Arthroscopic anterior inferior iliac spine decompression does not alter postoperative muscle strength.

PURPOSE: The purpose of this study was to assess the additional effect of anterior inferior iliac spine (AIIS) decompression on knee extensor and hip flexor strength and compare functional outcomes after arthroscopic FAI correction with and without AIIS decompression. METHODS: Sixty patients who underwent arthroscopic FAI correction surgery were divided into two groups matched for AIIS morphology: 31 patients who underwent arthroscopic FAI surgery only (without AIIS decompression) (FAI group) (AIIS Type I; n = 5, Type II; n = 26, Type III; n = 0) and 29 patients who underwent arthroscopic FAI surgery with AIIS decompression (AIIS group) (AIIS Type I; n = 5, Type II; n = 24, Type III; n = 0). Knee extensor and hip flexor strength were evaluated preoperatively and at 6 months after surgery. Patient-reported outcome (PRO) scores using the modified Harris hip score (MHHS), the nonarthritic hip score (NAHS) and iHOT-12 were obtained preoperatively and at 6 months after surgery. RESULTS: In the AIIS group, there was no significant difference between knee extensor strength pre- and postoperatively (n.s.). In the AIIS group, hip flexor strength was significantly improved postoperatively compared to preoperative measures (p < 0.05). In the FAI group, there were no significant improvements regarding muscle strength (n.s.). While there were no significant differences of preoperative and postoperative MHHS and NAHS between both groups (MHHS; n.s., NAHS; n.s.), the mean postoperative iHOT-12 in the FAI group was inferior to that in the AIIS group. (p < 0.01). The revision surgery rate for the AIIS group was significantly lower compared with that in the FAI group (p < 0.05). CONCLUSION: Anterior inferior iliac spine decompression, as a part of an arthroscopic FAI corrective procedure, had a lower revision surgery rate and did not compromise knee extensor and hip flexor strength, and it improved clinical outcomes comparable to FAI correction without AIIS decompression. AIIS decompression for FAI correction improved postoperative PRO scores without altering the muscle strength of hip flexor and knee extensor. LEVEL OF EVIDENCE: III.

Reconstruction of the Midfoot Using a Free Vascularized Fibular Graft After En Bloc Excision for Giant Cell Tumor of the Tarsal Bones: A Case Report.

We report the case of a 32-year-old Japanese female with a giant cell tumor of bone involving multiple midfoot bones. Giant cell tumors of bone account for approximately 5% of all primary bone tumors and most often arise at the ends of long bones. The small bones, such as those of the hands and feet, are rare sites for giant cell tumors. Giant cell tumors of the small bones tend to exhibit more aggressive clinical behavior than those of the long bones. The present patient underwent en bloc tumor excision involving multiple tarsals and metatarsals. We reconstructed the longitudinal arch of the foot with a free vascularized fibular graft. At the 2-year follow-up visit, bony union had been achieved, with no tumor recurrence.

Reoxygenation using a novel CO2 therapy decreases the metastatic potential of osteosarcoma cells.

Osteosarcoma is the most common primary solid malignant bone tumor. Despite substantial improvements in surgery and chemotherapy, metastasis remains a major cause of fatal outcomes, and the molecular mechanisms of metastasis are still poorly understood. Hypoxia, which is common in malignant tumors including osteosarcoma, increases expressions of hypoxia inducible factor (HIF)-1α, matrix metalloproteinase (MMP)-2 and MMP-9, and can induce invasiveness. As we previously showed a novel transcutaneous CO2 application to decrease HIF-1α expression and induce apoptosis in malignant fibrous histiocytoma, we hypothesize that transcutaneous CO2 application could suppress metastatic potential of osteosarcoma by improving hypoxic conditions. Here, we examined the effects of transcutaneous CO2 application on apoptosis, and development of pulmonary metastasis using a highly metastatic osteosarcoma cell line, LM8. Transcutaneous CO2 application significantly decreased tumor growth and pulmonary metastasis in LM8 cells. Apoptotic activity increased, and intratumoral hypoxia was improved with decreased expressions of HIF-1α, MMP-2 and MMP-9, significantly, in the CO2-treated tumors. In conclusion, we found that transcutaneous CO2 application can induce tumor cell apoptosis and might suppress pulmonary metastasis by improvement of hypoxic conditions with decreased expressions of HIF-1α and MMPs in highly metastatic osteosarcoma cell. These findings strongly indicate that this novel transcutaneous CO2 therapy could be a therapeutic breakthrough for osteosarcoma patients.

