Yamamoto, Keiko; Shimamoto, Takashi; Kiyohara, Yoshio

2016-10-01

In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 μg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial. © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Helping cancer patients across the care continuum: the navigation program at the Queen's Medical Center.

PubMed

Allison, Amanda L; Ishihara-Wong, Debra D M; Domingo, Jermy B; Nishioka, Jocelyn; Wilburn, Andrea; Tsark, JoAnn U; Braun, Kathryn L

2013-04-01

Research suggests that cancer patient navigation improves care, but few reports describe the variety of patients managed by a hospital-based navigation program. Differences in navigated patients by the intensity (low, medium, or high) of navigation services they received were examined. The 835 clients seen by the navigators in a hospital-based cancer center were first stratified by quarter and by four ethnic groups. Randomized selection from each group assured there would be equal representation for analysis of Hawaiians, Filipinos, Japanese, and Whites and even numbers over all time intervals. Five professionals extracted data from these case records on demographics, type/stage of cancer, diagnosis and treatment dates, barriers, and navigator actions. Clients had breast (30.0%), lung (15.8%), esophageal (6.7%), colon (5.8%), ovarian (4.2%), prostate (3.3%), and other cancers (34.2%). The median number of actions taken on behalf of a client was 4 (range 1-83), and the median number of days a case was open was 14 (range 1-216). High intensity cases (those receiving more assistance over longer periods of time) were more likely than low-intensity cases to need help with education and reassurance, transportation, care coordination, and covering costs. Although there were no demographic differences across intensity groups, Neighbor Island patients from Hawai'i, Maui, Moloka'i, Lana'i and Kaua'i were more likely to need help with arranging travel, care coordination, and costs associated with getting treatment (all at P=.05), and patients on public insurance were more likely to have stage 4 cancer (P=.001) and to need help with costs (P=.006). Findings suggest that this hospital-based navigation program is filling a real need of patients across the cancer care continuum. A triage protocol and an integrated data capture system could help improve the targeting and documentation of cancer patient navigation services.

Familial clustering in subgroups of gastric cancer stratified by histology, age group and location.

PubMed

Eto, K; Ohyama, S; Yamaguchi, T; Wada, T; Suzuki, Y; Mitsumori, N; Kashiwagi, H; Anazawa, S; Yanaga, K; Urashima, M

2006-09-01

To assess the risk of gastric cancer in a Japanese patient population with the disease by stratification with histology, age, tumour location and the association with family history of gastric or non-gastric tumours. A retrospective analysis of 1400 consecutive patients with gastric cancer and 13,467 age- and gender-matched controls from a pre-recorded database using conditional logistic regression models. Young patients (< or = 43 years of age) with gastric cancer of intestinal type had a strong association with family history of gastric cancer in first degree-relatives (OR=12.5). Moreover, when a history of gastric cancer was observed in both parents, there was an increased risk of gastric cancer intestinal type (OR=7.8), more commonly in the proximal and mid-stomach. In contrast, there was an increased risk of diffuse-type cancer when both parents suffered non-gastric cancers (OR=2.1). These data suggest that the degree of familial clustering differ in gastric cancer subgroups stratified by histology, age, and stomach location in this Japanese population.

The experience of Japanese adolescents and young adults after losing siblings to childhood cancer: three types of narratives.

PubMed

Kamibeppu, Kiyoko; Sato, Iori; Hoshi, Yasutaka

2015-01-01

The aim of this study was to describe Japanese adolescents' and young adults' experiences after losing siblings to childhood cancer. A conceptual framework of the transition and analysis based on narrative method were adopted from qualitative data from 6 Japanese adolescents and young adults who had lost their siblings to childhood cancer. It was revealed that the participants' psychological experience after the sibling's death was directed by their perceptions of their mothers' responses to bereavement. We also found that the psychological distance between participants and their mothers could be an important factor in enabling transition into mourning and in orienting the lost sibling in their mind. The stories obtained from these 6 participants were categorized into the following 3 types of narratives: "Mother in another world and the sibling who became a god," "Return of the loving mother and the sibling as savior," and "The poor mother and the sibling who needs my help to carry on her legacy." This typology will serve as a framework for grief care and future research. © 2014 by Association of Pediatric Hematology/Oncology Nurses.

A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours

PubMed Central

Nakagawa, K; Kudoh, S; Matsui, K; Negoro, S; Yamamoto, N; Latz, J E; Adachi, S; Fukuoka, M

2006-01-01

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB12) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0–2, and adequate organ function. Pemetrexed from 300 to 1200 mg m−2 was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB12. Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m−2, and infection and skin rash at 1200 mg m−2. The MTD/RD were determined to be 1200/1000 mg m−2, respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1200/1000 mg m−2, respectively, that is, a higher RD than without FA/VB12 (500 mg m−2). Pemetrexed with FA/VB12 showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study. PMID:16940981

Earthquake Preparedness Among Japanese Hemodialysis Patients in Prefectures Heavily Damaged by the 2011 Great East Japan Earthquake.

PubMed

Sugisawa, Hidehiro; Shimizu, Yumiko; Kumagai, Tamaki; Sugisaki, Hiroaki; Ohira, Seiji; Shinoda, Toshio

2017-08-01

The purpose of this study was to explore the factors related to earthquake preparedness in Japanese hemodialysis patients. We focused on three aspects of the related factors: health condition factors, social factors, and the experience of disasters. A mail survey of all the members of the Japan Association of Kidney Disease Patients in three Japanese prefectures (N = 4085) was conducted in March, 2013. We obtained 1841 valid responses for analysis. The health factors covered were: activities of daily living (ADL), mental distress, primary renal diseases, and the duration of dialysis. The social factors were: socioeconomic status, family structure, informational social support, and the provision of information regarding earthquake preparedness from dialysis facilities. The results show that the average percentage of participants that had met each criterion of earthquake preparedness in 2013 was 53%. Hemodialysis patients without disabled ADL, without mental distress, and requiring longer periods of dialysis, were likely to meet more of the earthquake preparedness criteria. Hemodialysis patients who had received informational social support from family or friends, had lived with spouse and children in comparison to living alone, and had obtained information regarding earthquake preparedness from dialysis facilities, were also likely to meet more of the earthquake preparedness criteria. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Preferences of advanced cancer patients for communication on anticancer treatment cessation and the transition to palliative care.

PubMed

Umezawa, Shino; Fujimori, Maiko; Matsushima, Eisuke; Kinoshita, Hiroya; Uchitomi, Yosuke

2015-12-01

The objective of this study was to clarify the communication preferences of patients with advanced cancer regarding discussions about ending anticancer treatment and transitioning to palliative care and to explore the variables associated with those preferences. Participants were 106 Japanese patients with cancer who had been informed at least 1 week earlier about the cessation of their anticancer treatment. They completed a survey measuring their preferences for communication about ending anticancer treatment and transitioning to palliative care as well as their demographic characteristics. Medical records were also examined to investigate medical characteristics. Results of the descriptive analysis indicated that patients strongly preferred their physicians to listen to their distress and concerns (96%), to assure them that their painful symptoms would be controlled (97.1%), and to explain the status of their illness and the physical symptoms that would likely occur in the future (95.1%). Multiple regression analyses identified the factors associated with these preferences: telling patients to prepare mentally and informing them of their expected life expectancy were associated with cancer site; sustaining hope was associated with cancer site and children; and empathic paternalism was associated with duration since cancer diagnosis. The majority of patients preferred their physicians to be realistic about their likely future and wanted to be reassured that their painful symptoms would be controlled. For patients with cancer at certain sites, those with children, and those more recently diagnosed, physicians should communicate carefully and actively by providing information on life expectancy and mental preparation, sustaining hope, and behaving with empathic paternalism. © 2015 American Cancer Society.

Clinical outcomes of radiotherapy for esophageal cancer between 2004 and 2008: the second survey of the Japanese Radiation Oncology Study Group (JROSG).

PubMed

Nishimura, Yasumasa; Jingu, Keiichi; Itasaka, Satoshi; Negoro, Yoshiharu; Murakami, Yuji; Karasawa, Katsuyuki; Kawaguchi, Gen; Isohashi, Fumiaki; Kobayashi, Masao; Itoh, Yoshiyuki; Ariga, Takuro

2016-02-01

This second questionnaire-based survey was performed to determine the clinical results of definitive esophageal cancer treatment with radiotherapy (RT) or chemoradiotherapy (CRT) between 2004 and 2008. Clinical results of definitive RT for patients were collected from major Japanese institutions. Patients were classified into three groups: (A) stage I, (B) resectable stages II-III, (C) unresectable stages III-IVA. For group A, all patients treated with RT alone or CRT were included. For groups B and C, only those treated with CRT were included. In total, 990 patients (group A 259, group B 333, group C 398 patients) were included from 11 institutions. In group A, 199 patients (78 %) were treated with CRT, and 60 patients (23 %) received RT alone. In groups B and C, 420 patients (57 %) were treated with full-dose cisplatin/5-FU, and 181 patients (25 %) with low-dose protracted-infusion cisplatin/5-FU. The median and range of the 5-year overall survival rate were 73 % (40-94 %) for group A, 40 % (0-57 %) for group B, and 18 % (6-26 %) for group C, respectively. The 5-year overall survival rates were consistently good for five high-volume centers where more than 20 patients/year with esophageal cancer were treated definitively as compared with the remaining six medium-volume centers (5-15 patients/year). The median and range of the incidence of grade ≥3 late toxicities were 10 % and 6-22 %, respectively. A wide disparity in 5-year overall survival rates among the institutions was still apparent in the second survey for groups A and B.

Comparable pharmacodynamics, efficacy, and safety of linagliptin 5 mg among Japanese, Asian and white patients with type 2 diabetes.

PubMed

Sarashina, Akiko; Friedrich, Christian; Crowe, Susanne; Patel, Sanjay; Graefe-Mody, Ulrike; Hayashi, Naoyuki; Horie, Yoshiharu

2016-09-01

The efficacy and safety of drugs can vary between different races or ethnic populations because of differences in the relationship of dose to exposure, pharmacodynamic response or clinical efficacy and safety. In the present post-hoc analysis, we assessed the influence of race on the pharmacokinetics, pharmacodynamics, efficacy and safety of monotherapy with the dipeptidyl peptidase-4 inhibitor, linagliptin, in patients with type 2 diabetes enrolled in two comparable, previously reported randomized phase III trials. Study 1 (with a 12-week placebo-controlled phase) recruited Japanese patients only (linagliptin, n = 159; placebo, n = 80); study 2 (24-week trial) enrolled Asian (non-Japanese; linagliptin, n = 156; placebo, n = 76) and white patients (linagliptin, n = 180; placebo, n = 90). Linagliptin trough concentrations were equivalent across study and race groups, and were higher than half-maximal inhibitory concentration, resulting in dipeptidyl peptidase-4 inhibition >80% at trough. Linagliptin inhibited plasma dipeptidyl peptidase-4 activity to a similar degree in study 1 and study 2. Linagliptin reduced fasting plasma glucose concentrations by a similar magnitude across groups, leading to clinically relevant reductions in glycated hemoglobin in all groups. Glycated hemoglobin levels decreased to a slightly greater extent in study 1 (Japanese) and in Asian (non-Japanese) patients from study 2. Linagliptin had a favorable safety profile in each race group. Trough exposure, pharmacodynamic response, and efficacy and safety of linagliptin monotherapy were comparable among Japanese, Asian (non-Japanese) and white patients, confirming that the recommended 5-mg once-daily dose of linagliptin is appropriate for use among different race groups. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil.

PubMed

Domingos, João Américo; Soares, Luana Silva; Bandeira, Larissa M; Bonin, Camila Mareti; Vicente, Ana C P; Zanella, Louise; Puga, Marco Antonio Moreira; Tozetti, Inês Aparecida; Motta-Castro, Ana Rita Coimbra; da Cunha, Rivaldo Venâncio

2017-01-01

The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL) in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs). The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs) and 18 healthy controls (HCs) in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host genetic

Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil

PubMed Central

Domingos, João Américo; Soares, Luana Silva; Bandeira, Larissa M.; Bonin, Camila Mareti; Vicente, Ana C. P.; Zanella, Louise; Puga, Marco Antonio Moreira; Tozetti, Inês Aparecida; Motta-Castro, Ana Rita Coimbra; da Cunha, Rivaldo Venâncio

2017-01-01

The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL) in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs). The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs) and 18 healthy controls (HCs) in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host genetic

A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

PubMed

Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

2015-03-01

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

Lower urinary tract symptoms and erectile dysfunction associated with depression among Japanese patients with late-onset hypogonadism symptoms.

PubMed

Takao, Tetsuya; Tsujimura, Akira; Okuda, Hidenobu; Yamamoto, Keisuke; Fukuhara, Shinichiro; Matsuoka, Yasuhiro; Miyagawa, Yasushi; Nonomura, Norio; Okuyama, Akihiko

2011-06-01

The aim of this study was to investigate the relation between lower urinary tract symptoms (LUTS), erectile dysfunction (ED) and depression in Japanese patients with late-onset hypogonadism (LOH) symptoms. The study comprised 87 Japanese patients with LOH symptoms (>27 points on the Aging Males Symptoms Scale). Thirty-four patients were diagnosed as having depression and the remaining 53 patients were diagnosed as not having depression by the Mini International Neuropsychiatric Interview. We compared the International Index of Erectile Function (IIEF) 5, International Prostate Symptom Score (IPSS), IPSS quality-of-life (QOL) index, King's Health Questionnaire (KHQ), endocrinological data, and free uroflow study between depression and non-depression patients and performed multiple logistic regression analysis. IIEF5 scores of depression patients were significantly lower than those of non-depression patients. In KHQ, only the category of general health perceptions was significantly higher in depression patients than non-depression patients. However, IPSS, QOL index, and endocrinological and uroflowmetric data showed no significant difference between the groups. Multiple logistic regression analysis revealed moderate and severe ED to be risk factors for depression. However, LUTS are not related to depression. Moderate and severe ED is correlated with depression, whereas LUTS are not related to depression in Japanese LOH patients.

Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies.

PubMed

Nishikawa, Masakatsu; Isshiki, Takaaki; Kimura, Takeshi; Ogawa, Hisao; Yokoi, Hiroyoshi; Miyazaki, Shunichi; Ikeda, Yasuo; Nakamura, Masato; Tanaka, Yuko; Saito, Shigeru

2017-04-01

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.Trial registration numbers: JapicCTI-101339 and JapicCTI-111550.

Prognosis after surgical treatment for pancreatic cancer in patients aged 80 years or older: a multicenter study.

PubMed

Sho, Masayuki; Murakami, Yoshiaki; Kawai, Manabu; Motoi, Fuyuhiko; Satoi, Sohei; Matsumoto, Ippei; Honda, Goro; Uemura, Kenichiro; Yanagimoto, Hiroaki; Kurata, Masanao; Akahori, Takahiro; Kinoshita, Shoichi; Nagai, Minako; Nishiwada, Satoshi; Fukumoto, Takumi; Unno, Michiaki; Yamaue, Hiroki; Nakajima, Yoshiyuki

2016-03-01

The optimal therapeutic strategy for very elderly pancreatic cancer patients remains to be determined. The aim of this study was to clarify the role of pancreatic resection in patients 80 years of age or older. A retrospective multicenter analysis of 1401 patients who had undergone pancreatic resection for pancreatic cancer was performed. The patients aged ≥ 80 years (n = 99) were compared with a control group <80 years of age (n = 1302). There were no significant differences in the postoperative complications and mortality between the two groups. However, the prognosis of octogenarians was poorer than that of younger patients for both resectable and borderline resectable tumors. Importantly, there were few long-term survivors in the elderly group, especially among those with borderline resectable pancreatic cancer. A multivariate analysis of the prognostic factors in the very elderly patients indicated that the completion of adjuvant chemotherapy was the only significant factor. In addition, preoperative albumin level was the only independent risk factor for a failure to complete adjuvant chemotherapy. This study demonstrates that the postoperative prognosis in octogenarian patients was not good as that in younger patients possibly due to less frequent completion of adjuvant chemotherapy. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Human Papillomavirus Infection and Its Possible Correlation with p63 Expression in Cervical Cancer in Japan, Mongolia, and Myanmar

PubMed Central

Shirendeb, Ulziibat; Hishikawa, Yoshitaka; Moriyama, Shingo; Win, Ne; Thu, Minn Minn Myint; Mar, Khin Swe; Khatanbaatar, Gerlee; Masuzaki, Hideaki; Koji, Takehiko

2009-01-01

Although human papillomavirus (HPV) 16 is the cause of cervical cancer in most countries including Japan, the involvement of cervical cancer with HPV types in Mongolian and Myanmar populations is largely unknown. We examined the expression of HPV in formalin-fixed and paraffin-embedded cervical tissues from 40 Japanese, 32 Mongolian, and 30 Myanmar cervical cancer patients. We performed immunohistochemistry using anti-HPV16 and anti-HPV 1, 6, 11, 16, 18 and 31 cocktail and then correlated it with the expression of Ki-67 and p63. HPV 16 was detected in 72%, 65% and 50% of Japanese, Mongolian and Myanmar cervical cancer patients, respectively, whereas 5 (13%) of the 40 patients, 8 (25%) of the 32 patients and 7 (23%) of the 30 patients in HPV 16-negative cancers were positive for other HPV types included in the cocktail, respectively. Ki-67 labeling index (LI) as well as p63 LI was significantly higher in HPV 16-positive patients than in HPV 16-negative ones in the Japanese and Mongolian samples. p63 expression was significantly associated with stage III and IV in Japan and Mongolia. These findings suggest that HPV 16 may be associated with cell proliferative activity and tumor progression, possibly depending upon the expression of p63 in the cervical cancer. In addition, immunohistochemical detection for distinguishing the type of HPV may also be useful for cervical cancer in the clinical setting. PMID:20126571

Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.

PubMed

Marks, Leonard S; Kojima, Munekado; Demarzo, Angelo; Heber, David; Bostwick, David G; Qian, Junqi; Dorey, Frederick J; Veltri, Robert W; Mohler, James L; Partin, Alan W

2004-10-01

To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues. The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence Ca

Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

PubMed

Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Tsuji, Ichiro; Tamakoshi, Akiko; Matsuo, Keitaro; Wakai, Kenji; Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka

2014-03-01

We reviewed epidemiological studies of soy intake and breast cancer among Japanese women. This report is one among a series of articles by our research group, which is evaluating the existing evidence concerning the association between health-related lifestyles and cancer. Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility. Five cohort studies and six case-control studies were identified. Among the cohort studies, two studies observed that total soy intake (in terms of total amounts of soy foods or soy isoflavones) was associated with a moderate (0.5 ≤ relative risk ≤ 0.67 with statistical significance) or strong (relative risk ≤ 0.5 with statistical significance) risk reduction of breast cancer in postmenopausal women. Among the case-control studies, two studies reported a weak (0.67 ≤ odds ratio ≤ 1.5 with statistical significance or 0.5 ≤ odds ratio ≤ 0.67 without statistical significance) inverse association between total soy intake and the risk of breast cancer. In the former, this association was observed in all women combined-premenopausal and postmenopausal women-but in the latter, the association was confined to postmenopausal women. The associations of intakes of individual soy foods with the risk of breast cancer were generally null. There is some evidence that supports the biological plausibility of a protective effect of isoflavones on breast cancer risk. We conclude that soy intake possibly decreases the risk of breast cancer among Japanese women.

Development and evaluation of a self-efficacy instrument for Japanese sleep apnea patients receiving continuous positive airway pressure treatment

PubMed Central

Saito, Ayako; Kojima, Shigeko; Sasaki, Fumihiko; Hayashi, Masamichi; Mieno, Yuki; Sakakibara, Hiroki; Hashimoto, Shuji

2015-01-01

The purpose of this study was to develop and evaluate a self-efficacy instrument for Japanese obstructive sleep apnea (OSA) patients treated with continuous positive airway pressure (CPAP). Analyzed subjects were 653 Japanese OSA patients (619 males and 34 females) treated with CPAP at a sleep laboratory in a respiratory clinic in a Japanese city. Based on Bandura’s social cognitive theory, the CPAP Self-Efficacy Questionnaire for Sleep Apnea in Japanese (CSESA-J) was developed by a focus group of experts, using a group interview of OSA patients for the items of two previous self-efficacy scales for Western sleep apnea patients receiving CPAP treatment. CSESA-J has two subscales, one for self-efficacy and the other for outcome expectancy, and consists of a total of 15 items. Content validity was confirmed by the focus group. Confirmatory factor analysis showed that the factor loadings of self-efficacy and outcome expectancy were 0.47–0.76 and 0.41–0.92, respectively, for the corresponding items. CSESA-J had a significant but weak positive association with the General Self-Efficacy Scale, and a strong positive association with “Self-efficacy scale on health behavior in patients with chronic disease.” Cronbach’s alpha coefficient was 0.85 for the self-efficacy subscale and 0.89 for the outcome expectancy subscale. The intraclass correlation coefficient using data from the first and second measurements with CSESA-J for a subset of 130 subjects was 0.93 for the self-efficacy and outcome expectancy subscales. These results support CSESA-J as a reliable and valid instrument for measuring the self-efficacy of Japanese OSA patients treated with CPAP. Further studies are warranted to confirm validity for female OSA patients and generalizability. PMID:25678832

Impact of diabetes mellitus on outcomes in Japanese patients undergoing coronary artery bypass grafting.

PubMed

Minakata, Kenji; Bando, Ko; Takanashi, Shuichiro; Konishi, Hiroaki; Miyamoto, Yoshihiro; Ueshima, Kenji; Sato, Tosiya; Ueda, Yuichi; Okita, Yutaka; Masuda, Izuru; Okabayashi, Hitoshi; Yaku, Hitoshi; Yasuno, Shinji; Muranaka, Hiroyuki; Kasahara, Masato; Miyata, Shigeki; Okamura, Yoshitaka; Nasu, Michihiro; Tanemoto, Kazuo; Arinaga, Koichi; Hisashi, Yosuke; Sakata, Ryuzo

2012-05-01

There have been no large-scale studies on the impact of diabetes mellitus (DM) on outcomes in Japanese patients undergoing coronary artery bypass grafting (CABG). A multi-institutional retrospective cohort study was conducted in 14 Japanese centers. All adult patients who underwent isolated CABG from 2007 to 2008 were included (n=1522, mean age: 68.5years). The definitions of DM were all patients admitted with diagnosis of DM and preoperative glycated hemoglobin (Hb) A1c≥6.5%. Univariate and multivariate analyses were performed to identify the risk of morbidity and mortality. There were 849 DM and 572 non-DM patients. Preoperative mean HbA1c were 7.1% in the DM group and 5.7% in the non-DM group (p<0.0001). Preoperative, intraoperative, and 3-day average postoperative blood glucose (BG) were 146mg/dl, 172mg/dl, and 168mg/dl in the DM group, and 103mg/dl, 140mg/dl, and 136mg/dl in the non-DM group (all p<0.0001). Although there were no significant differences in postoperative cardiovascular events, the incidence of infection was significantly higher in the DM group than in the non-DM group (9.2% vs 6.1%, p=0.036) on the univariate analysis. The all-cause death was also relatively higher in the DM group than in the non-DM group (2.1% vs 1.1%, p=0.12), and this was likely related to infection. DM patients had worse perioperative BG control, higher incidence of infection, and higher mortality than non-DM patients. These results indicate that perioperative BG control guidelines should be standardized to obtain better surgical outcomes in Japanese DM patients. Copyright © 2012. Published by Elsevier Ltd.

Prognostic models for renal cell carcinoma recurrence: external validation in a Japanese population.

PubMed

Utsumi, Takanobu; Ueda, Takeshi; Fukasawa, Satoshi; Komaru, Atsushi; Sazuka, Tomokazu; Kawamura, Koji; Imamoto, Takashi; Nihei, Naoki; Suzuki, Hiroyoshi; Ichikawa, Tomohiko

2011-09-01

The aim of the present study was to compare the accuracy of three prognostic models in predicting recurrence-free survival among Japanese patients who underwent nephrectomy for non-metastatic renal cell carcinoma (RCC). Patients originated from two centers: Chiba University Hospital (n = 152) and Chiba Cancer Center (n = 65). The following data were collected: age, sex, clinical presentation, Eastern Cooperative Oncology Group performance status, surgical technique, 1997 tumor-node-metastasis stage, clinical and pathological tumor size, histological subtype, disease recurrence, and progression. Three western models, including Yaycioglu's model, Cindolo's model and Kattan's nomogram, were used to predict recurrence-free survival. Predictive accuracy of these models were validated by using Harrell's concordance-index. Concordance-indexes were 0.795 and 0.745 for Kattan's nomogram, 0.700 and 0.634 for Yaycioglu's model, and 0.700 and 0.634 for Cindolo's model, respectively. Furthermore, the constructed calibration plots of Kattan's nomogram overestimated the predicted probability of recurrence-free survival after 5 years compared with the actual probability. Our findings suggest that despite working better than other predictive tools, Kattan's nomogram needs be used with caution when applied to Japanese patients who have undergone nephrectomy for non-metastatic RCC. © 2011 The Japanese Urological Association.

Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections.

PubMed

Aikawa, Naoki; Kusachi, Shinya; Mikamo, Hiroshige; Takesue, Yoshio; Watanabe, Shinichi; Tanaka, Yoshiyuki; Morita, Akiko; Tsumori, Keiko; Kato, Yoshiaki; Yoshinari, Tomoko

2013-06-01

Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7-14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1-90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4-96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3-69.7) with daptomycin and 47.4 % (95 % CI, 24.4-71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran-Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.

Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis.

PubMed

Seki, Shoji; Hirano, Norikazu; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Suzuki, Kayo; Watanabe, Kenta; Makino, Hiroto; Kanamori, Masahiko; Kimura, Tomoatsu

2017-08-01

Complications of adult spinal deformity surgery are problematic in osteoporotic individuals. We compared outcomes between Japanese patients treated perioperatively with teriparatide vs. low-dose bisphosphonates. Fifty-eight osteoporotic adult Japanese female patients were enrolled and assigned to perioperative teriparatide (33 patients) and bisphosphonate (25 patients) groups in non-blinded fashion. Pre- and post-operative X-ray and computed tomography imaging were used to assess outcome, and rates were compared between the groups and according to age. Pain scores and Oswestry Disability Indices (ODI) were calculated before and 2 years after surgery. Adjacent vertebral fractures and implant failure, fusion failure, and poor pain and ODI outcomes were significantly more common in the bisphosphonates group than the teriparatide group. Perioperative administration of teriparatide is more effective than that of low-dose bisphosphonates in preventing complications and maintaining fusion rates in osteoporotic Japanese females with spinal deformities undergoing surgery.

The effect of bezlotoxumab for prevention of recurrent Clostridium difficile infection (CDI) in Japanese patients.

