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Background Researchers have recently begun to seek cognitive explanations for physical symptoms with no obvious biological cause. Concepts such as somatization, somatosensory amplification, and somatosensory catastrophizing have been invoked to explain these phenomena. Somatosensory amplification occurs when these bodily sensations become stronger and more painful. Somatosensory catastrophizing is the tendency to attribute these bodily sensations to unbearable functional modulation or as signs of serious illness. This causes the sufferer to pay excessive attention to these physical sensations. However, there is no scale for evaluating somatosensory catastrophizing, and there are no standard diagnostic criteria. There were two objectives for this study: to develop a scale for evaluating somatosensory catastrophizing and to investigate relationships between somatosensory amplification, somatosensory catastrophizing, and physical symptoms. Methods In the first part of this study, in which we developed the scale, there were 231 student participants with an average age of 20.1 years. Of these, 57% of the participants were female. In the second part of the study, there were two groups of participants. The first group consisted of 158 non-patient subjects, 56% of whom were female, with an average age of 20.2 years. There were 33 outpatients receiving treatment for somatoform disorders in the second group. The average age of these participants, of whom 67% were female, was 48.8 years. The second part of the study was conducted using standardized self-rating questionnaires to assess somatosensory amplification and catastrophizing. Results We developed a 27-item scale, which we have called the Somatosensory catastrophizing scale (SSCS). The SSCS assesses five key areas, and our analysis confirmed it to be valid and highly reliable. The scale identified that the patient group from the second part of the study scored more highly than the control group for both somatosensory amplification and catastrophizing. Additionally, the results of covariance structure analyses revealed a significant causal relationship of the form “somatosensory amplifcation” via “somatosensory catastrophizing” to “physical symptoms”. This relationship held in both groups of participants. The key difference between the patient and non-patient groups was that somatosensory catastrophizing had a greater impact on the physical symptoms of the participants in the patient group. Conclusions In this study, we developed the SSCS, which enables us to measure somatosensory catastrophizing empirically. We then clarified the relationship between somatosensory amplification, somatosensory catastrophizing, and physical symptoms. In the future, we expect to be able to apply our new understanding to developing intervention techniques to mitigate the physical symptoms caused by somatosensory catastrophizing. Electronic supplementary material The online version of this article (doi:10.1186/s13030-017-0110-z) contains supplementary material, which is available to authorized users.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Partial breast irradiation (PBI) is an alternative to whole breast irradiation (WBI) for breast-conserving therapy (BCT). A randomised phase 3 trial demonstrated that PBI using multicatheter brachytherapy had an equivalent rate of local recurrence, disease-free survival, and overall survival as compared to WBI. However, limited data are available on PBI efficacy for young patients with breast cancer. We evaluated consecutive patients with Tis-2 (≤ 3 cm) N0-1 breast cancer who underwent BCT. For PBI, patients received radiotherapy using multicatheter brachytherapy in an accelerated manner with a dose of 32 Gy in eight fractions over 5–6 days. For WBI, patients received an external beam radiation therapy that was applied to the entire breast with a total dose of 50 Gy in fractions of 2 Gy for 5 weeks. Two hundred seventy-four patients with 278 lesions received PBI; 190 patients with 193 lesions received WBI. Patients aged

Background: At the 13th St Gallen International Breast Cancer Conference in 2013, a new definition of luminal A-like and luminal B-like breast cancer was proposed, involving the expression of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67. We examined the rate of concordance between the risk groups using the Oncotype DX recurrence score (RS) and the previous and newly proposed luminal subtypes with the standardized Ki-67 assessment. Method: The relationship between a previously and newly proposed, immunohistochemically defined luminal A and B subtype with the Oncotype DX RS of 41 cases of T1-2 N0-1 M0 (ER positive, HER2 negative) breast cancer was assessed. We first classified the patients into the previously defined luminal A and B subtypes, according to the level of Ki-67 as either “low” (

