Current Status of Uterine Leiomyosarcoma in the Tohoku Region: Results of the Tohoku Translational Center Development Network Survey.

BACKGROUND: To prepare for a future clinical trial for improving the long-term prognosis of patients with uterine leiomyosarcoma (ULMS), we conducted a multi-institutional survey in the Tohoku region of Japan. METHODS: We conducted a retrospective cohort study between 2011 and 2014 in member institutions of the Tohoku Translational Research Center Development Network. RESULTS: A total of 53 patients with ULMS were registered in 31 institutions for the present survey. The median patient age was 56 years, 67.9% of the patients were postmenopausal, 88.7% had a performance status of 0 or 1, and only 6 patients (11.3%) showed preoperative evidence of malignancy. Although retroperitoneal lymphadenectomy was performed in only 26.4% of patients, 64.2% patients were identified as having FIGO stage 1 disease; 73.6% were eligible to undergo complete surgery. Among 36 patients who were treated with postoperative chemotherapy, 28 (77.8%) received docetaxel and gemcitabine combination therapy. The most frequent recurrence site was the lungs, and the median progression-free survival of all enrolled patients was 11.7 months. However, the median progression-free survival and the median overall survival in patients with stages III and IV disease were 3.4 and 11.4 months, respectively. CONCLUSION: Although ULMS was associated with a high rate of complete or optimal surgery, the long-term prognosis was poor. Effective postoperative therapy should be developed to improve the long-term prognosis of patients with ULMS.

Potassium concentration on admission is an independent risk factor for target lesion revascularization in acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is accompanied by excessive production of catecholamines, which is characterized by a hypokalemic dip. A polymorphism of the adrenergic receptor has also been reported to be associated with target lesion revascularization (TLR) after coronary intervention. SUBJECTS AND METHODS: We enrolled 276 consecutive patients with AMI within 24 hours of symptom onset, who underwent emergency coronary intervention using bare metal stents and had examinations over a 5-10-month follow-up period. The patients were divided into tertiles based on their serum potassium level on admission (low K, <3.9; mid K, ≥ 3.9, <4.3; and high K, ≥ 4.3). RESULTS: Sixty-four TLRs were observed in the study. Increased potassium concentration was associated significantly with TLR. Patients in the high K group were about two and a half times more likely to have a TLR after AMI compared to those in the low K group. Multiple logistic analysis showed that potassium level on admission was an independent risk factor for TLR (odds ratio 1.69; confidence interval 1.04 to 2.74; P = 0.036). CONCLUSIONS: These findings indicated that increased potassium levels on admission might predict TLRs in AMI patients treated with bare metal stents.

Ovarian strumal carcinoid: a case report.

BACKGROUND: Carcinoid tumors of the ovary are rare tumors, histopathologically classified as monodermal teratomas and somatic-type tumors arising from dermoid cysts. Their malignancy varies from borderline to malignant. Carcinoid tumors can occur in young and elderly women, and are sometimes seen in mature teratoma, struma ovarii, or mucinous cystadenoma as a nodule or tumor. Strumal carcinoid and mucinous carcinoid present as special types of carcinoid tumors of the ovary. CASE REPORT: This report describes a 56-year-old woman who presented with a large pelvic mass on abdominal ultrasonography during a medical examination. The diameter of the pelvic tumor was approximately 11 cm and was suspected to be ovarian cancer. The values of CA125 and CEA were above their reference intervals on preoperative examination. Abdominal total hysterectomy and bilateral salpingo-oophorectomy were performed. Intraoperative frozen-section histopathology suggested a diagnosis of mucinous adenocarcinoma; therefore, partial omentectomy and pelvic lymphadenectomy were also performed. Permanent-section histopathology led to a final diagnosis of strumal carcinoid of the ovary, stage IA (FIGO 2014). Six years post-operation, the patient had no sign of recurrence.

SPON1 is an independent prognostic biomarker for ovarian cancer.

BACKGROUND: Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. METHODS: We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. RESULTS: The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. CONCLUSIONS: SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.

Prognostic Significance of Aberrant Claudin-6 Expression in Endometrial Cancer.