PubMed

Mikamo, Hiroshige; Aoyama, Norihiro; Sawata, Miyuki; Fujimoto, Go; Dorr, Mary Beth; Yoshinari, Tomoko

2018-02-01

Recurrent Clostridium difficile infection is considered as a significant health care burden. The global study (MODIFY II) of antibody treatment (bezlotoxumab) for the prevention of recurrent C. difficile infection includes Japanese patients (95 subjects); The aim of this subgroup analysis is to report the data obtained from Japanese patients. Patients with C. difficile infection receiving standard of care antibiotic treatment and a single infusion of bezlotoxumab 10 mg/kg, actoxumab 10 mg/kg + bezlotoxumab 10 mg/kg or placebo. Recurrent C. difficile infection through Week 12 was evaluated. In the Full Analysis Set (93 subjects), 91% were older than 65 years of age and 93% were hospitalized at the time of study entry. The standard of care antibiotic for C. difficile infection was metronidazole for 57 subjects and vancomycin for 36 subjects. The recurrent C. difficile infection rate was 46% in the placebo, 21% in the bezlotoxumab (p = 0.0197) and 28% in the actoxumab + bezlotoxumab group. No additive recurrent C. difficile infection-reducing effect with the addition of actoxumab was demonstrated. There were no events representing safety concern in bezlotoxumab. Among 54 clinical isolates of C. difficile as a baseline culture in Japanese patients, the common ribotypes were 052 (28%), 018 (19%), 002 (15%) and 369 (9%). It showed distinctly different distribution from that in the United States and Europe. The superior effect of bezlotoxumab 10 mg/kg in the prevention of recurrent C. difficile infection suggests that the agent will be useful in the rapidly aging Japanese society. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients.

PubMed

Zhao, Yang; Hosono, Katsuhiro; Suto, Kimiko; Ishigami, Chie; Arai, Yuuki; Hikoya, Akiko; Hirami, Yasuhiko; Ohtsubo, Masafumi; Ueno, Shinji; Terasaki, Hiroko; Sato, Miho; Nakanishi, Hiroshi; Endo, Shiori; Mizuta, Kunihiro; Mineta, Hiroyuki; Kondo, Mineo; Takahashi, Masayo; Minoshima, Shinsei; Hotta, Yoshihiro

2014-09-01

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74-90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p.C759F in arRP and p.E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.

Risk of lung cancer and consumption of vegetables and fruit in Japanese: A pooled analysis of cohort studies in Japan.

PubMed

Wakai, Kenji; Sugawara, Yumi; Tsuji, Ichiro; Tamakoshi, Akiko; Shimazu, Taichi; Matsuo, Keitaro; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka

2015-08-01

International reviews have concluded that consumption of fruit and vegetables might decrease the risk of lung cancer. However, the relevant epidemiological evidence still remains insufficient in Japan. Therefore, we performed a pooled analysis of data from four population-based cohort studies in Japan with >200 000 participants and >1700 lung cancer cases. We computed study-specific hazard ratios by quintiles of vegetable and fruit consumption as assessed by food frequency questionnaires. Summary hazard ratios were estimated by pooling the study-specific hazard ratios with a fixed-effect model. In men, we found inverse associations between fruit consumption and the age-adjusted and area-adjusted risk of mortality or incidence of lung cancer. However, the associations were largely attenuated after adjustment for smoking and energy intake. The significant decrease in risk among men remained only for a moderate level of fruit consumption; the lowest summary hazard ratios were found in the third quintile of intake (mortality: 0.71, 95% confidence interval 0.60-0.84; incidence: 0.83, 95% confidence interval 0.70-0.98). This decrease in risk was mainly detected in ever smokers. Conversely, vegetable intake was positively correlated with the risk of incidence of lung cancer after adjustment for smoking and energy intake in men (trend P, 0.024); the summary hazard ratio for the highest quintile was 1.26 (95% confidence interval 1.05-1.50). However, a similar association was not detected for mortality from lung cancer. In conclusion, a moderate level of fruit consumption is associated with a decreased risk of lung cancer in men among the Japanese population. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Body-Mass Index and Pancreatic Cancer Incidence: A Pooled Analysis of Nine Population-Based Cohort Studies With More Than 340,000 Japanese Subjects.

PubMed

Koyanagi, Yuriko N; Matsuo, Keitaro; Ito, Hidemi; Tamakoshi, Akiko; Sugawara, Yumi; Hidaka, Akihisa; Wada, Keiko; Oze, Isao; Kitamura, Yuri; Liu, Rong; Mizoue, Tetsuya; Sawada, Norie; Nagata, Chisato; Wakai, Kenji; Nakayama, Tomio; Sadakane, Atsuko; Tanaka, Keitaro; Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka

2018-05-05

A high body mass index (BMI) has been proposed as an important risk factor for pancreatic cancer. However, this association of BMI with pancreatic cancer risk has not been confirmed in Asian populations. We evaluated the association between BMI (either at baseline or during early adulthood) and pancreatic cancer risk by conducting a pooled analysis of nine population-based prospective cohort studies in Japan with more than 340,000 subjects. Summary hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI categories with a random-effects model. Among Japanese men, being obese at baseline was associated with a higher risk of pancreatic cancer incidence (≥30 kg/m 2 compared with 23 to <25 kg/m 2 , adjusted HR 1.71; 95% confidence interval [CI], 1.03-2.86). A J-shaped association between BMI during early adulthood and pancreatic cancer incidence was seen in men. In contrast, we observed no clear association among women, although there may be a positive linear association between BMI at baseline and the risk of pancreatic cancer (per 1 kg/m 2 , adjusted HR 1.02; 95% CI, 1.00-1.05). Pooling of data from cohort studies with a considerable number of Japanese subjects revealed a significant positive association between obesity and pancreatic cancer risk among men. This information indicates that strategies that effectively prevent obesity among men might lead to a reduced burden of pancreatic cancer, especially in Asian populations.

Population pharmacokinetic analysis for 10-monohydroxy derivative of oxcarbazepine in pediatric epileptic patients shows no difference between Japanese and other ethnicities.

PubMed

Sugiyama, Ikuo; Bouillon, Thomas; Yamaguchi, Masayuki; Suzuki, Hikoe; Hirota, Takashi; Fink, Martin

2015-04-01

Oxcarbazepine is an anti-epileptic drug, which is almost completely metabolized by cytosolic enzymes in the liver to the active 10-monohyroxy metabolite (MHD) following oral administration. The pharmacokinetic (PK) profiles of MHD were evaluated in pediatric epileptic patients and a possible ethnic difference in PK of MHD between Japanese and non-Japanese pediatric patients was assessed. A non-linear mixed effect modeling approach was used to determine the PK of MHD. A one-compartment population model with first-order absorption appropriately described the PK of MHD. No clinically relevant differences were found for using body surface area or weight to explain between-patient variability, therefore the final model included the effects of body weight on apparent clearance (CL/F) and apparent volume of distribution (V/F) of MHD, and in addition, the effect of 3 concomitant anti-epileptic drugs (carbamazepine, phenobarbital and phenytoin) on CL/F of MHD. Inclusion of ethnicity as a covariate in the final model, concluded no ethnic difference with respect to CL/F of MHD between Japanese and non-Japanese patients. Hence, oxcarbazepine can be generally applied using the same dosage and administration for the treatment of partial onset seizures in pediatric patients, regardless of ethnicity. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Satisfying the needs of Japanese cancer patients: a comparative study of detailed and standard informed consent documents.

PubMed

Sato, Keiko; Watanabe, Toru; Katsumata, Noriyuki; Sato, Tosiya; Ohashi, Yasuo

2014-02-01

Simplified informed consent forms have been successful in improving patient satisfaction and decreasing patient anxiety. However, unsolved problems remain about whether these documents improve comprehension and satisfaction of patients with standard literacy skills. s To investigate whether a detailed consent form explaining the key elements of informed consent, in comparison to a standard consent form, would increase the comprehension and satisfaction of adult cancer patients. Patients who were eligible for the National Surgical Adjuvant Study of Breast Cancer (protocol 01(N-SAS/BC-01)) were randomly selected to receive one of the following four versions: detailed document with graphics, detailed document without graphics, standard document with graphics, and standard document without graphics. The forms were written in plain language from the patients' point of view. A total of 85 patients were administered questionnaires via interview to assess levels of comprehension, satisfaction, and anxiety. Patients demonstrated a strong understanding of information regarding treatment and research. Patient comprehension did not differ significantly between the detailed document arms and the standard document arms. Patient satisfaction level increased according to the amount of information presented in the consent form; most patients preferred the detailed document with graphics. Anxiety and accrual rates in the parent study were not affected by informed consent procedures. Findings were limited to adults who had standard literacy skills and may not be generalizable to a population with lower literacy. Informed consent can be a significant experience for a population with standard literacy skills, as long as the document is easily comprehensible. Such information should be provided in a format that corresponds with patient needs, education levels, and preferences.

Dietary inflammatory index and risk of upper aerodigestive tract cancer in Japanese adults

PubMed Central

Abe, Makiko; Shivappa, Nitin; Ito, Hidemi; Oze, Isao; Abe, Tetsuya; Shimizu, Yasuhiro; Hasegawa, Yasuhisa; Kiyohara, Chikako; Nomura, Masatoshi; Ogawa, Yoshihiro; Hebert, James R.; Matsuo, Keitaro

2018-01-01

Background The inflammatory potential of diet that has been shown to be associated with cancer risk. We examined the association between dietary inflammatory potential as measured by the dietary inflammatory index (DII®) and risk of upper aerodigestive tract cancers in a Japanese case-control study. Results A positive association was observed between increasing DII scores and overall upper aerodigestive tract cancers, and across anatomic subsites. For upper aerodigestive tract cancers, the ORQ4vsQ1 = 1.73 (95% CI: 1.37–2.20); head and neck cancer, the ORQ4vsQ1 was 1.92 (95% CI: 1.42–2.59); and for esophageal cancer, the ORQ4vsQ1 was1.71 (95% CI: 1.54–1.90). Risks for hypopharyngeal and nasopharyngeal cancers were greatly elevated: (ORQ4vsQ1 = 4.05 (95% CI: 1.24–13.25) for hypopharyngeal cancer and ORQ4vsQ1 = 4.99 (95% CI: 1.14–21.79) for nasopharyngeal cancer. Conclusion A more pro-inflammatory diet was associated with an elevated risk of upper aerodigestive tract cancers after accounting for important confounders. All anatomic subsites, except larynx, showed the consistently elevated risk with increasing DII score. Those subsites with known etiological associations with persistent infection showed the largest elevation in risk. These results warrant further evaluation in future studies. Materials and Methods This is a case-control study of 1,028 cases and 3,081 age- and sex-matched non-cancer controls recruited at Aichi Cancer Center. DII scores were computed based on estimates of macro- and micro-nutrients from a self-administered food frequency questionnaire. Scores were further categorized into quartiles (based on the distribution in controls). Conditional logistic regression models were fit to estimate odds ratio (OR) and 95% confidence intervals (CIs) adjusted for smoking, ethanol consumption, alcohol flushing, number of teeth, and occupation group. PMID:29844870

Prostate Cancer Prognostic Factors Among Asian Patients Born in the US Compared to Those Born Abroad.

PubMed

Xu, Junjun; Goodman, Michael; Jemal, Ahemdin; Fedewa, Stacey A

2015-06-01

US surveillance data indicate that incidence of prostate cancer differs by place of birth among Asian men. However, it is less clear if the prognostic factors for prostate cancer also differ by place of birth. The study included 7,824 Asian prostate cancer patients diagnosed between 2004 and 2009 and reported to the Surveillance Epidemiology and End Results (SEER) program. Logistic regression models were used to evaluate the relation of place of birth (foreign born vs. US born) to three outcomes: prostate specific antigen (PSA) level, Gleason score, and T classification, adjusting for age, marital status, Rural-Urban Continuum Code, and SEER registry. All outcome variables were binary using different cutoffs: ≥ 4, ≥ 10 and ≥ 20 ng/ml for PSA; ≥ 7 and ≥ 8 for Gleason score; and ≥ T2 and ≥ T3 for T classification. Elevated PSA was more common among foreign born Asian men regardless of the cut point used. In the analysis comparing foreign born versus US born patients by ethnic group, the association with PSA was most pronounced at cut point of ≥ 20 ng/ml for Chinese men (OR 1.68, 95% CI 1.02-2.75), and at cut point of ≥ 4 ng/ml for Japanese men (OR 2.73, 95% CI 1.20-6.21). A statistically significant association with Gleason score was only found for Japanese men and only for the cutoff ≥ 7 (OR 1.71, 95% CI 1.12-2.61). There was no difference in clinical T classification between foreign-born and US-born Asian men. Inclusion of cases with missing place of birth or restriction of data to those who underwent radical prostatectomy did not substantially change the results. The data suggest that foreign-born Asian prostate cancer patients may have moderately elevated PSA levels at diagnosis compared with their US born counterparts. For the other prognostic markers, the associations were less consistent and did not form a discernible pattern.

Does the treatment of type 2 diabetes mellitus with the DPP-4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients?