[Background] Breast-conserving surgery (BCS) followed by whole-breast irradiation (WBI) has now become the standard treatment for early-stage breast cancer. However, WBI is associated with an increased risk of coronary events, especially in patients with preexisting cardiac risk factors. In radiotherapy (RT), the highest dose is likely delivered to the left anterior descending artery (LAD), which is the typical site for ischemic heart disease. We initiated a prospective, observational study on accelerated partial-breast irradiation (APBI) using multicatheter brachytherapy after BCS. In this study, we compared the radiation dose to LAD between patients receiving APBI and those receiving WBI. [Methods] The study participants included a cohort selected from consecutive patients who underwent BCS followed by RT since November 2007. In the WBI group, patients received 50 Gy in fractions of 2 Gy to the entire breast. APBI was initiated on the day of primary surgery in the form of multicatheter brachytherapy, at a dose of 32 Gy in 8 fractions. The planned target volume was defined as the estimated tumor volume plus a 20-mm margin. Dose distribution analysis was performed on the basis of postoperative CT using dose–volume histograms. LAD was outlined from its origin to each visible end using the planning CT images. First, the mean and maximal total doses to LAD were calculated. Second, the radiotherapeutic biologically effective dose of APBI was adjusted to that of WBI for comparisons between the two different RT schedules. [Results] Of the 359 consecutive patients who underwent BCS followed by RT, we retrospectively reviewed 182 patients for radiation dose to LAD. The 82 patients receiving WBI were randomly selected; 42 patients had right breast cancer and 40 had left breast cancer. We selected 100 consecutive APBI patients with left breast cancer treated between September 2009 and December 2013 because the LAD dose is considered to be virtually zero in right breast cancer patients. In the WBI patients, the mean and maximal total LAD dose were significantly higher in left breast cancer patients (2.1 ± and 8.2 ± 1.2 Gy, respectively) than in right breast cancer patients (0.4 ± 0.02 and 0.6 ± 0.03 Gy, respectively; p < 0.0001). Among the APBI patients, the total LAD doses were influenced by tumor location. The mean and maximal total LAD doses were significantly higher in patients with inner quadrants or central tumors (2.5 ± 0.2 and 4.4 ± 2.5 Gy, respectively) than in those with outer quadrant tumors (1.0 ± 0.1 and 2.1 ± 0.3 Gy, respectively; p < 0.0001). After adjustment for the total LAD dose, the mean and maximal total LAD doses were significantly decreased in APBI patients with outer quadrant tumors (1.1 ± 0.2 and 2.4 ± 0.4 Gy, respectively; p < 0.0001), but not in those with central and inner quadrant tumors (2.9 ± 0.3 and 5.4 ± 0.6 Gy, respectively). [Conclusions] Our results show that APBI may decrease the risk of coronary artery disease, especially in patients with outer quadrant tumors in the left breast. Although APBI should be carefully interpreted until mature phase-III data are available, the risk of ipsilateral breast tumor recurrences and LAD dose must be considered together while administering RT after BCS. Citation Format: Kazuhiko Sato, Yoshio Mizuno, Hiromi Fuchikami, Naoko Takeda, Takahiro Shimo, Jun Kubota, Yuko Inoue, Hiroshi Seto, Masahiro Kato. Comparison of cardiac dose between accelerated partial-breast irradiation and whole-breast irradiation in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-22.

Purpose Breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is the standard of care for breast cancer patients. However, there is a risk of coronary events with WBI therapy. In this study, we compared the radiation dose in the left anterior descending artery (LAD) in patients receiving partial breast irradiation (PBI) with WBI. Material and methods We evaluated consecutive patients who underwent adjuvant radiotherapy after BCS between October 2008 and July 2014. Whole breast irradiation patients received 50 Gy in fractions of 2 Gy to the entire breast. Partial breast irradiation was performed using multicatheter brachytherapy at a dose of 32 Gy in eight fractions. The mean and maximal cumulative doses to LAD were calculated. The radiotherapeutic biologically effective dose of PBI was adjusted to WBI, and radiation techniques were compared. Results Of 379 consecutive patients with 383 lesions receiving radiotherapy (151 WBI and 232 PBI lesions), 82 WBI and 100 PBI patients were analyzed. In WBI patients, the mean and maximal cumulative doses for left-sided breast cancer (2.13 ± 0.11 and 8.19 ± 1.21 Gy, respectively) were significantly higher than those for right-sided (0.37 ± 0.02 and 0.56 ± 0.03 Gy, respectively; p < 0.0001). In PBI patients with left-sided breast cancer, the doses for tumors in inner quadrants or central location (2.54 ± 0.21 and 4.43 ± 0.38 Gy, respectively) were significantly elevated compared to outer quadrants (1.02 ± 0.17 and 2.10 ± 0.29 Gy, respectively; p < 0.0001). After the adjustment, the doses in PBI patients were significantly reduced in patients with tumors only in outer quadrants (1.12 ± 0.20 and 2.43 ± 0.37 Gy, respectively; p = 0.0001). Conclusions Tumor control and dose to LAD should be considered during treatment since PBI may reduce the risk of coronary artery disease especially in patients with lateral tumors in the left breast.

Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups— WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)—since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap—that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

Lime plaster applied to walls and ceilings often contains vegetable oil for improving water resistance, and is considered to be harmless owing to its natural origin. The purpose of this study was to assess aldehyde emissions from plaster containing vegetable oil in order to predict the concentrations of aldehydes emitted into the indoor air. A passive emission chamber method was used to observe the emissions of aldehydes from vegetable oil when mixed with sodium hydroxide solution. The findings show that the alkalinity of calcium hydroxide in the plaster would accelerate the formation of aldehydes significantly. Furthermore, aldehyde emissions from the plaster to which vegetable oil was added were tested using a dynamic emission chamber (the small chamber method). A plaster containing soybean oil strongly emitted hexaldehyde throughout the test period. Plasters containing linseed oil or perilla oil strongly emitted propionaldehyde and acetaldehyde. The calculated indoor air concentrations of the aldehydes emitted from the lime plasters containing vegetable oil exceeded the air quality guidelines of the Japanese Ministry of Health, Labour, and Welfare, the Japanese Ministry of the Environment, and the German Federal Environmental Protection Agency. Moreover, these aldehydes are irritants and have unpleasant odours. Therefore, adding vegetable oil to plaster should be avoided to prevent sick-building syndrome.