BACKGROUND: Among the claudin (CLDN) family, CLDN6 exhibits aberrant expression in various cancers, but its biological relevance has not yet been established. We generated a monoclonal antibody (mAb) against human CLDN6 and verified its specificity. By immunohistochemical staining and semi-quantification, we evaluated the relationship between CLDN6 expression and clinicopathological parameters in tissues from 173 cases of endometrial cancer. RESULTS: The established mAb selectively recognized CLDN6 protein. Ten of the 173 cases (5.8%) showed high CLDN6 expression (score 3+), whereas 19 (11.0%), 18 (10.4%) and 126 (72.4%) cases revealed low CLDN6 expression (score 2+, 1+ and 0, respectively). In addition, intratumor heterogeneity of CLDN6 expression was observed even in the cases with high CLDN6 expression. The 5-year survival rates in the high and low CLDN6 groups was approximately 30% and 90%, respectively. Among the clinicopathological factors, the high CLDN6 expression was significantly associated with surgical stage III/IV, histological grade 3, lymphovascular space involvement, lymph node metastasis and distant metastasis. Furthermore, the high CLDN6 expression was an independent prognostic marker for overall survival of endometrial cancer patients (hazard ratio 3.50, p = 0.014). CONCLUSIONS: It can be concluded that aberrant CLDN6 expression is useful to predict poor outcome for endometrial cancer and might be a promising therapeutic target.

Effect of water temperature during ultrasonic denture cleaning.

Denture plaque is a biofilm composed of various microorganisms aggregated with saliva. Various denture cleansers and cleaning apparatuses have been developed and studied. However, the optimum water temperature for denture cleaning is unknown. Therefore, the present study investigated the effects of water temperature during ultrasonic denture cleaning. In vitro, resin disks with artificial Candida albicans biofilm were pressed onto Candida GE media after ultrasonic cleaning with water at different temperatures for 5 min. The media were subsequently cultured at 37°C for 24 h. The colonies formed were observed and colony areas were quantified using ImageJ software (US National Institutes of Health, Bethesda, MD, USA). In situ, the bacterial count and degree of cleanliness on the tissue surface of maxillary dentures were measured before and after ultrasonic cleaning with water at different temperatures for 5 min. Changes in bacterial counts and cleanliness were calculated for each temperature. The ratio of the area occupied by bacterial colonies in vitro and reduction rates in situ after cleaning with warm water were markedly less than those observed after cleaning with cold water. Therefore, ultrasonic denture cleaning with warm water is more effective.

Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia-reperfusion injury in mice with metabolic disorders.

Although considerable attention has focused on obesity, insulin resistance and abnormal lipid metabolism as coronary risk factors, it remains unclear how these pathogenic factors affect the inflammatory response after myocardial ischemia-reperfusion. This study was conducted to evaluate whether these metabolic disorders exacerbate myocardial ischemia-reperfusion injury, and to determine if ischemia-reperfusion injury could be modified with the thiazolidinedione, pioglitazone. Experiments were performed in KK-A(y) and C57BL/6J mice subjected to 40 min of ischemia followed by reperfusion. Infiltration of inflammatory cells in ischemic myocardium, and infarct size 3 days after reperfusion were significantly higher in KK-A(y) than C57BL/6J mice (p<0.05 and p<0.001, respectively). Furthermore, expression of chemokines, inflammatory cytokines and extracellular matrix proteins in ischemic myocardium was significantly higher in KK-A(y) than C57BL/6J mice 1 day after reperfusion. Pioglitazone treatment of KK-A(y) mice for 14 days significantly reduced the accumulation of inflammatory cells in ischemic myocardium, and infarct size 3 days after reperfusion compared to vehicle treatment (p<0.05 and p<0.05, respectively). Pioglitazone also attenuated expression of chemokines, inflammatory cytokines and extracellular matrix proteins in ischemic myocardium 1 day after reperfusion. In vitro experiments demonstrated that tumor necrosis factor-alpha (TNF-alpha) was significantly higher in cultured peritoneal macrophages from KK-A(y) than C57BL/6J mice, and pioglitazone significantly reduced TNF-alpha in macrophages from both types of mice. These findings suggest that metabolic disorders exacerbate ischemia-reperfusion injury as a result of overexpression of inflammatory mediators, and this effect might be improved, in part by the anti-inflammatory effects of pioglitazone.

Targeted deletion of class A macrophage scavenger receptor increases the risk of cardiac rupture after experimental myocardial infarction.

BACKGROUND: Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A-deficient (SR-A(-/-)) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction. METHODS AND RESULTS: Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A(-/-) and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A(-/-) mice than in WT mice (P=0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A(-/-) mice and 12% (6 of 51 mice) in WT mice (P=0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Real-time reverse transcription-polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A(-/-) mice compared with WT mice. Furthermore, SR-A(-/-) mice showed augmented expression of tumor necrosis factor-alpha and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-alpha and decreased interleukin-10 expression in activated SR-A(-/-) macrophages. CONCLUSIONS: The present findings suggest that SR-A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor-alpha and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.