PubMed

Foley, James E; Bhosekar, Vaishali; Kawamori, Ryuzo

2016-01-01

Previous work suggests that Japanese patients with type 2 diabetes mellitus (T2DM) may respond more favorably to a DPP-4 (dipeptidyl peptidase-4) inhibitor than Caucasians. We aimed to compare the efficacy of the DPP-4 inhibitor vildagliptin (50 mg twice daily [bid]) between Japanese and Caucasian populations. This analysis pooled data from 19 studies of drug-naïve patients with T2DM who were treated for 12 weeks with vildagliptin 50 mg bid as monotherapy. The pool comprised Japanese patients (n=338) who had been treated in Japan and Caucasian patients (n=1,275) who were treated elsewhere. Change from baseline (Δ) in glycated hemoglobin (HbA1c) at 12 weeks (in millimoles per mole) versus baseline HbA1c (both in percentage National Glycohemoglobin Standardization Program units [NGSP%] and millimoles per mole) for each population was reported. Universal HbA1c in millimoles per mole was calculated from either the Japanese Diabetes Society or the NGSP% HbA1c standards. At baseline, mean values for Japanese and Caucasian patients, respectively, were as follows: age, 59 years and 56 years; % male, 69% and 57%. The average HbA1c was reduced from 7.90% to 6.96% (Japanese Diabetes Society) and from 8.57% to 7.50% (United States National Glycohemoglobin Standardization Program), while HbA1c was reduced from 63 mmol/mol to 53 mmol/mol and from 70 mmol/mol to 58 mmol/mol in Japanese and Caucasians, respectively. ΔHbA1c increased with increasing baseline in both populations. The slopes were the same (0.41, r (2)=0.36; and 0.41, r (2)=0.15), and the intercepts were 15.4 mmol/mol and 17.2 mmol/mol, respectively. In Japanese patients, mean ΔHbA1c was greater by 1.7 mmol/mol (0.2% NGSP HbA1c) at any given baseline HbA1c than in Caucasians (P=0.01). The present pooled analysis suggests that Japanese patients respond better to vildagliptin treatment compared with Caucasians. However, when glycemic control was corrected by using the same glycemic standard, the difference in HbA1c

Relationship between airborne pollen count and treatment outcome in Japanese cedar pollinosis patients.

PubMed

Takasaki, Kenji; Enatsu, Kaori; Kumagami, Hidetaka; Takahashi, Haruo

2009-05-01

In Japan, information on daily Japanese cedar pollen counts is made public during pollen season. If symptom severity and treatment outcome are predictable according to these pollen counts, management of seasonal allergic rhinitis may become more precise. The aims of the study were to evaluate the relationship between airborne pollen counts, symptom severity and treatment outcome in Japanese cedar pollinosis patients. In the randomized study, patients with moderate to most severe Japanese pollinosis were treated with fexofenadine (60 mg BD) or fexofenadine and nasal corticosteroids for 2 weeks. During the same period daily airborne pollen counts were measured. A total of 105 adult patients were enrolled. No difference of treatment efficacy was seen among groups. Detailed results of efficacy and safety were previously described elsewhere. In univariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study tended to affect symptom severity (P = 0.053) and the mean cumulative amount of airborne pollen during the treatment period tended to show difference among five treatment outcome categories (P = 0.066). In multivariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study was identified as the only significant factor of symptom severity (P = 0.0327) and cumulative amount of airborne pollen during the treatment period (P = 0.027) and allergic history (P = 0.027) were significant factors of treatment outcomes. No serious adverse effect was reported during the study. The amount of airborne pollen may be predictive of both symptom severity and treatment outcome.

Dimensional analyses of frontal posed smile attractiveness in Japanese female patients.

PubMed

Hata, Kyoko; Arai, Kazuhito

2016-01-01

To identify appropriate dimensional items in objective diagnostic analysis for attractiveness of frontal posed smile in Japanese female patients by comparing with the result of human judgments. Photographs of frontal posed smiles of 100 Japanese females after orthodontic treatment were evaluated by 20 dental students (10 males and 10 females) using a visual analogue scale (VAS). The photographs were ranked based on the VAS evaluations and the 25 photographs with the highest evaluations were selected as group A, and the 25 photos with the lowest evaluations were designated group B. Then 12 dimensional items of objective analysis selected from a literature review were measured. Means and standard deviations for measurements of the dimensional items were compared between the groups using the unpaired t-test with a significance level of P < .05. Mean values were significantly smaller in group A than in group B for interlabial gap, intervermilion distance, maxillary gingival display, maximum incisor exposure, and lower lip to incisor (P < .05). Significant differences were observed only in the vertical dimension, not in the transverse dimension. Five of the 12 objective diagnostic items were correlated with human judgments of the attractiveness of frontal posed smile in Japanese females after orthodontic treatment.

Cancer-specific mortality of Asian Americans diagnosed with cancer: a nationwide population-based assessment.

PubMed

Trinh, Quoc-Dien; Nguyen, Paul L; Leow, Jeffrey J; Dalela, Deepansh; Chao, Grace F; Mahal, Brandon A; Nayak, Manan; Schmid, Marianne; Choueiri, Toni K; Aizer, Ayal A

2015-06-01

Racial disparities in cancer survival outcomes have been primarily attributed to underlying biologic mechanisms and the quality of cancer care received. Because prior literature shows little difference exists in the socioeconomic status of non-Hispanic whites and Asian Americans, any difference in cancer survival is less likely to be attributable to inequalities of care. We sought to examine differences in cancer-specific survival between whites and Asian Americans. The Surveillance, Epidemiology, and End Results Program was used to identify patients with lung (n = 130 852 [16.9%]), breast (n = 313 977 [40.4%]), prostate (n = 166 529 [21.4%]), or colorectal (n = 165 140 [21.3%]) cancer (the three leading causes of cancer-related mortality within each sex) diagnosed between 1991 and 2007. Fine and Gray's competing risks regression compared the cancer-specific mortality (CSM) of eight Asian American groups (Chinese, Filipino, Hawaiian/Pacific Islander, Japanese, Korean, other Asian, South Asian [Indian/Pakistani], and Vietnamese) to non-Hispanic white patients. All P values were two-sided. In competing risks regression, the receipt of definitive treatment was an independent predictor of CSM (hazard ratio [HR] = 0.37, 95% confidence interval [CI] = 0.35 to 0.40; HR = 0.55, 95% CI = 0.53 to 0.58; HR = 0.61, 95% CI = 0.60 to 0.62; and HR = 0.27, 95% CI = 0.25 to 0.29) for prostate, breast, lung, and colorectal cancers respectively, all P < .001). In adjusted analyses, most Asian subgroups (except Hawaiians and Koreans) had lower CSM relative to white patients, with hazard ratios ranging from 0.54 (95% CI = 0.38 to 0.78) to 0.88 (95% CI = 0.84 to 0.93) for Japanese patients with prostate and Chinese patients with lung cancer, respectively. Despite adjustment for potential confounders, including the receipt of definitive treatment and tumor characteristics, most Asian subgroups had better CSM than non-Hispanic white patients. These findings suggest that underlying genetic

Clinical and molecular investigation of 14 Japanese patients with complete TFP deficiency: a comparison with Caucasian cases.

PubMed

Bo, Ryosuke; Yamada, Kenji; Kobayashi, Hironori; Jamiyan, Purevsuren; Hasegawa, Yuki; Taketani, Takeshi; Fukuda, Seiji; Hata, Ikue; Niida, Yo; Shigematsu, Yosuke; Iijima, Kazumoto; Yamaguchi, Seiji

2017-09-01

Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder of mitochondrial fatty-acid oxidation. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is often reported in Caucasian countries due to a common mutation. However, the molecular and clinical basis of complete TFP deficiency has not been extensively reported. In this study, 14 Japanese cases (13 families) with complete TFP deficiency, including 9 previously reported cases, were analyzed to clarify the clinical and molecular characteristics of TFP deficiency. The clinical types of the 14 patients were as follows: 12 cases of neonatal (n=7) or myopathic (n=5) types and 2 cases of intermediate type. Peripheral neuropathy was found in four cases and hypocalcemia due to hypoparathyroidism, which is rarely reported in Caucasian patients, had developed in four cases. Maternal hemolysis, elevated liver enzymes and low platelet count syndrome and acute fatty liver of pregnancy were noted in two and one mothers, respectively. Fourteen mutations were identified in 26 alleles in Japanese patients, including two novel mutations (HADHA: c.361C>T, and HADHA-HADHB: g.26233880_ 26248855del), although no common mutations were found. This study suggests that the molecular and clinical aspects of Japanese patients with TFP deficiencies differ from those of Caucasian patients.

Post-bronchoscopy pneumonia in patients suffering from lung cancer: Development and validation of a risk prediction score.

PubMed

Takiguchi, Hiroto; Hayama, Naoki; Oguma, Tsuyoshi; Harada, Kazuki; Sato, Masako; Horio, Yukihiro; Tanaka, Jun; Tomomatsu, Hiromi; Tomomatsu, Katsuyoshi; Takihara, Takahisa; Niimi, Kyoko; Nakagawa, Tomoki; Masuda, Ryota; Aoki, Takuya; Urano, Tetsuya; Iwazaki, Masayuki; Asano, Koichiro

2017-05-01

The incidence, risk factors, and consequences of pneumonia after flexible bronchoscopy in patients with lung cancer have not been studied in detail. We retrospectively analyzed the data from 237 patients with lung cancer who underwent diagnostic bronchoscopy between April 2012 and July 2013 (derivation sample) and 241 patients diagnosed between August 2013 and July 2014 (validation sample) in a tertiary referral hospital in Japan. A score predictive of post-bronchoscopy pneumonia was developed in the derivation sample and tested in the validation sample. Pneumonia developed after bronchoscopy in 6.3% and 4.1% of patients in the derivation and validation samples, respectively. Patients who developed post-bronchoscopy pneumonia needed to change or cancel their planned cancer therapy more frequently than those without pneumonia (56% vs. 6%, p<0.001). Age ≥70 years, current smoking, and central location of the tumor were independent predictors of pneumonia, which we added to develop our predictive score. The incidence of pneumonia associated with scores=0, 1, and ≥2 was 0, 3.7, and 13.4% respectively in the derivation sample (p=0.003), and 0, 2.9, and 9.7% respectively in the validation sample (p=0.016). The incidence of post-bronchoscopy pneumonia in patients with lung cancer was not rare and associated with adverse effects on the clinical course. A simple 3-point predictive score identified patients with lung cancer at high risk of post-bronchoscopy pneumonia prior to the procedure. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Prevalence, symptomatic features, and factors associated with sleep disturbance/insomnia in Japanese patients with type-2 diabetes.

PubMed

Narisawa, Hajime; Komada, Yoko; Miwa, Takashi; Shikuma, Junpei; Sakurai, Mamoru; Odawara, Masato; Inoue, Yuichi

2017-01-01

To clarify the prevalence and symptomatic characteristics of sleep disturbance/insomnia among type-2 diabetes mellitus (DM) Japanese patients. A cross-sectional survey of Japanese patients with the disorder was conducted. Participants consisted of 622 type-2 DM patients (mean 56.1±9.56 years) and 622 sex- and age-matched controls. Participants' scores in the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), the Japanese version of the 12-item Center for Epidemiologic Studies Depression Scale (CES-D), the Medical Outcomes Study 8-item Short Form Health Survey (SF-8), and the glycated hemoglobin A1c (HbA1c) of type-2 DM patients were analyzed. There were 253 poor sleepers (43.9%) in the type-2 DM group as a result of dichotomization with the PSQI-J cutoff total score of 5.5. The type-2 DM group recorded a higher mean PSQI-J total score ( P <0.01) and manifested poorer sleep maintenance. Poor sleepers in both groups had lower mental component summary from SF-8 (MCS), physical component summary from SF-8 (PCS), and CES-D than good sleepers, and good sleepers in both groups had higher MCS, PCS, and CES-D than poor sleepers. Higher body mass index, presence of smoking habit, and living alone were significantly associated with sleep disturbance/insomnia symptoms, but HbA1c was not associated with sleep disturbance/insomnia in the type-2 DM group. Individuals affected with type-2 DM are likely to experience sleep problems, characterized by disturbance in sleep maintenance. Sleep disturbance/insomnia symptoms in DM patients might considerably reduce health-related quality of life.

Improving cancer patient care: development of a generic cancer consumer quality index questionnaire for cancer patients.

PubMed

Booij, Judith C; Zegers, Marieke; Evers, Pauline M P J; Hendriks, Michelle; Delnoij, Diana M J; Rademakers, Jany J D J M

2013-04-23

To develop a Consumer Quality Index (CQI) Cancer Care questionnaire for measuring experiences with hospital care of patients with different types of cancer. We derived quality aspects from focus group discussions, existing questionnaires and literature. We developed an experience questionnaire and sent it to 1,498 Dutch cancer patients. Another questionnaire measuring the importance of the quality aspects was sent to 600 cancer patients. Data were psychometrically analysed. The response to the experience questionnaire was 50 percent. Psychometric analysis revealed 12 reliable scales. Patients rated rapid and adequate referral, rapid start of the treatment after diagnosis, enough information and confidence in the healthcare professionals as most important themes. Hospitals received high scores for skills and cooperation of healthcare professionals and a patient-centered approach by doctors; and low scores for psychosocial guidance and information at completion of the treatment. The CQI Cancer Care questionnaire is a valuable tool for the evaluation of the quality of cancer care from the patient's perspective. Large scale implementation is necessary to determine the discriminatory powers of the questionnaire and may enable healthcare providers to improve the quality of cancer care. Preliminary results indicate that hospitals could improve their psychosocial guidance and information provision.

Personality traits of Japanese patients in remission from an episode of primary unipolar depression.

PubMed

von Zerssen, D; Asukai, N; Tsuda, H; Ono, Y; Kizaki, Y; Cho, Y

1997-07-01

Personality traits were assessed by means of the Munich Personality Test (MPT) in 75 Japanese subjects, 27 patients in remission from an episode of moderate to severe primary unipolar depression, with melancholic features during one episode or more of the disorder, in 24 patients in remission from other non-organic mental disorders and in 24 healthy controls. Compared with healthy controls, unipolar depressives displayed decreased Frustration Tolerance and elevated Rigidity as well as a stronger Orientation towards Social Norms. No significant difference was found between patients in remission from either unipolar depression or other mental disorders. However, the increase in Rigidity in comparison with healthy subjects was significant in the depressives only whereas the other patients, in contrast to the depressives, had significantly lower scores in Extraversion than the healthy subjects. Our results in Japanese patients are similar to findings of previous German studies, including two high risk studies, in which the same assessment instrument was used. This suggests that, beyond cultural differences, Rigidity, possibly in combination with a strong Orientation towards Social Norms and a reduced Frustration Tolerance, is a stable vulnerability marker for at least the more severe forms of primary unipolar depression.

