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The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34-190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K + (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34-190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with a poor prognosis and, thus, novel therapeutic strategies for SS are urgently required. In the present study, we investigated the functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells. c-MET-activated Yamato-SS cells showed higher anchorage-independent growth ability and less sensitivity to chemotherapeutic agents than did c-MET-inactivated SYO-1 or HS-SY-II cells. INC280, a selective c-MET inhibitor, inhibited growth of Yamato-SS cells both in vitro and in vivo but not that of SYO-1 or HS-SY-II cells. INC280 induced cell cycle arrest and apoptosis, and blocked phosphorylation of c-MET and its downstream effectors in Yamato-SS cells. Co-expression of HGF and c-MET in SS clinical samples correlated with a poor prognosis in patients with SS. Taken together, activation of HGF/c-MET signaling in an autocrine fashion leads to an aggressive phenotype in SS and targeting of this signaling exerts superior antitumor effects on c-MET-activated SS. HGF/c-MET expression status is a potential biomarker for identification of SS patients with a worse prognosis who can benefit from c-MET inhibitors., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Synovial sarcoma (SS) is an aggressive soft tissue tumour with poor prognosis. Using five human SS cell lines, we examined the cytotoxic effects of trabectedin (ET-743; Yondelis(®)), a novel marine natural product, which was approved in Europe for the treatment of soft tissue sarcomas (STS). The significant growth inhibitory effects were observed in all SS cell lines below nanomolar concentration of trabectedin. Furthermore, trabectedin significantly suppressed the tumour growth in xenograft models. Flow cytometer analysis in vitro and immunohistochemical analysis in vivo revealed its effect of cell cycle inhibition and apoptosis induction. We also examined the expression of ERCC1, 5 and BRCA1 in SS cell lines and clinical samples, and majority of them showed highly trabectedin-sensitive pattern as previously reported in other cancers. Our preclinical data indicated that trabectedin could be a promising therapeutic option for patients with SS.

Objective: This study aimed to report the clinical outcomes for patients with osteoid osteoma (OO) treated by radiofrequency ablation (RFA) using a three-dimensional (3D) navigation system., Methods: We performed RFA using a 3D navigation system on 32 patients with clinically and radiologically diagnosed OO. This study included 25 males and 7 females with a median age of 20 years (range, 10-39 years). The median duration of follow-up was 18 months (range, 1-65 months). We investigated technical specifications, tumor localization, technical success, clinical success, biopsy success, complications, incomplete treatment, and recurrences., Results: Eighteen tumors were located in the femur, seven in the tibia, two in the humerus, and one each in the fibula, scapula, patella, lumbar vertebra, and acetabula. All procedures were technically successful, and pain relief was achieved in all patients. However, local recurrence developed in one patient, needing additional RFA. The clinical success rate was 96.8%. Biopsy showed OO in 12 patients (37%). Complications occurred in three patients (9%), two cases of fractures and one of osteomyelitis., Conclusions: A 3D navigation provides real-time imaging and enables us to set the RFA needle in the correct position, particularly in case of OO-aroused complex anatomical structures. Our initial results indicated that radiofrequency ablation using a 3D navigation system is feasible and safe for patients with OO., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Synovial sarcoma is a malignant soft tissue sarcoma which arises near joints. The most frequent metastasis sites of synovial sarcoma are the lungs, lymph nodes, and bone. Pancreatic metastasis is quite rare; only 3 cases have been reported worldwide to date. We herein present the 4th case of pancreatic metastasis from synovial sarcoma., Methods and Results: A 32-year-old man underwent extended excision of synovial sarcoma in the left pelvis and femur in 2009. In 2013, follow-up contrast-enhanced computed tomography revealed a 35-mm heterogeneously enhanced mass in the pancreas body. Endoscopic ultrasound-guided fine needle aspiration of the mass revealed a diffuse proliferation of atypical spindle cells in a fascicular arrangement. Because the histology was quite similar to the resected specimen of synovial sarcoma in 2009, the mass was suspected to be a metastasis from synovial sarcoma. Laparoscopic distal pancreatectomy with adjuvant adriamycin/ifosfamide chemotherapy was subsequently performed. Synovial sarcoma-specific SS18-SSX1 (synovial sarcoma translocation, chromosome 18-synovial sarcoma X1) or SS18-SSX2 chimera mRNA was detected in the resected specimen, confirming the diagnosis of metastasis from synovial sarcoma. The patient did well for 30 months without recurrence., Conclusion: This case suggests that pancreatic metastasis from synovial sarcoma can be successfully treated by metastasectomy with adjuvant chemotherapy., Competing Interests: The authors report no conflicts of interest.

The prognostic significance of the SYNTAX (Synergy between PCI with Taxus and cardiac surgery) score has recently been demonstrated in patients with stable multivessel or left main coronary artery disease (CAD). The present study determines whether adding the SYNTAX score to Framingham risk score (FRS), left ventricular ejection fraction (LVEF) and presence of myocardial infarction (MI) by late gadolinium enhancement (LGE) magnetic resonance imaging can improve the risk stratification in patients with stable CAD. We calculated the SYNTAX score in 161 patients with stable CAD (mean age: 66 ± 10 years old). During a mean follow-up of 2.3 years, 56 (35 %) of 161 patients developed cardiovascular events defined as cardiovascular death, non-fatal MI, cerebral infarction, unstable angina pectoris, hospitalization due to heart failure and revascularization. Multivariate Cox regression analysis selected triglycerides [hazard ratio (HR): 1.005 (95 % confidence interval (CI): 1.001-1.008), p < 0.008], presence of LGE [HR: 6.329 (95 % CI: 2.662-15.05), p < 0.001] and the SYNTAX score [HR: 1.085 (95 % CI: 1.044-1.127), p < 0.001] as risk factors for future cardiovascular events. Adding the SYNTAX score to FRS, EF and LGE significantly improved the net reclassification index (NRI) [40.4 % (95 % CI: 18.1-54.8 %), p < 0.05] with an increase in C-statistics of 0.089 (from 0.707 to 0.796). An increase in C-statistics and significant improvement of NRI showed that adding the SYNTAX score to the FRS, LVEF and LGE incrementally improved risk stratification in patient with stable CAD.

