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Takeshi Ebara - Top 30 Publications

Association Between Laryngopharyngeal Reflux and Radiation-induced Mucositis in Head and Neck Cancer.

We investigated whether laryngopharyngeal reflux (LPR) is a risk factor for radiation-induced mucositis.

Psychological distress in post-partum women after non-invasive prenatal testing (NIPT) in Japan.

The purpose of this study was to clarify the characteristics of psychological mental distress in post-partum women after non-invasive prenatal testing (NIPT) in Japan.

Reliability of smartphone-based gait measurements for quantification of physical activity/inactivity levels.

Objective measurements using built-in smartphone sensors that can measure physical activity/inactivity in daily working life have the potential to provide a new approach to assessing workers' health effects. The aim of this study was to elucidate the characteristics and reliability of built-in step counting sensors on smartphones for development of an easy-to-use objective measurement tool that can be applied in ergonomics or epidemiological research.

Maximum standardized uptake value on FDG-PET predicts survival in stage I non-small cell lung cancer following carbon ion radiotherapy.

The present study (University Hospital Medical Information Network study no. UMIN000003797) aimed to evaluate whether the maximum standardized uptake value (SUVmax) of pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is prognostic factor for stage I non-small cell lung cancer (NSCLC) treated with carbon ion radiotherapy (C-ion RT). Patients treated between June 2010 and June 2013 at Gunma University Heavy Ion Medical Center (Maebashi, Japan) on a prospective protocol were included in the present study. Patients with T1a-b and T2a NSCLC were treated with C-ion RT at a dose of 52.8 Gy [relative biological effectiveness (RBE)] and 60.0 Gy (RBE), respectively, in four fractions. Prior to treatment, all patients underwent FDG-PET, in which the SUVmax of primary tumors was evaluated. Local control, progression-free survival (PFS), and overall survival (OS) were calculated. A total of 45 patients were analyzed and the median follow-up period was 28.9 months. The 2-year local control, PFS and OS rates for all patients were 93, 78 and 89%, respectively. The mean SUVmax of primary tumors was 5.5, and patients were divided into higher (≥5.5) and lower (<5.5) SUVmax groups. The 2-year PFS rates were 61 and 89% for the higher and lower SUVmax groups, respectively (P=0.01), and the 2-year OS rates for the higher and lower SUVmax groups were 76 and 96%, respectively (P=0.01). The higher SUVmax group exhibited a significantly worse PFS and OS compared with the lower SUVmax group; however, the SUVmax was not associated with the local control rate. In total, 2 patients (4%) experienced grade 2 or 3 radiation pneumonitis, with their symptoms improved through conservative treatment. No patients experienced any grade 4 or 5 toxicities. The results of the present study indicate that pretreatment SUVmax is a prognostic indicator for outcomes in patients with stage I NSCLC treated with C-ion RT.

Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer.

The aim of our study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin in combination with thoracic radiotherapy for patients with locally advanced stage III non-small cell lung cancer (NSCLC).

Quantitative analysis of organophosphate insecticide metabolites in urine extracted from disposable diapers of toddlers in Japan.

Epidemiological studies linking insecticide exposure to childhood neurodevelopment have been gaining global attention. Despite the rapid development of the central nervous system in early childhood, studies regarding the biological monitoring of insecticide exposure in diapered children are limited. In this study, we aimed to clarify the concentrations of organophosphate (OP) insecticide metabolites in toddler urine extracted from disposable diapers in Japan.

Background of couples undergoing non-invasive prenatal testing in Japan.

Our purpose was to assess the background of couples who were undergoing non-invasive prenatal testing (NIPT) in Japan.

Successful treatment of radiation-induced mucositis with proton pump inhibitor administration: A report of two laryngeal cancer cases.

