Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318, and rs3803662) associated with breast cancer risk in Japanese women.

BACKGROUND: Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. METHODS: In previous case-control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. RESULTS: There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5 cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6 cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). CONCLUSIONS: SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.

Recurring radiation-induced angiosarcoma of the breast that was treated with paclitaxel chemotherapy: a case report.

BACKGROUND: Angiosarcoma of the breast is very rare and can be divided into primary and secondary angiosarcoma. Radiation-induced angiosarcoma (RIAS) is classified as secondary angiosarcoma. Diagnosis of RIAS is difficult due to its rarity, and the interpretation of pathological imaging is complicated. In the National Comprehensive Care Network (NCCN) guidelines, the first choice of treatment is surgery with negative margins. Adjuvant radiotherapy (RT) for close soft tissue margins should be considered. Preoperative or adjuvant chemotherapy of nonmetastatic disease is not recommended for angiosarcoma. We report a case of RIAS, which was impossible to diagnose with core needle biopsy (CNB) but was diagnosed by excisional biopsy. The patient was then administered adjuvant chemotherapy using conjugated paclitaxel (PTX). CASE PRESENTATION: A 62-year-old woman noticed a tumor in her right breast. She had a history of right breast cancer and had undergone breast-conserving surgery, RT, and tamoxifen therapy 8 years previously. CNB, which was performed twice, was inconclusive. The tumor was surgically excised and pathological analysis yielded a diagnosis of angiosarcoma. She then underwent a right mastectomy. One month after she underwent right mastectomy, a nodule reappeared on the skin of her right breast, and excisional biopsy revealed recurrence of angiosarcoma. A few weeks later another nodule reappeared near the post-operative scar and excisional biopsy revealed recurrence of angiosarcoma. We assumed that surgical therapy was insufficient because the patient experienced relapse of angiosarcoma after complete mastectomy. After the second recurrence, we treated her with systemic chemotherapy using PTX. There was no evidence of recurrence 8 months after chemotherapy. CONCLUSION: Although angiosarcoma is difficult to diagnose, many patients have a poor prognosis. Therefore, prompt treatment intervention is desired. Moreover, there is little evidence regarding adjuvant therapy of angiosarcoma since it is a rare disease. We consider that adjuvant therapy helped to effectively prevent recurrence in the patient after complete excision.

Influence of breast density on breast cancer risk: a case control study in Japanese women.

BACKGROUND: Mammography is the standard examination for breast cancer screening of woman aged ≥ 40 years. High breast density on mammography indicates that mammary gland parenchyma occupy a high percentage of the breast. The objective of this study was to investigate factors associated with breast density and the risk of high breast density for breast cancer. METHODS: A multicenter case-control study was performed in 530 patients and 1043 controls. Breast density was classified as C1-C4 using the Breast Imaging Reporting and Data System (BI-RADS). Clinical factors were obtained from questionnaires or medical records, and the influence of each factor (breast density, menopausal status, body mass index (BMI), parity, presence or absence of breastfeeding history, age at menarche, age at first birth, and familial history of breast cancer) on breast cancer risk in all patients was calculated as an age-adjusted odds ratio (OR). Multivariate logistic regression analyses were then performed in all patients and in pre- and postmenopausal and BMI-stratified groups using factors with a significant age-adjusted OR as adjustment factors. RESULTS: Age-adjusted ORs for breast cancer were significant for breast density, BMI, parity, and breast feeding, but not for age at menarche, age at first birth, or family history of breast cancer. In multivariate analysis, there was a significant correlation between breast density and breast cancer in postmenopausal women (OR for C1 vs. C2 1.90 [95% CI 1.34-2.70]; C1 vs. C4 2.85 [95% CI 1.10-7.16]). This correlation was also significant in patients in the third BMI quartile (22.3-24.5 kg/m2) (OR for C1 vs. C4 8.76 [95% CI 2.38-42.47]); and fourth BMI quartile (>24.5 kg/m2) (OR for C1 vs. C2 1.92 [95% CI 1.17-3.15]; C1 vs. C4 11.89 [95% CI 1.56-245.17]). CONCLUSION: Breast density on mammography is a risk factor for breast cancer after adjustment for other risk factors. This risk is particularly high in postmenopausal women and those with a high BMI.