Purpose: To standardize the methods to measure Ki-67, there is an interest in automating the assessment of Ki-67. Therefore, we reviewed the possibility of introducing an automated analyzer to standardize the Ki-67 evaluation method. Methods: We retrospectively reviewed a clinical database of patients who underwent surgery for early breast cancer at Tokyo-West Tokushukai Hospital. Among them, those who underwent preoperative core needle biopsy (CNB) were enrolled. The concordance rates of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 by local pathologists were reviewed (valuations made by local pathologists), and nonmatching cases (from August 2008 to October 2011) were reassessed both by central review and using an automated analyzer with virtual slides. The results were compared with the evaluations made by local pathologists, and we reexamined the concordance rate by using central review and the automated analyzer. Results: The concordance rate of Ki-67 evaluations made by local pathologists in the preoperative CNB and surgical specimens was 78.7% in 287 cases pathologically assessed from October 2008 to March 2013. This rate was significantly lower (p in clear improvement in matching of 22 (92.1%) and 24 (93.1%) of 37 cases, respectively. Conclusion: The concordance rate of Ki-67 in preoperative CNB and surgical specimens was lower than that of other biological markers; however, they were nearly equal by reassessment using central review and an automated analyzer.

Sick-building syndrome (SBS) is a range of symptoms such as eye irritation, sore throat, and headaches that occur when entering a newly constructed or refurbished building. Volatile organic compounds (VOCs) are suspected to be one of the major causes of SBS. However, although Ministry of Health, Labour, and Welfare of Japan set the guideline values for 13 VOCs, the incidences of SBS patients have not decreased. In addition, there have been reports that when people complained symptoms of SBS, most of them also claimed to smell an odour. Furthermore, the occurrence of SBS symptoms depends largely on the person’s sensitivity. In this study, the correlation between the sum of VOCs(C2-C16) including aldehydes (ΣVOCs) and SBS symptoms were examined by statistics. The odour was quantified using the odour threshold ratio (OTR) and the correlation between the total odour threshold ratio (TOTR: sum of the OTR) and SBS symptoms was investigated. These correlations were examined separately for sensitive and insensitive groups. TOTR and the concentration level of ΣVOCs were correlated with SBS symptoms among sensitive people. The findings indicate that TOTR, in addition to ΣVOCs, could be used as a new risk indicator for human health regarding indoor air quality.

Background: Breast-conserving surgery (BCS) followed by whole breast irradiation (WBI) has become the standard of care for treating patients with early-stage breast cancer. Recently, various radiation techniques followed by BCS have been reported. We have been investigating “personalized radiotherapy after BCS” ranging from accelerated partial breast irradiation (APBI) to WBI with regional nodal irradiation (RNI) based on the axillary node status. In this study, we compared different cohorts that received personalized radiotherapy. Method: Of 317 consecutive patients who underwent BCS followed by radiotherapy since November 2007, 187 who received APBI and 122 who received WBI were analyzed. Results: The local-only recurrence rate was 1.1% in the APBI group and 3.3% in the WBI group, and the regional-only recurrence rate was 1.1% for APBI and 0.8% for WBI. Conclusions: The clinical efficacy of APBI for local control after BCS was comparable to that of WBI ± RNI. Although this study was based on a small number of patients with a short follow-up period, the feasibility of breast-conserving therapy using multicatheter brachytherapy to achieve acceptable clinical outcomes was demonstrated.

A diffusive sampling device, the DSD-NH3, has been developed for measurement of ammonia in air. The DSD-NH3 comprises silica gel impregnated with phosphoric acid as the absorbent, a porous sintered polyethylene tube that acts as a diffusive membrane, and a small polypropylene syringe that is used for the elution of analytes from the absorbent. Silica gel impregnated with phosphoric acid is used as absorbent for the DSD-NH3; basic gases in ambient air, including ammonia, are trapped in the DSD-NH3 device by their reaction with phosphoric acid in the sampler to form their corresponding phosphoric acid salts. After collection, the DSD-NH3 samplers are eluted by water. Cations in the eluate, including ammonium ions, are analyzed by ion chromatography. A side-by-side comparison was made with active samplers, demonstrating good correlation (r2 = 0.996). The sampling rate (94.5 ml min−1) was determined from comparison with an active sampling method and sampling rates. The sampling rate is also calculated from the respective molecular weights according to a rule based on Graham’s law. The theoretical sampling rate with the DSD-NH3 is 95.4 ml min−1 and agrees with the experimental value (94.5 ml min−1). Little influence of wind velocity on the sampler was observed. The relative standard deviations for ammonia concentrations were 4.7% with face velocity ranging 0–5.0 m/s.

