The current management of clear cell sarcoma.

Clear cell sarcoma (CCS) is a rare melanocytic soft tissue sarcoma with a high propensity for lymphatic metastasis and poor prognosis. It is characterized by the translocation of t (12;22), resulting in the rearrangement of the EWSR1 gene and overexpression of MET. Despite improvements in the diagnosis and treatment of soft tissue sarcomas, the management of CCSs remains challenging owing to their rarity, unique biological behaviour and limited understanding of their molecular pathogenesis. The standard treatment for localized CCSs is surgical excision with negative margins. However, there is an ongoing debate regarding the role of adjuvant chemotherapy, radiotherapy and lymphadenectomy in the management of this disease. CCSs are usually resistant to conventional chemotherapy. Targeted therapies, such as sunitinib and MET inhibitors, may provide promising results. Immunotherapy, particularly immune checkpoint inhibitors, is currently under investigation as a potential treatment option for CCSs. Further research is needed to better understand the biology of CCSs and develop effective therapeutic strategies. The purpose of this review is to provide a comprehensive overview of current knowledge and advances in the diagnosis and treatment of CCSs.

Development of Therapeutic Agent for Osteoarthritis via Inhibition of KIAA1199 Activity: Effect of Ipriflavone In Vivo.

This study aimed to clarify the effects of ipriflavone, which effectively reduces KIAA1199 activity, on osteoarthritis (OA) development and progression in an in vivo OA mouse model. The OA model mice were divided into the ipriflavone (200 mg/kg/day) group and the control group. OA onset and progression were evaluated with the Mankin score, and KIAA1199 expression and hyaluronan (HA) accumulation were analyzed by immunostaining. The molecular weight of HA in the cartilage tissue and serum HA concentration were analyzed by chromatography and competitive HA enzyme-linked immunoassay. The effects of ipriflavone on the bovine cartilage explant culture under the influence of IL-1ß were also investigated. In the ipriflavone group, Safranin-O stainability was well-preserved, resulting in significant reduction of the Mankin score (p = 0.027). KIAA1199 staining positivity decreased and HA stainability was preserved in the ipriflavone group. The serum HA concentration decreased, and the molecular weight of HA in the cartilage tissue increased in the ipriflavone group. The results of the cartilage explant culture indicated that ipriflavone could reduce GAG losses and increase the molecular weight of HA. Thus, ipriflavone may have an inhibitory effect on OA development/progression. Ipriflavone could be a therapeutic drug for OA by targeting KIAA1199 activity.

Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well-differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra-tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good-prognosis and the poor-prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]-log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P < .001) and poor distant metastasis-free survival (DMFS) (P < .001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis.

Limitations and benefits of FDG-PET/CT in NF1 patients with nerve sheath tumors: A cross-sectional/longitudinal study.

The purposes of this study were to re-confirm the usefulness of PET/CT in the differentiation of benignity/malignancy of neurogenic tumors in NF1 patients, and to analyze the natural course of plexiform neurofibroma (pNF) and clarify whether PET/CT is also useful for detecting tumors other than neurogenic tumors. PET/CT was prospectively imaged in 36 NF1 patients. There were 14 malignant peripheral nerve sheath tumors (MPNSTs) in 14 patients, and 54 pNFs in 30 patients. Nine patients had both MPNST and pNF. Maximal standardized uptake value (SUVmax) was significantly higher in MPNST (median 7.6: range 4.1-10.4) (P < .001) compared with that of pNF (median 3.7: range 1.6-9.3). The cut-off value of 5.8 resulted in a sensitivity of 78.6% and specificity of 88.9%. Median age was 29 y, and median maximum tumor diameter was 82 mm in 14 MPNST patients. The 5-y overall survival rate was 46.8%. Three patients with low-grade MPNST were alive without disease at the time of this report. In 9 patients in which pNF and MPNST co-existed, 2 showed a higher SUVmax of pNF than that of MPNST. Natural history analysis of pNF (n = 43) revealed that no factors significantly correlated with increased tumor size. Nine lesions other than neurogenic tumors were detected by PET/CT including 5 thyroid lesions and 3 malignant neoplasms. This study revealed the usefulness and limitation of PET/CT for NF1 patients. In the future, it will be necessary to study how to detect over time the malignant transformation of pNF to MPNST, via an intermediate tumor.

Clinical value of serum bone resorption markers for predicting clinical outcomes after use of bone modifying agents in metastatic bone tumors: A prospective cohort study.

