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Osteosarcoma is a rare malignant tumor that commonly occurs in children. Anticancer drugs, for example, cisplatin, aid in postsurgery recovery but induce side effects such as renal damage, affecting the life prognosis of patients. Decursin which is one of the bioactive components has been reported for its anti-inflammatory, antioxidant, and antitumor effects, but the effect on osteosarcoma is unexplained. In this study, the research theme was to examine the sensitizing effect of decursin and its influence on cisplatin-induced nephrotoxicity. The cell viability and half maximal inhibitory concentration (IC50), apoptosis induction, and effect on cell cycle and Akt pathways were examined. In vivo, we examine the effects of decursin on tumors and mice bodies. Additionally, the effects of the cisplatin-decursin combination were evaluated in vitro and in vivo. Decursin suppressed cell viability and induced apoptosis via the cell cycle. Decursin also inhibited the Akt pathway by suppressing the phosphorylation of Akt. It enhanced apoptosis induction and lowered cell viability in combination with cisplatin. The increasing tumor volume was suppressed in the decursin-administrated group with further suppression in combination with cisplatin compared to sole cisplatin administration. The decrease in renal function and renal epithelial cell damage caused by cisplatin was improved by the combinatorial treatment with decursin. Therefore, decursin demonstrated an antitumor effect on the osteosarcoma cells and a renal protective effect in combination with cisplatin. Therefore, decursin is a prospective therapeutic agent against osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Pleomorphic liposarcoma is the rarest subtype of liposarcoma. Pleomorphic liposarcomas are generally unresponsive to chemotherapy and radiotherapy. Moreover, metastasis in the liver, as the first and sole site, from a primary extremity soft tissue sarcoma, including pleomorphic liposarcoma, is extremely rare. Information regarding the appropriate management of these lesions is limited. Case presentation: A 50-year-old Japanese woman presented with a mass in the left thigh. Imaging examination revealed a soft tissue sarcoma on the left posterior thigh. The tumor was histologically diagnosed as pleomorphic liposarcoma. Computed tomography examination for assessment of metastases incidentally detected a huge liver mass. Wide excision of sarcoma was performed prior to chemotherapy. Right trisectionectomy was necessary to achieve hepatic clearance; however, the future liver remnant volume was insufficient. Therefore, we decided to administer anthracycline-based chemotheraphy to shrink the tumor. After seven courses of adriamycin-based chemotherapy, the liver tumor size was reduced from 211 mm × 106 mm × 180 mm to 105 mm × 66 mm × 90 mm. Finally, a right hemihepatectomy was performed. The patient was continuously monitored and was metastasis or local recurrence free within 5 months after liver surgery. Conclusion: Chemotherapy is effective in some cases for the treatment of unresectable liver metastases of pleomorphic liposarcoma, and complete resection is possible with conversion surgery. If the patient's general condition permits, anthracycline-based chemotherapy can be used for the treatment of stage 4 pleomorphic liposarcoma. [ABSTRACT FROM AUTHOR]

Background: Surgical site infection (SSI) is a common complication following orthopedic implantation. We developed an iodine coating for titanium implants to reduce implant-related infections and conducted a prospective clinical study to evaluate the efficacy and potential drawbacks of iodine-supported implants. Patients and methods: Between July 2008 and July 2017, 653 patients (377 male and 27 female patients; mean age, 48.6) with postoperative infection or a compromised status were treated using iodine-loaded titanium implants. The mean follow-up period was 41.7 months. In 477 patients, iodine-supported implants were used to prevent infection and in 176 patients, to treat active infection (one-stage surgery, 89 patients; two-stage surgery, 87 patients). In the limbs and pelvis, the primary diagnoses included the following: 161 tumors, 92 deformities/shortening, 47 pseudarthrosis, 42 fractures, 32 infected TKA, 25 osteoarthritis, 21 pyogenic arthritis, 20 infected THA, and 6 osteomyelitis. In the spinal cases, there were 136 cases of tumors, 36 cases of pyogenic spondylitis, and 35 cases of degeneration. Five modes of implant failure were identified and classified as follows: soft tissue failure (type 1), aseptic loosening (type 2), structural failure (type 3), infection (type 4), and tumor progression (type 5). Results: The overall failure rate in our series was 26.3% (172/653). There were 101 mechanical failures, including 22 type 1, 20 type 2, and 59 type 3 failures. Non-mechanical causes accounted for 71 failures, including 45 type 4 and 26 type 5 failures. The overall incidence of infections was 6.8%. The mean time to the onset of infection after implantation was 9.1 months. The overall infection rate was 3.7% in the prevention cases and 15.3% in the treatment cases. There was no difference between one-stage replacement (14.6%) and two-stage replacement (16.0%). There were 11 cases of treatment for SSI of spine surgery, and the re-infection rate was 0% using iodine-coated instruments. Conclusions: The five modes of failure of the iodine-supported implant were satisfactory compared with previous reports. In particular, because the infection rate of iodine-coated implants used for compromised hosts is low compared with other methods, postoperative infection is more easily controlled. It can be considered highly effective for spinal infections that require one-stage revision surgery. Level of evidence IV. Trial registration Prospective, Observation study. [ABSTRACT FROM AUTHOR]

Purpose: CD81 is a member of the tetraspanin family of membrane proteins. Recently, it has been shown that CD81 may be involved in cancer cell proliferation and metastasis. As yet, however, there have been few reports on the expression and role of CD81 in osteosarcoma. Methods: The expression of CD81 was investigated in human osteoblast cell line hFOB1.19 and in human osteosarcoma cell lines Saos2, MG63 and 143B. The expression of CD81 was inhibited in osteosarcoma cells using siRNA after which cell proliferation, migration and invasion were assessed. We also used Western blotting to investigate the phosphorylation status of Akt, Erk, JNK and p38, and measured the expression of MMP-2, MMP-9 and MT1-MMP. In addition, we used a CRISPR/Cas9 system to stably knock out CD81 expression in 143B cells, transplanted the cells into mice, and assessed tumor formation and lung metastasis in these mice compared to those in the control group. Results: We found that CD81 was expressed in the human osteoblast cell line and in all osteosarcoma cell lines tested. The osteosarcoma cell line 143B exhibited a particularly high level of expression. In addition, we found that osteosarcoma cell proliferation, migration and invasion were decreased after CD81 inhibition, and that the phosphorylation of Akt and Erk was suppressed. Also, the expression levels of MMP-2, MMP-9 and MT1-MMP were found to be suppressed, with MMP-9 showing the greatest suppression. In vivo, we found that mice transplanted with CD81 knockout 143B cells exhibited significantly less tumor formation and lung metastasis than mice in the control group. Conclusion: Based on our findings we conclude that inhibition of CD81 suppresses intracellular signaling and reduces tumorigenesis and lung metastasis in osteosarcoma cells. [ABSTRACT FROM AUTHOR]