Objective: The incidence of Ewing sarcoma is lower in non-Caucasian populations, compared with Caucasian populations, for unknown reasons. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy, with no difference in outcome between skeletal and extraskeletal Ewing sarcoma. However, there are few studies of Ewing sarcoma in non-Caucasian populations, with especially few comparing outcomes between skeletal and extraskeletal Ewing sarcoma. Thus, the purpose of this study is to determine whether the outcomes and prognostic factors of Ewing sarcoma in the Japanese population are similar to those in Caucasian populations and to determine whether skeletal and extraskeletal Ewing sarcoma have similar outcomes in Japanese patients., Methods: We retrospectively evaluated the outcomes of 74 Japanese patients with Ewing sarcoma treated between 1981 and 2011 from the Osaka University Orthopaedic Oncology Group., Results: Extraskeletal Ewing sarcoma, tumors in the extremities, localized disease at presentation and diagnosis after 2000 were significantly associated with a favorable outcome. Among patients with localized disease at presentation, a significantly better outcome was observed for those with extraskeletal Ewing sarcoma, those who underwent a VDC/IE based or VAIA chemotherapy protocol, and those who were diagnosed after 2000. In the multivariable analyses, extraskeletal Ewing sarcoma was an independent predictor of increased overall survival among all patients and the subset of patients with localized disease., Conclusions: The outcome of patients with Ewing sarcoma in Japan has improved in the last decade. The outcomes and prognostic factors are similar for Japanese and Caucasian patients, though in this series of Japanese patients, a better prognosis was observed for patients with extraskeletal rather than skeletal Ewing sarcoma., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The distribution of late gadolinium enhancement (LGE) on the cardiac MRI (CMR) indicates myocardial fibrosis and provides information of possible reentry substrates. QT dynamicity reflecting repolarization abnormalities has gained attention as a potential prognostic predictive factor., Objective: To clarify the correlation between the LGE distribution on CMR and QT dynamicity represented by the QT/RR relationship., Methods: CMR and QT/RR analyses using Holter monitoring were performed in 34 patients (24 males, 60 ± 11 years) with ventricular tachycardia (VT) and/or ventricular fibrillation (VF). The LGE on CMR was scored using a 4-point score in 17 left ventricular segments. The sum of the LGE scores was calculated for each patient. The QT/RR slope and daytime/nighttime QT/RR ratio (day/night ratio) were calculated. The correlation between the slope or the day/night QT/RR ratio and late enhancement findings was analyzed., Results: All patients were divided into 23 LGE positive (LGE(+)) and 11 LGE negative (LGE(-)) patients. The slopes of the QTe/RR and QTa /RR were significantly steeper in the LGE(+) than in LGE(-) patients (0.21 ± 0.03 vs 0.13 ± 0.02; P < 0.001, 0.19 ± 0.03 vs 0.13 ± 0.02; P < 0.001, respectively), and both slopes were significantly correlated with the total LGE scores (r = 0.83, P < 0.001; r = 0.71, P < 0.001, respectively). In the LGE(+) patients, the QTe day/night (1.37 ± 0.38 vs 0.91 ± 0.33; P = 0.002) and QTa day/night ratios (1.33 ± 0.26 vs 1.06 ± 0.30; P = 0.011) were significantly greater than those in the LGE(-) patients., Conclusion: The LGE distribution was closely related to the QT dynamicity, suggesting that a combination of these markers can be a powerful tool for understanding the background pathophysiology., (© 2015 Wiley Periodicals, Inc.)

Background: Phase contrast (PC) cine-magnetic resonance imaging (MRI) of the coronary sinus allows for noninvasive evaluation of coronary flow reserve (CFR), which is an index of left ventricular microvascular function. The objective of this study was to investigate coronary flow reserve in patients with heart failure with preserved ejection fraction (HFpEF)., Methods and Results: We studied 25 patients with HFpEF (mean and SD of age: 73±7 years), 13 with hypertensive left ventricular hypertrophy (LVH) (67±10 years), and 18 controls (65±15 years). Breath-hold PC cine-MRI images of the coronary sinus were obtained to assess blood flow at rest and during ATP infusion. CFR was calculated as coronary sinus blood flow during ATP infusion divided by coronary sinus blood flow at rest. Impairment of CFR was defined as CFR <2.5 according to a previous study. The majority (76%) of HFpEF patients had decreased CFR. CFR was significantly decreased in HFpEF patients in comparison to hypertensive LVH patients and control subjects (CFR: 2.21±0.55 in HFpEF vs 3.05±0.74 in hypertensive LVH, 3.83±0.73 in controls; P<0.001 by 1-way ANOVA). According to multivariable linear regression analysis, CFR independently and significantly correlated with serum brain natriuretic peptide level (β=-68.0; 95% CI, -116.2 to -19.7; P=0.007)., Conclusions: CFR was significantly lower in patients with HFpEF than in hypertensive LVH patients and controls. These results indicated that impairment of CFR might be a pathophysiological factor for HFpEF and might be related to HFpEF disease severity., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: As there are no reports of studies in patients with pelvic chondrosarcoma treated with carbon ion radiotherapy (CIRT), the aim of this study was to evaluate the applicability of CIRT for patients with chondrosarcoma of the pelvis., Methods: The medical records of 31 patients with chondrosarcoma of the pelvis treated either by surgical resection or by CIRT between 1983 and 2014 were reviewed. There were 22 males and 9 females with a median age of 43 years (range 16-77 years). The median duration of follow-up was 66 months (range 5-289 months). Twenty-four patients underwent surgery, and 7 patients received CIRT (70.4 GyE in 16 fractions over 4 weeks)., Results: The overall local recurrence rate was 32 %, and the estimated overall 5- and 10-year survival rates were 72 and 57 %, respectively. The mean Musculoskeletal Tumor Society functional score was 59 %. The treatment procedures (surgery or CIRT) did not affect overall survival (P = 0.347). However, the patients who underwent surgery had impaired function compared with those who received CIRT (P = 0.03)., Conclusion: Although more patients need to be monitored to assess the clinical and functional outcomes of CIRT for patients with chondrosarcoma of the pelvis, this treatment might offer an acceptable alternative.