Changes in plasma von Willebrand factor-cleaving protease (ADAMTS13) levels in patients with unstable angina.

INTRODUCTION: Increased plasma levels of von Willebrand factor (VWF) have been reported in acute myocardial infarction (AMI). Recently, we showed reduced activity of a VWF-cleaving protease (ADAMTS13) in AMI patients. However, there is no information as to whether ADAMTS13 affects the pathogenesis of unstable angina (UA). Thus, the purpose of this study was to examine changes in plasma VWF and ADAMTS13 levels in UA patients. MATERIALS AND METHODS: Plasma VWF and ADAMTS13 levels (mU/ml) were measured in 45 patients with UA, 55 with stable exertional angina (SEA) and 47 with chest pain syndrome (CPS) at the time of coronary angiography. Levels were also measured in 15 UA patients after 6 months of follow-up. RESULTS: VWF antigen levels (mU/ml) increased significantly in UA patients compared with SEA or CPS (2129.3+/-739.5, 1571.8+/-494.2 and 1569.5+/-487.0, respectively; P < 0.0001 in UA vs. SEA or CPS). ADAMTS13 antigen levels (mU/ml) were significantly lower in UA patients than SEA or CPS (737.3+/-149.5, 875.3+/-229.0 and 867.7+/-195.5, respectively; P < 0.01 in UA vs. SEA or CPS). Furthermore, there was a significant inverse correlation between VWF and ADAMTS13 antigen levels (r = -0.302, P = 0.0002). The antigen levels at 6 months of follow-up were not different compared to the acute phase in the 15 UA patients that had repeated blood sampling. CONCLUSIONS: These findings suggest that there is prolonged thrombogenicity in UA patients represented as an imbalance between VWF and ADAMTS13 activity.

Delayed Birth-Related Femur Fracture after Cesarean Section: A Case Report.

Background Birth-related femur fractures are rare. They have been reported following difficult delivery and are commonly diagnosed immediately after birth or on the following day. However, some birth-related femur fractures are diagnosed several days after birth. Mechanisms underlying the development of delayed femur fracture are incompletely understood. Case We report the case of a girl diagnosed with a left spiral femur fracture with associated edema and hypoesthesia on postpartum day 9. A nondisplacement femur fracture was identified on plain radiography at birth after cesarean section; however, it was undiagnosed due to the lack of symptoms. She was treated with plaster cast fixation; the physical examination at age 1 was normal. Herein, the diagnosis of birth-related femur fracture according to plain radiography findings suggests that the symptoms related to birth trauma develop several days after birth. Conclusion Birth-related fracture should be considered in all neonatal femur fracture cases and in patients with no symptoms at birth. Neonates delivered in the breech presentation by cesarean section should be carefully monitored after birth. The findings of the present case further our understanding of the pathogenic mechanisms underlying delayed diagnosis of birth-related femur fracture.

Serial changes in von Willebrand factor-cleaving protease (ADAMTS13) and prognosis after acute myocardial infarction.

Von Willebrand factor (VWF), a cofactor in platelet adhesion and aggregation, increases hemostasis and thrombosis. Recently, a metalloprotease that cleaves VWF multimers has been identified, namely ADAMTS13. The aim of this study was to investigate the relation between serial changes in plasma VWF and ADAMTS13 and the prognosis after acute myocardial infarction (AMI). We measured serial changes of plasma VWF and ADAMTS13 antigen levels in 92 patients with AMI and 40 control subjects. VWF levels were significantly higher in patients with AMI compared with controls (p <0.01) on admission, peaked 3 days after admission, and remained high for 14 days. In contrast, on admission, ADAMTS13 levels were significantly lower in patients with AMI compared with controls (p <0.0001), with minimum antigen levels reached after 3 days, and remained lower for 14 days. The ratio of VWF/ADAMTS13 antigen levels was higher in patients with AMI compared with controls throughout the time course. Cox hazards analysis revealed that the early increase of VWF and VWF/ADAMTS13 ratio levels and the early decrease of ADAMTS13 levels were significant predictors of future thrombotic events during the 1-year follow-up period. Kaplan-Meier analysis demonstrated that patients with major decreases of ADAMTS13 levels and high increases of VWF/ADAMTS13 levels had significantly greater probabilities for development of thrombotic events (p = 0.0104 and 0.0209, respectively). In conclusion, these findings suggest that monitoring the changes of VWF and ADAMTS13 antigen levels in the early phase might be valuable for predicting and preventing thrombosis during 1-year follow-up in patients with AMI.