Purpose: The aim of this study was to assess the reliability of Ki-67 expression on core needle biopsy (CNB) and the surgical specimens of invasive breast cancer. We examined the concordance rate of Ki-67 expressions, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status from a CNB with from a surgery in invasive breast cancer. Methods: A retrospective study was conducted on a clinical database of patients who underwent surgery for early breast cancer. Of these, 193 patients who underwent CNB before the surgery were enrolled. A cut-off value of 20% was used for Ki-67-positive criteria. Expression of estrogen receptor (ER), progesterone receptor (PgR), and HER2 were examined and compared with that of Ki-67. To evaluate discordance between the pathologists’ earlier assessments, we re-examined Ki-67 expression among the Ki-67 discordant group in a central laboratory. Results: The concordance rate for Ki-67 expression between the two specimen types was 77.7%, which was significantly lower than that for ER, PgR, and HER2 expression (95.9%, 88.1%, and 91.6%, respectively). The concordance rate for re-examined Ki-67 expression among the Ki-67 discordant group improved to 93.8% and was not significantly different from that for the other receptors. Conclusion: The concordance rate for Ki-67 expression between biopsy and surgical specimens was significantly lower than that for ER, PgR, and HER2 expressions, but re-examination of Ki-67 expression in a central laboratory revealed no significant difference among the receptors, suggesting the need for standard pathological assessment of Ki-67 expression for clinical use as a predictive marker of breast cancer.

Background: Previous research has compared the efficacies of accelerated partial breast irradiation (APBI) and wholebreast irradiation (WBI). APBI immediately after surgery may provide more benefit after intraoperative insertion of catheters. Although balloon catheter-based APBI is available in the US, it is difficult in Japanese women, who have relatively small breasts. With the applicators being implanted during tumor removal, APBI can be started immediately after surgery. The aim of this study was to assess the safety and efficacy of APBI using the intraoperative open-cavity implant technique. Method: Patients (age≥40 years) with invasive breast cancer (diameter≤3 cm) were enrolled. Before lumpectomy, the insertion of applicators and delivery doses were simulated by computed tomography (CT). After confirmation of free margins and negative sentinel nodes (SNs) using frozen section analysis, applicators were inserted. Postoperative CT-based dose distribution analysis was performed using dose-volume histograms. APBI was started on the day of surgery, delivering 32 Gy in 8 fractions over the following 5-6 days, and it covered a distance of 2 cm from tumor margins. This observational study was approved by the institutional review board of our hospital. Results: From October 2008 to July 2012, 157 women (160 lesions) were enrolled (age 55.0 years

Nicotine has been used as a selective marker to evaluate environmental tobacco smoke (ETS). In this study, as imple andprecise nicotine measurement method using a solid phase cartridge (Sep-Pak R Plus PS-2) followed by GC-MS analysis was evaluated. Prior to use, the solid phase cartridge was coated with potassium hydroxide (KOH), and indoor air was then passed through it. After the air sampling, nicotine was eluted from the cartridge with 10µg/ml triethylamine/dichloromethane, and the eluent was analyzed by GC-MS. The nicotine recovery from the spiked cartridge was more than 80% for an air sampling time of 12 hr, and the method detection limit (MDL) for the air sampling with an air volume of 72 l was 0.35µg/m 3 .W hen the cartridge was used for indoor air measurement, the nicotine concentrations in the smoking room ranged from 12.9µg/m 3 to 86.6µg/m 3 ,w hich were proportional to the number of smoked cigarettes.

This paper reports a case study about the relationship between the symptoms of multiple chemical sensitivity (MCS) and indoor air chemicals. In April 2014, a 40-year-old man visited the Environmental Medical Clinic, Chiba University, claiming repeated symptoms of MCS after purchasing an electronic piano. Samples of indoor air from the living room of the patient’s house were collected and chemicals were analysed eight times – when an electronic piano and toys for children were either present or absent, and the floor heating system was on and off. Indoor air in a university office, and outdoor air were used as controls. As a result, it was found that the concentrations of 13 VOCs, for which the Ministry of Health Labour and Welfare of Japan (MHLW) set guideline values, were lower than the guideline values in all the samples. The total volatile organic compounds (TVOC) in three indoor air samples collected from the patient’s house were 550, 520, and 460 μg/m 3 ; slightly higher than the target value (400 μg/m 3 ) of TVOC set by the MHLW. The patient claimed to have the symptoms in all three cases. Furthermore, symptoms were reduced or eliminated when ventilation was conducted, or the patient was exposed to the outdoor air. A tendency was found that symptoms were strengthened as TVOC increased. In conclusion, MCS symptoms in this case were related to indoor air quality, and symptoms appeared even when the 13 VOCs for which the guideline values are set were lower than the guideline values. Therefore, it can be said that TVOC could be used as an indicator of the effects of indoor air quality on human health.