Seasonal allergic conjunctivitis induced by Japanese pear pollen.

PubMed

Yanagisawa, S; Nagaki, Y; Hiraki, S; Kadoi, C; Hayasaka, S; Teranishi, H

1999-01-01

To evaluate the ocular findings in patients with Japanese pear (Pyrus pyrifolia Nakai) pollinosis. Twenty-two farmers working on artificial pollination in Japanese pear orchards were examined for ocular itching, conjunctival conditions, presence of eosinophils in the conjunctival specimen, and nasal symptoms. Serum IgE antibody to Japanese pear pollen was determined in 16 farmers. Of the 22 subjects, 3 (Nos. 3, 4, and 13) exhibited ocular itching, conjunctival hyperemia, eosinophils in the conjunctival specimen, and positive serum IgE antibodies to Japanese pear pollen. In these patients, the conjunctivitis disappeared after treatment with topical cromoglycate. The present study demonstrated that seasonal allergic conjunctivitis may be induced by Japanese pear pollen (entomophilous flower pollen).

Awareness and correlates of the role of physical activity in breast cancer prevention among Japanese women: results from an internet-based cross-sectional survey.

PubMed

Miyawaki, Rina; Shibata, Ai; Ishii, Kaori; Oka, Koichiro

2014-07-07

Although considerable evidence has demonstrated that physical activity is associated with breast cancer prevention, few studies have assessed the level of awareness of this association. Awareness is a key first step to successful of behavior change. Increasing awareness may contribute to promote physical activity and prevent breast cancer at the population level. The present study examined the prevalence and correlates of awareness about the role of physical activity in breast cancer prevention among Japanese women. 1,000 Japanese women aged 20-69 years (mean age: 44.3 ± 13.4 years) who responded to an internet-based cross-sectional survey. Awareness of the role of physical activity in breast cancer prevention, knowledge of breast cancer (symptom, risk factor, screening), exposure to information about physical activity and cancer, a self-reported physical activity, and sociodemographic variables (age, marital status, having a child, education level, employment status, and household income) were obtained. Force-entry logistic regression analysis was used. The prevalence of awareness was 31.5% (95% CI: 28.6-34.4). Factors significantly associated with awareness included sociodemographic variables, exposure to information, and knowledge of breast cancer. Being married (AOR, 95% CI: 1.75, 1.05-2.92) was positively related to awareness, while having children (0.65, 0.36-0.86) was negatively related. College graduates or those with higher levels of education (1.50, 1.01-2.22) were significantly more likely to be aware than those who had not graduated high school. Moreover, exposure to information (2.11, 1.51-2.95), and high knowledge of symptoms (2.43, 1.75-3.36) were positively associated with awareness. Finally, low knowledge of risk factors (0.30, 0.22-0.40) was negatively associated with awareness. Japanese women through internet-based study were poorly aware of the role of physical activity in breast cancer prevention. Awareness was especially low among

An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients.

PubMed

Mukai, Hirofumi; Watanabe, Toru; Ando, Masashi; Katsumata, Noriyuki

2006-12-01

We report three cases of patients with advanced cancer who showed severe hepatic damage, and two of whom died of fulminant hepatitis. All the patients were taking Agaricus blazei (Himematsutake) extract, one of the most popular complementary and alternative medicines among Japanese cancer patients. In one patient, liver functions recovered gradually after she stopped taking the Agaricus blazei, but she restarted taking it, which resulted in deterioration of the liver function again. The other patients who were admitted for severe liver damage had started taking the Agaricus blazei several days before admission. Although several other factors cannot be completely ruled out as the causes of liver damage, a strong causal relationship between the Agaricus blazei extract and liver damage was suggested and, at least, taking the Agaricus blazei extract made the clinical decision-making process much more complicated. Doctors who are aware of their patients taking the extract may accept it probably because they believe there is no harm in a complementary and alternative medicine. When unexpected liver damage is documented, however, doctors should consider the use of the Agaricus blazei extract as one of its causal factors. It is necessary to evaluate many modes of complementary and alternative medicines, including the Agaricus blazei extract, in rigorous, scientifically designed and peer-reviewed clinical trials.

Long-term safety and effectiveness of brexpiprazole in Japanese patients with schizophrenia: A 52-week, open-label study.

PubMed

Ishigooka, Jun; Iwashita, Shuichi; Tadori, Yoshihiro

2018-06-01

This study assessed the long-term safety, tolerability, and maintenance of the therapeutic effect of brexpiprazole in Japanese patients with schizophrenia. This 52-week, open-label, flexible-dose (1-4 mg/day) study included patients with schizophrenia who continued treatment from a short-term randomized placebo-controlled fixed-dose (1, 2, or 4 mg/day) trial and de novo patients who switched from other antipsychotics. A total of 282 patients (184 de novo and 98 rolled over from short-term trial) entered the 52-week treatment with brexpiprazole, and 150 (53.2%) patients completed the week-52 assessment. Treatment-emergent adverse events (TEAE) were experienced by 235/281 patients (83.6%), and TEAE reported by ≥10% of all patients were nasopharyngitis (23.1%) and worsening of schizophrenia (22.4%). During the study, most of the TEAE were mild or moderate in severity, and there were no deaths, and no clinically meaningful mean changes in laboratory values, vital signs, or electrocardiogram parameters. Mean scores for the Positive and Negative Syndrome Scale total and Clinical Global Impression-Severity remained stable until week 52. Brexpiprazole was generally safe and well tolerated and maintained therapeutic effects in the long-term treatment of Japanese patients with schizophrenia. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure

PubMed Central

Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Ito, Masahiro; Tokuoka, Shoji; Sugiyama, Hiromi; Soda, Midori; Ozasa, Kotaro; Mabuchi, Kiyohiko

2014-01-01

Thyroid cancer risk following exposure to ionizing radiation in childhood and adolescence is a topic of public concern. To characterize the long-term temporal trend and age-at-exposure variation in the radiation-induced risk of thyroid cancer, we analyzed thyroid cancer incidence data for the period from 1958 through 2005 among 105,401 members of the Life Span Study cohort of Japanese atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases (excluding those with microcarcinoma with a diameter <10 mm) were identified as a first primary among the eligible subjects. Using a linear dose–response model, the excess relative risk of thyroid cancer at 1 Gy of radiation exposure was estimated as 1.28 (95% confidence interval: 0.59–2.70) at age 60 after acute exposure at age 10. The risk decreased sharply with increasing age-at-exposure and there was little evidence of increased thyroid cancer rates for those exposed after age 20. About 36% of the thyroid cancer cases among those exposed before age 20 were estimated to be attributable to radiation exposure. While the magnitude of the excess risk has decreased with increasing attained age or time since exposure, the excess thyroid cancer risk associated with childhood exposure has persisted for >50 years after exposure PMID:22847218

Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population.

PubMed

Yamaoka, Yuko; Suehiro, Yutaka; Hashimoto, Shinichi; Hoshida, Tomomi; Fujimoto, Michiyo; Watanabe, Michiya; Imanaga, Daiki; Sakai, Kouhei; Matsumoto, Toshihiko; Nishioka, Mitsuaki; Takami, Taro; Suzuki, Nobuaki; Hazama, Shoichi; Nagano, Hiroaki; Sakaida, Isao; Yamasaki, Takahiro

2018-04-01

Accumulating evidence shows an overabundance of Fusobacterium nucleatum in colorectal tumor tissues. However, the correlation between the absolute copy number of F. nucleatum in colorectal cancer tissues and colorectal cancer progression is unclear from previous reports. Therefore, we performed a study to compare the abundance of F. nucleatum in colorectal tissues with clinicopathologic and molecular features of colorectal cancer. We collected 100 colorectal cancer tissues and 72 matched normal-appearing mucosal tissues. Absolute copy numbers of F. nucleatum were measured by droplet digital PCR. The detection rates of F. nucleatum were 63.9% (46/72) in normal-appearing mucosal tissues and 75.0% (75/100) in CRC tissue samples. The median copy number of F. nucleatum was 0.4/ng DNA in the normal-appearing colorectal mucosa in patients with colorectal cancer and 1.9/ng DNA in the colorectal cancer tissues (P = 0.0031). F. nucleatum copy numbers in stage IV colorectal cancer tissues were significantly higher than those in the normal-appearing mucosa in patients with colorectal cancer (P = 0.0016). The abundance of F. nucleatum in colorectal cancer tissues correlated with tumor size and KRAS mutation and was significantly associated with shorter overall survival times; this trend was notable in the patients with stage IV colorectal cancer. Focusing on normal-appearing mucosa in the patients with colorectal cancer, the F. nucleatum copy number was significantly higher in the patients with stage IV rather than stages I-III. These results suggest that determining F. nucleatum levels may help predict clinical outcomes in colorectal cancer patients. Further confirmatory studies using independent datasets are required to confirm our findings.

Long-term efficacy and safety of lamotrigine monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures: An open-label extension study.

PubMed

Yasumoto, Sawa; Ohtsuka, Yoko; Sato, Katsuaki; Kurata, Atsuyo; Numachi, Yotaro; Shimizu, Masahiro

2018-05-31

To investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures. Six Japanese patients and one South Korean patient were enrolled in the extension phase of the study after completing the 12-week maintenance phase of an open-label clinical study of LTG monotherapy. During the extension phase, patients underwent efficacy and safety evaluation every 12 weeks. Of the seven patients, six patients completed the extension phase. The seizure-free rate confirmed by hyperventilation (HV)-electroencephalography ranged from 71.4% to 100.0% at each visit up to Week 168 of the extension phase. Similar effects were confirmed by HV-clinical signs and seizure diaries. Although no unexpected adverse events were observed, one Japanese patient was withdrawn from the extension phase due to mild drug-related rash developed 842 days after the start of LTG. Although the number of patients is limited, long-term LTG monotherapy appeared to be effective and generally well tolerated in Japanese and South Korean pediatric patients with typical absence seizures. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

One-Year Outcomes following Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in Japanese Patients: The APOLLO Study.

PubMed

Oshima, Yuji; Kimoto, Kenichi; Yoshida, Noriko; Fujisawa, Kimihiko; Sonoda, Shozo; Kubota, Toshiaki; Murata, Toshinori; Sakamoto, Taiji; Yoshida, Shigeo; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2017-01-01

To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses. The primary endpoint assessed was the proportion of patients maintaining baseline best-corrected visual acuity (BCVA) at 1 year. Fifty eyes with PCV were included in the study. BCVA was maintained or improved in 97.6% of the patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR 1 year after the initiation of aflibercept treatment (p < 0.001). Mean central foveal thickness decreased from 356 to 239 μm (p < 0.001). Complete regression of polypoidal lesions was seen in 72.5% after 1 year of treatment. One year of IVA resulted in stabilization of BCVA and anatomical improvement in Japanese PCV patients. © 2017 S. Karger AG, Basel.

Clinical Characteristics, Management, and Outcomes of Japanese Patients Hospitalized for Heart Failure With Preserved Ejection Fraction　- A Report From the Japanese Heart Failure Syndrome With Preserved Ejection Fraction (JASPER) Registry.

PubMed

Nagai, Toshiyuki; Yoshikawa, Tsutomu; Saito, Yoshihiko; Takeishi, Yasuchika; Yamamoto, Kazuhiro; Ogawa, Hisao; Anzai, Toshihisa

2018-05-25

Despite the specific characteristics of heart failure with preserved ejection fraction (HFpEF) having been demonstrated predominantly from registries in Western countries, important international differences exist in terms of patient characteristics, management and medical infrastructure between Western and Asian countries.Methods and Results:We performed nationwide registration of consecutive Japanese hospitalized HFpEF patients with left ventricular EF ≥50% from 15 sites between November 2012 and March 2015. Follow-up data were obtained up to 2 years post-discharge. A total of 535 patients were registered. The median age was 80 years and 50% were female. The most common comorbid conditions were hypertension (77%) and atrial fibrillation (AF: 62%), but body mass index was relatively low. In-hospital mortality rate was 1.3% and the median length of hospitalization was 16 days. By 2 years post-discharge, 40.8% of patients had all-cause death or HF hospitalization. Approximately one-half of deaths had a cardiac cause. Lower serum albumin on admission was one of the strongest independent determinants of worse clinical outcome. Japanese HFpEF patients were less obese, but had a substantially higher prevalence of AF and lower incidence of subsequent events compared with previous reports. Our findings indicated that specific preventative and therapeutic strategies focusing on AF and nutritional status might need to be considered for Japanese hospitalized patients with HFpEF.

Visual reproduction on the Wechsler Memory Scale-Revised as a predictor of Alzheimer's disease in Japanese patients with mild cognitive impairments.

PubMed

Hori, Takumi; Sanjo, Nobuo; Tomita, Makoto; Mizusawa, Hidehiro

2013-01-01

The Visual Reproduction (VR) test is used to assess mild cognitive impairment (MCI), but the characteristics of visual memory in Japanese MCI patients remain unclear. VR scores of 27 MCI patients were evaluated using the Wechsler Memory Scale-Revised. Scores of MCI, no-dementia, and Alzheimer's disease (AD) groups were then compared. The annual conversion rate of MCI to AD was 18.8%. Mean VR-I and VR-II baseline scores for MCI patients were 33.3 ± 5.6 and 20.5 ± 14.0, respectively. Mean VR-II scores for converted and nonconverted MCI patients were 7.2 ± 8.7 and 29.8 ± 9.3, respectively. It is likely that VR-II and VR-II/I scores are more sensitive for predicting conversion to AD in Japanese than in American MCI patients. Our results indicate that VR is a sensitive and useful measure for predicting the conversion of Japanese MCI patients to AD within 2 years. Copyright © 2013 S. Karger AG, Basel.