Treatment of chronic post-traumatic hyperextension deformity of proximal interphalangeal joint using the suture anchor: a case report.

We present a case of chronic post-traumatic hyperextension of the PIP joint of the little finger. The volar plate was reattached at the original attachment site of the proximal phalanx using two suture anchors and tenodesis of the radial half slip of the FDS tendon was added. An acceptable result was obtained.

Optimization of antitumor treatment conditions for transcutaneous CO2 application: An in vivo study.

Carbon dioxide (CO2) therapy can be applied to treat a variety of disorders. We previously found that transcutaneous application of CO2 with a hydrogel decreased the tumor volume of several types of tumors and induced apoptosis via the mitochondrial pathway. However, only one condition of treatment intensity has been tested. For widespread application in clinical antitumor therapy, the conditions must be optimized. In the present study, we investigated the relationship between the duration, frequency, and treatment interval of transcutaneous CO2 application and antitumor effects in murine xenograft models. Murine xenograft models of three types of human tumors (breast cancer, osteosarcoma, and malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma) were used to assess the antitumor effects of transcutaneous CO2 application of varying durations, frequencies, and treatment intervals. In all human tumor xenografts, apoptosis was significantly induced by CO2 treatment for ≥10 min, and a significant decrease in tumor volume was observed with CO2 treatments of >5 min. The effect on tumor volume was not dependent on the frequency of CO2 application, i.e., twice or five times per week. However, treatment using 3- and 4-day intervals was more effective at decreasing tumor volume than treatment using 2- and 5-day intervals. The optimal conditions of transcutaneous CO2 application to obtain the best antitumor effect in various tumors were as follows: greater than 10 min per application, twice per week, with 3- and 4-day intervals, and application to the site of the tumor. The results suggest that this novel transcutaneous CO2 application might be useful to treat primary tumors, while mitigating some side effects, and therefore could be safe for clinical trials.

AICAR induces mitochondrial apoptosis in human osteosarcoma cells through an AMPK-dependent pathway.

The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) modulates cellular energy metabolism, and promotes mitochondrial proliferation and apoptosis. Previous studies have shown that AICAR has anticancer effects in various cancers, however the roles of AMPK and/or the effects of AICAR on osteosarcoma have not been reported. In the present study, we evaluated the effects of AICAR on tumor growth and mitochondrial apoptosis in human osteosarcoma both in vitro and in vivo. For in vitro experiments, two human osteosarcoma cell lines, MG63 and KHOS, were treated with AICAR, and the effects of AICAR on cell growth and mitochondrial apoptosis were assessed by WST assays, TUNEL staining, and immunoblot analyses. In vivo, human osteosarcoma-bearing mice were treated with AICAR, and the mitochondrial proliferation and apoptotic activity in treated tumors were assessed. In vitro experiments revealed that AICAR activated AMPK, inhibited cell growth, and induced mitochondrial apoptosis in both osteosarcoma cell lines. In vivo, AICAR significantly reduced osteosarcoma growth without apparent body weight loss and AICAR increased both mitochondrial proliferation and apoptotic activity in treated tumor tissues. AICAR showed anticancer effects in osteosarcoma cells through an AMPK-dependent peroxisome proliferator­activated receptor-γ coactivator-1α (PGC-1α)/mitochondrial transcription factor A (TFAM)/mitochondrial pathway. The findings in this study strongly suggest that AICAR could be considered as a potent therapeutic agent for the treatment of human osteosarcoma.