Background: The presence of myocardial scar detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging has been described as a good independent predictor of mortality in patients with hypertrophic cardiomyopathy (HCM). Time-domain T-wave alternans (TWA) is also a potential predictor of cardiac mortality in patients with left ventricular dysfunction., Objective: The purpose of this study was to elucidate the relationship between LGE distribution and TWA in patients with HCM., Methods: CMR and TWA analyses using Holter monitoring were performed in 42 patients with HCM. The average transmural extent of LGE was scored as 1-4 in each segment, and the sum of the LGE scores (total LGE score) was calculated for each patient. The correlation between the maximal time-domain TWA voltage and LGE findings was analyzed, and the differences in time-domain TWA voltage, total LGE score, and cardiac function assessed by CMR imaging in the presence or absence of ventricular tachycardia (VT) were also compared., Results: The total LGE score was significantly and positively correlated with the maximal time-domain TWA voltage (r = 0.59; P < .001). Furthermore, the total LGE score and maximal time-domain TWA voltage were significantly greater in patients who had episodes of VT (n = 21) than in those without VT (23 ± 7 vs. 10 ± 8; P < .001 and 87 ± 26 μV vs. 62 ± 12 μV; P < .001, respectively). However, the left ventricular ejection fraction did not statistically differ between patients with VT and those without VT (56% ± 14% vs. 61% ± 7%; P = .102)., Conclusion: The magnitude of the localized LGE was significantly correlated with abnormalities in ventricular repolarization as assessed by TWA and QT dispersion., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the prognostic value of myocardial focal fibrosis quantified by late gadolinium enhanced (LGE) magnetic resonance imaging (MRI) in patients with heart failure with preserved ejection fraction (HFpEF)., Methods: One-hundred eleven HFpEF patients (mean age: 70 ± 14 years, 55 (50%) female) were enrolled. We excluded patients with previous history of coronary artery disease and/or ischemic pattern of hyper enhancement on LGE MRI. Myocardial enhancement was defined using signal intensity >2SD above the mean signal intensity of a remote myocardium. Major adverse cardiovascular events were defined as cardiovascular death and heart failure requiring hospitalization., Results: During a mean follow up period of 851 ± 609 days, 10 events (2 cardiovascular death, 8 hospitalization for heart failure decompensation) were observed. Area under the receiver operating characteristics curve of LGE% for the detection of future events was 0.721 (95% CI: 0.628-0.802). Multivariate Cox proportional hazard analysis showed that LGE% is an independent predictor of future events after the adjustment with prognostic 5 factors - age, diabetes mellitus, New York Heart Association classification, history of heart failure hospitalization and left ventricular ejection fraction - which were identified in the I-PRESERVE study (Irbesartan in Heart Failure with Preserved Ejection Fraction Study) (hazard ratio=7.913, 95% CI: 1.603-39.05, P=0.012)., Conclusions: Larger size of LGE was significantly associated with high rate of future cardiovascular death and heart failure hospitalization, suggesting that the quantification of myocardial focal fibrosis by LGE MRI could be useful for the risk stratification in HFpEF patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The presence of a myocardial scar detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been described as a predictor of all-cause mortality in hypertrophic cardiomyopathy (HCM). However, the detailed spatial relationship between LGE site and electrical abnormality is unclear in high-risk HCM with malignant arrhythmia., Objective: The purpose of this study was to elucidate the detailed relationship between the site on CMR imaging and the electrically damaged site, a potential origin of ventricular arrhythmias in patients with HCM., Methods: Fifty consecutive HCM patients underwent contrast-enhanced CMR. Of those patients, 18 patients with ventricular tachycardia underwent electrophysiology study including endocardial mapping of the left ventricle (LV). The LGE area was calculated at 12 different LV sites: anterior, lateral, posterior, and septal segments of the basal, middle, and apical portions. At each LV site, the bipolar electrogram, effective refractory period (ERP), and monophasic action potential were recorded., Results: LGE-positive segments demonstrated a significantly lower amplitude (4.0 ± 2.8 mV vs 7.3 ± 3.6 mV; P < .001), longer duration (54.7 ± 17.8 vs 40.6 ± 7.8 ms; P < .001), longer ERP (320 ± 42 ms vs 284 ± 37 ms; P = .001), and longer monophasic action potential duration measured at 90% repolarization (321 ± 19 ms vs 283 ± 25 ms; P < .001) than did LGE-negative segments. The LGE area negatively correlated with the amplitude (r = -0.59; P < .001) and positively correlated with the duration (r = 0.64; P < .001), ERP (r = 0.44; P < .001), and action potential duration measured at 90% repolarization (r = 0.63; P < .001). All the observed VTs originated from LGE-positive segments., Conclusion: The spatial distribution of LGE significantly correlates with depolarizing and repolarizing electrical damage in high-risk HCM with malignant ventricular arrhythmia., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: In patients with soft tissue sarcoma of the wrist and hand, limb salvage operation is extremely challenging for surgeons in attempting a complete tumor resection with negative surgical margins. In this study, we report four patients with soft tissue sarcoma of the wrist and hand treated by limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts., Methods: The patients were all male, and the mean age at the time of surgery was 45 years. Histological diagnoses included clear cell sarcoma in two patients, synovial sarcoma in one, and angiosarcoma in one. All four patients had high grade tumors, wherein three had American Joint Committee on Cancer (AJCC) stage III disease and one with AJCC stage IV disease. The tumors were resected en bloc with involved tendons. The tendons were isolated from the resected tissues, irradiated ex vivo, and re-implanted into the host tendons. In one patient, the bone was resected additionally because of tumor invasion to the bone. Hand function was evaluated using Musculoskeletal Tumor Society (MSTS) rating system., Results: Of the four patients, three died of distant metastatic disease. The remaining patient lives and remains disease-free. The mean follow-up period was 33 months. One patient had local recurrence outside the irradiated graft at 20 months after surgery. The functional rating was 22. Lower scores were seen in patients with reconstruction of flexor tendons than extensor tendons., Conclusions: Limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts is an acceptable method in selected patients with soft tissue sarcoma of the wrist and hand.

Background: Intravenous administration of magnesium (Mg(2+)) is effective for polymorphic ventricular tachycardia via homogenization of transmural ventricular repolarization. Mg(2+) likely plays some role in the heterogeneity of repolarization in J wave syndromes., Objective: To investigate the relationship between the repolarization parameters and serum Mg(2+), potassium (K(+)), and calcium (Ca(2+)) levels in J wave syndromes., Methods: Thirteen J-wave syndrome patients (Brugada and early repolarization [ER] syndromes), with documented episodes of ventricular fibrillation (VF), and 13 ER pattern (ERP) or Brugada type ECG patients were enrolled (25 males, mean age 48 ± 15 years). The 12-lead ECG-derived parameters including the QT, QT dispersion (QTd), Tpeak-Tend (Tp-e) interval, Tp-e dispersion (Tp-ed), Tp-e/QT ratio, and activation recovery interval (ARI) dispersion were calculated; the correlations between these parameters and electrolytes including Mg(2+), K(+), and Ca(2+) were analyzed., Results: Although there was no association between serum K(+) or Ca(2+) and QTd, there was a strong negative correlation between serum Mg(2+) and QTd in J wave syndrome patients with a history of VF (r = -0.715, p = 0.006). Also, there was a tendency for a negative correlation between Mg(2+) and Tp-ed or ARI dispersion in J wave syndrome patients with a history of VF (r = -0.513, p = 0.072 and r = -0.53, p = 0.063, respectively). On the other hand, in 13 patients with a Brugada type ECG or ERP, no correlation was observed between serum Mg(2+) and the QTd, Tp-ed or ARI dispersion., Conclusion: Serum Mg(2+) may play an important role in the cardiac repolarization process in J wave syndromes.