Cognitive behavioral therapy for depression in Japanese Parkinson’s disease patients: a pilot study

PubMed Central

Shinmei, Issei; Kobayashi, Kei; Oe, Yuki; Takagishi, Yuriko; Kanie, Ayako; Ito, Masaya; Takebayashi, Yoshitake; Murata, Miho; Horikoshi, Masaru; Dobkin, Roseanne D

2016-01-01

Objectives This study evaluated the feasibility of cognitive behavioral therapy (CBT) for Japanese Parkinson’s disease (PD) patients with depression. To increase cultural acceptability, we developed the CBT program using manga, a type of Japanese comic novel. Methods Participants included 19 non-demented PD patients who had depressive symptoms (GRID-Hamilton Rating Scale for Depression score ≥8). A CBT program comprising six sessions was individually administered. We evaluated the feasibility and safety of the CBT program in terms of the dropout rate and occurrence of adverse events. The primary outcome was depressive symptom reduction in the GRID-Hamilton Rating Scale for Depression upon completion of CBT. Secondary outcomes included changes in the self-report measures of depression (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale-Depression), anxiety (Hospital Anxiety and Depression Scale-Anxiety, State and Trait Anxiety Inventory, Overall Anxiety Severity and Impairment Scale), functional impairment, and quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey). Results Of the 19 participants (mean age =63.8 years, standard deviation [SD] =9.9 years; mean Hohen–Yahr score =1.7, SD =0.8), one patient (5%) withdrew. No severe adverse event was observed. The patients reported significant improvements in depression (Hedges’ g =−1.02, 95% confidence interval =−1.62 to −0.39). The effects were maintained over a 3-month follow-up period. Most of the secondary outcome measurements showed a small-to-moderate but nonsignificant effect size from baseline to post-intervention. Conclusion This study provides preliminary evidence that CBT is feasible among Japanese PD patients with depression. Similar approaches may be effective for people with PD from other cultural backgrounds. The results warrant replication in a randomized controlled trial. PMID:27354802

Contributions of the Japanese Gynecologic Oncology Group (JGOG) in Improving the Quality of Life in Women With Gynecological Malignancies.

PubMed

Futagami, Masayuki; Yokoyama, Yoshihito; Shimada, Muneaki; Sato, Shinya; Miyagi, Etsuko; Tozawa-Ono, Akiko; Suzuki, Nao; Fujimura, Masaki; Aoki, Yoichi; Sagae, Satoru; Sugiyama, Toru

2017-04-01

The Japanese Gynecologic Oncology Group (JGOG) is leading Japan in the treatment of gynecological malignancies. The JGOG consists of three treatment committees focusing on uterine cervical cancer, endometrial cancer, and ovarian cancer. Each committee makes efforts to improve treatment and diagnosis. In addition, the Supportive and Palliative Care Committee was established in 2015. Novel studies of supportive care and palliative care have been initiated by this committee. Furthermore, surveys about not only treatment results such as overall survival rates but also quality of life (QOL) and cost-effectiveness assessments are performed by the ovarian cancer committee. Improvements of patients' QOL in the treatment of gynecological malignancies were divided into three concepts as follows: QOL associated with cancer treatment, health care after cancer therapy, and progression of cancer. In this review, we report the contributions and future plans for the improvement of QOL in patients with gynecological malignancies.

Prevalence of scars and "mini-scars", and their impact on quality of life in Japanese patients with acne.

PubMed

Hayashi, Nobukazu; Miyachi, Yoshiki; Kawashima, Makoto

2015-07-01

There have been very few studies on the prevalence and severity of acne scars in Japanese patients. The aim of the present study was to investigate the prevalence of acne scars and their impact on the quality of life (QOL) in Japanese acne patients. Acne scars were classified as mini-scars (atrophic scars of ≥0.5 and <2 mm in diameter) atrophic scars (≥2 mm in diameter), and hypertrophic scars. The severity of acne and acne scars were evaluated. The background of patients and their QOL in relation to acne were assessed. Of 240 subjects, 218 (90.8%) had scars. All patients with scars had mini-scars; 61.2% and 14.2% of 240 had atrophic scars and hypertrophic scars, respectively. Severe scarring was found in patients who had experienced severe acne symptoms, although 15.0% of patients with scars had experienced only mild acne symptoms. The total Dermatology Life Quality Index score was significantly higher in patients with scars than in patients without scars (5.9 ± 4.4 vs 4.2 ± 4.1). Almost all the patients had small atrophic scars with a diameter of 0.5 or more and less than 2 mm, which we have termed "mini-scars". Acne scars had a negative impact on patient QOL. Early initiation of treatment is recommended to avoid acne scars. © 2015 Japanese Dermatological Association.

Effect of low-dose aspirin on primary prevention of cardiovascular events in Japanese diabetic patients at high risk.

PubMed

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Sugiyama, Seigo; Jinnouchi, Hideaki; Waki, Masako; Doi, Naofumi; Horii, Manabu; Kawata, Hiroyuki; Somekawa, Satoshi; Soeda, Tsunenari; Uemura, Shiro; Saito, Yoshihiko

2013-01-01

Benefit of low-dose aspirin for primary prevention of cardiovascular events in diabetes remains controversial. The American Diabetes Association (ADA), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend aspirin for high-risk diabetic patients: older patients with additional cardiovascular risk factors. We evaluated aspirin's benefit in Japanese diabetic patients stratified by cardiovascular risk. In the JPAD trial, we enrolled 2,539 Japanese patients with type 2 diabetes and no history of cardiovascular disease. We randomly assigned them to aspirin (81-100 mg daily) or no aspirin groups. The median follow-up period was 4.4 years. We stratified the patients into high-risk or low-risk groups, according to the US recommendation: age (older; younger) and coexisting cardiovascular risk factors. The risk factors included smoking, hypertension, dyslipidemia, family history of coronary artery disease, and proteinuria. Most of the patients were classified into the high-risk group, consisting of older patients with risk factors (n=1,804). The incidence of cardiovascular events was higher in this group, but aspirin did not reduce cardiovascular events (hazard ratio [HR], 0.83; 95% confidence interval [CI]: 0.58-1.17). In the low-risk group, consisting of older patients without risk factors and younger patients (n=728), aspirin did not reduce cardiovascular events (HR, 0.55; 95% CI: 0.23-1.21). These results were unchanged after adjusting for potential confounding factors. Low-dose aspirin is not beneficial in Japanese diabetic patients at high risk.

Population pharmacokinetics of intravenous acetaminophen in Japanese patients undergoing elective surgery.

PubMed

Imaizumi, Tsuyoshi; Obara, Shinju; Mogami, Midori; Iseki, Yuzo; Hasegawa, Makiko; Murakawa, Masahiro

2017-06-01

Intravenous (i.v.) acetaminophen is administered during surgery for postoperative analgesia. However, little information is available on the pharmacokinetics of i.v. acetaminophen in Japanese patients undergoing surgery under general anesthesia. The study was approved by the Institutional Review Board and registered at UMIN-CTR (UMIN000013418). Patients scheduled to undergo elective surgery under general anesthesia were enrolled after obtaining written informed consent. During surgery, 1 g of i.v. acetaminophen was administered over 15, 60, or 120 min. Acetaminophen concentrations (15 or 16 samples per case) were measured at time points from 0-480 min after the start of administration (liquid chromatography-mass spectrometry/tandem mass spectrometry; limit of quantitation 0.1 μg/mL). The predictive performance of three published pharmacokinetic models was evaluated. Population pharmacokinetics were also analyzed using a nonlinear mixed-effect model based on the NONMEM program. Data from 12 patients who underwent endoscopic or lower limb procedures were analyzed (male/female = 7/5, median age 55 years, weight 63 kg). Anesthesia was maintained with remifentanil and propofol or sevoflurane. The pharmacokinetic model of i.v. acetaminophen reported by Würthwein et al. worked well. Using 185 datapoints, the pharmacokinetics of i.v. acetaminophen were described by a two-compartment model with weight as a covariate but not age, sex, or creatinine clearance. The median prediction error and median absolute prediction error of the final model were -1 and 10%, respectively. A population pharmacokinetic model of i.v. acetaminophen in Japanese patients was constructed, with performance within acceptable ranges.

Genetic, epidemiologic and clinicopathologic studies of Japanese Asian patients with Birt-Hogg-Dubé syndrome.

PubMed

Furuya, Mitsuko; Yao, Masahiro; Tanaka, Reiko; Nagashima, Yoji; Kuroda, Naoto; Hasumi, Hisashi; Baba, Masaya; Matsushima, Jun; Nomura, Fumio; Nakatani, Yukio

2016-11-01

Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder characterized by fibrofolliculomas, pulmonary cysts and renal cell carcinomas (RCCs). The affected individuals inherit germline mutations in the folliculin gene (FLCN). We investigated the mutation spectrum and clinicopathologic findings of 312 patients from 120 different families (119 Japanese and 1 Taiwanese). A total of 31 different FLCN sequence variants were identified. The majority were c.1285dupC (n = 34), c.1533_1536delGATG (n = 25), and c.1347_1353dupCCACCCT (n = 19). Almost all patients presented with pulmonary cysts. The incidence of RCCs in FLCN mutation carriers over the age of 40 was 34.8% (40/115). Fifty-five RCC lesions were surgically resected; most were either chromophobe RCC (n = 24; 43.6%) or hybrid oncocytic/chromophobe tumors (19; 34.5%). Seventy-six of 156 FLCN mutation carriers (120 probands and 36 sibs, 48.7%) had skin papules; however, cutaneous manifestations were so subtle that only one patient voluntarily consulted dermatologists. Japanese Asian BHD families have three FLCN mutational hotspots. Recurrent episodes of pneumothoraces are the major symptoms suggestive of a BHD diagnosis in our cohort. Characteristic features of lung and kidney lesions may be more informative than fibrofolliculomas as diagnostic criteria for BHD in the Japanese Asian population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

PubMed Central

Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

2012-01-01

Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients.

PubMed

Gejyo, Fumitake; Saito, Akira; Akizawa, Tadao; Akiba, Takashi; Sakai, Tatsuya; Suzuki, Masashi; Nishi, Shinichi; Tsubakihara, Yoshiharu; Hirakata, Hideki; Bessho, Masami

2004-12-01

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic

Safety and benefits of a tablet combining losartan and hydrochlorothiazide in Japanese diabetic patients with hypertension.

PubMed

Kinouchi, Kenichiro; Ichihara, Atsuhiro; Sakoda, Mariyo; Kurauchi-Mito, Asako; Itoh, Hiroshi

2009-12-01

This study was conducted to determine the effects of a tablet combining losartan/hydrochlorothiazide (L/HCTZ) in comparison with losartan alone in Japanese diabetic patients with hypertension. Thirty consecutive Japanese diabetic patients with hypertension were randomly assigned to group A, receiving losartan alone for the first 3 months, then L/HCTZ for the next 3 months, or group B, receiving L/HCTZ for the first 3 months, then losartan alone for the next 3 months. Clinical and biological parameters were obtained before, and 3 and 6 months after the start of this study. The decreases in systolic and diastolic blood pressure (BP) during treatment with L/HCTZ were significantly greater than in treatment with losartan alone. Both treatments significantly and similarly decreased urinary albumin excretion, the cardio-ankle vascular index (CAVI) and augmentation index (AI). There was no significant difference in metabolic change during both the mono- and combination pharmacotherapies. The tablet combining L/HCTZ significantly reduced systolic and diastolic BP compared with the losartan monotherapy, and offered benefits similar to losartan monotherapy for albuminuria, arterial stiffness assessed by the CAVI and AI, and metabolic effects. Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic patients with hypertension.

VCP gene analyses in Japanese patients with sporadic amyotrophic lateral sclerosis identify a new mutation.

PubMed

Hirano, Makito; Nakamura, Yusaku; Saigoh, Kazumasa; Sakamoto, Hikaru; Ueno, Shuichi; Isono, Chiharu; Mitsui, Yoshiyuki; Kusunoki, Susumu

2015-03-01

Accumulating evidence has proven that mutations in the VCP gene encoding valosin-containing protein (VCP) cause inclusion body myopathy with Paget disease of the bone and frontotemporal dementia. This gene was later found to be causative for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, occurring typically in elderly persons. We thus sequenced the VCP gene in 75 Japanese patients with sporadic ALS negative for mutations in other genes causative for ALS and found a novel mutation, p.Arg487His, in 1 patient. The newly identified mutant as well as known mutants rendered neuronal cells susceptible to oxidative stress. The presence of the mutation in the Japanese population extends the geographic region for involvement of the VCP gene in sporadic ALS to East Asia. Copyright © 2015 Elsevier Inc. All rights reserved.