Numerical study of sediment and 137Cs discharge out of reservoirs during various scale rainfall events.

Contamination of reservoirs with radiocesium is one of the main concerns in Fukushima Prefecture, Japan. We performed simulations using the three-dimensional finite volume code FLESCOT to understand sediment and radiocesium transport in generic models of reservoirs with parameters similar to those in Fukushima Prefecture. The simulations model turbulent water flows, transport of sediments with different grain sizes, and radiocesium migration both in dissolved and particulate forms. To demonstrate the validity of the modeling approach for the Fukushima environment, we performed a test simulation of the Ogaki Dam reservoir over Typhoon Man-yi in September 2013 and compared the results with field measurements. We simulated a set of generic model reservoirs systematically varying features such as flood intensity, reservoir volume and the radiocesium distribution coefficient. The results ascertain how these features affect the amount of sediment or 137Cs discharge downstream from the reservoirs, and the forms in which 137Cs is discharged. Silt carries the majority of the radiocesium in the larger flood events, while the clay-sorbed followed by dissolved forms are dominant in smaller events. The results can be used to derive indicative values of discharges from Fukushima reservoirs under arbitrary flood events. For example the generic model simulations indicate that about 30% of radiocesium that entered the Ogaki Dam reservoir over the flood in September 2015 caused by Typhoon Etau discharged downstream. Continued monitoring and numerical predictions are necessary to quantify future radiocesium migration in Fukushima Prefecture and evaluate possible countermeasures since reservoirs can be a sink of radiocesium.

Antitumor effect of YM155, a novel small-molecule survivin suppressant, via mitochondrial apoptosis in human MFH/UPS.

Survivin is a member of the inhibitor of apoptosis family, which is known to inhibit mitochondrial apoptosis. Survivin is highly expressed in cancers and plays an important role in cancer cell survival, and increased survivin expression is an unfavorable prognostic marker in cancer patients. YM155, a novel small-molecule survivin suppressant, selectively suppresses survivin expression, resulting in the induction of apoptosis in various malignancies. However, the roles of survivin in human malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (MFH/UPS) have not been studied. In the present study, we examined survivin expression in human musculoskeletal tumor tissues, and the effect of survivin inhibition by siRNA or YM155 on apoptotic activity in human MFH/UPS cell lines. In tumor tissues, mRNA expression of survivin was significantly higher in MFH/UPS samples than in benign schwannomas. Moreover, in vitro studies revealed that both survivin siRNA and YM155 suppressed survivin expression and inhibited MFH/UPS cell proliferation in a dose- and a time-dependent manner. Further, the numbers of apoptotic cells significantly increased with YM155 treatment. in vivo, tumor volume in YM155-treated groups was significantly reduced without significant bodyweight loss. Increased apoptotic activity along with decreased survivin expression was also observed in YM155-treated tumors. The findings in this study strongly suggest that survivin suppressants, including YM155, contribute to the suppression of human MFH/UPS cell growth via promoting mitochondrial apoptosis, and that survivin may be a potent therapeutic target for the novel treatment of human MFH/UPS.

Predicting the long-term (137)Cs distribution in Fukushima after the Fukushima Dai-ichi nuclear power plant accident: a parameter sensitivity analysis.