Background: Use of an implant is one of the risk factors for surgical site infection (SSI) after malignant bone tumor resection. We developed a new technique of coating titanium implant surfaces with iodine to prevent infection. In this retrospective study, we investigated the risk factors for SSI after malignant bone tumor resection and to evaluate the efficacy of iodine-coated implants for preventing SSI.Methods: Data from 302 patients with malignant bone tumors who underwent malignant bone tumor resection and reconstruction were reviewed. Univariate analyses were performed, followed by multivariate analysis to identify risk factors for SSI based on the treatment and clinical characteristics.Results: The frequency of SSI was 10.9% (33/302 tumors). Pelvic bone tumor (OR: 4.8, 95% CI: 1.8-13.4) and an operative time ≥ 5 h (OR: 3.4, 95% CI: 1.2-9.6) were independent risk factors for SSI. An iodine-coated implant significantly decreased the risk of SSI (OR: 0.3, 95% CI: 0.1-0.9).Conclusion: The present data indicate that pelvic bone tumor and long operative time are risk factors for SSI after malignant bone tumor resection and reconstruction, and that iodine coating may be a promising technique for preventing SSI. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common primary malignancy of bone. Although outcomes of patients with osteosarcoma have improved since the introduction of chemotherapy, outcomes of metastatic or unresectable osteosarcomas are still unsatisfactory. To improve osteosarcoma outcomes, the development of novel systemic therapies for osteosarcoma is needed. Since the 1880s, various immunotherapies have been utilized in patients with osteosarcoma and some patients have shown response to the treatment. Based on recent studies about the role of the immune system in malignancies, immunotherapies including immune modulators such as interleukin-2 and muramyl tripeptide, dendritic cells, immune checkpoint inhibitors, and engineered T cells have been utilized in patients with malignancies. Although there are limited reports of immunotherapies for osteosarcoma, immunotherapy is thought to be a promising treatment option for treating osteosarcomas. In this review, an overview of various immunotherapies for osteosarcoma is provided and their potential as adjuvant therapies is discussed. [ABSTRACT FROM AUTHOR]

Background: Ewing's sarcoma is a primary malignant tumor of bone occurring mostly in childhood. Few effective reconstruction techniques are available after wide resection of Ewing's sarcoma at the distal end of the tibia. Reconstruction after wide resection is especially difficult in children, as it is necessary to consider the growth and activity of the lower limbs.Case Presentation: A 12-year-old Japanese boy had presented with right lower leg pain at age 8 years. Imaging examination showed a bone tumor accompanied by a large extra-skeletal mass in the distal part of his tibia. The tumor was histologically diagnosed as Ewing's sarcoma. The patient received chemotherapy, followed by wide resection. Reconstruction consisted of a bone transport method involving external fixation of Taylor Spatial Frame. To prevent infection after surgery, the external fixation pin was coated with iodine. One year after surgery, the patient showed poor consolidation of bone, so iliac bone transplantation was performed on the extended bones and docking site of the distal tibia. After 20 months, tibia formation was good. Three years after surgery, there was no evidence of tumor recurrence or metastases; bone fusion was good, and he was able to run.Conclusions: The bone transport method is an effective surgical method of reconstruction after wide resection of a bone tumor at the distal end of the tibia, if a pin can be inserted into the distal bone fragment. Coating external fixation pins with iodine may prevent postoperative infection. [ABSTRACT FROM AUTHOR]

Background: Postoperative deep infection after bone tumor surgery remains a serious complication. Although there are numerous reports about risk factors for postoperative deep infection in general surgery, there is only a small number of reports about those for bone tumor surgery. This retrospective study aimed to identify risk factors for postoperative deep infection after bone tumor resection. Methods: We reviewed data of 681 patients (844 bone tumors) who underwent surgery. Associations between variables, including age, recurrent tumor, pathological fracture, surgical site (pelvis/other), chemotherapy, biological reconstruction, augmentation of artificial bone or bone cement, the use of an implant, intraoperative blood loss, operative time, additional surgery for complications, and postoperative deep infection were evaluated. Results: The rate of postoperative deep infection was 3.2% (27/844 tumors). A pelvic tumor (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.0–11.3) and use of an implant (OR: 9.3, 95% CI: 1.9–45.5) were associated with an increased risk of deep infection. Conclusions: This retrospective study showed that pelvic tumor and use of an implant were independent risk factors for deep infection. This information will help surgeons prepare an adequate surgical plan for patients with bone tumors. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer (DTC) is relatively rare and can metastasize to both the lungs and bones. The great majority of bone metastases occur in red marrow regions where blood flow is high. Only one patient has been described with direct DTC metastasis to the subchondral bone of the femoral head.Case Presentation: The patient was a 68-year-old Japanese female who had presented with left hip joint pain at age 63 years. At age 51 years, she had been diagnosed with DTC and underwent partial excision. X-rays showed partial femoral head collapse, suggesting osteoarthritis or idiopathic necrosis of the left femoral head. Three years later, a (131) I whole-body scan showed accumulation in the left femoral head, resulting in a diagnosis of DTC metastasis to the left femoral head. Bipolar hip arthroplasty was performed. Examination of the excised femoral head resulted in a final diagnosis of metastasis of follicular thyroid cancer, which was limited histopathologically to the subchondral bone of the femoral head.Conclusion: Tumor metastasis to the subchondral bone of the femoral head is exceedingly rare. Overall survival of patients with bone metastasis is improved by complete resection. Differential diagnosis of patients with a previous history of DTC who present with femoral head collapse should include bone metastasis of DTC. [ABSTRACT FROM AUTHOR]

Deep infection associated with implants remains a serious complication of orthopedic surgery. We developed iodine coating for titanium implants. In this study, we performed a clinical trial of iodine-coated megaprostheses to evaluate its safety and antibacterial effects. Forty-seven patients with malignant bone tumor or pyogenic arthritis were treated using iodine-supported titanium megaprostheses between July 2008 and May 2013. The mean age was 53.6 years (range, 15–85 years). Twenty-six patients were males and 21 were females. The diagnoses included malignant bone tumor in 29 cases, infected total knee arthroplasty in 11 cases, chronic osteomyelitis due to pyogenic arthritis in six cases and loosening of total knee arthroplasty in one case. The iodine-supported implants used were 42 Kyocera Limb Salvage System and five KOBELCO K-MAX K-3. These megaprostheses were used to prevent infection in 21 patients, treat active infections in 26 patients. The mean follow-up period was 30.1 months (range, 8–50). Infection was prevented in 20 out of 21 patients. Only one patient had surgical site infection caused by Pseudomonas aeruginosa and was cured by intravenous administration of antibiotics alone without removal of the implant. In 26 treatment cases involving one- or two-stage revision surgery, infection subsided without any additional surgery. In all cases, there were no signs of infection at the time of the last follow-up. White blood cell and C-reactive protein levels returned to normal within four weeks after surgery. To confirm systemic effects of iodine, thyroid hormone levels in the blood were examined. Abnormalities of thyroid gland function were not detected. Loosening of the implants was not observed. Excellent bone ingrowth and ongrowth were found around iodine-supported megaprostheses. The iodine-supported titanium megaprostheses are highly effective and show promise for the prevention and treatment of infections in large bone defects. No cytotoxicity or adverse effects were detected with this treatment. [ABSTRACT FROM AUTHOR]