Bisphosphonates are now well established as successful agents for the prevention and treatment of postmenopausal osteoporosis and corticosteroid-induced bone loss. Bisphosphonates have also recently become important in the management of cancer-induced bone disease, and they now have a widely recognized role for patients with multiple myeloma and bone metastases secondary to breast cancer and prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic activity, the efficacy of such compounds in the oncological setting could also be due to direct anti-tumor effect. However, the effect of bisphosphonates to ovarian and endometrial cancers has not been elucidated. Thus, we examined the direct effect of bisphosphonates on the various ovarian cancer cell lines. Except for etidronate, all of bisphosphonates examined had the direct inhibitory effects on proliferation of all ovarian cancer cell lines used. Especially, pamidronate had the most marked inhibitory effect and inhibited dose-dependently the proliferation of ovarian cancer cell lines. KFr 13 cells among ovarian cancer cell lines used was the most sensitive to pamidronate and the caspase 3 activity was markedly stimulated by treatment with pamidronate, suggesting induction of apoptosis.

To supply safe and high-quality drinking water to the inhabitants of the volcanic Izu-Oshima island during periods of volcanic inactivity, quality analysis of groundwater from 17 sites and multivariate analysis were performed. The analytical indices were divided into four groups by cluster and correlation analyses : (a) 11 indices (Na, Ca, Cl-, etc.) were that related to seawater intrusion, (b) 6 indices (HCO3-, B, As, Li, SiO2 and water temperature) were that related to water-rock interaction in the volcanic area (WRI), (c) 2 indices (pH and NO3--N) were that inversely related to WRI and (d) the 4 other indices. Principal component analysis revealed that 68% of the original data set could be explained by only 2 principal components and that the water quality was influenced mainly by seawater intrusion and WRI. The first principal component corresponded to the overall influences of seawater intrusion as the major factor and WRI as the minor factor. The second principal component represented the influence of WRI. The samples of groundwater were grouped according to scores of each first and second principal component. Although the sites of water wells were contiguous, they showed different water quality owing to the influences of seawater intrusion and WRI. Concentrations of arsenic and boron in groundwater from some sites were strongly influenced by WRI and exceeded the Japanese criteria for drinking water. This indicates the importance of monitoring these elements in the groundwater of Izu-Oshima island.

Objectives . We have reported that single weekly paclitaxel has moderate activity in heavily pretreated ovarian cancer patients and is associated with a favorable toxicity profile. The purpose of this study was to reconfirm the effect of weekly paclitaxel in more number of cases. Methods . Although 39 patients were enrolled, 37 patients with recurrent or persistent ovarian cancer previously treated with between one and three chemotherapeutic regimens containing platinum were eligible. Patients had measurable or assessable disease defined by clinical exam, radiographic studies, or serum CA 125. One cycle of treatment consisted of paclitaxel 80 mg/m 2 /week in 1-h infusion, 3 weeks on, 1 week off, and repeated at least twice. Two patients were withdrawn because of refusal of further treatment for neuropathy after the first cycle. Clinical responses were defined by established criteria. Results . Thirty-seven patients were included in this intent-to-treat study. The overall clinical response rate was 45.9% (5 complete responses, 12 partial responses). The clinical response rate in patients with measurable tumor was 25.0% (2 complete responses, 1 partial response), while that in patients without measurable tumor and with assessable CA 125 levels was 56.0% (3 complete responses, 11 partial responses). Clinical response rate in patients with chemotherapy-free interval more than 6 months had about twice higher than that in patients with chemotherapy-free interval less than 6 months. The clinical response rate by number of prior regimens revealed that as number of prior regimens increases, the response rate decreases. Conclusion . Weekly paclitaxel has significant antitumor activity in heavily pretreated patients with recurrent or persistent ovarian carcinoma and warrants as second or third line chemotherapy in such setting.

The long-term use of hormonal therapy is important for the treatment of patients with breast cancer. Therefore, we evaluated the methods used for measuring adherence and examined factors that influence compliance. Our goal was to improve overall adherence to the treatment.Retrospective analyses by using electronic medical records and questionnaires were performed on 294 patients with breast cancer. The patients were classified into 2 groups based on the mean number of days when a dose was missed over a period of 28 days: group A(range, 0-3 days, n=272)and group B (range, B4 days, n=22). Factors that may influence adherence, including age, duration of hormonal therapy, the drug administered in hormonal therapy, the surgical method, axillary lymph node dissection, and adjuvant chemotherapy, were compared between both groups.The adherence rates calculated from electronic medical records and questionnaires were similar. The proportion of patients younger than 50 years was 30% in group A and 50% in group B(p0.05). Additionally, there was a difference in the duration of hormone therapy(752 days vs 981 days in groups A and B, respectively; p0.05). Additional factors that are related to low-risk cancer-related procedures, such as breast conserving surgery, may also be linked to poor adherence.Young age and long duration of hormonal therapy are possibly related to poor adherence. Therefore, pharmacists should identify and manage these patients to increase adherence.