Radioactive materials deposited on the land surface of Fukushima Prefecture from the Fukushima Dai-ichi Nuclear Power Plant explosion is a crucial issue for a number of reasons, including external and internal radiation exposure and impacts on agricultural environments and aquatic biota. Predicting the future distribution of radioactive materials and their fates is therefore indispensable for evaluation and comparison of the effectiveness of remediation options regarding human health and the environment. Cesium-137, the main radionuclide to be focused on, is well known to adsorb to clay-rich soils; therefore its primary transportation mechanism is in the form of soil erosion on the land surface and transport of sediment-sorbed contaminants in the water system. In this study, we applied the Soil and Cesium Transport model, which we have developed, to predict a long-term cesium distribution in the Fukushima area, based on the Universal Soil Loss Equation and simple sediment discharge formulas. The model consists of calculation schemes of soil erosion, transportation and deposition, as well as cesium transport and its future distribution. Since not all the actual data on parameters is available, a number of sensitivity analyses were conducted here to find the range of the output results due to the uncertainties of parameters. The preliminary calculation indicated that a large amount of total soil loss remained in slope, and the residual sediment was transported to rivers, deposited in rivers and lakes, or transported farther downstream to the river mouths. Most of the sediment deposited in rivers and lakes consists of sand. On the other hand, most of the silt and clay portions transported to river were transported downstream to the river mouths. The rate of sediment deposition in the Abukuma River basin was three times as high as those of the other 13 river basins. This may be due to the larger catchment area and more moderate channel slope of the Abukuma River basin than those of the other rivers. Annual sediment outflows from the Abukuma River and the total from the other 13 river basins were calculated as 3.2 × 10(4)-3.1 × 10(5) and 3.4 × 10(4)-2.1 × 10(5)ty(-1), respectively. The values vary between calculation cases because of the critical shear stress, the rainfall factor, and other differences. On the other hand, contributions of those parameters were relatively small for (137)Cs concentration within transported soil. This indicates that the total amount of (137)Cs outflow into the ocean would mainly be controlled by the amount of soil erosion and transport and the total amount of (137)Cs concentration remaining within the basin. Outflows of (137)Cs from the Abukuma River and the total from the other 13 river basins during the first year after the accident were calculated to be 2.3 × 10(11)-3.7 × 10(12) and 4.6 × 10(11)-6.5 × 10(12)Bqy(-1), respectively. The former results were compared with the field investigation results, and the order of magnitude was matched between the two, but the value of the investigation result was beyond the upper limit of model prediction.

Sediment and (137)Cs behaviors in the Ogaki Dam Reservoir during a heavy rainfall event.

We performed a simulation of sediment and (137)Cs behaviors in the Ogaki Dam Reservoir, one of the main irrigation reservoirs in the Fukushima prefecture, Japan, during a heavy rainfall event occurred in 2013. The one-dimensional river and reservoir simulation scheme TODAM, Time-dependent One-dimensional Degradation and Migration, was applied for calculating the time dependent migration of sediment and (137)Cs in dissolved and sediment-sorbed forms in the reservoir. Continuous observational data achieved in the upper rivers were used as the input boundary conditions for the simulation. The simulation results were compared with the continuous data achieved in the lower river and we confirmed the predicted values of sediment and (137)Cs in sediment-sorbed form at the exit of reservoir satisfactorily reproduced the observational data. We also performed sediment and (137)Cs behavioral simulation by changing the water level of the reservoir, because such a dam operation could control the quantities of sediment and (137)Cs discharge from and/or deposition in the reservoir. The simulation clarified that the reservoir played an important role to delay and buffer the movement of radioactive cesium in heavy rainfall events and the buffer effect of the reservoir depended on particle sizes of suspended sediment and the water level. It was also understood that silt deposition was the main source of the bed contamination (except for the initial fallout impact), while clay was the main carrier of (137)Cs to the lower river at a later stage of rainfall events.

Regulation of mitochondrial proliferation by PGC-1α induces cellular apoptosis in musculoskeletal malignancies.

A number of studies have reported that decreased mitochondrial numbers are linked with neoplastic transformation and/or tumor progression, including resistance to apoptosis. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a multi-functional transcriptional coactivator that regulates the activities of multiple nuclear receptors and transcriptional factors involved in mitochondrial biogenesis. In this study, we observed that the number of mitochondria in sarcoma tissues, such as osteosarcoma and malignant fibrous histiocytoma, is significantly lower than that in normal muscle tissue or benign tumors, and that increasing the number of mitochondria by PGC-1α overexpression induces mitochondrial apoptosis in human sarcoma cell lines. The findings suggest that decreased mitochondrial numbers may contribute to musculoskeletal tumor progression, and that regulation of mitochondrial numbers by PGC-1α could be a potent therapeutic tool for human malignancies.