Background: Pin tract infection is one of the most common complications of external fixation. We developed techniques to coat titanium implant surfaces with iodine. This study clinically evaluated the infection-preventive effects and biological safety of iodine-coated external fixation pins. Patients and methods: Iodine-supported pins were placed in 39 limbs of 38 patients. The mean age of the patients was 33.6 years. Twenty-six patients were men and 12 were women. In all patients, the iodine-coated pins were used to prevent infection. There were 476 pin insertion sites. Pin sites were classified according to the Checketts-Otterburn classification (grade 1-6). White blood cells (WBC) and C-reactive protein (CRP) were measured pre- and postoperatively in all patients. To confirm whether iodine from the implant affected physiological functions, thyroid hormone levels in the blood were monitored. The change in the amount of iodine deposited in the body over time was calculated by examining the removed pins. Results: External fixation was used for a mean duration of 6 months. Grade 1 infection was found in 2.5 % of patients, and grade 2 infection in 1.1 %. There was no patient with an infection of grade 3 or higher. Median WBC levels were in the normal range, and median CRP levels returned to <0.3 mg/dl within 3 weeks after surgery. Abnormalities of thyroid gland function were not detected. The amount of iodine was maintained for a long time, with approximately 40 % remaining after 1 year. Conclusions: Iodine-supported titanium pins were able to decrease the pin tract infection rate and had no impact on thyroid function. These results suggest that iodine-coated titanium pins are biologically safe and effective at preventing pin tract infections. [ABSTRACT FROM AUTHOR]

Background: Postoperative infection associated with implants remains a serious complication in orthopedic surgery. Several biomaterial surface treatments have been proposed as a means of reducing the incidence of implant-associated infections. In this study, a clinical trial was performed using an iodine-supported titanium that suppresses the microbial activities. Methods: A total of 222 patients with postoperative infection or compromised status were treated using iodine-supported titanium implants. The mean age of the patients was 49.4 years (range 5-85 years). One hundred twenty-seven patients were male and 95 were female. In 158 patients, iodine-supported implants were used to prevent infection, such as compromised hosts and conditions, and in 64 patients to treat active infection. White blood cell (WBCs) and C-reactive protein (CRP) levels were measured pre- and postoperatively in all patients. To confirm whether iodine from the implant affected physiological functions, thyroid hormone levels in the blood were examined. Both examinations were conducted sequentially for a year. Radiological evaluations were performed regularly after the operation. The chronological changes of the iodine amount were evaluated using half pins removed after completion of external fixation. Results: The mean follow-up period was 18.4 months (range 3-44 months). Acute infection developed in three tumor cases among the 158 patients on preventive therapy. All three recovered without removal of the implants. Infection was cured in all 64 patients with infection. Median WBC levels were in the normal range, and median CRP levels returned to <0.5 within 4 weeks after surgery. Abnormalities of thyroid gland function were not detected. None of the patients experienced loosening of the implants. There were two patients with mechanical implant failure, which was treated by re-implantation. Excellent bone ingrowth and ongrowth were found around all hip and tumor prostheses. One year later, the amount of iodine on external fixation pins remained about 20-30 %. Conclusions: Iodine-supported titanium implants can be very effective for preventing and treating infections after orthopedic surgery. Cytotoxicity and adverse effects were not detected. [ABSTRACT FROM AUTHOR]

Background: In the treatment of osteosarcoma, the chemotherapeutic effect influences decisions regarding the surgical margin, continuation of chemotherapy, and choice of anticancer drugs for further chemotherapy. Therefore, it is necessary to evaluate the response to chemotherapy in the middle of the chemotherapy course. In this study, we investigated the use of Tc-hexakis-2-methoxyisobutyl-isonitrile (Tc-MIBI) scintigraphy in evaluating the response to chemotherapy of patients with osteosarcoma in comparison with Tl scintigraphy and angiography. Methods: A total 45 patients with osteosarcoma were examined using Tc-MIBI scintigraphy, Tl scintigraphy, and angiography to evaluate their response to chemotherapy. The percentage reduction in the uptake ratios (ΔUR) calculated as 100 × [(prechemotherapy value − postchemotherapy value)/prechemotherapy value] were compared with histological assessments. Similarly, changes in tumor vascularity assessed by angiograms were compared with histological assessments. On the angiographic findings, the results were classified as complete response (CR), partial response (PR), no change (NC), or progressive disease (PD). On the images, ΔUR in Tc-MIBI ≥ 30% and ΔUR in Tl ≥ 30% were classified as responder, as were CR and PR in angiograms. The therapeutic effect was assessed by histopathological examination of the resected specimens. The tumors of poor responders showed less than 90% necrosis, whereas the tumors of good responders showed 90% or more necrosis. Results: Sensitivity, specificity, and accuracy were 73.9, 84.2, and 78.6%, respectively, for Tc-MIBI (κ = 0.57); 80.0, 61.1, and 72.1%, respectively, for Tl (κ = 0.42); and 91.7, 35.0, and 65.9%, respectively for angiography (κ = 0.28). Conclusion: Tc-MIBI could be effectively used to predict the final response to chemotherapy of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Chondroid lipoma, first described in 1993 by Meis and Enzinger, is a very rare lipomatous tumor. Because it is a benign tumor, it does not require radiotherapy, chemotherapy, or extensive resection. However, histologically, it is often confused with a sarcoma. It is crucial to differentiate chondroid lipoma from sarcoma to avoid choosing an inappropriate treatment strategy. Although MRI, radiography, and ultrasound have been used to evaluate chondroid lipomas, imaging cannot accurately differentiate chondroid lipoma from sarcoma. Case presentation: A 39-year-old man presented to a local clinic with a 1-month history of a painless mass in his left neck. Results of a needle biopsy suggested an atypical lipomatous tumor, and the patient was referred to our hospital. Physical examination revealed a hard and mobile mass in the left neck. Plain X-ray radiographs showed an absence of calcification in the soft tissue mass. MRI revealed a well-defined and lobulated mass, and on T1-weighted images, the lesion showed heterogeneity, with higher signal intensity than that of muscle. On T2-weighted images, the septum had low-signal intensity. On T2-weighted fat-suppressed images, the signal of the mass was completely suppressed. The SUVmax of the mass on FDG PET was 1.84. An additional needle biopsy was performed, and on the basis of the results, we arrived at a diagnosis of well-differentiated liposarcoma. The mass was resected marginally. Macroscopically, the mass was encapsulated and markedly harder than well-differentiated liposarcoma. Histologically, the tumor was composed of myxoid and cartilaginous matrix, and mature fat cells and lipoblast-like cells were present. The final diagnosis was chondroid lipoma, and no recurrence was observed 1 year after surgery. Conclusions: Chondroid lipoma is an extremely rare benign soft tissue tumor that is often confused with sarcoma. It is very important to differentiate chondroid lipoma from sarcoma when the SUVmax value of the mass is low, even when biopsy results suggest that it is a sarcoma. [ABSTRACT FROM AUTHOR]