Bone modifying agents (BMAs) have become a standard treatment to prevent skeletal-related events (SREs) in bone metastases (BMs). The aim of our study is to determine the clinical value of serum bone resorption markers for predicting clinical outcomes after using BMAs in patients with BM. Patients were enrolled between May 2013 and October 2017 at the Nagoya University Hospital, Japan. We prospectively observed changes in pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) during treatment with BMAs. The relationship between serum markers before and after treatment and clinical outcomes such as progression of bone disease (BD), SREs and overall survival (OS) were evaluated. Pearson chi-square test and Kaplan-Meier product limit methods were used for analysis. Sixty-seven patients were analyzed. The primary tumor sites were 21 lung, 16 breast and 30 others. Forty and 27 patients were treated with Denosumab and Zoledronic acid, respectively. Progression of BDs, SREs and death were observed in 10, 16 and 31 cases, respectively. The median follow-up period after using BMAs was 12.3 (range 0.3-66.3) months. ICTP at 3-4 weeks was significantly correlated with increasing BD progression, SREs and death after treatment in both the whole and lung cancer cohorts. Base line ICTP and TRACP-5b were also associated with increasing BD progression in the whole cohort. Our study showed that early posttreatment ICTP is useful for predicting BD progression, SREs and OS after use of BMAs in patients with BM and even in patients with lung cancer BM.

Desmoid with biweekly methotrexate and vinblastine shows similar effects to weekly administration: A phase II clinical trial.

Low-dose methotrexate (MTX) plus vinblastine (VBL) chemotherapy is an effective treatment for desmoid-type fibromatosis (DF). However, previous reports have described a weekly regimen, with no reports available on a biweekly one. The aim of this study was to determine the clinical outcomes of a biweekly regimen in a cohort prospectively treated in our single institution. Since 2010, we have prospectively treated refractory DF patients with biweekly MTX (30 mg/m2 ) + VBL (6 mg/m2 ). Efficacy, progression-free survival (PFS), and correlating factors were analyzed. Adverse events (AEs) were recorded. In total, 38 patients received low-dose MTX + VBL therapy, and its efficacy was assessed in 37 of them. Nineteen (51%) patients showed partial response (PR). Clinical benefit rate was 95%. PFS at 5 y was 80.8%. In PR cases, median time to response was 10 mo. Longer duration of therapy was significantly associated with the response of PR (P = .007) by univariate analysis. There was no clear association between various clinicopathological factors, including tumor size, location, catenin beta-1 (CTNNB1) mutation status with effect. Only 3 AEs of grade 3/4 were observed. Tumor regrowth after MTX + VBL discontinuation was observed in 5 (20%) of 25 patients. Biweekly administration of MTX + VBL chemotherapy was well tolerated compared with weekly administration, and its efficacy was anticipated in DF patents, although the time needed to achieve a response may be relatively long. The treatment interval should be determined taking into account both the condition of the tumor and the patient's preference.

Functional evaluation following deltoid muscle resection in patients with soft tissue sarcoma.

BACKGROUND: The present study aimed to determine functional outcomes in patients undergoing deltoid muscle resection for soft tissue sarcoma. METHODS: Between 2002 and 2014, 18 patients with soft tissue sarcoma of the shoulder who underwent wide resection including the deltoid muscle, and were followed up for more than 12 months, were retrospectively included in the study. In all, 11 patients were male and 7 were female. The median age was 59 years, median follow-up duration was 37 months. The extent of resection of deltoid muscle, with or without rotator cuff damage, reconstruction methods, adjuvant therapy, oncological outcomes, and the International Society of Limb Salvage (ISOLS) score as functional outcomes were analyzed. RESULTS: Six patients underwent total resection, and twelve underwent partial resections of deltoid muscle. The rotator cuff was resected in four patients. Soft tissue reconstruction was performed in 17 patients using a pedicled latissimus dorsi muscle flap. Two local recurrences and three distant metastases occurred during follow-up. Median overall survival was 72 months. The mean ISOLS score was 25.0 points (±4.6points). Univariate analysis revealed that there was no significant difference in ISOLS score regarding the extent of deltoid muscle resection. Multivariate analysis identified only combined resection of the rotator cuff as a significant prognostic factor for poor functional outcomes (P < 0.001). CONCLUSIONS: The extent of resection of the deltoid muscle might not affect the functional outcomes determined by ISOLS score. If the rotator cuff is resected concurrently, satisfactory functional outcomes might not be obtained.

Cardiac metastases from primary myxoid liposarcoma of the thigh: a case report.