Introduction: We reported impaired QT-rate dependence in early repolarization syndrome (ERS); however, contemporary data have shown peak incidence of sudden cardiac death (SCD) in ERS and Brugada syndrome (BrS) at mid-night and early morning. Taken together, we analyzed the nocturnal QT-rate dependence in both syndromes., Methods and Results: A total of 172 subjects were enrolled: 11 ERS, 11 BrS patients, 50 subjects with an uneventful ER pattern (ERP), and 100 non-J-wave control subjects. Ambulatory ECG-derived parameters (QT, QTc, and QT/RR slope) and day-night QT difference were analyzed and compared. Among the groups, there was no significant difference in the average QT or QTc; however, the 24-hour QT/RR slope was significantly smaller in ERS and BrS patients (0.103 ± 0.01 and 0.106 ± 0.01, respectively) than in the control group (0.156 ± 0.03, P < 0.001). Detailed analysis showed a lower day-night QT difference in ERS and BrS patients (19 ±18.7 and 24 ±14 milliseconds, respectively) than in the controls (40 ± 22 milliseconds, P = 0.007) with the lowest QT/RR slopes seen in the ERS and BrS groups from 0 to 3:00 am (QT/RR; 0.076 ± 0.02 vs. 0.092 ± 0.04 vs. 0.117 ± 0.04, for the ERS, BrS, and controls, respectively, P = 0.004) and from 3 to 6 am (QT/RR 0.074 ± 0.03 vs. 0.079 ± 0.02 vs. 0.118 ± 0.04, P < 0.001)., Conclusion: In a large population of age- and gender-matched groups, both ERS and BrS patients showed attenuated QT-rate dependence and impaired QT day-night modulation that may provide a baseline reentrant substrate. Importantly, QT/RR maladaptation was most evident at mid-night and early morning, which may explain the propensity of such patients to develop SCD during this critical period., (© 2014 Wiley Periodicals, Inc.)

Periosteal chondromas are rare benign cartilaginous tumors that arise adjacent to the cortex beneath the periosteum. These lesions are usually slow-growing and rarely exceed 3 cm in the greatest dimension. Here, we describe a 17-year-old boy who had a giant periosteal chondroma of the right distal femur, which was treated with intralesional resection and intensive curettage. In addition, we report a novel application of a bioresorbable plate in the management of the large bone defect after resection of a benign bone tumor.

Purpose: Soft tissue sarcoma of the hand is rare, and one of the most common histological diagnosis is synovial sarcoma. We report the clinical outcomes of patients with synovial sarcoma of the hand and discuss treatment strategies., Methods: We reviewed five patients with synovial sarcoma of the hand treated at our institutions from 1983 to 2013. The mean patient age at the time of diagnosis was 36.6 years (range, 20-62 years). Two patients underwent marginal excision after neoadjuvant chemotherapy, followed by radiation therapy, one underwent wide local excision and two received chemotherapy and radiation therapy., Results: The average duration of follow-up for all patients was 88.2 months (range, 14-218 months). Two patients continuously remained disease free, two experienced local recurrence requiring additional surgery and then showed no evidence of disease, and one who had distant metastasis at diagnosis died of the disease. No patients developed lymph node metastasis. The estimated 5-year overall survival was 80%., Conclusions: Our case series suggests that patients with localised synovial sarcoma of the hand may have favourable outcomes. Wide excision or marginal excision, followed by radiation therapy combined with chemotherapy, represent acceptable treatment strategies for synovial sarcoma of the hand. Regional lymph node dissection does not seem to be essential for synovial sarcoma of the hand.

We describe three cases of J-wave syndrome in which ventricular fibrillation (VF) was probably induced by corticosteroid therapy. The patients involved were being treated with prednisolone for concomitant bronchial asthma. One of the three patients had only one episode of VF during her long follow-up period (14 years). Two patients had hypokalemia during their VF episodes. Corticosteroids have been shown to induce various types of arrhythmia and to modify cardiac potassium channels. We discuss the possible association between corticosteroid therapy and VF in J-wave syndrome based on the cases we have encountered.

Synovial sarcoma (SS) is a malignant soft-tissue tumor characterized by the recurrent chromosomal translocation SS18-SSX. Vascular endothelial growth factor (VEGF)-targeting anti-angiogenic therapy has been approved for soft-tissue sarcoma, including SS; however, the mechanism underlying the VEGF signal for sarcomagenesis in SS is unclear. Here, we show that SS18-SSX directs the VEGF signal outcome to cellular growth from differentiation. Synovial sarcoma cells secrete large amounts of VEGF under spheroid culture conditions in autocrine fashion. SS18-SSX knockdown altered the VEGF signaling outcome, from proliferation to tubular differentiation, without affecting VEGF secretion, suggesting that VEGF signaling promoted cell growth in the presence of SS18-SSX. Thus, VEGF inhibitors blocked both host angiogenesis and spheroid growth. Simultaneous treatment with VEGF and chemokine (C-X-C motif) (CXC) ligand 12 and CXC receptor 4 inhibitors and/or ifosfamide effectively suppressed tumor growth both in vitro and in vivo. SS18-SSX directs the VEGF signal outcome from endothelial differentiation to spheroid growth, and VEGF and CXC receptor 4 are critical therapeutic targets for SS., (© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Background: Epithelioid sarcoma (EpS) is a high-grade malignant soft-tissue sarcoma characterized by local recurrences and distant metastases. Effective treatments for EpS have not been established and thus novel therapeutic approaches against EpS are urgently required. mTOR inhibitors exert antitumor effects on several malignancies but AKT reactivation by mTOR inhibition attenuates the antitumor effects of mTOR inhibitors. This reactivation is receptor tyrosine kinase (RTK)-dependent due to a release of negative feedback inhibition. We found that c-MET was the most highly activated RTK in two human EpS cell lines, Asra-EPS and VAESBJ. Here we investigated the functional and therapeutic relevance of mTOR and/or c-MET signaling pathways in EpS both in vitro and in vivo., Methods: We first examined the effects of an mTOR inhibitor, RAD001 (everolimus), on cell proliferation, cell cycle, AKT/mTOR signaling, and xenograft tumor growth in EpS cell lines. Next, we determined whether RAD001-induced AKT reactivation was blocked by silencing of c-MET or treatment with a selective c-MET inhibitor, INC280. Finally, we evaluated the antitumor effects of RAD001 combined with INC280 on EpS cell lines compared with either single agent or control in vitro and in vivo., Results: Constitutive AKT phosphorylation was observed in Asra-EPS and VAESBJ cells. RAD001 suppressed EpS cell growth by inducing cell cycle arrest but enhanced AKT phosphorylation, which resulted in intrinsic resistance to mTOR inhibitors. In both EpS cell lines, RAD001-induced AKT phosphorylation was dependent on c-MET signaling. INC280 inhibited phosphorylation of c-MET and its downstream molecules, and decreased RAD001-induced phosphorylation of both AKT and ERK in EpS. Compared with a single agent or control, the combination of RAD001 and INC280 exerted superior antitumor effects on the growth of EpS cell lines in vitro and in vivo., Conclusions: Targeting of mTOR and c-MET signaling pathways significantly abrogates the growth of EpS in preclinical models and may be a promising therapeutic approach for patients with EpS.