Presently, the relationship between laryngopharyngeal reflux (LPR) and radiation-induced mucositis has not been fully explored. In the present study, we report 2 cases of laryngeal cancer in which radiation-induced mucositis ameliorated after proton pump inhibitor (PPI) administration. Case 1 was diagnosed with T1aN0M0 right glottis carcinoma and was treated with radiation therapy. Grade 3 mucositis occurred after administration of 46Gy irradiation. PPI was administered and mucositis ameliorated quickly without cessation of radiation therapy. Case 2 was diagnosed with T2N0M0 supraglottic cancer and was treated with concurrent chemoradiation therapy. Grade 3 mucositis occurred after administration of 44Gy irradiation. PPI was administered and mucositis ameliorated quickly without cessation of chemoradiation therapy. In both cases, a remarkable therapeutic effect of PPI was observed in the perilaryngeal areas including the epiglottic vallecula, arytenoid, and postcricoid area. In both cases, LPR involvement was suspected before the onset of radiation therapy. The two cases presented here, indicated a causal relationship between LPR and radiation-induced mucositis. In cases of severe mucositis in the perilaryngeal area in patients with LPR prior to radiation therapy, PPI administration may be an effective therapeutic option.

Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.

The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging.

Incidence, risk factors, and dose-volume relationship of radiation-induced rib fracture after carbon ion radiotherapy for lung cancer.

The purpose of this study was to assess the incidence, risk factors, and dose-volume relationship of radiation-induced rib fracture (RIRF) after carbon ion radiotherapy for lung cancer.

Assessing cumulative dose distributions in combined radiotherapy for cervical cancer using deformable image registration with pre-imaging preparations.

The purpose of the study was to evaluate the feasibility of deformable image registration (DIR) in assessing cumulative dose distributions of the combination of external beam radiotherapy (EBRT) and fractionated intracavitary brachytherapy (ICBT) for cervical cancer.

Malignant melanoma of the nasal cavity treated with stereotactic radiotherapy using CyberKnife: report of 2 cases.

Radiotherapy with high doses per fraction may have the potential to control radioresistant tumors, such as malignant melanoma. Here we report 2 cases with malignant melanoma of the nasal cavity treated with hypofractionated stereotactic radiotherapy using CyberKnife®.

Genotyping analysis for the 46 C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss.

Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII) deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL, because of the small sample size.

Dosimetric analysis between carbon ion radiotherapy and stereotactic body radiotherapy in stage I lung cancer.

To evaluate dosimetric differences between carbon ion radiotherapy (C-ion RT) and stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC).

Non-specific psychological distress in women undergoing noninvasive prenatal testing because of advanced maternal age.

The objective of our study was to describe our clinical experience in providing noninvasive prenatal testing (NIPT) for fetal aneuploidy to pregnant women, highlighting the degree of non-specific psychological distress.

Phase II study of oral S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer.

To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).

Quantitative medical cost-effectiveness analysis of molecular-targeting cancer drugs in Japan.

In Japan, both incidence and mortality rates of cancers have continuously increased and medical costs are growing more rapidly than the overall economy of Japan. However, there is no consensus threshold for cost-effectiveness in medical care, and few studies have investigated cost-effectiveness of medical care in Japan. The present study was to determine the direct costs of molecular-targeting drugs that were recently approved in Japan through simple and quantitative calculations. Thus, we calculated an incremental cost-effectiveness ratio (ICER) and the cost per life-year gained (LYG) by using reported data from randomized clinical trials for various cancers.

Technical approach to individualized respiratory-gated carbon-ion therapy for mobile organs.

We propose a strategy of individualized image acquisitions and treatment planning for respiratory-gated carbon-ion therapy. We implemented it in clinical treatments for diseases of mobile organs such as lung cancers at the Gunma University Heavy Ion Medical Center in June 2010. Gated computed tomography (CT) scans were used for treatment planning, and four-dimensional (4D) CT scans were used to evaluate motion errors within the gating window to help define the internal margins (IMs) and planning target volume for each patient. The smearing technique or internal gross tumor volume (IGTV = GTV + IM), where the stopping power ratio was replaced with the tumor value, was used for range compensation of moving targets. Dose distributions were obtained using the gated CT images for the treatment plans. The influence of respiratory motion on the dose distribution was verified with the planned beam settings using 4D CT images at some phases within the gating window before the adoption of the plan. A total of 14 lung cancer patients were treated in the first year. The planned margins with the proposed method were verified with clinical X-ray set-up images by deriving setup and internal motion errors. The planned margins were considered to be reasonable compared with the errors, except for large errors observed in some cases.

A seven-year disease-free survivor of malignant pleural mesothelioma treated with hyperthermia and chemotherapy: a case report.

Validation of nomogram-based prediction of survival probability after salvage re-irradiation of head and neck cancer.