We herein report a rare case of mesenchymal hamartoma of the chest wall in a 10-year-old girl. She complained of chest pain and was diagnosed with a large chest wall tumor originating from the left fourth rib. Malignancy such as osteosarcoma or chondrosarcoma could not be ruled out with imaging studies. Therefore, we performed a core needle biopsy assisted by thoracoscopy, which revealed no malignancy. Therefore, extended resection with chest wall reconstruction was unnecessary, and thoracoscopy-assisted tumor excision with only the removal of the involved fourth rib was performed without chest wall reconstruction. The postoperative course was satisfactory with no thoracic deformity and no recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Spindle cell lipoma is an uncommon adipocytic tumor. Intramuscular lesions of this tumor are very rare. In this report, we describe a case of a patient with intramuscular spindle cell lipoma localized in a deltoid.Case Presentation: A 58-year-old Japanese man visited us because of a soft tissue mass on the lateral aspect of the left shoulder that had been noticed 2 years prior. The spherical tumor, which measured 5 cm × 4 cm, was elastic and firm on palpation and immobile. Magnetic resonance imaging revealed that the lesion was localized in the left deltoid muscle. A needle biopsy was performed to make a histological diagnosis. With a pre-operative diagnosis of intramuscular lipoma, we removed the tumor with the patient under general anesthesia. The tumor was removed with surrounding musculature and fascia. The pathological diagnosis was intramuscular spindle cell lipoma in the left deltoid muscle.Conclusions: There are several kinds of lipomas. Spindle cell lipoma is a relatively rare variant (1.5% of all adipocytic neoplasms) that is histologically distinct and characterized by the replacement of mature fat by a mixture of mature adipocytes and undifferentiated spindle cells. There are only five other reported cases of intramuscular spindle cell lipoma in the literature, to our knowledge. The case of our patient is very interesting, as to date there have been few reported patients with a diagnosis of an intramuscular spindle cell lipoma in a deltoid. [ABSTRACT FROM AUTHOR]

Background: The high rate of aseptic loosening of cemented stems has led to their frequent use in endoprosthetic reconstruction. However, problems, such as stem breakage and stress shielding at the insertion site, remain. The Japanese Musculoskeletal Oncology Group (JMOG) has developed Kyocera Modular Limb Salvage System (KMLS) cementless stems with a unique tapered press-fit and short fixation design. This study aimed to clarify the short-term postoperative outcomes of this prosthesis and validate the stem design.Methods: One hundred cases of KMLS cementless stems (51 male patients; median age, 49 years; mean follow-up period, 35 months), with a minimum follow-up of 2 years, for the proximal femur (PF), distal femur (DF), and proximal tibia were prospectively registered for use. Prosthesis survival, complication rates, postoperative functional, and radiographical evaluation were analyzed. Complications or failures after insertion of the KMLS endoprostheses were classified into five types and functional results were analyzed according to the MSTS scoring system at postoperative 1 year. The diaphyseal interface and anchorage were graded by the ISOLS system at postoperative 2 years.Results: The overall prosthesis survival rates at 2 and 4 years were 88.2 and 79.6%, respectively. The prosthesis-specific survival rate excluding infection and tumor recurrence was 90.2 and 87.9%, respectively. Younger age (p = 0.045) and primary tumor (p = 0.057) were associated with poor prognosis of prosthesis-specific survival excluding infection and tumor recurrence. Complications were observed in 31 patients, 13 patients underwent revision surgery. The mean MSTS functional score at 1 year postoperatively was 68%. Early implant loosening was significantly more common in the DF (p = 0.006) and PF/DF straight stem (p = 0.038). The ISOLS radiographic evaluation at 2 years after surgery revealed good bone remodeling and anchorage in most cases (bone remodeling: 90% / excellent and good, anchorage: 97% / excellent and good).Conclusions: Tumor endoprosthesis long-term fixation to the diaphysis of the lower extremity remains challenging. The KMLS cementless stem with a unique tapered press fit design showed good short-term results in maintaining bone stock. To prevent early loosening, a curved stem should be used in PF and DF, but long-term follow-up is necessary. [ABSTRACT FROM AUTHOR]

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5- HT3 receptor antagonists, neurokinin-1 receptor antagonists ( NK-1RAs), and dexamethasone for multiple high emetogenic risk ( HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting ( CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. [ABSTRACT FROM AUTHOR]

Background: Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities. Methods: The study included 20 patients (12 men and 8 women) with frozen autografts (FFP, 13 cases; PFP, 7 cases). The mean age of the subjects was 36.3 years (range 11-79 years), and the mean follow-up period was 56.4 months (range 12-142 months). Results: Final bone union occurred in 11 patients in the FFP group (84.6 %) and in 7 patients in the PFP group (100 %). The mean union period in patients who did not need additional surgery was 9.8 months (range 4-21 months) in the FFP group and 4.8 months (range 2-7 months) in the PFP group. Postoperative complications occurred in 8 cases: infection in 3 cases, fracture in 3 cases, and joint destruction in 2 cases. Six FFP patients, and 2 PFP patients (two cases of fracture), developed postoperative complications. Conclusions: The union period was shorter and the rate of postoperative complications was lower with the PFP than with the FFP. We considered that early blood flow recovery might have led to the above results in the PFP. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy is essential to improve the prognosis of the patients with osteosarcoma, and the response to chemotherapy is an important prognostic factor. In this study, the impact of various radiological examinations on overall survival (OS) and event-free survival (EFS) was evaluated. Method: Eighty-two patients with high-grade osteosarcoma were included in this study, and we evaluated the following factors for prognostic significance: age (≥40 years), gender (male), tumor location (truncal site), metastatic disease, histological response to chemotherapy, radiological response to chemotherapy assessed using X-ray, angiography, CT, MRI, 201Tl scintigraphy, and 99mTc-MIBI scintigraphy (99mTc-MIBI), and combined radiological score (CRS). Results: Univariate analyses revealed that metastatic disease, histological response, 99mTc-MIBI, and CRS were significantly correlated with OS. Multivariate analyses showed that metastatic disease (OS: HR 35.9, P<0.001; EFS: HR 17.32, P<0.001) was an independent predictor of OS and EFS. Tumor location (HR 36.1, P = 0.003), histological response (HR 31.1, P = 0.036), and 99mTc-MIBI (HR 18.4, P = 0.038) were significant prognostic factors for OS. Moreover, CRS was a marginally significant predictor of OS and EFS. Conclusion: The chemotherapeutic effects evaluated by 99mTc-MIBI and CRS could be considered as prognostic factors in osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Several reports suggest diffusion of anticancer agents from bone cement may suppress tumor growth. New drug delivery systems have been developed that incorporate anticancer drugs into calcium phosphate cement (CPC) to maintain high concentrations of anticancer drugs at local sites. We investigated whether CPC implants containing anticancer drugs and caffeine, which enhance the cytocidal effect of anticancer drugs, would enhance their antitumor effects on rat osteosarcomas (SOSN2 cells). Methods: We calculated the release of cisplatin (CDDP) and caffeine from the CPC and bone cement. The following CPCs were prepared: CPC-only, CPC containing caffeine, CPC containing cisplatin, and CPC containing cisplatin and caffeine. We performed cell growth inhibition assays on SOSN2 cells using culture media previously used to incubate each CPC. We transplanted SOSN2 cells into the tibias of rats, excised the tumor 3 days after transplantation, implanted each CPC and observed subsequent tumor growth. Results: The in vitro sustained-release test demonstrated greater amounts and more persistent release of CDDP and caffeine from CPC than from bone cement and also showed CPC could release the majority of its loaded CDDP and caffeine. Culture media containing CDDP and caffeine inhibited in vitro proliferation of SOSN2 cells, and this inhibitory effect was greater than the inhibition resulting from CDDP alone. Experiments with an in vivo rat model demonstrated greater tumor growth inhibition with CPC containing CDDP and caffeine than with CPC containing CDDP alone. Conclusions: The study results suggest CPC containing CDDP and caffeine potentiate antitumor effects and may be effective as a local chemotherapeutic method of treating malignant bone tumors. [ABSTRACT FROM AUTHOR]