The purpose of this study is to examine the carotenoid effects on lung tumorigenesis induced by intratracheal instillation of diesel exhaust particles (DEP) into mice weekly for 20 wk. It was suggested that active oxygen radicals might play an important role in DEP-induced lung tumorigenesis. Mice were divided to 4 groups of diet containing 0.02% of palm oil carotene, 0.02% of beta-carotene, or no carotenoid with or without DEP. The BF group (4% fat) and the HF group (16% fat) were prepared for each diet group. The experimental period was 12 mo. By the administration of palm oil carotene, neither adenocarcinoma nor adenoma was found in the BF group. In the HF group with palm oil carotene, no adenocarcinoma was observed, and adenoma was reduced. Adenoma in the HF group was not greatly reduced by beta-carotene, but rather increased in the BF group. No adenocarcinoma was found in either the BF or the HF groups with beta-carotene. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in palm carotene groups was lower than in the other groups, while that in beta-carotene groups was not. From these results, palm oil carotene was suggested to prevent lung tumorigenesis by its protective effect on DNA from active oxygen. Beta-carotene was supposed to have different effects from palm oil carotene on lung tumorigenesis. Besides the chemopreventive effect, the growth of mice was inhibited by the administration of palm oil carotene. Further studies are necessary to elucidate the mechanisms of carotenoid effects.

症例: 66歳女性. 1967年子宮全摘除. 1987年血液透析導入. 1996年7月下旬頃より右腰部痛, 下腹部痛, 発熱を認め, 腹部CTで右腎に腫瘤性病変を指摘され7月30日当科入院となった. 尿閉, 尿路感染を認め, 抗生物質投与および間歇導尿・膀胱洗浄を続け全身状態の改善を待って右腎摘出術を予定していたが, 8月8日38℃を超える発熱を認めたため膿腎症の診断で経皮的腎瘻術施行. 腎瘻術後は解熱傾向となり全身状態も改善した. 本症例は子宮全摘除術の合併症として神経因性膀胱を生じ, 尿閉, 尿路感染症を合併し, 腎盂腎炎, 膿腎症へと進展したと考えられた.長期透析患者での発熱の原因として尿路感染症を見逃してはならず, また膿腎症を発症した場合には, 経皮的腎瘻術による尿ドレナージを完全に行えば保存的に治療可能と考えられた.

Background: Breast-conserving surgery (BCS) followed by whole-breast irradiation (WBI) are the standard of care for treating early-stage breast cancer. The efficacy of accelerated partial breast irradiation (APBI) has recently been investigated as an alternative to WBI. Although we previously reported that multicatheter brachytherapy in APBI is feasible in Japanese patients, long-term data of several APBI techniques have not yet been obtained. Here we estimated the long-term efficacy of multicatheter brachytherapy in Japanese patients with breast cancer to validate its use an individualized case–control (ICC) analysis. Method: From October 2008 to March 2013, a total of 184 consequent patients with 188 tumors underwent BCS followed by multicatheter brachytherapy. A total of 120 consecutive patients (mean age, 55.1 years) with 122 tumors (pN0) who had at least 1 year of follow-up were enrolled in this analysis. Before lumpectomy, the insertion of applicators and delivery doses were simulated by computed tomography. After confirming the free margins and negative sentinel node metastases by frozen section analysis, the applicators were inserted. APBI therapy was initiated on the same day of surgery on the basis of the dose distribution analysis, at 32 Gy in 8 fractions over 5–6 days with a 2-cm tumor margin coverage. Regarding our prospective follow-up policy in this observational study, all patients had a predefined schedule including clinical examination every 3–4 months and mammography and breast magnetic resonance imaging (MRI) every 12 months. We performed ICC analysis to estimate the number of patients with ipsilateral breast tumor recurrence (IBTR). The 10-year risk of IBTR for each patient when undergoing with WBI was calculated using the web-based decision-making tool IBTR! and was adjusted during the real-time follow-up period using data obtained from an overview by the Early Breast Cancer Trialists’ Collaborative Group. Results: The median follow-up period was 3.1 years (range, 1.1–4.4 years). Most tumors (92.6%) were ?2 cm in diameter, and 89.4% were estrogen receptor-positive. Hormone therapy was administered in 86.7% and adjuvant chemotherapy in 20.0% patients. If all patients received WBI after BCS, we estimated IBTR in this group to be 1.1–2.8. Although 1 IBTR was observed, no tumor bed recurrence was recorded. Conclusions: Although this study involved only a small number of patients and short follow-up period, only 1 IBTR case was recorded, which was within the estimated range of local recurrence. Multicatheter brachytherapy using this technique may offer the same rates of local control as WBI in Japanese patients.

The expression of platelet derived growth factors (PDGF), the PDGF-Receptor (R) (alpha and beta types), epidermal growth factor (EGF)-Receptor (R) and sex hormone (oestrogen and progesterone) receptors was studied in 22 meningiomas. All tumours were PDGF-R beta type positive and 21 (95%) were PDGF positive. Only 2 (9%) were PDGF-R alpha type positive, 13 (59%) were EGF-R positive. The expression of these proteins was not related to the histological type or the malignancy of the meningiomas although the expression of PDGF and PDGF-R beta tended to be stronger in malignant meningiomas. Oestrogen and progesterone receptor protein were examined in 19 patients (10 females and 9 males). None of the meningioma cells revealed oestrogen receptor protein while 17 (89%) of the 19 meningiomas were positive for progesterone receptor protein. The expression of progesterone receptor was not related to histological type or malignancy. Our studies suggest that the autocrine system, through PDGF and PDGF-R type beta, may play an important role in the tumourigenicity of meningiomas. EGF-R was present in almost half and progesterone receptor in most of the meningiomas. There was no correlation between the expression of either PDGF, PDGF-R or EGF-R and the expression of progesterone receptor protein.