Treatment outcomes after salvage re-irradiation in patients with recurrent head and neck cancer vary widely due to heterogeneous patient characteristics, and it is difficult to evaluate optimal re-irradiation schedules. This study aimed to validate a nomogram, originally developed by Tanvetyanon et al., used to predict the survival probability of patients with recurrent head and neck cancer after re-irradiation.

Interaction of radiation and gefitinib on a human lung cancer cell line with mutant EGFR gene in vitro.

To investigate the effect of gefitinib in combination with irradiation using HCC827 cells, a human lung cancer cell line bearing epidermal growth factor receptor (EGFR) mutation.

Long-term results of curative intraluminal high dose rate brachytherapy for endobronchial carcinoma.

The treatment strategy of central lung tumors is not established. Intraluminal brachytherapy (ILBT) is widely used for palliative treatment of endobronchial tumors, however, it is also a promising option for curative treatment with limited data. This study evaluates the results after ILBT for endobronchial carcinoma.

Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma.

Postoperative hemithoracic irradiation is regarded as an important part of the curative treatment for resectable malignant pleural mesothelioma (MPM). Because the clinical target volume in postoperative MPM is irregular and surrounded by dose-limiting critical structures, intensity-modulated radiation therapy (IMRT) is thought to be suitable. However, postoperative hemithoracic IMRT remains experimental due to a high incidence of fatal pneumonitis. Therefore, a Phase I dose escalation study for hemithoracic IMRT using helical tomotherapy was planned, and the results of the first three patients are herein reported because this technique may provide benefits to such patients. For 3 patients with postoperative MPM, who were treated by extrapleural pneumonectomy (EPP), a radiation dose of 45.0 Gy in 25 fractions was given to cover 95% of the PTV. The lung V5s of the three patients were 14.3%, 10.0%, and 31.3%, respectively. The V5s of the present plans was smaller than that of the recent IMRT planning studies. The lung V20s of these patients were 2.4%, 2.2%, and 4.3%, respectively. Their MLDs were 4.3 Gy, 3.4 Gy, and 5.8 Gy, respectively. The follow-up periods of the patients were 26, 14 and 9 months from initiation of IMRT, respectively. All patients were alive, although local and contralateral recurrences had developed in 1 patient. Only 1 patient had Grade 2 acute esophagitis and nausea. There was no treatment-related pneumonitis. Hemithoracic IMRT using helical tomotherapy may play a crucial role in adjuvant treatment for MPM after EPP.

Merits and demerits of engaging in athletic, academic and part-time job roles among university student-athletes in Japan.

Although role conflict management is necessary for the prevention of dropout from participation in sports, little has been known about it, especially regarding Japanese university student-athletes. Hence, this study examined the aspects of merit and demerit involved in their performances of academic, athletic, part-time job, family and human relationship roles. The merits and demerits were evaluated using the theoretical concepts of negative spillover (NSP), positive spillover (PSP), compensation and segmentation. In the research, a total of 108 participants (63 males, 45 females) described information about their multiple roles in the Multiple Roles Map (MRM) form. NSP with high frequency rates (3rd quartile) showed demerit that negative condition in athletic and part-time job roles tended to disturb performance of other roles (male ≥ 17.5%, female ≥ 15.6%). The results of PSP showed merit that positive condition in the athletic, part-time job and academic roles contributes to accomplishment of good performance in other roles (male ≥ 19.0%, female ≥ 17.8%). Compensation indicated that negative conditions in the roles were compensated by satisfaction in the human relationships and family roles and private time (male ≥ 9.5%, female ≥ 11.1%). The family role was segmented from other roles (male ≥ 71.4%, female ≥ 68.9%). Sharing these findings will be effective in helping to solve role conflict problems of university student-athletes in Japan.

Expression of hypoxia-inducible factor 1α predicts clinical outcome after preoperative hyperthermo-chemoradiotherapy for locally advanced rectal cancer.