Infections following limb-saving surgeries still happen frequently and are refractory to treatment, even though the treatment of massive bone defects caused by bone resection of bone tumors has improved gradually. Once infections become intractable, they generally result in amputations in spite of all kinds of treatment. We report the case of a patient who developed an intractable infection after limb-saving surgery utilizing a massive frozen autograft and a tumor prosthesis, but whose limb was finally successfully salvaged by multiple surgical interventions. We conclude that continued perseverance in treatment after infections may enable preservation of the limb and restoration of good function. [ABSTRACT FROM AUTHOR]

We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra‐craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12–80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow‐up period (24–316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence. [ABSTRACT FROM AUTHOR]

Benign metastasizing leiomyoma (BML) is a rare disease that is characterized by well‐differentiated smooth muscle tumors occurring extrauterine site in women with a history of uterine leiomyoma. The lung is the most common metastatic site for BML. A 48‐year‐old woman, who had histories of laparoscopic myomectomy and transabdominal total hysterectomy, visited an orthopedics complaining of a mass in her left thigh and difficulty in walking. Magnetic resonance imaging (MRI) and fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography revealed multiple mass lesions in her both thighs and left femur as well as both lungs. She was referred to our hospital for further examination. We diagnosed her tumors as BML according to histopathological analysis of tumor specimen. The left thigh tumor was resected and the treatment with gonadotropin releasing hormone agonist regressed the size of the residual tumors by approximately 30%. BML should be considered when multiple soft tissue tumors are found in women with a history of leiomyomas. [ABSTRACT FROM AUTHOR]

Background: The reduction of microbial infections can substantially improve the success of implant surgery. The iodine-supported implants that were developed by us for infection prevention were featured at the recent International Consensus Meeting on Musculoskeletal Infection and were partly incorporated into the consensus guidelines. For future clinical application, we examined (1) whether iodine can be added to metals with different surface roughness, (2) differences in surface roughness before and after processing, and (3) the effect of sterilization on the iodine content.Methods: Four Ti-6Al-4V metals were prepared with different surface roughness values by polishing, blasting and plasma spraying. Before and after processing, the surface structure of metals was observed using a scanning electron microscope and stylus instruments. Before and after sterilization, iodine contents were measured by X-ray fluorescence spectroscopy.Results: After processing, sufficient iodine contents with an antimicrobial effect were detected for each metal. These iodine contents decreased after sterilization but were higher than the lowest content of iodine observed to have an antimicrobial effect in a previous study, indicating that the antimicrobial effect persists even after sterilization. After processing, surface roughness was greater for polishing metal. With general surface processing, iodine processing was possible.Conclusions: Our results indicated that surface roughness is affected by the processing method and that the iodine content should be set according to the sterilization method. Considering these factors, iodine processing can be used for clinical applications. [ABSTRACT FROM AUTHOR]

Background: In chronic lateral ankle instability (CLAI), the instability of the ankle joint results in repeated microtrauma to the articular cartilage. How the lesion condition or stage is affected by the presence of lateral instability in medial osteochondral lesions of the talus (OLT) is unclear. We aimed to examine whether CLAI is associated with the size and staging of medial OLT on radiographs, magnetic resonance (MR) images, and arthroscopy.Methods: Forty-five patients with medial OLTs in 45 ankles were reviewed. Radiographs were assessed for damage and lesion classification. The tibio-talar tilting angle (TTA) was measured. The patients were divided into two groups: the CLAI group and the stable group. The lesion classification on radiographs, MR images, and arthroscopy, and size on MR images were statistically compared.Results: The CLAI group had a mean TTA of 8.15 ± 3.41°, whereas the stable group had a mean TTA of 2.24 ± 1.64°. The CLAI group had a lower clinical score than the stable group at the initial visit to our clinic. The CLAI group presented with lesions of significantly shorter longitudinal and transverse diameters. Stages of medial OLT on radiographs, MR images, and arthroscopic evaluation were earlier in the CLAI group than those in the stable group.Conclusions: Patients with CLAI presented in the early stages of OLT and had significantly smaller lesions than those without CLAI. The patients without CLAI may be selected for surgery at an early phase. [ABSTRACT FROM AUTHOR]

Background: We have developed iodine-supported titanium implants, which were shown to have good anti-bacterial effects for Methicillin-sensitive Staphylococcus aureus (MSSA) in our past basic research. However, PJI can be caused by various bacteria including MRSA, Pseudomonas aeruginosa, MSSE, and fungus. The purpose of this study was to investigate whether these implants also have good antibacterial attachment effects for MRSA, P. aeruginosa, MSSE, and fungus.Methods: Ti-6Al-4V titanium plates were either left untreated (Ti), treated with oxide film on the Ti surface by anodization (Ti-O), or treated with an iodine coating on oxidation film (Ti-I). The antibacterial activity of the TiI was measured by experimental methods according to Japanese Industrial Standard (JIS) protocols. Implants in this study were exposed to MRSA (ATCC43300), P. aeruginosa (ATCC27853), MSSE (ATCC35984), and Candida Albicans (ATCC10231). Colonies were counted immediately after the bacteria attached to the metal surface and again after 24 h incubation. The difference in the number of bacteria on each metal plate was statistically investigated and an antibacterial activity value was calculated. An effective antibacterial active value of more than 2.0 was judged to be effective according to JIS protocol.Results: No countable viable bacteria were observed on the Ti-I surface. For all bacteria there was a significant difference in the mean number of viable bacteria between Ti-I and Ti or Ti-O. Antibacterial activity value in Ti-I and Ti-O was more than 5.9 and 3.6 respectively for MRSA, more than 2.8 and zero for P. aeruginosa, more than 4.3 and zero for MSSE, and more than 4.7 and zero for C. Albicans.Conclusions: This study showed that iodine-supported titanium implants have good antimicrobial attachment effects for MRSA, P. aeruginosa, MSSE, and C. Albicans. Iodine-supported titanium implants could have great potential as innovative antibacterial implants that can prevent early onset periprosthetic joint infection. [ABSTRACT FROM AUTHOR]

Purpose: We have developed iodine-supported titanium implants that suppress microbial activities and conducted in vivo and in vitro studies to determine their antimicrobial properties.Methods: The implants were Ti-6Al-4 V titanium implants either untreated (Ti), treated with oxide film on the Ti surface by anodization (Ti-O), or treated with an iodine coating on oxidation film (Ti-I). The strain of bacteria used in this study was Gram-positive Staphylococcus aureus strain ATCC 25923. We analyzed the antibacterial attachment effects in vivo by using rats. The attachment bacteria on the implant surface were evaluated using a spread-plate method assay. A biofilm study was performed in vitro. The biofilm formed after bacterial attachment was qualitatively studied with fluorescence microscopy (FM) and scanning electron microscopy (SEM). Also, the formed biofilm was quantitatively studied with a spread-plate method assay.Results: In vivo analysis of antimicrobial attachment effects showed that the mean viable bacterial number was significantly lower on Ti-I than Ti or Ti-O surfaces. In the in vitro biofilm study, FM and SEM images showed thick and mature biofilm formation on Ti and Ti-O and thin, small biofilm formation on Ti-I. A quantitative biofilm analysis found a significant difference in the number of viable bacteria between Ti-I and Ti or Ti-O.Conclusions: This study showed that iodine-supported implants have a good antibacterial attachment effect and inhibit biofilm formation and growth. Iodine-supported implants may have great potential as innovative antibacterial implants that can prevent implant related infection in orthopaedic surgery. [ABSTRACT FROM AUTHOR]