Schwannoma is a benign peripheral nerve sheath tumor derived from Schwann cells. Bone scalloping, including spinal foramen enlargement, develops when the tumor is located adjacent to a bone and is a characteristic radiological feature. In the present study, to investigate the pathomechanism of bone resorption, the expression of noggin (a potent antagonist of bone morphogenetic protein) was analyzed in schwannoma tissues and compared with that observed in other soft tissue tumors. Quantitative polymerase chain reaction analysis revealed that the mRNA levels of noggin in schwannomas were significantly increased compared with the levels in other tumors. The gene product of noggin was only detected in a subset of schwannomas using immunohistochemistry and western blot analysis. Furthermore, the tissue extract from a noggin-producing schwannoma was found to inhibit osteoblastic differentiation in MC3T3 mouse osteoblastic cells in a dose-dependent manner. These findings indicate that bone scalloping in radiology may be induced by schwannoma-secreted noggin. In addition, noggin may have potential as a novel molecular and diagnostic marker for identifying certain types of schwannoma.

Background: Clear cell sarcoma (CCS) is a therapeutically unresolved, aggressive, soft tissue sarcoma (STS) that predominantly affects young adults. This sarcoma is defined by t(12;22)(q13;q12) translocation, which leads to the fusion of Ewing sarcoma gene (EWS) to activating transcription factor 1 (ATF1) gene, producing a chimeric EWS-ATF1 fusion gene. We established a novel CCS cell line called Hewga-CCS and developed an orthotopic tumor xenograft model to enable comprehensive bench-side investigation for intensive basic and preclinical research in CCS with a paucity of experimental cell lines., Methods: Hewga-CCS was derived from skin metastatic lesions of a CCS developed in a 34-year-old female. The karyotype and chimeric transcript were analyzed. Xenografts were established and characterized by morphology and immunohistochemical reactivity. Subsequently, the antitumor effects of pazopanib, a recently approved, novel, multitargeted, tyrosine kinase inhibitor (TKI) used for the treatment of advanced soft tissue sarcoma, on Hewga-CCS were assessed in vitro and in vivo., Results: Hewga-CCS harbored the type 2 EWS-ATF1 transcript. Xenografts morphologically mimicked the primary tumor and expressed S-100 protein and antigens associated with melanin synthesis (Melan-A, HMB45). Pazopanib suppressed the growth of Hewga-CCS both in vivo and in vitro. A phospho-receptor tyrosine kinase array revealed phosphorylation of c-MET, but not of VEGFR, in Hewga-CCS. Subsequent experiments showed that pazopanib exerted antitumor effects through the inhibition of HGF/c-MET signaling., Conclusions: CCS is a rare, devastating disease, and our established CCS cell line and xenograft model may be a useful tool for further in-depth investigation and understanding of the drug-sensitivity mechanism.

We examined efficacy of the mTOR inhibitor RAD001 to seek novel therapies for synovial sarcoma (SS). Although RAD001 had significant anti-tumor effects, its sensitivity differed among cell lines. Phospho-receptor tyrosine kinase (RTK) array analyses revealed c-MET phosphorylation in highly mTOR inhibitor-sensitive cells and PDGFRα (which induces intrinsic resistance to mTOR inhibitor) activation in less sensitive cells. Combined treatment with RAD001 and the PDGFR inhibitor pazopanib showed anti-tumor effects in xenograft models with less sensitive cells. Thus, evaluating activated RTKs in clinical samples may predict sensitivity to mTOR inhibitors, raising the possibility of a tailored therapy for SS., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Concentrated growth factor (CGF) is an autologous leukocyte-rich and platelet-rich fibrin (L-PRF) biomaterial termed "second-generation platelet concentrate". CGF contains autologous osteoinductive platelet growth factors and an osteoconductive fibrin matrix. The purpose of this study was to assess the ability of CGF combined with bone marrow stromal cells (BMSCs) to heal critical-size rat calvaria defects in vivo and to modulate the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. In the in-vivo study, the CGF group regenerated bone better than the control group, and combined therapy with CGF and BMSCs almost completely repaired critical-size bone defects within 12 weeks after surgery. In the in-vitro study, the CGF extract, at concentrations between 1 and 10%, promoted proliferation, osteogenic maturation, and mineralization of hTERT-E6/E7 human MSCs in a dose-dependent manner but had an inhibitory effect at higher concentrations. In conclusion, a CGF extract promoted the proliferation, osteogenic maturation, and mineralization of mesenchymal stem cells in vitro, and combination therapy with CGF and BMSCs resulted in excellent healing of critical-size bone defects in vivo.

Background: Whereas we can use several human epithelioid sarcoma (ES) cell lines for basic and preclinical research, an angiomatoid ES cell line has not been reported to date. We have treated a case of an angiomatoid ES developing in the right upper extremity of a 67-year-old man., Methods: An angiomatoid ES cell line, Asra-EPS was newly established and characterized for its morphology, growth rate and chromosomal analysis. Tumorigenicity of Asra-EPS cells was also analyzed in athymic nude mice., Results: Asra-EPS cells were round, polygonal or spindle-shaped with an abundant cytoplasm and have been maintained continuously in vitro for over 150 passages during more than 15 months. These cells secreted cancer antigen 125 (CA 125), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) into the culture medium. Asra-EPS cells were tumorigenic when implanted in nude mice with tumors reaching a volume of 1000 mm3 at around 50 days. Histological features of tumors formed in mice were essentially the same as those of the original tumor, exhibiting a multinodular proliferation of eosinophilic epithelioid and spindle-shaped cells with prominent areas of hemorrhage and blood-filled cystic spaces strikingly corresponding to the potential of hemorrhagic cyst formation in the original tumor. They showed immunopositive staining for cytokeratins (AE1/AE3 and CAM5.2), epithelial membrane antigen (EMA), vimentin, CD31, CD34 and CA 125, but negative for integrase interactor 1 (INI-1) and factor VIII-related antigen., Conclusions: The established cell line represents a biologically relevant new tool to investigate the molecular pathology of human angiomatoid ES and to evaluate the efficacy of novel therapeutics both in vitro and in vivo.