Hypoxia-inducible factor 1α (HIF-1α) is an intrinsic marker of tumor hypoxia. It has been considered that hypoxic conditions reduce radiosensitivity, but the role of HIF-1α in patients treated with preoperative therapy for rectal cancer is still unclear. The aim of this study was to evaluate the predictive value of tumor response to preoperative hyperthermo-chemoradiotherapy (HCRT) and the prognostic significance of HIF-1α expression in patients with locally advanced rectal cancer. Between 2003 and 2006, 50 patients with histologically proven rectal adenocarcinoma who underwent HCRT followed by surgery were investigated. HIF-1α expression was immunohistochemically evaluated using pre-treatment biopsies. The total radiation dose was 40-50 Gy and chemotherapy consisted of 5-FU and LV administered by continuous infusion on Day 1-5, Day 15-19, and Day 29-33 during radiotherapy. Hyperthermia treatment was performed for once a week for 2-5 sessions. The surgical operation was performed 8 weeks after HCRT and each resected specimen was graded by histological criteria of the Japanese Classification of Colorectal Carcinoma. The effects of HIF-1α on clinical outcomes were analyzed by univariate and multivariate analysis. Positive HIF-1α expression was recognized in 42.0% of samples (21/50). Resected specimens that showed pathological grades 1, 2, and 3 numbered 17, 24, and 9 cases, respectively. There were no significant differences between the HIF-1α-positive group and HIF-1α-negative group for pathological grading and pCR. Overall survival (OS) rate at 3 years in the HIF-1α-negative group was 85.2%, which was significantly better than the 60.6% in the HIF-1α-positive group. Recurrence-free survival (RFS) rate at 3 years in the HIF-1α-negative group was 82.8%, being significantly better than 47.6% in the HIF-1α-positive group. In addition, elevated HIF-1α expression was significantly correlated with recurrence-free survival and metastasis-free survival rate in multivariate analysis. HIF-1α expression might be predictive of recurrence-free survival and metastasis-free survival rate for rectal cancer patients treated with HCRT.

Interaction of radiation and pemetrexed on a human malignant mesothelioma cell line in vitro.

To investigate the interaction of the cytotoxic activity of the combination of pemetrexed and radiation in a human mesothelioma cell line.

Rectal bleeding after high-dose-rate brachytherapy combined with hypofractionated external-beam radiotherapy for localized prostate cancer: the relationship between dose-volume histogram parameters and the occurrence rate.

To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis.

Indoor air pollution and health of children in biomass fuel-using households of Bangladesh: comparison between urban and rural areas.

Indoor air pollutants from biomass combustion pose a risk for respiratory diseases in children. It is plausible that distinct differences in the indoor air quality (IAQ) exist between urban and rural areas in developing countries since the living environment between these two areas are quite different. We have investigated possible differences in IAQ in urban and rural Dhaka, Bangladesh and the association of such differences with the incidence of respiratory and some non-respiratory symptoms in children of families using biomass fuel.

L-type amino-acid transporter 1 expression predicts the response to preoperative hyperthermo-chemoradiotherapy for advanced rectal cancer.

To evaluate whether expression of L-type amino acid transporter 1 (LAT1) in pretreatment rectal cancer biopsies is predictive of tumour response to neoadjuvant hyperthermo-chemoradiotherapy (HCRT).

The benefit of small bowel and pelvic bone sparing in excluding common iliac lymph node region from conventional radiation fields in patients with uterine cervical cancer: a dosimetric study.

The purpose of this study was to compare dose reduction to the small bowel and sacral bone by two-field and four-field techniques when the common iliac lymph node region is excluded from the radiation field in external beam radiotherapy of uterine cervical cancer. Thirteen patients with cervical cancer were entered into the study. Conventional treatment plans based on bony landmarks were made with parallel-opposed two-field technique (C2F) and four-field box technique (C4F). Modified C2F (M2F) and C4F (M4F) plans of excluding the common iliac lymph node region from the conventional radiation fields were created in reference to the bifurcations of pelvic arteries in computed tomography images. For each patient, the dose volume histograms for the small bowel and sacral bone resulting from the C2F, C4F, M2F, and M4F plans were compared. The volumes were obtained at 10 levels of prescribed dose, at increments of 10%, from 5 Gy to 50 Gy. By sparing both small bowel and sacral bone, the M2F and M4F plans were significantly better than the C2F and C4F plans at any dose level (p < 0.05), respectively. In addition, the M4F plan was significantly better than the M2F plan in sparing both small bowel at 10-50% of the prescribed dose (p < 0.05) and sacral bone at 40-100% of the prescribed dose (p < 0.05). The present study suggests that modified treatment planning could be useful for selected patients for reducing small bowel complications and insufficiency fracture after radiotherapy.