Transcutaneous application of CO2 enhances the antitumor effect of radiation therapy in human malignant fibrous histiocytoma.

Sarcomas are relatively resistant because of hypoxia. We previously demonstrated that the transcutaneous CO(2) therapy reduced hypoxic conditions in human malignant fibrous histiocytoma (MFH). Therefore, we hypothesized that transcutaneous CO(2) therapy could enhance the antitumor effect of radiation therapy in human MFH. Our purpose was to evaluate the effects of transcutaneous CO(2) therapy on the antitumor efficacy of X-ray irradiation using MFH. First, in an in vitro study, we assessed apoptotic activity and reactive oxygen species (ROS) production using flow cytometric and immunoblot analysis at 24 h after X-ray irradiation under three different oxygen conditions (normoxic, reoxygenated and hypoxic). In addition, in the in vivo study, 24 male athymic BALB/c nude mice with MFH tumors that were inoculated in the dorsal subcutaneous area were randomized into four groups: control, CO(2), X-ray irradiation and combination (CO(2) and X-ray irradiation). Treatments were performed twice weekly for 2 weeks, four times in total. Tumor volume was calculated. All tumors were excised and apoptotic activity, ROS production, related proteins and HIF-1α expression were assessed using flow cytometric and immunoblot analysis. The in vitro study revealed that X-ray irradiation induced increased apoptosis and ROS production in MFH cells under normoxic and reoxygenated conditions relative to hypoxic conditions (P<0.01). In the in vivo study, tumor volume in the combination group was reduced to 28, 42 and 47% of that in the control, CO(2), and X-ray groups, respectively (P<0.05). Apoptotic activity and ROS production in the combination group were strongly increased with decreasing HIF-1α expression relative to the control, CO(2) and X-ray groups. The transcutaneous CO(2) system enhanced the antitumor action of X-ray irradiation and could be a novel therapeutic tool for overcoming radio-resistance in human malignancies.

'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells.

Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a 'decoy' for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has 'non-decoy' functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.

PKD1 negatively regulates cell invasion, migration and proliferation ability of human osteosarcoma.

Osteosarcoma (OS) is a primary malignancy of the bone, with a tendency to metastasize early. Despite intensive chemotherapy and surgical resection, more than 30% of patients develop distant metastases, and the prognosis of patients with metastases is essentially poor. Members of the protein kinase D (PKD) family are serine/threonine kinases, and have been studied in various cancers. Among the three different isoforms of this family, PKD1 is one of the best understood for its role in human malignancies; however, its role in musculoskeletal tumors has not been studied. In the present study, we investigated the role of PKD1 in human OS. We first analyzed PKD1 mRNA expression in human musculoskeletal tumor tissue samples by quantitative real-time PCR. PKD1 expression in OS samples was significantly lower than that in benign schwannoma samples, and this was correlated with metastatic potential. In in vitro studies, overexpression of PKD1 by plasmid transfection decreased OS cell invasion, migration and proliferation, and significantly decreased matrix metalloproteinase (MMP)2 mRNA expression. Conversely, siRNA knockdown of PKD1 increased invasion, migration and proliferation of OS cells, and MMP2 expression was markedly increased. Furthermore, overexpression of PKD1 significantly reduced in vivo tumor growth of OS cells. These results demonstrated that low expression of PKD1 may contribute to increased cell invasion, migration and proliferation ability of human OS. Taken together, our findings strongly suggest that PKD1 may negatively regulate the malignant potential of human OS, and may be a therapeutic target for human OS in the clinical setting.

Transcutaneous application of carbon dioxide (CO2) induces mitochondrial apoptosis in human malignant fibrous histiocytoma in vivo.