Japanese Structure Survey of Radiation Oncology in 2005 Based on Institutional Stratification of Patterns of Care Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teshima, Teruki; Numasaki, Hodaka; Shibuya, Hitoshi

2008-09-01

Purpose: To evaluate the structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and improve any deficiencies. Methods and Materials: A questionnaire-based national structure survey was conducted between March 2006 and February 2007 by the Japanese Society of Therapeutic Radiology and Oncology. These data were analyzed in terms of the institutional stratification of the Patterns of Care Study. Results: The total numbers of new cancer patients and total cancer patients (new and repeat) treated with radiotherapy in 2005 were estimated at approximately 162,000 and 198,000, respectively. In actual use were 765more » linear accelerators, 11 telecobalt machines, 48 GammaKnife machines, 64 {sup 60}Co remote-controlled after-loading systems, and 119 {sup 192}Ir remote-controlled after-loading systems. The linear accelerator systems used dual-energy function in 498 systems (65%), three-dimensional conformal radiotherapy in 462 (60%), and intensity-modulated radiotherapy in 170 (22%). There were 426 Japanese Society of Therapeutic Radiology and Oncology-certified radiation oncologists, 774 full-time equivalent radiation oncologists, 117 medical physicists, and 1,635 radiation therapists. Geographically, a significant variation was found in the use of radiotherapy, from 0.9 to 2.1 patients/1,000 population. The annual patient load/FTE radiation oncologist was 247, exceeding the Blue Book guidelines level. Patterns of Care Study stratification can clearly discriminate the maturity of structures according to their academic nature and caseload. Conclusions: The Japanese structure has clearly improved during the past 15 years in terms of equipment and its use, although the shortage of manpower and variations in maturity disclosed by this Patterns of Care Study stratification remain problematic. These constitute the targets for nationwide improvement in quality assurance and quality control.« less

Lung cancer in younger patients.

PubMed

Abbasowa, Leda; Madsen, Poul Henning

2016-07-01

Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. To assess the age differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly diagnosed lung cancer patients were included. Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours, a significantly higher proportion of the younger patients presented with advanced stage disease (p = 0.0392). Combined modality therapy was more common in younger patients (p = 0.0009), while chemotherapy appeared less prevalent among the elderly (p = 0.0015). Lung cancer in younger patients comprises a distinct clinicopathological entity with more frequent advanced stage disease and a significantly greater proportion with a family history of cancer. Implementing genetic background assessments and considering lung cancer as a possible diagnosis in younger, symptomatic patients, is of paramount importance. none. The study was approved by the -Danish Data Protection Agency.

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

PubMed

Yokoyama, Shota; Tsuji, Hideyuki; Hiraoka, Sachiko; Nishihara, Masayuki

2016-01-01

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

Yokukansan for the treatment of preoperative anxiety and postoperative delirium in colorectal cancer patients: a retrospective study.

PubMed

Wada, Saho; Inoguchi, Hironobu; Hirayama, Takatoshi; Matsuoka, Yutaka J; Uchitomi, Yosuke; Ochiai, Hiroki; Tsukamoto, Shunsuke; Shida, Dai; Kanemitsu, Yukihide; Shimizu, Ken

2017-09-01

Yokukansan (YKS), a Japanese traditional herbal medicine for neurosis and insomnia, is speculated to be useful for perioperative psychiatric symptoms in cancer patients, but there exists little empirical evidence. This study provides preliminary data about the efficacy, feasibility, and side effects of YKS for the treatment of preoperative anxiety and postoperative delirium in cancer patients. We retrospectively reviewed the medical records of colorectal cancer patients who took YKS for preoperative anxiety, evaluating the following: (1) patient characteristics, (2) feasibility of taking YKS, (3) changes in preoperative anxiety based on the Clinical Global Impression (CGI) scale and Edmonton Symptom Assessment System-revised (ESAS-r-anxiety), (4) incidence of postoperative delirium and (5) YKS-related side effects. We reviewed 19 medical records. There was a significant difference between ESAS-r-anxiety scores (P = 0.028) before and after taking YKS, but no difference between CGI scores (P = 0.056). The incidence of postoperative delirium was 5.2% (95% CI = 0.0-14.5). One patient could not complete the course of YKS during the perioperative administration period, but there were no side effects of Grade 2 or worse according to the Common Terminology Criteria for Adverse Events v4. Cancer patients could safely take YKS before surgery. There was a significant improvement in preoperative anxiety after taking YKS, and the incident rate of postoperative delirium was lower than in previous studies. These results suggest that YKS may be useful for perioperative psychiatric symptoms in cancer patients. Further well-designed studies are needed to substantiate our results. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effects of Anma therapy (Japanese massage) on health-related quality of life in gynecologic cancer survivors: A randomized controlled trial.

PubMed

Donoyama, Nozomi; Satoh, Toyomi; Hamano, Tetsutaro; Ohkoshi, Norio; Onuki, Mamiko

2018-01-01

Anma therapy (Japanese massage therapy, AMT) significantly reduces the severity of physical complaints in survivors of gynecologic cancer. However, whether this reduction of severity is accompanied by improvement in health-related quality of life is unknown. Forty survivors of gynecologic cancer were randomly allocated to either an AMT group that received one 40-min AMT session per week for 8 weeks or a no-AMT group. We prospectively measured quality of life by using the Japanese version of the European Organization for Research and Treatment of Cancer QLQ-C30 version 3.0 (EORTC QLQ-C30) at baseline and at 8-week follow-up. The QLQ-C30 response rate was 100%. Hospital Anxiety Depression Scale (HADS), Profile of Mood States (POMS), and Measure of Adjustment to Cancer were also prespecified and prospectively evaluated. The QLQ-C30 Global Health Status and Quality of Life showed significant improvement at 8 weeks (P = 0.042) in the AMT group compared with the no-AMT group, and the estimated mean difference reached a minimal clinically important difference of 10 points (10.4 points, 95% CI = 1.2 to 19.6). Scores on fatigue and insomnia showed significant improvement in the AMT group compared with the no-AMT group (P = 0.047 and 0.003, respectively). There were no significant between-group improvements in HADS anxiety and depression scales; however, POMS-assessed anger-hostility showed significant improvement in the AMT group compared with the no-AMT group (p = 0.028). AMT improved health-related quality of life in gynecologic cancer survivors. AMT can be of potential benefit for applications in oncology.

Improving cancer patient care: development of a generic cancer consumer quality index questionnaire for cancer patients

PubMed Central

2013-01-01

Background To develop a Consumer Quality Index (CQI) Cancer Care questionnaire for measuring experiences with hospital care of patients with different types of cancer. Methods We derived quality aspects from focus group discussions, existing questionnaires and literature. We developed an experience questionnaire and sent it to 1,498 Dutch cancer patients. Another questionnaire measuring the importance of the quality aspects was sent to 600 cancer patients. Data were psychometrically analysed. Results The response to the experience questionnaire was 50 percent. Psychometric analysis revealed 12 reliable scales. Patients rated rapid and adequate referral, rapid start of the treatment after diagnosis, enough information and confidence in the healthcare professionals as most important themes. Hospitals received high scores for skills and cooperation of healthcare professionals and a patient-centered approach by doctors; and low scores for psychosocial guidance and information at completion of the treatment. Conclusions The CQI Cancer Care questionnaire is a valuable tool for the evaluation of the quality of cancer care from the patient’s perspective. Large scale implementation is necessary to determine the discriminatory powers of the questionnaire and may enable healthcare providers to improve the quality of cancer care. Preliminary results indicate that hospitals could improve their psychosocial guidance and information provision. PMID:23617741

Lifestyle characteristics assessment of Japanese in Pittsburgh, USA.

PubMed

Hirooka, Nobutaka; Takedai, Teiichi; D'Amico, Frank

2012-04-01

Lifestyle-related chronic diseases such as cancer and cardiovascular disease are the greatest public health concerns. Evidence shows Japanese immigrants to a westernized environment have higher incidence of lifestyle-related diseases. However, little is known about lifestyle characteristics related to chronic diseases for Japanese in a westernized environment. This study is examining the gap in lifestyle by comparing the lifestyle prevalence for Japanese in the US with the Japanese National Data (the National Health and Nutrition Survey in Japan, J-NHANS) as well as the Japan National Health Promotion in the twenty-first Century (HJ21) goals. Japanese adults were surveyed in Pittsburgh, USA, regarding their lifestyle (e.g., diet, exercise, smoking, stress, alcohol, and oral hygiene). The prevalence was compared with J-NHANS and HJ21 goals. Ninety-three responded (response rate; 97.9%). Japanese men (n = 38) and women (n = 55) in Pittsburgh smoke less than Japanese in Japan (P < 0.001 for both genders). Japanese in Pittsburgh perform less physical activity in daily life and have lower prevalence of walking more than 1 h per day (P < 0.001 for both genders). Japanese women in Pittsburgh have significantly higher prevalence of stress than in Japan (P = 0.004). Japanese men in Pittsburgh do not reach HJ21 goal in weight management, BMI, use of medicine or alcohol to sleep, and sleep quality. Japanese women in Pittsburgh do not reach HJ21 goal in weight management and sleep quality. In conclusion, healthy lifestyle promotion including exercise and physical activity intervention for Japanese living in a westernized environment is warranted.

Risk of Japanese carriers of hyperphosphorylated paratarg-7, the first autosomal-dominantly inherited risk factor for hematological neoplasms, to develop monoclonal gammopathy of undetermined significance and multiple myeloma.

PubMed

Grass, Sandra; Iida, Shinsuke; Wikowicz, Aleksandra; Preuss, Klaus-Dieter; Inagaki, Atsushi; Shimizu, Kazuyuki; Ziepert, Marita; Ueda, Ryuzo; Pfreundschuh, Michael

2011-03-01

Hyperphosphorylated paratarg-7 (pP-7) is a frequent target of paraproteins in German patients with monoclonal gammopathy of undetermined significance (MGUS)/multiple myeloma (MM). The frequency of MGUS/MM is lower in Japan than in Europe. As pP-7, the first molecularly defined autosomal-dominant risk factor for any hematological neoplasm, is inherited in a dominant fashion, we determined the incidence of the pP-7 carrier state in a Japanese population, and compared the frequency of pP-7-specific paraproteins and the pP-7 carrier state in Japanese and German patients with MGUS/MM. Peripheral blood from 111 Japanese patients with MGUS/MM and 278 healthy blood donors was analyzed for the pP-7 carrier state by isoelectric focusing and for pP-7-specific antibodies by ELISA. The Japanese group was compared with 252 German MGUS/MM patients and 200 healthy controls. Five of 111 (4.5%) Japanese and 35/252 (13.9%) German IgA/IgG MGUS/MM patients had a pP-7-specific paraprotein (P=0.009). The prevalence of healthy pP-7 carriers in the Japanese study group was 1/278 (0.36%), whereas it was 4/200 in the German group (P=0.166). The relative risk for pP-7 carriers developing MGUS/MM had an odds ratio of 13.1 in the Japanese and 7.9 in the German group. In conclusion, the fraction of pP-7 carriers with a pP-7-specific paraprotein is lower among Japanese than in German patients with MGUS/MM, but pP-7 carriers in both ethnic groups have a high risk of developing MGUS/MM. © 2011 Japanese Cancer Association.

Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study.

PubMed

Eto, Y; Ohashi, T; Utsunomiya, Y; Fujiwara, M; Mizuno, A; Inui, K; Sakai, N; Kitagawa, T; Suzuki, Y; Mochizuki, S; Kawakami, M; Hosoya, T; Owada, M; Sakuraba, H; Saito, H

2005-01-01

Fabry Disease (alpha-galactosidase A deficiency) is an X-linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL-3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open-label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The study design mirrored the design of the completed phase 3 clinical trial that led to approval of the product agalsidase beta. The 13 Japanese, male Fabry patients enrolled in the study received the enzyme replacement therapy over a period of 20 weeks as biweekly infusions. All selected efficacy end points showed improvements that were comparable with findings from the phase 3 study. These improvements included reductions of GL-3 accumulation in both kidney and skin capillary endothelial cells to (near) normal levels (92% of patients). Kidney and plasma GL-3 levels decreased by 51.9% and 100%, respectively, by ELISA. Renal function remained normal. Fabry-associated pain, and quality of life, showed improvement over baseline in multiple categories. Related adverse events were mild or moderate in intensity and mostly infusion-associated (fever and rigors). As expected, IgG antibody formation was observed in 85% of the patients, but had no effect on treatment response. These results suggest that treatment with agalsidase beta is safe and effective in Japanese patients with Fabry disease. With regard to safety and efficacy, no differences were observed as compared to the caucasian population.

Physical Disabilities Related to the Depressive Mental States of Japanese Patients with Subacute Myelo-optico-neuropathy.

PubMed

Konishi, Tetsuro

2018-05-18

Objective The aim of this study was to clarify the clinical conditions related to the depressive mental states in Japanese patients with subacute myelo-optico-neuropathy (SMON), caused by clioquinol intoxication more than 40 years previously. Materials and methods The changes in the mental states with aging were investigated in 25 Japanese SMON patients (mean age: 77.2 years old, range: 53-90) using a Japanese version of the Zung Self-rating Depression Scale (J-SDS) questionnaires with supportive interviews by the clinical psychotherapist and medical checkup records. These mental and medical examinations were repeated more than twice within 2 to 11 years' interval. The J-SDS questionnaires were also examined in 25 age-matched non-SMON elderly people. Results The total J-SDS scores of most of the SMON patients decreased with age without significant changes in the mean Barthel index scores during this study period. The mean J-SDS scores at the first and latest studies were significantly higher than in the age-matched healthy elderly people. The total J-SDS scores of the latest study were significantly correlated with the degree of physical disability, such as the inverse total Barthel index scores, severity of SMON or gait disturbance, but not with the age. Conclusion The total J-SDS scores of most of the SMON patients tended to decrease with age. Repeating mental supportive interviews and medical examinations by experts helped to improve the depressive mental state and revealed close relationship between the mental state and the physical disabilities of the SMON patients.

The Association Between Pain and Quality of Life for Patients With Cancer in an Outpatient Clinic, an Inpatient Oncology Ward, and Inpatient Palliative Care Units.