Effects of crystalloids and colloids on microcirculation, central venous oxygen saturation, and central venous-to-arterial carbon dioxide gap in a rabbit model of hemorrhagic shock.

OBJECTIVE: The effects of hydroxyethyl starch (HES) on microcirculation, central venous oxygen saturation (ScvO2), and the central venous-to-arterial carbon dioxide gap (dCO2) are studied in a rabbit model of hemorrhagic shock for elucidating the advantages and drawbacks of resuscitation with HES compared with crystalloids. METHODS: An ear chamber and sublingual mucosa were used to examine blood vessels by intravital microscopy. Hemorrhagic shock was induced by removing nearly half of the blood volume. Twenty-two rabbits received 20 mL of HES by intravenous infusion immediately after bloodletting. Additional HES was then administered intravenously to a total volume of 100 mL. The other 22 rabbits (control) were intravenously given 40 mL of normal saline solution (NSS), followed by additional NSS to a total volume of 200 mL, administered under the same conditions as HES. RESULTS: After the infusion, the vessel density and perfusion rate of the sublingual microcirculation recovered in the HES group. The arteriolar diameter, blood flow velocity, and blood flow rate of the ear microcirculation were maintained in this group, and microcirculatory failure did not develop. In the NSS group, however, all 5 of the aforementioned measured variables were significantly smaller than those in the HES group after the completion of infusion. The recovery of ScvO2 and dCO2 to the respective baseline values was significantly better in the HES group than in the NSS group. CONCLUSION: Intravenous infusion of HES effectively maintains adequate tissue oxygenation and perfusion in hemorrhagic shock.

Introduction of thromboelastometry-guided administration of fresh-frozen plasma is associated with decreased allogeneic blood transfusions and post-operative blood loss in cardiopulmonary-bypass surgery.

BACKGROUND: Cardiac surgery is frequently associated with excessive blood loss requiring multiple blood transfusions which are, in turn, associated with increased morbidity and mortality. We evaluated the effectiveness of rotational thromboelastometry (ROTEM®)-guided administration of fresh-frozen plasma (FFP) with regards to blood loss, transfusion requirements, and major post-operative complications. MATERIALS AND METHODS: Coagulation management in 68 prospective patients undergoing cardiac surgery with cardiopulmonary bypass was based on a treatment algorithm guided by ROTEM® measurements. The primary end-point was blood loss at 24 hours after surgery. Secondary end-points were: (i) need for allogeneic blood products after cardiopulmonary bypass and 24 hours post-operatively, and (ii) post-operative complications until discharge. The results were compared with those of a retrospective, control group of 69 patients who received empirical coagulation management before implementation of the ROTEM®-guided algorithm. RESULTS: Although patients with significantly lower haemoglobin levels received less packed red blood cells (PRBC) (840 vs 1,120 mL; p=0.031) and FFP (480 vs 720 mL; p=0.007) after introduction of the ROTEM® algorithm, the intra-operative blood loss and post-operative haemoglobin levels were similar in the ROTEM® and the retrospective control groups. In addition to significantly reduced blood loss and decreased requirements for PRBC (30.8 vs 62.3%; p<0.001) and FFP (25.0 vs 56.5%; p<0.001), the amounts of PRBC (315 vs 840 mL; p<0.001) and FFP (480 vs 840 mL; p=0.001) received during the first 24 hours after surgery were significantly reduced in the ROTEM® group, as was the duration of post-operative hospitalisation. DISCUSSION: Compared with empirical treatment, timely ROTEM®-guided FFP administration during cardiac surgery can reduce not only overall blood product use and blood loss but also the duration of hospitalisation.

Association Between Platelet Count and Postoperative Blood Loss in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass and Fresh Frozen Plasma Administration Guided by Thromboelastometry.