The thiosulfate-hydrogen peroxide reaction system generates thiosulfate radical anion and hydroxyl radical. When 2′-deoxyguanosine (dG) was included in the system, it was hydroxylated at the C-8 position, and the hydroxylation was markedly enhanced by addition of a trace amount of iron ion.

Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P -0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.

Polycyclie aromatic hydrocarbons (PAHs) accumulated in human lung samples from men (n = 236) and women (n = 128) were determined by high-performance liquid chromatography (HPLC) to examine their association with lung cancer. The mean values for benzo[a]pyrene (BaP), benzo[k]fluoranthene (BkF), and benzo[g,h,i]perylene (BghiP) in lungs (ng/g dry lung) of Japanese autopsied patients were 0.54, 0.44, and 0.87, respectively. The modal values were 0.3, 0.3 and 0.5, respectively. Each of the PAH concentrations was highly correlated with the others (r > 0.83). PAH concentrations in the lungs showed age-related increases with low correlation-coefficient values. BaP, BkF and BghiP concentrations in lungs of various subgroups were in the following order: male > female; and lung cancer > all cancers > non-cancer among male not female group. Only BghiP concentration in the lungs of the male smoker group is significantly higher (P < 0.10) than that of the male non-smoker group. Even among non-smoker groups, PAH concentrations in the lungs of male group were significantly higher than those of female group. In the male population, excess exposure to PAHs together with fine carbon particles, such as tobacco smoke or diesel exhaust, correlated with increased prevalence of lung cancer.

Reaction of malonaldehyde with adenosine at pH 4.5 gave three major adducts including a novel one containing diastereomeric dioxazatricycloundecene residue, formed by addition of three malonaldehyde units.

Background Prenatal human immunodeficiency virus (HIV) testing is essential for the prevention of mother-to-child transmission. However, false-positive results of screening testing are a concern as they may cause unnecessary emotional stress to pregnant women waiting for confirmatory test results. In regions with an extremely low prevalence, the positive predictive values of screening are unacceptably low rate. Here, we propose a HIV screening algorithm consisting of serial two fourth-generation enzyme immunoassays to reduce the number of false-positive screening results. Methodology/Principal Findings When 6461 pregnant women presenting to two maternity hospitals located in the Tokyo metropolitan area of Japan from September, 2004 to January, 2006 were tested using Enzygnost HIV Integral as a first screening test, 27 showed positive reactions. When these positive reaction samples were tested using VIDAS HIV DUO Quick as a second screening test, only one of them had a positive reaction, and the remaining 26 were nonreactive. Confirmatory Western blots and nucleic acid amplification test also showed that one was positive and the remaining 26 were negative; the subject who was positive with the confirmatory tests was identical to the subject who was positive with the second screening test. Thus, by adding the second screening test, the false-positive rate was improved from 0.4% to 0%, and the positive predictive value from 3.7% to 100%, compared with the single screening test. Conclusion By applying our serial screening algorithm to HIV testing in maternity hospitals, many uninfected pregnant women would not need to receive confirmatory tests and be subjected to emotional turmoil while waiting for their confirmatory test results. This algorithm would be suitable for HIV testing of pregnant women living in low prevalence regions such as Japan.

Screening method of endometrial cancer (EC) has not been established yet. Our study was to explore serum biomarkers of EC patients using surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS). Serum samples from 65 EC patients and 40 controls were analyzed by SELDI-TOF MS (training set). Single- and multi-variant analyses were performed to compare protein profiles in serum of EC patients and healthy controls. Subsequently, blind test set including 40 EC patients and 40 controls were analyzed for validation. A panel of four biomarker candidates were selected in training set analysis. These markers could also distinguish stage I patients from controls. Among them, two biomarkers were purified and identified as apolipoprotein A1 and a modified form of apolipoprotein C1. Screening for blind test set using dual-biomarker analysis yielded a sensitivity of 82% and a specificity of 86%. Involvement of apolipoproteins with EC is first suggested in this study. In addition to possibility of screening method for EC, findings of these new biomarkers might be related with carcinogenesis or predisposition to EC.

A new method for the determination of a guanosine—malonaldehyde adduct, β- d -ribofuranosylpyrimido[1,2- a ]purin-10(3 H )-one (GMA), in rat and human urine is described. The method involves rapid pretreatment using, in sequence, polyamide, ion-exchange and reversed-phase cartridges; determination is by means of high-performance liquid chromatography with a thiobarbituric acid reactor in series with a fluorescence detector. This device can quantitatively determine the adduct at the sub-picomole level. This rapid, selective and sensitive method is suitable for the determination of guanine—malonaldehyde adducts in biological samples, such as human and rat urine. A semi-preparative method for the extraction and purification of these adducts from rat urine and for their identification by mass spectrometry and high-performance liquid chromatography with ultraviolet detection is also reported.