Purpose: It has previously been found that valgus hindfoot alignment (HFA) improves 3 weeks following total knee arthroplasty (TKA) for varus knee osteoarthritis (OA). In the present study, HFA was evaluated prior to TKA, as well as 3 weeks and 1 year following TKA. Using these multiple evaluations, the chronological effects of TKA on HFA were investigated.Methods: The study included 71 patients (73 legs) who underwent TKA for varus knee OA. Radiograph examinations of the entire limb and hindfoot were performed in the standing position prior to TKA, as well as 3 weeks and 1 year following TKA. The varus-valgus angle was used as an indicator of HFA in the coronal plane. Patients were divided into two groups according to the preoperative varus-valgus angle: a hindfoot varus group (varus-valgus angle <76°) and a hindfoot valgus group (varus-valgus angle ≥76°). The changes in the varus-valgus angle were evaluated and compared in both groups.Results: In the hindfoot valgus group, the mean ± standard deviation varus-valgus angle significantly declined from 80.5 ± 3.1° prior to TKA to 78.6 ± 3.7° 3 weeks following TKA and 77.1 ± 2.7° 1 year following TKA. However, in the hindfoot varus group, the mean varus-valgus angle prior to TKA (72.7 ± 2.6°) did not differ significantly from the mean varus-valgus angles 3 weeks (72.3 ± 3.3°) or 1 year (73.5 ± 3.0°) following TKA.Conclusions: HFA improved chronologically in legs with hindfoot valgus as a result of the alignment compensation ability of the hindfoot following TKA. However, no improvement was noted in legs with hindfoot varus because the alignment compensation ability of the hindfoot had been lost. The patients with hindfoot varus should be attended for ankle pain in the outpatient clinic after TKA.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. PPARγ is essential in adipocyte differentiation from precursor cells. Its antitumorigenic effects are reported in certain malignancies; however, its effects in liposarcoma are unclear.Methods: We analyzed PPARγ expression using immunohistochemistry (IHC) in 46 patients with myxoid liposarcoma [MLS; median age, 47 years (range, 14-90 years) and mean follow-up period, 91 months (range, 13-358 months)]. PPARγ mRNA expression levels were measured by quantitative reverse transcription polymerase chain reaction. Further, we evaluated the correlation of PPARγ expression with clinical outcomes.Results: We found that the metastasis-free survival rate was significantly higher in lower PPARγ expressers [34 patients with labeling index (LI) <50 %] than in higher expressers (12 patients with LI ≥50 %; p = 0.01). Cox multivariate analysis revealed that a higher PPARγ level was an independent predictor of metastasis (relative risk = 6.945, p = 0.026). Furthermore, using 28 fresh MLS specimens, we confirmed an increased PPARγ mRNA expression level in the higher LI group (p = 0.001).Conclusions: In this study, higher PPARγ expression in MLS was a risk factor associated with distant metastasis; therefore, it would be a novel prognostic marker for MLS. Further analyses will help to understand the correlation between PPARγ expression and tumor malignancy in liposarcoma. [ABSTRACT FROM AUTHOR]

Nephrotoxicity is the major dose-limiting toxicity of cisplatin (CDDP). The aim of this study was to develop a pharmacokinetic (PK)/toxicodynamic (TD) model of CDDP-induced acute renal injury in rats and to simulate nephrotoxicity at various dosing rates. CDDP was administered to rats by a 30-s bolus or a 2-h infusion (1.0, 2.5, 5.0, and 7.5 mg/kg). Unbound CDDP concentrations in plasma and urine were determined up to 2 h after administration in the PK study, and plasma creatinine (Cr) levels were monitored for up to 7 days as an index of nephrotoxicity in the TD study. The PK was linear and was fitted with a traditional 2-compartment model. The TD was nonlinear and differed between dosing rates. The creatinine concentration profiles were fitted with a signal transduction–indirect response model. Population analysis using a nonlinear mixed-effect model was adapted to the developed PK/TD model and was well-validated. Dosing simulations from the developed population PK/TD model indicated that CDDP-induced nephrotoxicity was due to not only C max but also the time above the toxic concentration of CDDP. Prolongation of infusion time will not necessarily attenuate acute nephrotoxicity. This study demonstrated the potential utility of PK/TD modeling for preventing nephrotoxicity. [ABSTRACT FROM AUTHOR]