Triphasic Mitral Inflow Pattern in a Patient with Congenital Absence of the Pericardium.

A healthy 19-year-old man was referred to our hospital due to an elongated left heart border on chest radiograph. Transthoracic echocardiography showed a posteriorly deviated left ventricular apex, increased right ventricular dimension, and hypokinesis of the interventricular septum. Pulsed Doppler echocardiogram revealed a triphasic mitral inflow pattern. Myocardial longitudinal strain rate imaging revealed that the early diastolic strain rate abruptly decreased to a negative value and then became positive at the left ventricular apex. In this case of an absent pericardium, the triphasic mitral inflow pattern might have been caused by an early diastolic shortening and subsequent elongation at the apex.

Acute Multiple Cerebral Infarction in a Patient with an Accessory Mitral Valve.

A 96-year-old woman developed hemiparesis 2 weeks after orthopedic surgery. Magnetic resonance imaging revealed multiple cerebral infarctions in the bilateral hemisphere. Transthoracic echocardiography revealed a mobile structure attached to the anterior mitral leaflet that protruded toward the left ventricular outflow tract. The structure was identified as an accessory mitral valve. Doppler echocardiography showed that there was no significant left ventricular outflow obstruction. This is a rare case of a silent accessory mitral valve that was detected after multiple cerebral infarctions.

A Prospective Multicenter Study Using a Virtual 3 Fr Percutaneous Coronary Intervention System: The V3 Registry.

OBJECTIVES: To evaluate the safety and feasibility of virtual 3 Fr (V3), sheathless 5 Fr percutaneous coronary intervention (PCI). BACKGROUND: A small-diameter guiding catheter (GC) makes less-invasive PCI possible. The V3 is an extremely slender PCI system; however, the outcome of using this system has not yet been determined. METHODS: The V3 registry is a prospective, multicenter, non-randomized study that enrolled patients who underwent elective V3-PCI. The primary endpoint was clinical success rate, and the secondary endpoints were PCI success rate in all cases, major adverse cardiac and cerebrovascular event (MACCE) at 30 days, and access-site complications. RESULTS: A total of 260 patients with 321 lesions were enrolled. Of this group, 70% were male and the mean age was 70.8 ± 10.0 years. Type B2/C lesions comprised 50.7% of the total. The clinical success rate was 95.8%, and the PCI success rate was 99.2%. PCI failure was reported in 2 chronic total occlusion cases. No MACCE was reported. Although there was no major bleeding, hematoma occurred at the puncture site in 12.7% of cases. There was a single radial artery occlusion (0.4%) without symptoms. CONCLUSIONS: PCI with the V3 was safe and feasible. Radial artery occlusion and major bleeding complications were extremely low. However, access-site hematoma frequently complicated catheter exchange.

Influence of weather conditions on the frequent onset of acute myocardial infarction.

BACKGROUND: This study was conducted to clarify the influence of weather conditions on the onset of acute myocardial infarction (AMI) in Kumamoto. METHODS: We studied 642 consecutive patients (males 433, females 209; 71±13 years) who were admitted with AMI. Days of frequent onset (F-days) were defined as days on which ≥2 patients had been admitted for AMI, whereas days of non-frequent onset (N-days) indicated those with fewer than 2 admissions for AMI. Meteorological factors, including the mean atmospheric pressure and rainfall, the mean, maximum, and minimum temperature, intra-day temperature difference, humidity, wind speed, and the number of sunlight hours, were analyzed. All variables were measured on the day of onset of AMI and on each of the 2 days immediately prior to the day of onset. RESULTS: There were 86 F-days and 1740 N-days. F-days were significantly associated with lower air temperature (mean, maximum, and minimum), higher intra-day temperature difference, lower humidity, and longer daily duration of sunlight compared with N-days. In addition, meteorological factors for frequent onset of AMI affected older subjects to a greater extent than either young or female subjects. Multiple logistic regression analysis showed that minimum temperature two days before onset was associated with the frequent onset of AMI (odds ratio, 0.805; p<0.05). CONCLUSION: Lower minimum temperature on the 2nd day preceding the onset is an independent risk factor for the frequent onset of AMI. The association between low ambient temperature and frequent onset of AMI was stronger in elderly and female subjects.