Two patients with metastatic angiosarcoma of the brain are described. In one, a 17-year-old man, the tumor was located at the pineal region and exhibited significant vascularity. It was sensitive to radiation therapy and disappeared after radiation of 50 Gy; however, it recurred after 1 year and a new lesion was found in the liver. The other patient is a 31-year-old woman who experienced sudden onset of headache. Computed tomography scan revealed three separate masses in the brain. One tumor was surgically removed. The other two were sensitive to radiation therapy and disappeared after radiation of 40 Gy. A new lesion was found in the femur 16 months after the operation. Brain metastasis from angiosarcoma is exceedingly rare. Both patients developed symptoms with intracranial hemorrhage. The diagnosis of the metastatic lesions preceded diagnosis of the primary lesion by 12 and 16 months, respectively. Ulex europaeus 1 lectin and factor VIII were very useful in establishing the diagnosis of angiosarcoma.

マロンアルデヒド(MA)およびアルキルMA誘導体は核酸塩基のうちグアニン(Gua)と結合して三環の蛍光性のピリミドプリノン類(R-PP)を生成する。今回,核酸修飾反応の速度と変異原性との関係を明らかにする目的で,1M塩酸溶液中における種々のMA誘導体(R-MA)とGuaとの反応速度を測定した。

This is the second reported case of a malignant fibrous histiocytoma of the heart that metastasized to the brain. A 33-year-old woman developed headache, nausea, and ataxic gait 9 months after removal of the tumor from the left atrium of the heart. Computed tomographic and magnetic resonance imaging scans disclosed multiple metastatic tumors in the brain. Although dramatic improvement in her symptoms and signs followed the removal of the brain tumors, she died of tumor recurrence in the left atrium 3 months after the removal of the metastatic brain tumors.

Although taxol has shown significant activity in advanced ovarian cancer, peripheral neuropathy is likely to become the major dose-limiting toxicity. We describe a case of advanced ovarian carcinoma who developed difficulty walking because of marked pain in the lower extremities and loss of proprioception 25 days after treatment with weekly taxol (80 mg/m(2)x3).

The reaction of 1, 1, 3, 3-tetraethoxypropane with guanosine under strongly acidic conditions resulted in the formation of diastereomeric oxadiazabicyclononene residues linked to guanine base. The diastereomers were decomposed by heat, giving changed pyrimido[1, 2-a]purin-10(3H)-one nucleoside (3) in a good yield. A convenient method for the preparation of 3, which includes the thermal decomposition process of the diastereomers, was developed.

A rare case of suprasellar pituitary adenoma arising from the pars tuberalis in a 53-year-old woman is presented. The tumor was located exclusively above the diaphragma sellae, and no invasion into the sella turcica was noted.

Hexaorganoditin was synthesized by electrolysis of R3SnX (R=alykyl, phenyl; X=OCHO, SPh, H) in high yield, and polystannane was alos prepared from Ph2Sn(SPh)2 in good yield.

3034 Background: Treatment with a combination of HER2-targeted therapies has emerged as an addition of trastuzumab to neoadjuvant chemotherapy regimens in breast cancer patients and it goes on increasing. For clinical HER2 determination, immunohistochemical (IHC) analysis is an attractive method and all IHC 2+ cases are categorized as equivocal and should be reflexed to fluorescence in situ hybridization (FISH) testing. However, research in recent years with respect to false-negative cases for HER2 testing have been reported, and it comes to the question of what considering the indication for trastuzumab in the neoadjuvant chemotherapy. To clarify these controversial points in applying the results of HER2 testing in the clinical setting, we performed a retrospective analysis of core needle biopsy (CNB) and surgical specimen results. Methods: 422 patients underwent primary operations for early breast cancer at Tokyo-West Tokushukai Hospital (Tokyo, Japan) from October 2008 to December 2012. Among these patients, 262 patients who received CNB prior to operation were enrolled. Those patients who received preoperative chemotherapy or had DCIS were excluded. With regard to diagnostic criteria, HER2 positivity was defined as either 3+ by IHC or FISH analysis amplification ratio of ≥2.2. In addition, if in any cases which CNB samples or surgical specimens showed HER2-positive had defined true HER2-positive cases, we assessed the false-negative results of the HER2 test via IHC using CNB samples and surgical specimens. Results: In a matched cohort of 262 patients, 59 cases showed HER2-positive (five cases were CNBs negative to surgical specimens positive, 14 cases were CNBs positive to surgical specimens negative, and 40 cases were both positive). If we decide for selection of trastuzumab target cases by CNBs only, we make mistakes in indications of trastuzumab for five (8.5%) of 59 HER2-positive cases who were CNBs negative to surgical specimens positive. Conclusions: There are quite a few cases show false negatives for HER2 testing in CNB samples. In cases of considering the indication for trastuzumab in the neoadjuvant chemotherapy, even if the CNB samples resulted in negative, we consider that retesting with FISH analysis should be carried out.