Purpose: In this study, magnetic resonance angiography (MRA) was performed in the early phase after anterior cruciate ligament (ACL) reconstruction to analyse the changes in nutrient blood vessels and blood flow to the femoral and tibial tunnels and the intraosseous tendon grafts.Methods: The subjects were 30 patients who underwent single-bundle ACL reconstruction with an autogenous hamstring tendon. MRA was performed at 2, 3, and 6 months postoperatively (n = 10 at each time point). The mean overall signal-to-noise ratios (SNRs) in the tunnel regions and in the region of the tendon graft were compared in each femur and tibia.Results: Blood vessels from arteries reached the femoral and tibial tunnels 2 months postoperatively. The tunnel walls showed high signal intensity, while the intraosseous tendon grafts had lower intensity. SNRs showed significant differences between the femoral and tibial tunnels overall and the intraosseous tendon grafts. At 3 and 6 months postoperatively, the signal intensity of the tunnel walls was decreased significantly, while that of the intraosseous tendon grafts was also decreased, but not significantly. At these times, the SNRs of the femoral and tibial tunnels did not differ significantly, both overall and in the region of the intraosseous tendon grafts.Conclusion: Revascularization around the femoral and tibial tunnels occurred at 2 months postoperatively, with blood flow subsequently decreasing over time until 6 months. This revascularization may be involved in bone tendon healing and maturation of the tendon graft within the bone tunnels. Evaluations of revascularization by MRA may show the maturation stage of the graft and guide medical rehabilitation.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Background context Surgical site infection (SSI) associated with instruments remains a serious and common complication in patients who undergo total en bloc spondylectomy (TES). It is very important that the risk factors for SSI are known to prevent it. Purpose The purpose of the study was to identify independent risk factors for SSI after TES and evaluate the positive effect of iodine-supported spinal instruments in the prevention of SSI after TES. Study design This is a retrospective clinical study. Patient sample One hundred twenty-five patients who underwent TES for vertebral tumor were evaluated. Outcome measures Incidence rate of SSI, risk factors for SSI after TES, and safety of iodine-supported spinal instruments were the outcome measures. Methods Risk factors for SSI were analyzed using logistic regression. In recent 69 patients with iodine-supported spinal instruments, the thyroid hormone levels in the blood were examined to confirm if iodine from the implant influenced thyroid function. Postoperative radiological evaluations were performed regularly. Results The rate of SSI was 6.4% (8/125 patients). By multivariate logistic regression, combined anterior and posterior approach and nonuse of iodine-supported spinal instruments were associated with an increased risk of SSI. The rate of SSI without iodine-supported spinal instruments was 12.5%, whereas the rate with iodine-supported spinal instruments was 1.4%. This difference was statistically significant. There were no detected abnormalities of thyroid gland function with the use of iodine-supported instruments. Among the 69 patients with iodine-supported spinal instruments, 2 patients required additional surgery because of instrument failure. However, there were no obvious involvements with the use of iodine-supported spinal instruments. Conclusions This study identified combined anterior and posterior approach and nonuse of iodine-supported spinal instruments to be independent risk factors for SSI after TES. Iodine-supported spinal instrument was extremely effective for prevention of SSI in patients with compromised status, and it had no detection of cytotoxic or adverse effects on the patients. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) is widely used in the study of the central nervous system. DTI represents a potential diagnostic tool for the peripheral nerve. However, more detailed information is needed for application of DTI in the clinical setting. In this study, peripheral degeneration and regeneration were evaluated using DTI-based analyses in a rabbit model. The changes in DTI parameters were compared to histological and functional changes after nerve injury. We used a high magnetic field (7.04 T) MRI system. Japanese white male rabbits were used as the model of sciatic nerve crush injury. MR images were obtained before injury and at 2, 4, 6 and 8 weeks post-injury. The DTI parameters of fractional anisotropy (FA), axial diffusivity (λ || ), and radial diffusivity (λ ⊥ ) were calculated. Our results showed decreased FA and increased λ ⊥ during the degenerative phase after sciatic nerve injury. In contrast, increased FA and decreased λ ⊥ were observed during the regenerative phase. FA changes were correlated with axon number and with motor function recovery, assessed with the toe-spreading index. This study clearly demonstrates the validity of applying DTI parameters to the in vivo evaluation of peripheral nerve regeneration. Furthermore, results suggest that DTI can be a potent tool for predicting the extent of functional recovery after peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Background: Low-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist. Patients and methods: Nine cases of histologically diagnosed Broder grade 1 osteosarcoma were retrospectively reviewed. The pathological diagnoses included parosteal osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic osteosarcoma in four, four, and one cases, respectively. Results: Duration from initial surgical intervention including biopsy to final diagnosis as low-grade osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy specimens included fibrous dysplasia in three cases, chondroblastoma in one case, and a giant cell tumor in one case. The average number of histological examinations was 1.8. Low-grade osteosarcomas are well suited for biological reconstruction: seven cases were reconstructed by frozen autografts, distraction osteogenesis, or vascularized bone grafts. Conclusion: Low-grade osteosarcomas can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the diagnosis of a low-grade osteosarcoma is not established on the basis of radiologic findings, care should be exercised, even when a biopsy suggests a benign lesion. Low-grade osteosarcomas should be treated with wide excision, even after an intralesional excision. Biological reconstruction might be a better option for low-grade osteosarcomas. [ABSTRACT FROM AUTHOR]

Highlights: [•] Transduced siTNF into the synovium by sonoporation reduced TNF-α gene expression. [•] Although sonoporation elevated skin temperature, there were no adverse effects. [•] Transduced siTNF into the joints of CIA rats by sonoporation inhibited synovitis. [ABSTRACT FROM AUTHOR]

The bone is a metabolically active organ which undergoes repeated remodeling cycles of bone resorption and formation. In this study, we revealed a robust and extremely long-lasting circadian rhythm in ex vivo culture maintained for over six months from the femoral bone of a PERIOD2Luciferase mouse. Furthermore, we also identified robust circadian clocks in flat bones. High- or low-magnification real-time bioluminescence microscopic imaging revealed that the robust circadian rhythms emanated from the articular cartilage and the epiphyseal cartilage within the growth plate of juvenile animals. Stimulation by forskolin or dexamethasone treatment caused type 0 phase resetting, indicating canonical entraining properties of the bone clock. Together, our findings from long-term ex vivo culture revealed that “tissue-autonomous” circadian rhythm in the articular cartilage and the growth plate of femoral bone functions for several months even in an organ culture condition, and provided a useful in vitro assay system investigating the role of the biological clock in bone formation or development. [ABSTRACT FROM AUTHOR]

We investigated the effects of stress-shielding on both viscoelastic properties and microstructure of collagen fibers in the Achilles tendon by proton double-quantum filtered (1H-DQF) NMR spectroscopy. The right hind-limbs of 20 Japanese white rabbits were immobilized for 4 weeks in a cast with the ankle in plantarflexion. Dynamic viscoelasticity of the Achilles tendons was measured using a viscoelastic spectrometer. Proton DQF NMR signals were analyzed to determine the residual dipolar coupling of bound water molecules in the Achilles tendons. Both the dynamic storage modulus ( E′) and dynamic loss modulus ( E″) decreased significantly in the Achilles tendons of the stress-shielding group. The results of the 1H-DQF NMR examination demonstrated significantly reduced residual dipolar coupling in the Achilles tendons of this same group. The disorientation of collagen fibers by stress-shielding should contribute to degradation of the dynamic storage and loss moduli. The alterations of the collagen fiber orientation that contributed to the function of tendinous tissue can be evaluated by performing an analysis of 1H DQF NMR spectroscopy. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1708-1712, 2013 [ABSTRACT FROM AUTHOR]

Background: A variety of surgical procedures are now available for tissue reconstruction after osteosarcoma excision, and an important prognostic factor is the evaluation of response to chemotherapy using histology. Although tumor-bearing autografts are useful tools for reconstruction, re-use of the primary tumor may make it difficult to assess the histological response to chemotherapy, since the entire tumor cannot be analyzed. Here, we analyzed the prognostic value of the histological response in the patients who received frozen tumor-bearing autografts for reconstruction. Method: Retrospective analysis of the medical records of 51 patients with high-grade osteosarcoma of the extremities was performed. All patients received reconstruction using frozen tumor-bearing autografts. Tumor necrosis was evaluated in extraskeletal masses and cancellous bone. Results: Five-year overall survival of patients with good and poor response to chemotherapy was 82.9% and 46.4%, respectively (P = 0.044), and 5-year event-free survival was 57.7% and 36.0%, respectively (P = 0.329). Multivariate analysis revealed that a poor histological response to chemotherapy was a significant prognostic factor for overall survival (P = 0.033). Conclusion: Histological response is an important and reliable prognostic factor in patients undergoing reconstruction using frozen tumor-bearing autografts. [ABSTRACT FROM AUTHOR]