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple factors, including reduced coagulation factors and a low platelet count.Methods and Results:In this study, we undertook a post hoc analysis to identify factors associated with increased postoperative blood loss in 97 patients undergoing cardiac surgery with CPB, with fresh frozen plasma administered according to a ROTEM-guided algorithm. We identified 24 patients for the top quartile of postoperative blood loss, >528 mL and defined as having excessive blood loss. Using Spearman's rank correlation test and multivariable linear regression, we reanalyzed the participants' demographic, surgical and anesthetic variables, laboratory test results, blood loss, and transfusion data. Univariate analysis indicated that patients who experienced higher postoperative blood loss received a significantly higher heparin dose, had a higher requirement for fresh frozen plasma transfusion during surgery, and had a significantly lower hematocrit and platelet count at the end of surgery compared with patients without excessive blood loss. Multivariate analysis showed that platelet count at the end of surgery (odds ratio 0.780, 95% confidence interval 0.629-0.967; P=0.024) was an independent factor for excessive blood loss. CONCLUSIONS: Low platelet count at the end of surgery was associated with excessive postoperative bleeding during cardiac surgery with CPB.

Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT.

INTRODUCTION: The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. METHODS: We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. RESULTS: The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland-Altman analysis. CONCLUSION: It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

Management of a Patient With Antiphospholipid Syndrome Undergoing Aortic Valve Replacement Using the Hepcon Hemostasis Management System Plus and Rotational Thromboelastometry: A Case Report.

A 72-year-old woman with antiphospholipid syndrome underwent aortic valve replacement. Her preoperative activated partial thromboplastin time was 61.7 seconds and activated clotting time was 219 seconds. During cardiopulmonary bypass, the Hepcon Hemostasis Management System (HMS) Plus determined the heparin dose needed to maintain whole-body heparin at 3 U/mL. After cardiopulmonary bypass, 100 mg of protamine was administered based on heparin-protamine neutralization, and the activated clotting time decreased. We applied rotational thromboelastometry (ROTEM) to diagnose residual heparin using the INTEM/HEPTEM clotting time ratio. The HMS and ROTEM are useful for heparin-protamine control in antiphospholipid syndrome.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

In vitro and in vivo effects of hemodilution on kaolin-based activated clotting time predicted heparin requirement using a heparin dose-response technique.

PURPOSE: The heparin dose-response (HDR) technique is based on activated clotting time (ACT) response to a fixed-dose heparin bolus, which varies substantially among patients. It is unclear, however, whether hemodilution-associated reductions in coagulation and anticoagulation factors affect the HDR slope. METHODS: For in vitro hemodilution, aliquots of whole blood from healthy volunteers were diluted 9:1 and 8:2 v/v with normal saline. For in vivo hemodilution, a prospective observational study was performed on 46 patients who underwent elective cardiovascular surgery with or without cardiopulmonary bypass. HDR slope, antithrombin (AT) activity, complete blood count, and other coagulation parameters were compared after induction of anesthesia and after hemodilution with 500 ml of intravenous fluid. RESULTS: In vitro 10 and 20 % hemodilution significantly increased the HDR slope relative to baseline, reducing the heparin requirement. Hemodilution of heparinized samples significantly prolonged ACT, whereas there was no significant change in non-heparinized blood. The percent changes in fibrinogen and AT activity were significantly greater at 20 % than those of the other coagulation variables. In vivo, hemodilution significantly increased the HDR slope and reduced heparin requirement. The percent change in fibrinogen due to hemodilution was significantly greater than the change in AT activity. Target ACTs of 300 and 450 s were not achieved in 83.3 and 53.8 % of patients, respectively. CONCLUSION: In vitro and in vivo hemodilution significantly increased the HDR slope and reduced the requirement for heparin. In vitro, the HDR slope did not change in parallel but became steeper, depending on the degree of hemodilution.