Mitochondria play an essential role in cellular energy metabolism and apoptosis. Previous studies have demonstrated that decreased mitochondrial biogenesis is associated with cancer progression. In mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the activities of multiple nuclear receptors and transcription factors involved in mitochondrial proliferation. Previously, we showed that overexpression of PGC-1α leads to mitochondrial proliferation and induces apoptosis in human malignant fibrous histiocytoma (MFH) cells in vitro. We also demonstrated that transcutaneous application of carbon dioxide (CO(2)) to rat skeletal muscle induces PGC-1α expression and causes an increase in mitochondrial proliferation. In this study, we utilized a murine model of human MFH to determine the effect of transcutaneous CO(2) exposure on PGC-1α expression, mitochondrial proliferation and cellular apoptosis. PGC-1α expression was evaluated by quantitative real-time PCR, while mitochondrial proliferation was assessed by immunofluorescence staining and the relative copy number of mitochondrial DNA (mtDNA) was assessed by real-time PCR. Immunofluorescence staining and DNA fragmentation assays were used to examine mitochondrial apoptosis. We also evaluated the expression of mitochondrial apoptosis related proteins, such as caspases, cytochorome c and Bax, by immunoblot analysis. We show that transcutaneous application of CO(2) induces PGC-1α expression, and increases mitochondrial proliferation and apoptosis of tumor cells, significantly reducing tumor volume. Proteins involved in the mitochondrial apoptotic cascade, including caspase 3 and caspase 9, were elevated in CO(2) treated tumors compared to control. We also observed an enrichment of cytochrome c in the cytoplasmic fraction and Bax protein in the mitochondrial fraction of CO(2) treated tumors, highlighting the involvement of mitochondria in apoptosis. These data indicate that transcutaneous application of CO(2) may represent a novel therapeutic tool in the treatment of human MFH.

Protein kinase Cδ in tumorigenesis of human malignant fibrous histiocytoma.

Protein kinase Cδ (PKCδ), an isoform of PKC, has been shown to act as a critical mediator of tumor progression and apoptosis; however, its role in musculoskeletal tumors is still unknown. In the current study, we examined the expression of PKCδ in human musculoskeletal tumor tissue samples, and investigated the effects of siRNA downregulation of PKCδ on human malignant fibrous histiocytoma (MFH) cell proliferation, migration, and apoptosis, to elucidate its functional roles in musculoskeletal tumorigenesis. Of note, real-time PCR analysis revealed that mRNA expression of PKCδ in high-grade musculoskeletal MFH tumors was significantly lower than that in benign schwannomas. siRNA downregulation of PKCδ significantly increased human MFH cell proliferation and migration, and markedly suppressed apoptosis. These findings suggest that PKCδ has a negative effect on tumorigenesis and/or acts as a pro-apoptotic kinase in human MFH cells. The data presented here could be applied in the development of new therapeutic avenues, with the elevation of PKCδ expression being one potential strategy to prevent MFH progression. Thus, PKCδ may be a potent therapeutic target for human MFH.

The effect of bevacizumab on tumour growth of malignant fibrous histiocytoma in an animal model.

BACKGROUND: Bevacizumab is a specific inhibitor of angiogenesis and a neutralising antibody against vascular endothelial growth factor (VEGF). The effect of bevacizumab was evaluated on malignant fibrous histiocytoma (MFH) in vivo using an animal model. MATERIALS AND METHODS: MFH cell line, NaraH, was implanted to athymic nude mice which were randomly divided into a treatment and a control group. The change in body weight and tumour volume were evaluated and immunohistochemical analysis was performed of microvessel density (MVD) and VEGF expression in the tumour tissue. RESULTS: Bevacizumab significantly induced inhibition of tumour growth, reducing tumour volume to 48% at the end of experiment. Intratumoural MVD was significantly decreased in the bevacizumab treatment group compared to the control group. A positive correlation was found between tumour volume and MVD. CONCLUSION: Bevacizumab suppressed MFH tumour growth by inhibiting tumoural angiogenesis. The current study suggests that bevacizumab may be a novel therapeutic agent for MFH.