Background: Clear cell sarcoma is a rare malignant tumor of soft tissue which is most commonly encountered in the extremities, especially in the foot and ankle. This tumor is slow-growing and looks like a benign tumor; it is therefore often treated inadequately and its high rate of recurrence and metastases results in a poor prognosis. Caffeine has been used as a chemotherapy potentiator that inhibits DNA damage repair and enhances the cytocidal effects of anti-cancer drugs. This study reports the effect of caffeine-potentiated chemotherapy for clear cell sarcoma in five patients. Methods: Caffeine-potentiated chemotherapy was administered to five patients with clear cell sarcoma. Three to five courses of intra-arterial chemotherapy using cisplatin, doxorubicin and caffeine were administered preoperatively, at 3-week intervals. Conservatively, wide margin surgery was performed following the preoperative chemotherapy. Intravenous cisplatin and doxorubicin with caffeine were administered three to six times to the patients who responded to the preoperative chemotherapy. This study evaluated the response to chemotherapy, recurrence, metastasis and the overall prognosis in these five patients. Results: Four of the eligible patients responded to preoperative chemotherapy. Local recurrence occurred in only one of the five patients. Distant metastasis newly developed in one patient. All five patients survive. Conclusion: Caffeine-potentiated chemotherapy can be effective treatment for clear cell sarcoma not only as initial therapy, but also as salvage therapy. [ABSTRACT FROM AUTHOR]

Background: Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli. Methods: Thirty-one patients with malignant bone and soft tissue tumors were enrolled in this study. All the patients had metastatic tumors and/or recurrent tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cells were then treated with or without 1) tumor lysate (TL), 2) TL + TNF-α, 3) OK-432. The generated DCs were mixed and injected in the inguinal or axillary region. Treatment courses were performed every week and repeated 6 times. A portion of the cells were analyzed by flow cytometry to determine the degree of differentiation and maturation of the DCs. Serum IFN-c and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy. Results: Approximately 50% of PBMCs differentiated into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation of the TL/TNF-α-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. Serum IFN-γ and serum IL- 12 showed significant elevation at one and three months after DC-based immunotherapy. Conclusions: Although TL-pulsed DCs exhibit tumor specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, the TL/TNF-α-pulsed DCs showed remarkable maturation. The combination of IL-4/GM-CSF/TL/TNF-α resulted in the greatest differentiation and maturation for DC-based immunotherapy for patients with bone and soft tissue tumors. [ABSTRACT FROM AUTHOR]

Abstract: Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including −196 and −73°C for 20min, 60 and 100°C for 30min, 60°C for 10h following −80°C for 12h as an allograft model, and 4°C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the −196, −73, 60, 100°C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the −196, −73, 60, 100°C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment. [Copyright &y& Elsevier]

Background: The shoulder girdle is a common site for malignant bone and soft tissue tumors. Total scapulectomy represents an attractive alternative to amputation when the whole scapula is invaded with tumor and the neurovascular bundle can be preserved during tumor resection. The purpose of this study was to investigate functional outcomes after total scapulectomy. Patients and methods: The study comprised seven patients, four of whom underwent soft tissue reconstruction for joint stabilization, including suture of the biceps tendon onto the clavicle or humeral head, reattachment of the rotator cuff, and/or humeral suspension. The remaining three patients did not undergo soft tissue reconstruction; instead, only the remaining muscles were sutured. Results: Mean Enneking functional score was 57%. Preservation of elbow, wrist and finger motion resulted in an acceptable level of postoperative limb function. No significant differences in function were observed between the soft tissue reconstruction group and the non-reconstruction group. Conclusion: Total scapulectomy is a feasible alternative to amputation as it preserves acceptable elbow and hand function. [ABSTRACT FROM AUTHOR]

The article describes the case of a 14-year-old Japanese female patient who was diagnosed with high-grade undifferentiated pleomorphic sarcoma of pelvis. The patient complained of a two-week history of pain in her right hip after falling on an icy road. Physical and radiographic tests on the patient revealed osteolytic lesion around the right acetabulum. The patient received caffeine-potentiated chemotherapy and underwent curettage and bone graft.

Standardizing limb salvage surgery for malignant bone tumors should result in improved limb function after tumor excision and reconstruction. Recently, we developed and clinically applied a method of biological reconstruction using tumor-bearing autografts treated with liquid nitrogen. We report this newly modified technique using pedicle frozen autografts to save the continuity of anatomical structures. We treated 33 malignant bone tumor patients. Diagnoses of the tumors were 17 osteosarcomas, 11 metastatic tumors, 2 Ewing’s sarcomas, 2 chondrosarcomas, and 1 undifferentiated pleomorphic sarcoma. The sites of the tumors were 23 femurs, 5 tibias, 4 humeri, and 1 calcaneus. Operative procedures consisted of exposing the tumor, performing one-site osteotomy or joint dislocation, rotating and freezing the tumor lesion in liquid nitrogen for 20 min, and reconstruction using intramedullary nailing, plates, or composite arthroplasty. Postoperative function was excellent in 25 patients (75.7%), good in 5 patients (15.1%), and fair in 3 patients (9.0%). At the final follow-up, 8 patients had died at a mean of 17 months postoperatively, and 18 patients remained disease-free for a mean follow-up period of 30 months (range 7–69 months). Seven patients were alive but with disease. Complications were encountered in 12 patients, including 4 deep infections, 3 fractures, 3 local recurrences from surrounding soft tissue, 2 nonunions, and 1 collapse. All were managed successfully. The pedicle frozen autograft, which was newly developed to solve drawbacks of previously reported free frozen autografts, achieved success for reconstruction of malignant bone tumors. This is a new, simple, effective surgical technique for biological reconstruction that is still investigated but has potential for development. [ABSTRACT FROM AUTHOR]

Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction. [ABSTRACT FROM AUTHOR]

We analyzed the influence of treadmill running on rheumatoid arthritis (RA) joints using a collagen-induced arthritis (CIA) rat model. Eight-week-old male Dark Agouti rats were randomly divided into four groups: The control group, treadmill group (30 min/day for 4 weeks from 10-weeks-old), CIA group (induced CIA at 8-weeks-old), and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by μ-CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of tumor necrosis factor-α and Connexin 43; production was significantly suppressed by treadmill running. On μ-CT of the talus, bone volume fraction (BV/TV) was significantly decreased in the CIA group. Marrow star volume (MSV), an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. Bone destruction in the talus was significantly increased with CIA and was suppressed by treadmill running. On tartrate-resistant acid phosphate and alkaline phosphatase (TRAP/ALP) staining, the number of osteoclasts around the pannus was decreased by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction. [ABSTRACT FROM AUTHOR]

Background: To investigate the differences in the characteristics of femoral neck and trochanteric fractures between urban and rural areas of Kyoto Prefecture in Japan.Methods: Fracture type (neck vs. trochanteric), age, sex, place where fracture occurred (indoors vs. outdoors), and cause of injury were surveyed among patients aged ≥65 years who sustained hip fractures between 2008 and 2010 and who were treated at 1 of 13 participating hospitals (5 urban, 8 rural). The ratio of sick beds to total number of beds at the participating hospitals was 19.6% (2,188/11,158) in the urban area and 34.9% (1,963/5,623) in the rural area. We also investigated the incidence of hip fracture in Tango medical district as a representative rural area.Results: There were 1,346 neck (mean age, 82.4 years) and 1,606 trochanteric fractures (mean age, 85.0 years). The ratio of neck to trochanteric fractures was higher in the urban area than in the rural area in all age groups (65-74, 75-84, and ≥ 85 years). There were no apparent differences in place or cause of injury. The incidence of hip fracture in the women of Tango medical district was lower than the national average.Conclusions: There was a difference in the ratio of neck to trochanteric fractures between urban and rural areas. This difference is estimated to be caused by the high and low incidence of neck fracture in urban and rural areas, respectively. [ABSTRACT FROM AUTHOR]