A 70-year-old man visited a urological clinic with a chief complaint of pollakiuria, which was refractory to various medications. Pelvic magnetic resonance imaging (MRI) revealed a mass 6 cm in diameter immediately next to the left side of the bladder. The patient was referred to our hospital for further examination. Since he had a past history of neurofibroma of cauda equina, we suspected neurofibromatosis type 1. (18)Fluorodeoxyglucose (FDG)-positron emission tomography (PET) demonstrated a high accumulation of FDG in the pelvic mass. Under a diagnosis of neurogenic tumor, surgery was performed. As an examination of frozen section during the surgery led us to suspect a sarcoma, the tumor was excised radically. The pathological examination demonstrated diffuse large B cell lymphoma.

Introduction: Almost all current investigations on early repolarization syndrome (ERS) have focused on the J-wave characteristics and ST-segment configuration; however, few have reported on ventricular repolarization indexes in ERS., Methods and Results: A total of 145 subjects were enrolled: 10 ERS patients, 45 uneventful ER pattern (ERP) subjects, and 90 healthy controls without J waves or ST-segment elevation. Ambulatory ECG-derived parameters (QT, QTc(B), QTc(F), T peak-Tend(Tpe), and QT/RR slope) were measured and statistically compared. Among the groups, there was no significant difference in the average QT and QTc(B); however, ERS patients had the shortest QTc(F) and longest Tpe (QTc(F): 396.2 ± 19 vs 410.4 ± 20 vs 419.2 ± 19 milliseconds, P = 0.036, Tpe: 84.9 ± 12 vs 70.4 ± 11 vs 66.9 ± 15 milliseconds, P < 0.001, for the ERS, ERP, and control groups, respectively). Importantly, the 24-hour QT/RR slope was significantly smaller in the ERS than ERP and control groups (QT/RR: 0.105 ± 0.01 vs 0.154 ± 0.02 vs 0.161 ± 0.03, respectively; P < 0.001). When analyzing the diurnal and nocturnal QT/RR slopes, ERS patients had small diurnal and nocturnal QT/RR slopes while the ERP and control groups had large diurnal and small nocturnal QT/RR slopes (diurnal QT/RR: 0. 077 ± 0.01 vs 0.132 ± 0.03 vs 0.143 ± 0.03, P < 0.001; nocturnal QT/RR: 0.093 ± 0.02 vs 0.129 ± 0.03 vs 0.130 ± 0.04, P = 0.02 in the ERS, ERP, and control groups, respectively)., Conclusion: ERS patients had a continuously depressed diurnal and nocturnal adaptation of the QT interval to the heart rate. Such abnormal repolarization dynamics might provide a substrate for reentry and be an important element for developing ventricular fibrillation in the ERS cohort., (© 2012 Wiley Periodicals, Inc.)

Prosthetic replacement for the reconstruction of bone tumor is the standard method in limb salvage surgery. However, the breakages of prosthesis in these patients are frequent because the patients are young and active. Removal of the broken stem remained in the bone medulla is a highly difficult technical procedure in revision surgery. This article describes a new method to remove the well-fixed broken femoral stem with a hollow trephine reamer in patients with prosthetic replacement of the distal femur for primary bone tumors.

Osteosarcoma (OS) is the most common malignant bone tumor and the prognosis depends on pulmonary metastases, which arise from multi-step progression of malignant tumors. We herein aimed to clarify the critical step of pulmonary metastasis using the syngeneic mouse spontaneous highly metastatic OS LM8 and parental Dunn cell lines, to identify new candidate molecules to suppress pulmonary metastasis. We first investigated the chronological detection of circulating tumor cells (CTCs) from mice with either cell line. LM8 CTCs appeared faster, at a higher rate and with a greater number compared to Dunn CTCs. Cultured cells from CTCs of LM8 showed higher proliferative ability than cells from the primary site in suspension culture, which mimicked the environment of the bloodstream for CTCs. The proliferative ability of LM8 cells was also higher than that of Dunn cells in 3D collagen culture with low stiffness (-150 Pa; close to conditions in the lung). We next focused on the extravasation step. LM8 showed higher migration ability compared to Dunn with transendothelial migration assay. We also found a disruption in endothelial barrier function throughout co-culture with LM8 using time-lapse imaging. In addition, LM8 secreted high levels of vascular endothelial growth factor (VEGF), while VEGF signal inhibition with a small molecule tyrosine kinase inhibitor (pazopanib) decreased disruption of the vascular barrier and transendothelial migration of LM8. Finally, daily oral administration of pazopanib reduced the rate and size of pulmonary metastasis in vivo. Collectively, these results show anti-VEGF therapy as a candidate for pulmonary metastasis of OS.

From 1997 to 2003, 40 patients (all <40 years of age) with non-metastatic osteosarcoma of the extremities were treated with OOS-D and definitive surgery. Two cycles of doxorubicin 90 mg/m(2) plus cisplatin 120 mg/m(2) and ifosfamide 15 g/m(2) were given as neoadjuvant chemotherapy, and two cycles of doxorubicin/cisplatin and ifosfamide, and two cycles of high-dose methotrexate (10-12 g/m(2)) were given post-operatively. All patients underwent limb salvage surgeries, and 66% showed good response to neoadjuvant chemotherapy. With a median follow-up period of 117 months, 31 of the evaluable 40 patients were continuously disease-free, 7 were currently alive with no evidence of disease, and 2 died of disease. There was no local recurrence. The 5-year event-free and overall survival rates were 83 and 98%, respectively. The 10-year event-free and overall survival rates were 80 and 95%, respectively. The major form of toxicity was haematological one.