Perioperative posterior reversible encephalopathy syndrome in a patient with no history of hypertension: a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome is characterized by reversible neurological symptoms with leukoencephalopathy detectable by computed tomography (CT) and magnetic resonance (MR) imaging. CASE PRESENTATION: We here present a patient with no history of hypertension who, after being transferred back to the ward after undergoing total hysterectomy under general anesthesia, had several seizures and lost consciousness. Posterior reversible encephalopathy syndrome was suspected on the basis of brain CT images and clinical findings. She was treated with respiratory support, sedative drugs, and anticonvulsants, and MR imaging confirmed a diagnosis of posterior reversible encephalopathy syndrome. She regained consciousness and responsiveness the following day. CONCLUSIONS: Clinically, posterior reversible encephalopathy syndrome resembles cerebral infarction or intracranial hemorrhage; MR imaging is useful for differentiating it from these conditions. Including this condition in the differential diagnosis and instituting appropriate treatment is important in minimizing the risk of development of irreversible neurological damage during the perioperative period.

[The Use of Thromboelastometry and Tranexamic Acid Reduces Blood Loss and Transfusion Requirements in Cardiac Surgery under Cardiopulmonary Bypass].

BACKGROUND: We evaluated whether using thromboelastometry and tranexamic acid influenced blood loss and transfusion requirements in cardiac surgery requiring cardiopulmonary bypass. METHODS: We perfomed a retrospective analysis examining perioperative coagulation results, and the transfusion requirements of concentrated red cells (CRCs), fresh frozen plasma (FFP) and platelet administration between 12 months before and 10 months after thromboelastometry and tranexamic acid had been introduced in our institution. We also recorded patients' demographic details, the surgery performed and patient outcomes. RESULTS: After the introduction of thromboelastometry and tranexamic acid, fewer units of CRC were transfused during surgery, and fewer patients required postoperative CRC transfusion. Intra- and postoperative FFP requirements were also reduced. Intraoperative blood loss, blood loss in the first 24 hr after surgery, and length of hospital stay were also reduced. CONCLUSIONS: The use of ROTEM and tranexamic acid can potentially reduce blood loss and transfusion requirements in cardiac surgery.

Reappearance of circulating heparin in whole blood heparin concentration-based management does not correlate with postoperative bleeding after cardiac surgery.

OBJECTIVE: The Hepcon Heparin Management System (HMS) facilitates administration of higher heparin and lower protamine doses, which may affect bleeding potential due to heparin rebound. The present study evaluated heparin rebound in patients for whom the Hepcon HMS was used to determine whether point-of-care tests detect residual heparin and residual heparin is associated with postoperative blood loss. DESIGN: Prospective study. SETTING: Tertiary care center affiliated with a university hospital. PARTICIPANTS: Adults undergoing elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: In blood samples obtained at baseline, at 2 minutes, and at 1, 2, 4, 6, and 24 hours after heparin neutralization, heparin concentrations were measured using an automated chromogenic assay. Activated coagulation time (ACT), activated partial thromboplastin time (APTT), and thromboelastometry 2 hours after heparin neutralization also were examined in the last 22 study patients enrolled. MEASUREMENTS AND MAIN RESULTS: All 31 patients had measurable heparin levels 2 hours after protamine administration; 22 patients exhibited a primary failure to reverse heparin after protamine administration, and 9 patients had measureable heparin levels 2 hours after complete heparin reversal (ie, heparin rebound). The thromboelastometric variable, INTEM-CT:HEPTEM-CT ratio, correlated with heparin concentration (r=0.72), but ACT (r=-0.12), APTT (r=0.36), and whole blood heparin concentration, determined using the Hepcon HMS, did not. Peak heparin concentration (0.18±0.07 U/mL) at 4 hours was not correlated with mediastinal blood loss. CONCLUSION: Circulating heparin detected by the chromogenic assay was too low to be clinically significant based on postoperative bleeding, although all 31 patients had residual heparin or heparin rebound at 2 hours after protamine administration with use of the Hepcon HMS.

Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1-3 lymph node metastases.

BACKGROUND: Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer. METHODS: From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS). RESULTS: Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037). CONCLUSION: Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1-3 metastatic lymph nodes.

The discordance between primary breast cancer lesions and pulmonary metastatic lesions in expression of aldehyde dehydrogenase 1-positive cancer cells.