PubMed

Mikan, Fukiko; Wada, Makoto; Yamada, Michiko; Takahashi, Ayaka; Onishi, Hideki; Ishida, Mayumi; Sato, Kazuki; Shimizu, Sachiko; Matoba, Motohiro; Miyashita, Mitsunori

2016-09-01

This study was designed to clarify the association between pain and quality of life (QOL) of Japanese patients with cancer using a cancer-specific QOL scale (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C15-PAL) in 3 care settings (outpatient, inpatient, and palliative care units [PCUs]). We examined the above-mentioned purpose for the total of 404 patients. In outpatients, physical, emotional functioning (EF), and global health status/QOL (QL item) were significantly correlated with average pain, and their correlation coefficients were -0.37 to -0.46 (P < .0001). In inpatients, they were -0.33 (P = .006), -0.26 (P = .030), and -0.31 (P = .012). In the PCU patients, they were -0.12 (P = .316), -0.30 (P = .009), and -0.28 (P = .015). Patients' pain had an association with physical and emotional QOL, and the association was smaller in the PCU patients than the others. © The Author(s) 2016.

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

PubMed

Kotooka, Norihiko; Kitakaze, Masafumi; Nagashima, Kengo; Asaka, Machiko; Kinugasa, Yoshiharu; Nochioka, Kotaro; Mizuno, Atsushi; Nagatomo, Daisuke; Mine, Daigo; Yamada, Yoko; Kuratomi, Akiko; Okada, Norihiro; Fujimatsu, Daisuke; Kuwahata, So; Toyoda, Shigeru; Hirotani, Shin-Ichi; Komori, Takahiro; Eguchi, Kazuo; Kario, Kazuomi; Inomata, Takayuki; Sugi, Kaoru; Yamamoto, Kazuhiro; Tsutsui, Hiroyuki; Masuyama, Tohru; Shimokawa, Hiroaki; Momomura, Shin-Ichi; Seino, Yoshihiko; Sato, Yasunori; Inoue, Teruo; Node, Koichi

2018-02-15

Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

PubMed Central

2009-01-01

Background The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model. Methods Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model. Results The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range. Conclusion Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10

Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care

PubMed Central

Nishimura, Toshihide; Kato, Harubumi; Ikeda, Norihiko; Kihara, Makoto; Nomura, Masaharu; Kato, Yasufumi; Marko-Varga, György

2012-01-01

An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib) and TARCEVA (Erlotinib) treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care. PMID:22685658

Successful treatment by pembrolizumab in a patient with end-stage renal disease with advanced non-small cell lung cancer and high PD-L1 expression.

PubMed

Ishizuka, Shiho; Sakata, Shinya; Yoshida, Chieko; Takaki, Akira; Saeki, Sho; Nakamura, Kazuyoshi; Fujii, Kazuhiko

2018-05-10

We report a 66-year-old Japanese male with end-stage renal disease (ESRD) and advanced non-small cell lung cancer (NSCLC) who was on hemodialysis. The patient harbored high programmed death ligand 1 (PD-L1) expression and was successfully treated with pembrolizumab. Laboratory examination upon diagnosis showed elevated serum creatinine (6.58 mg/dL). We administered pembrolizumab (200 mg/body) and repeated every 3 weeks. His renal dysfunction gradually progressed, hemodialysis was initiated after eight courses of pembrolizumab, and the antitumor effect was maintained at five months after hemodialysis initiation. Therefore, pembrolizumab can be administered for patients with ESRD and advanced NSCLC, who harbor high PD-L1 expression, during preparation for hemodialysis. Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia.

PubMed

Tomiyama, Y; Miyakawa, Y; Okamoto, S; Katsutani, S; Kimura, A; Okoshi, Y; Ninomiya, H; Kosugi, H; Nomura, S; Ozaki, K; Ikeda, Y; Hattori, T; Katsura, K; Kanakura, Y

2012-05-01

Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has shown efficacy and safety in chronic immune thrombocytopenia (ITP). However, ethnic differences in eltrombopag exposure have been reported: area under the curve exposure to eltrombopag was 87% greater among ITP patients of East Asian descent than among ITP patients of non-East Asian ITP descent. To evaluate the efficacy and safety of eltrombopag by using, in Japanese ITP patients, lower starting (12.5 mg) and maximum (50 mg) doses of eltrombopag than the standard starting (50 mg) and maximum (75 mg) doses approved in the USA and Europe. We examined 23 Japanese patients with previously treated chronic ITP with a platelet count of < 30,000 μL(-1) in a multicenter study comprising a randomized, double-blind, placebo-controlled phase for 6-week evaluation (15 eltrombopag, and eight placebo) and an open-label phase for 6-month evaluation (23 eltrombopag). The response rate (platelet count of ≥ 50,000 μL(-1) ) at week 6 of the 6-week double-blind phase was 60% in eltrombopag-treated patients and 0% in placebo-treated patients. Ten of 23 patients (43.5%) responded for ≥ 75% of predefined assessment visits during the 6-month open-label phase. Notably, 22% (5/23) of patients responded to 12.5 mg of eltrombopag, which was administered within the first 3 weeks of eltrombopag treatment. Bleeding decreased with eltrombopag treatment as compared with baseline. Eltrombopag was generally well tolerated; one patient experienced a transient ischemic attack on day 9. Eltrombopag (12.5-50 mg) is effective for the management of Japanese patients with chronic ITP (NCT00540423). © 2012 International Society on Thrombosis and Haemostasis.

Age and Prevalence of Esophageal Reflux Disease in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

PubMed

Ikeda, Yoshio; Furukawa, Shinya; Sakai, Takenori; Niiya, Tetsuji; Miyaoka, Hiroaki; Miyake, Teruki; Yamamoto, Shin; Senba, Hidenori; Yamamoto, Yasunori; Arimitsu, Eiji; Yagi, Sen; Utsunomiya, Hiroki; Tanaka, Keiko; Takeshita, Eiji; Matsuura, Bunzo; Miyake, Yoshihiro; Hiasa, Yoichi

2016-12-01

Only limited epidemiological evidence exists regarding the relationship between age and gastroesophageal reflux disease (GERD) among Japanese patients with type 2 diabetes mellitus. The purpose of the present study is to investigate this issue among Japanese patients with type 2 diabetes mellitus. A multicenter cross-sectional study was conducted in 847 Japanese patients with type 2 diabetes mellitus. Subjects were divided into quartiles according to age: (1) 19 ≤ age < 56, (2) 56 ≤ age < 64, (3) 64 ≤ age < 71, and (4) 71 ≤ age < 89. GERD was defined as present when a subject had a Carlsson-Dent self-administered questionnaire (QUEST) score ≥4. The prevalence of GERD was 31.5 %. Younger age was independently associated with a higher prevalence of GERD: the adjusted odds ratios (95 % confidence intervals) for GERD in relation to age < 56, 56 ≤ age < 64, 64 ≤ age < 71, and ≥71 were 3.73 (2.16-6.53), 1.98 (1.21-3.27), 1.66 (1.05-2.68), and 1.00 (reference), respectively (P for trend = 0.001). Among 201 patients with PPI or histamine H 2 -receptor antagonist (H2RA), less than 56 years of age was independently positively associated with GERD: the adjusted OR was 5.68 (95 % CI 1.55-22.18) (P for trend = 0.02). Younger age may be independently positively associated with GERD among Japanese type 2 diabetes mellitus patients, regardless of the use of PPI or H2RA.

Mortality in Japanese with life-styles similar to Seventh-Day Adventists: strategy for risk reduction by life-style modification.

PubMed

Hirayama, T

1985-12-01

Using 16 years of follow-up results of a prospective cohort study for 122,261 men, 95% of the census population, aged 40 years and older in 29 Health Center Districts in Japan as subjects, we compared the age-standardized mortality rates for cancer of each site and other causes of death in Japanese with life-styles similar to those of Seventh-Day Adventists (SDA), i.e., no smoking, no drinking, no meat consumption daily and eating green and yellow vegetables daily, with those of Japanese with opposite life-styles. Compared with the latter Japanese, the risks were one-fifth or less in Japanese with SDA-like life-styles for cancers of the mouth, pharynx, esophagus, and lung, and subarachnoid hemorrhage. Risks were less than one-half for cancers of all sites, stomach, and liver, and for peptic ulcer and heart disease. As a single factor, the addition of daily smoking was observed to elevate the risk most strikingly in Japanese who followed SDA life patterns. Influences of further addition of habits of daily drinking of alcohol and dietary changes were significant for cancers of the esophagus, liver, and bladder and other selected diseases. Strategies for cancer prevention by means of life-style modification, e.g., increased consumption of green and yellow vegetables, were discussed.

Diagnostic and prognostic value of plasma and tissue ubiquitin-like, containing PHD and RING finger domains 1 in breast cancer patients.

PubMed

Geng, Yao; Gao, Yanfang; Ju, Huangxian; Yan, Feng

2013-02-01

Ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) has been reported to play an important role in breast carcinogenesis. This work investigated the correlation of UHRF1 DNA level in plasma with clinical characteristics of breast cancer and its clinical significance in breast cancer diagnosis. The expression of UHRF1 in primary breast cancer tissue was examined by Western blot. The UHRF1 DNA levels in plasma and UHRF1 mRNA expression in tissues were determined by accurate real-time quantitative PCR. The associations of UHRF1 levels with clinical variables were evaluated using standard statistical methods. The UHRF1 DNA in plasma of 229 breast cancer patients showed higher expression than healthy controls, which showed high specificity up to 76.2% at a sensitivity of 79.2%, and was significantly associated with c-erbB2 positive status, cancer stage and lymph node metastasis. High UHRF1 DNA level in plasma was significantly associated with short progression-free survival. The UHRF1 DNA level in plasma is highly correlative with breast cancer and its status and stage, and may be a potential independent diagnostic and prognostic factor for both breast cancer and the survival of breast cancer patients. © 2012 Japanese Cancer Association.

Attitudes and Perceptions of Cancer Patients Toward Biospecimen Donation for Cancer Research: A Cross-Sectional Survey Among Chinese Cancer Patients.

PubMed

He, Na; Guo, Yan; He, Min; Qiang, Wanmin; Li, Haixin

2017-08-01

High-quality biospecimen collection from consented patients is crucial for cancer research activities. Patients' attitudes and willingness toward specimen donation influence high-quality biospecimen collection for cancer research activities. We carried out a cross-sectional study among randomly selected patients from 11 cancer departments of Tianjin Medical University Cancer Institute and Hospital between August 2014 and August 2015. A total of 784 patients were included to complete a 30-item self-administered survey. We evaluated the patients' willingness to consider providing leftover samples and additional samples for cancer research purposes. Among 784 patients, 683 (87.1%) and 653 (83.3%) were willing to donate leftover tissue and surplus blood after diagnosis, respectively. Six hundred thirty-one (80.5%) were favorably disposed to consider donating both tissue and blood samples for future cancer research. Female patients showed less willingness to donate biospecimens or related clinical data for research. First-hospitalized or older patients were less willing to provide leftover biospecimens or additional blood samples or even clinical data for research. By contrast, patients with a higher education level were more likely to donate leftover tissues after biopsy or surgery for research activities. Most Chinese cancer patients were willing to consider donating blood and tissue samples for cancer research. Several factors, including age, gender, first hospitalization, and education level, can influence their willingness to donate biospecimens. We need to provide proper education to increase understanding of patients in biobanking activities. This study provides novel empirical data on the likelihood of donating surplus and additional biospecimens and clinical health information among Chinese cancer patients.

Japanese Competitiveness and Japanese Management.

ERIC Educational Resources Information Center

Minabe, Shigeo

1986-01-01

Analyzes and compares Japanese and American industrial policy and labor practices. Proposes that certain aspects of the Japanese system be adapted by American businesses for purpose of increasing international competitiveness. Proposes specific actions and plans for both the Japanese and American systems. (ML)

Relationship between environmental factors, age of onset and familial history in Japanese patients with psoriasis.

PubMed

Bayaraa, Bolortuya; Imafuku, Shinichi

2018-06-01

Psoriasis is a chronic inflammatory disease that often involves the skin and joints. Psoriasis develops at any age and the distribution of age of onset of psoriasis is bimodal in Japan. Also, male predominance is distinct in Japanese psoriatic patients. To clarify the relationship between sex difference and habitual/environmental status, age and incidence of familial psoriasis, we analyzed data from the Fukuoka University Psoriasis Registry. A total of 1120 Japanese patients (751 men, 369 women) were analyzed. The male/female ratio was 2.03:1. Smoking and drinking habit, known as risk factors of psoriasis, were significantly more prevalent in men. Age-specific psoriasis-onset rate standardized by population showed bimodal distribution in both men and women; the younger peak was in their 30s for men and 10s in women; the second peak was in the 50s for both sexes. A familial history of psoriasis was seen in 6.3% of patients overall; however, female patients showed a significantly higher rate (8.7%) compared with men (5.1%, P = 0.024). When stratified by age of onset, the frequency of familial history was much higher among women with onset at less than 30 years (15.4%), compared with 30 years or more (5.3%, P = 0.0026). Our data suggest that genetic factors have a stronger influence in young women who experience fewer environmental factors such as smoking and drinking. This is the first study to show that there is a difference in the incidence of familial psoriasis depending on age of onset of psoriasis in Japan. © 2018 Japanese Dermatological Association.

Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials.

PubMed

Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Kawai, Shinichi; Sugiyama, Naonobu; Yuasa, Hirotoshi; Yamashita, Noriaki; Sugiyama, Noriko; Wagerle, Lorin Craig; Vlahos, Bonnie; Wajdula, Joseph

2015-03-01

Abstract Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.

Fruit and vegetable intake and the risk of overall cancer in Japanese: A pooled analysis of population-based cohort studies.