Compartment syndrome of the arm is a rare condition because of the large capacity of the arm compartment. Although several cases of compartment syndrome of the forearm associated with vascular access procedures have been reported, the literature contains few detailed reports of compartment syndrome of the arm caused by transcather angiography or angioplasty. This article presents 4 cases of compartment syndrome of the anterior arm caused by transcatheter angiography or angioplasty; all patients required surgical treatment and anticoagulation therapy. Following urgent fasciotomy and hemostasis, 1 patient experienced recurrent bleeding and another exhibited delayed complex regional pain syndrome of the forearm. The remaining 2 cases had good outcomes. Because all patients had been prescribed various oral anticoagulants, their compartment syndrome was considered a complication of thrombolytic therapy. In addition, because all patients had a history of multiple arterial diseases, atherosclerosis was considered to be severely advanced and the vessels to be easily damaged. Due to the authors' experiences with these 4 cases, they recommend that surgery be performed under general rather than local anesthesia and that the bleeding site be sutured or ligated. Compression of the bleeding point alone could allow heavy bleeding or recurrence of bleeding to occur because of the influence of anticoagulation therapy. Continuous bleeding of the arm may expand into the volar compartment of the forearm, leading to a condition similar to chronic compartment syndrome. Effective hemostasis, in addition to early decompressive fasciotomy, is essential in compartment syndrome caused by the catheter procedure., (Copyright 2013, SLACK Incorporated.)

Introduction: Recently, great attention has been paid to the risk stratification of asymptomatic patients with an electrocardiographic early repolarization (ER) pattern. We investigated several repolarization parameters including the Tpeak-Tend interval and Tpeak-Tend/QT ratio in healthy individuals and patients with J wave syndrome who were aborted from sudden cardiac death., Methods and Results: Ninety-two subjects were enrolled: 12 patients with ventricular fibrillation associated with J waves, 40 healthy subjects with an uneventful ER pattern and 40 healthy control subjects (C) without any evident J waves. Using ambulatory electrocardiogram recordings, the average QT interval, corrected QT interval (QTc), Tpeak-Tend (Tp-e) interval, which is the interval from the peak to the end of the T wave, and Tp-e/QT ratio were calculated. Using ANOVA and post hoc analysis, there was no significant difference in the average QT and QTc in all 3 groups (QT; 396 ± 27 vs 405 ± 27 vs 403 ± 27 m, QTc; 420 ± 26 vs 421 ± 21 vs 403 ± 19 milliseconds in the C, ER pattern and J groups, respectively). The Tp-e interval and Tp-e/QT ratio were significantly more increased in the J wave group than the ER Pattern group (Tp-e: 86.7 ± 14 milliseconds vs 68 ± 13.2 milliseconds, P < 0.001, Tp-e/QT; 0.209 ± 0.04 vs 0.171 ± 0.03, P < 0.001), but they did not significantly differ between the C and ER pattern groups (Tp-e: 68.6 ± 7.5 vs 68 ± 13.2, P = 0.97, Tp-e/QT 0.174 ± 0.02 vs 0.171 ± 0.03, P = 0.4)., Conclusion: As novel markers of heterogeneity of ventricular repolarization, Tpeak-Tend interval and Tp-Te/QT ratio are significantly increased in patients with J wave syndromes compared to age and sex-matched uneventful ER., (© 2012 Wiley Periodicals, Inc.)

We describe a case of early repolarization syndrome in which augmented J waves were documented during an electrical storm associated with hypokalemia. The patient was referred to our hospital for therapy to treat recurrent ventricular fibrillation (VF). The 12-lead electrocardiogram showed giant J waves associated with hypokalemia during multiple episodes of VF. Although antiarrhythmic agents or deep sedation were not effective for the VF, an intravenous supplementation of potassium completely suppressed the VF with a reduction in the J-wave amplitude. Our report discusses the possible relationship between hypokalemia and VF in early repolarization syndrome., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Background: Treatment of soft-tissue sarcomas involving the inguinal region remains challenging because of difficulties in achieving wide surgical margins due to anatomical features. The study aimed to analyze the oncologic and functional outcomes of wide resection with vascular reconstruction for inguinal soft-tissue sarcomas., Methods: Three men and seven women were treated for inguinal soft-tissue sarcomas by wide surgical resection with vascular reconstruction., Results: Arteries and veins were replaced in nine patients, and artery replacement alone was carried out in one patient. Femoral nerve resections were performed in six patients. One patient and five patients developed local recurrence and distant metastases, respectively. Limb salvage was achieved in 9 of 10 patients (90%). Six patients and one patient developed vascular (arterial graft occlusion [n = 1], lymphedema [n = 5]) and nonvascular (hematoma [n = 1]) complications, respectively. Five-year arterial primary patency was 77%. Five-year disease-free and overall survival rates were 45% and 77%, respectively. Functional outcome scores at latest follow-up averaged 87.5% for Musculoskeletal Tumor Society 1993., Conclusions: En-bloc resection of major critical structures along with tumor and vascular reconstructions using synthetic grafts is a feasible option in limb salvage surgery for inguinal soft-tissue sarcomas., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Liposarcomas are separated into clinicopathological entities by a characteristic morphological spectrum and distinctive genetic changes. Myxoid liposarcoma (MLS) represents one such entity with specific chromosomal translocations leading to the generation of fusion genes, the human translocation liposarcoma (TLS)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) or the Ewing sarcoma (EWS)-CHOP. In the present study, four cases of liposarcoma with detection of TLS-CHOP or EWS-CHOP, whose postoperative diagnosis was other than MLS (one well-differentiated liposarcoma, two de-differentiated liposarcomas and one unclassified) were examined for medical records, imaging data and histopathology. Clinical records demonstrated that three of the four cases were considerably difficult to diagnose definitively, and histopathological re-examination pointed out areas of myxomatous change as a minor component (<10%). Their dominant components (>90%) resembled pleomorphic sarcoma, pleomorphic malignant fibrous histiocytoma and monophasic synovial sarcoma. The current cases may represent an extreme variant of the morphological spectrum within MLS. In cases of difficulty in making definitive diagnosis of soft tissue sarcoma by standard histopathological examination and identification of myxoid stroma even as a minor component, analyzing TLS-CHOP and EWS-CHOP fusion genes may aid the diagnosis of unusual MLS.

Large infarcts are associated with a terminal QRS-distortion in ST-elevation myocardial infarction (STEMI) patients. Late gadolinium enhancement (LGE) on the cardiac MRI (CMR) can depict an infarct distribution. However, less is known about the relationship between the LGE findings and QRS-distortion on admission, including the best ECG-lead location to reveal the QRS-distortion (DIS-lead) in STEMI patients. Fifty STEMI patients successfully treated with percutaneous coronary intervention were classified into two groups according to whether the QRS-distortion was positive (+) or negative (-). The LGE on a recent CMR was classified into 12 left ventricular segments (Basal-Middle-Apical × Anterior-Septal-Inferior-Lateral). The coincidences between the segmental LGE scores and DIS-lead were investigated. All patients were divided into 23 QRS-distortion (+) and 27 QRS-distortion (-) groups. The total LGE score was significantly greater in the QRS-distortion (+) group (14.7 ± 6.8 versus 9.6 ± 6.2, P < 0.01). The highest LGE score in 96% of QRS-distortion (+) patients was 4, and a score 4 segment indicated a good selection of the DIS-lead (86.4%). QRS-distortion in the ECG on admission represents severe transmural infarction in the LGE using CMR, which represents large infarcts in STEMI patients.