BACKGROUND: We evaluated the expression of aldehyde dehydrogenase 1 (ALDH1) between primary breast lesions and pulmonary metastatic (PM) lesions in breast cancer patients. METHODS: We retrospectively analyzed the clinicopathological features and the expression statuses of ER, PR, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions and evaluated the discordance rates in the expressions of these markers between the primary and metastatic lesions, and also the prognostic value of these factors. RESULTS: None of the PM patients had metastases at any other sites, and all had undergone curative breast cancer surgery. The pulmonary operation was partial resection in 15 (88 %) patients and lobectomy in 2 (12 %) patients. The median overall survival (OS) after resection of the PNs (OS) was 48 months. The discordance rates in the expressions of ER, PR, HER2, Ki67 and ALDH-1 between the primary and metastatic lesions were 0, 29, 21, 43 and 50 %, respectively. CONCLUSION: There was significant discordance in the biomarkers between the primary tumors and the metastatic lesions.

Current problems and working status of female anesthesiologists in Japan.

The rapid growth of the elderly population and the progress in surgical techniques in Japan have led to increased numbers of patients who undergo surgery. Anesthetics are essential for surgery. A survey conducted by the Japanese Society of Anesthesiologists showed that, during the past 10 years, the proportion of females among all the members has increased from 27 to 35 %, and the proportion of female councilors has risen from 3.9 to 6.7 %. However, the conditions of full-time employment remain inadequate for female physicians. Therefore, many female physicians in their 30s or older do not work as anesthesiologists. To support female anesthesiologists and their vital roles in surgical diagnosis and treatment, return-to-work assistance programs have been developed. It is also necessary to improve the working conditions for female anesthesiologists to allow them to continue their work, and to provide education for young female physicians to enhance their professional pride.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Association between mammographic breast density and lifestyle in Japanese women.

A high mammographic breast density is considered to be a risk factor for breast cancer. However, only a small number of studies on the association between breast density and lifestyle have been performed. A cross-sectional study was performed using a survey with 29 questions on life history and lifestyle. The breast density on mammography was classified into 4 categories following the BI-RADS criteria. The subjects were 522 women with no medical history of breast cancer. The mean age was 53.3 years old. On multivariate analysis, only BMI was a significant factor determining breast density in premenopausal women (parameter estimate, -0.403; p value, 0.0005), and the density decreased as BMI rose. In postmenopausal women, BMI (parameter estimate, -0.196; p value, 0.0143) and number of deliveries (parameter estimate, -0.388; p value, 0.0186) were significant factors determining breast density;breast density decreased as BMI and number of deliveries increased. Only BMI and number of deliveries were identified as factors significantly influencing breast density. BMI was inversely correlated with breast density before and after menopause, whereas the influence of number of deliveries on breast density was significant only in postmenopausal women in their 50 and 60s.

[A case of postoperative convulsive seizure following tranexamic acid infusion during aortic valve replacement].

We present a case of postoperative convulsive seizure in an 84-year-old man who underwent an aortic valve replacement. The patient had hypertension associated with hyperaldosteronism and chronic interstitial nephritis. The duration of cardiopulmonary bypass was 74 min. A generalized seizure lasting approximately 1 minute occurred at 1 hour after the patient's arrival in the intensive care unit. A total of 9 generalized seizures, which were aborted by the intravenous administration of diazepam (5 mg), occurred every 30 min. For seizure control, the continuous administration of midazolam (2 mg x hr(-1)) was initiated. On the day after the discontinuation of the midazolam, a generalized seizure recurred and an infusion of sodium thiopental was started. No further seizures were observed. On the sixth postoperative day, the patient was extubated and discharged without any neurological abnormalities. Imaging showed old small areas of cerebral infarction in the basal ganglia, which were not thought to have contributed to the seizures. The blood sugar, sodium, and calcium levels were within the normal limits. The seizures were likely due to a total dose of 8 g of tranexamic acid (TXA) administered intraoperatively. Possible mechanisms of TXA-induced seizures include blockage of inhibitory cortical y -aminobutyric acid-A receptors.