Synovial chondromatosis of the small joints of the hand is rare. Here, we present a case of synovial chondromatosis in the metacarpophalangeal joint that did not show calcification on radiographs. Synovectomy and resection of cartilagenous loose bodies was successful and there was no recurrence after eight months.

Stereoselective vinylogous Mannich reaction of 2-trimethylsilyloxyfuran with L-gulose-derived chiral nitrones in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate was investigated. The selectivity was strongly influenced by the bulkiness of the C-substituent of the nitrone: for example, C-benzyloxymethyl nitrone afforded four stereoisomers, whereas bulky C-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]nitrone gave a single stereoisomer. The latter product was elaborated to afford key synthetic intermediates for polyoxin C and dysiherbaine.

Prosthetic reconstruction in two patients with malignant bone tumors of the distal tibia was conducted. The diagnoses were metastatic bone tumor in one patient and low grade central osteosarcoma in another. The mean duration of follow-up was 5.5 years (3 and 8 years). Reconstruction was achieved using custom-made prosthesis (JMM, Japan Medical Materials), which replaced the distal tibia. In the patient with metastasis, local recurrence occurred 8 months after the primary surgery and the recurrent tumor was resected. Both patients were free from neoplastic disease at the latest follow-up. The average functional scores according to the system of the Musculoskeletal Tumor Society were 25 and 23. Custom-made prostheses allow an early return to functional weight-bearing without major complications. This technique provides a safe and effective method of stabilization for properly selected malignant tumors of the distal tibia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The Gsg2 (Haspin) gene encodes a serine/threonine protein kinase and is predominantly expressed in haploid germ cells. In proliferating somatic cells, Gsg2 is shown to be expressed weakly but plays an essential role in mitosis. Although the Gsg2 minimal promoter recognized by the spermatogenic cell-specific nuclear factor(s) has been found, to date, the molecular mechanism that differentially controls Gsg2 expression levels in germ and somatic cells remains to be sufficiently clarified. In this study, we analyzed the DNA methylation status of the upstream region containing the Gsg2 promoter. We found a tissue-dependent and differentially methylated region (T-DMR) upstream (-641 to -517) of the authentic promoter that is hypomethylated in germ cells but hypermethylated in other somatic tissues. Profiling of Gsg2 expression and DNA methylation status at the T-DMR in spermatogenic cells indicated that the hypomethylation of the T-DMR is maintained during spermatogenesis. Using the reporter assay, we also demonstrated that DNA methylation at the T-DMR of Gsg2 reduced the promoter activity by 60-80%, but did not fully suppress it. Therefore, the T-DMR functions as a modulator in a DNA methylation-dependent manner. In conclusion, Gsg2 is under epigenetic control.

Chondrosarcomas are the most frequently occurring primary malignant chest wall tumors. Furthermore, the lungs serve as the most frequent sites for metastases. Pulmonary metastases from sarcomas usually appear as round nodules of varying sizes on roentgenograms. Here, we report an unusual clinical and radiographic presentation of pulmonary metastasis from a costal chondrosarcoma. Bilateral pulmonary metastases developed soon after wide surgical resection. Thoracic computed tomography revealed unusual radiological findings: consolidation accompanied with ground-glass opacity. To confirm the metastasis, we recommend a transbronchial biopsy in cases where unusual pulmonary findings are detected., (© 2011 Emori et al; licensee BioMed Central Ltd.)

In this paper, in-situ cathodoluminescence (CL) stress analysis of a silicon oxide (SiO(x)) thin film prepared by wet thermal oxidation is described. The specially-developed uniaxial tensile loading jig was used to apply tensile displacement to the SiO(x) film specimen. CL spectra of the specimen during tensile loading were obtained, and the peak position of around 1.85 eV emission band was monitored for tensile stress analysis. The peak position gradually shifted towards higher/lower energy side when tensile displacement increased/decreased. The tensile stress-to-emission energy ratio of 6.21-8.97 x 10(2) GPa/eV was estimated on the basis of linear elastic theory, which demonstrated that CL is able to provide information on stress induced in the film. Scanning electron microscopy (SEM) revealed that the fracture of SiO(x) and SCS laminated structure occurred at the vicinity of SiO(x) film surface.

The proximal tibia is a common site for primary bone tumors. Proximal tibial tumors may invade the adjacent soft-tissue by destroying the cortex and may further invade neurovascular bundles. We treated a patient with primary bone tumor of the proximal tibia with neurovascular invasion by extracorporeally irradiated autograft-prosthetic composite arthroplasty with vascular reconstruction. In cases of concomitant allograft arthroplasty and vascular reconstruction, we recommend that vascular reconstruction be performed before arthroplasty to minimize ischemia time. Good oncological and functional outcomes were achieved 75 months after surgery. Therefore, this reconstruction technique can be considered as a good treatment option., (Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Systemic capillary leak syndrome (SCLS) is a life-threatening disorder which presents with periodic episodes of hypovolemic shock, due to plasma leakage to the extra-vascular space reflected by accompanying hypoalbuminemia, hemoconcentration and edema often with associated monoclonal gammopathy. We describe a 28-year-old woman with SCLS who required aggressive fluid resuscitation and was successfully treated with corticosteroid, terbutaline, and theophylline. At exacerbation, the levels of serum granulocyte colony-stimulating factor (G-CSF) were increased. Thus, G-CSF might play an important role and can be a useful biomarker for the severity of attacks in SCLS.

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A gene (GLA), and the disease is a relatively prevalent cause of left ventricular hypertrophy mimicking idiopathic hypertrophic cardiomyopathy. We assessed clinically 5 patients of a three-generation family and also searched for GLA mutations in 10 family members. The proband had left ventricular hypertrophy with localized thinning in the basal posterior wall and late gadolinium enhancement (LGE) in the near-circumferential wall in cardiovascular magnetic resonance images and her sister had vasospastic angina pectoris without organic stenosis of the coronary arteries. LGE notably appeared in parallel with decreased α-galactosidase A activity and increased NT-pro BNP in our patients. We detected a new GLA missense mutation (G195V) in exon 4, resulting in a glycine-to-valine substitution. Of the 10 family members, 5 family members each were positive and negative for this mutation. These new data extend our clinical and molecular knowledge of GLA gene mutations and confirm that a novel missense mutation in the GLA gene is important not only for a precise diagnosis of heterozygous status, but also for confirming relatives who are negative for this mutation.