BACKGROUND: Myxoid liposarcoma is well known to have an unusual proclivity for extrapulmonary metastasis. However, cardiac metastasis of myxoid liposarcoma is very rare, even in patients with advanced disease. CASE PRESENTATION: A 40-year-old man was diagnosed with myxoid liposarcoma of the right thigh and treated with wide resection. Two years after the surgery, a low-density area in the left ventricle was found on follow-up chest computed tomography, and was suspected of being metastatic disease. He underwent surgical treatment, and the lesion was pathologically confirmed as metastasis of myxoid liposarcoma. Fifteen months later, he complained of slight dyspnea and developed metastatic disease in the right atrium. He was treated with surgical excision, followed by radiotherapy. Although there was no recurrence in the heart since the second cardiac metastasectomy, multiple metastases occurred in the abdominal cavity, lungs, and muscles. He finally died of the disease 2 years after the second cardiac metastasectomy. CONCLUSION: We experienced a case of primary myxoid liposarcoma in the thigh, accompanied by ectopic and metachronous cardiac metastases. Although this condition is rare, we should follow-up patients with myxoid liposarcoma, considering the possibility of cardiac metastasis.

Predictors of complications in heat-treated autograft reconstruction after intercalary resection for malignant musculoskeletal tumors of the extremity.

BACKGROUND: Biological reconstruction with recycled heat-treated autografts has been an option for a segmental skeletal defect after intercalary resection for malignant musculoskeletal tumors in the extremity. This study was undertaken to evaluate the clinical outcomes in patients treated with this procedure and identify factors affecting the incidence of complications. METHODS: We retrospectively reviewed 24 patients treated with heat-treated autografts after intercalary resection at our institution between 1992 and 2015. RESULTS: The survival rate of the heat-treated autografts was 70.1% at 10 years. Of the 48 host-graft junctions in the 24 patients, nonunion occurred in 18 junctions (38%). In the univariate analysis, location in the upper extremity, intercalary grafts without vascularized fibula autografts (VFG), and junction at the diaphysis significantly increased the rate of nonunion (P = 0.003, P = 0.003, and P = 0.031, respectively). Location in the upper extremity was an independent factor associated with nonunion in the multivariate analysis (P = 0.006). Upper extremity location and intercalary grafts without VFG were also significant factors for bone absorption (P = 0.042 and P < 0.001, respectively). CONCLUSIONS: Our results can provide useful information to devise possibly novel clinical approaches to patients requiring intercalary reconstruction of the extremity.

Single metastasis of myxoid liposarcoma from the thigh to thyroid gland: a case report.

BACKGROUND: Thyroid metastasis of soft tissue sarcoma is very rare, and the diagnosis is especially difficult when only a single lesion is present. CASE PRESENTATION: A 50-year-old man was diagnosed with myxoid liposarcoma of the right thigh and treated with wide resection. Two and a half years after the surgery, a growing low-density area was incidentally observed in the right lobe of his thyroid gland on follow-up chest computed tomography. Fine needle aspiration biopsy was performed twice, and the thyroid mass was suspected of being a sarcoma metastasis. He was treated by hemithyroidectomy, and the lesion was pathologically confirmed as a metastasis of myxoid liposarcoma. CONCLUSION: We experienced single thyroid gland metastasis in patients with myxoid liposarcoma in whom a growing mass is observed in the thyroid gland after radical surgery of the primary site.

Antitumor effects of 4-methylumbelliferone, a hyaluronan synthesis inhibitor, on malignant peripheral nerve sheath tumor.

Hyaluronan (HA) has been shown to play important roles in the growth, invasion and metastasis of malignant tumors. Our previous study showing that high HA expression in malignant peripheral nerve sheath tumors (MPNST) is predictive of poor patient prognosis, prompted us to speculate that inhibition of HA synthesis in MPNST might suppress the tumorigenicity. The aim of our study was to investigate the antitumor effects of 4-methylumbelliferone (MU), an HA synthesis inhibitor, on human MPNST cells and tissues. The effects of MU on HA accumulation and tumorigenicity in MPNST cells were analyzed in the presence or absence of MU in an in vitro as well as in vivo xenograft model using human MPNST cell lines, sNF96.2 (primary recurrent) and sNF02.2 (metastatic). MU significantly inhibited cell proliferation, migration and invasion in both MPNST cell lines. HA binding protein (HABP) staining, particle exclusion assay and quantification of HA revealed that MU significantly decreased HA accumulation in the cytoplasms and pericellular matrices in both MPNST cell lines. The expression levels of HA synthase2 (HAS2) and HA synthase3 (HAS3) mRNA were downregulated after treatment with MU. MU induced apoptosis of sNF96.2 cells, but not sNF02.2 cells. MU administration significantly inhibited the tumor growth of sNF96.2 cells in the mouse xenograft model. To the best of our knowledge, our study demonstrates for the first time the antitumor effects of MU on human MPNST mediated by inhibition of HA synthesis. Our results suggest that MU may be a promising agent with novel antitumor mechanisms for MPNST.

Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis.

Pigmented villonodular synovitis (PVNS) is a benign, translocation-derived neoplasm. Because of its high local recurrence rate after surgery and occurrence of osteochondral destruction, a novel therapeutic target is required. The present study aimed to evaluate the significance of protein expression possibly associated with the pathogenesis during the clinical course of PVNS. In 40 cases of PVNS, positivity of colony-stimulated factor 1 (CSF1), its receptor (CSF1R), and receptor activator of nuclear factor kappa-B ligand (RANKL) were immunohistochemically determined. The relationship between the positivity and clinical outcomes was investigated. High positivity of CSF1 staining intensity was associated with an increased incidence of osteochondral lesions (bone erosion and osteoarthritis) (p = 0.009), but not with the rate of local recurrence. Positivity of CSF1R and RANKL staining was not associated with any clinical variables. The number of giant cells was not correlated with positivity of any of the three proteins, or with the clinical outcome. Focusing on knee cases, CSF1 positivity was also associated with the incidence of osteochondal change (p = 0.02). CSF1R positivity was high in cases which had local recurrence, but not significantly so (p = 0.129). Determination of CSF1 and CSF1R expression may be useful as a prognosticator of the clinical course and/or outcomes of PVNS.

In vivo heat-stimulus-triggered osteogenesis.

Several studies have reported that heat stress stimulates the activity of osteoblastic cells in vitro. However, few have addressed the effects of heat stress on osteogenesis in vivo, nor have the optimal temperatures for bone formation been determined. The aim of the present study was to investigate the effects of hyperthermia treatment on osteogenesis in a rat tibial defect model. Forty-four Sprague Dawley rats were divided into two groups with or without hyperthermia treatment. A 3-mm circular defect in the proximal tibia filled with magnetite cationic liposomes embedded in alginate beads was subjected to hyperthermia treatment (43-46 °C). Radiological assessment at 2 weeks after the treatment showed that significantly stimulated osteogenesis was observed in the hyperthermia group as compared to the control group (p = 0.003). Histomorphometrical analysis at 2 weeks revealed a significant increase of newly formed bone in the hyperthermia group, compared with the control group (p < 0.001). Area of newly formed bone in each hyperthermia group was significantly increased as compared with the control group (43 °C; p = 0.005, 44 °C; p = 0.019, 45 °C; p = 0.003, and 46 °C; p = 0.003, respectively). Alkaline phosphatase was overexpressed at the surfaces of newly formed bone adjacent to magnetite cationic liposome implantation. Our results demonstrate for the first time that heat stimulus accelerates osteogenesis in vivo, and may thus be of interest as a novel and promising tool to induce osteogenesis clinically as well.

Low-dose chemotherapy with methotrexate and vinblastine for patients with desmoid tumors: relationship to CTNNB1 mutation status.

BACKGROUND: This study was conducted to determine the efficacy and safety of low-dose chemotherapy with methotrexate (MTX) and vinblastine (VBL) for patients with desmoid tumors refractory to meloxicam treatment, focusing in particular on the relationship between the efficacy of this chemotherapy and catenin ß-1 (CTNNB1) mutation status. PATIENTS AND METHODS: Since March 2003, patients pathologically diagnosed with extraperitoneal desmoid tumors have been prospectively treated with meloxicam, a COX-2 inhibitor, at our institution. Patients with inoperable tumors who were resistant to meloxicam treatment underwent MTX and VBL therapy every other week. The responses of all patients were evaluated, and factors that were correlated with efficacy were analyzed, including CTNNB1 mutation status. RESULTS: Sixty-eight patients were prospectively treated with meloxicam. MTX + VBL therapy was administered in 15 patients. Six patients showed a partial response. Only one patient presented disease progression. A few patients showed grade 3-4 treatment-related toxicity with the administration of MTX and VBL every other week. Intriguingly, CTNNB1 status did not affect the efficacy of this treatment. CONCLUSION: MTX and VBL treatment every other week is well tolerated and achieved a favorable response in patients resistant to meloxicam treatment, regardless of CTNNB1 mutation status.

EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma.

Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.

Nuclear expression of ß-catenin predicts the efficacy of meloxicam treatment for patients with sporadic desmoid tumors.

This study aimed to determine the prevalence of ß-catenin nuclear positivity as a prognostic factor in patients with desmoid tumors (DTs) treated with meloxicam, a cyclooxygenase-2 (COX-2) selective inhibitor. Between 2003 and 2012, consecutive 31 patients with extraabdominal, sporadic DTs were prospectively treated with meloxicam as a systemic medical therapy. Immunohistochemistry was performed on formalin-fixed material to quantify the nuclear expression of ß-catenin and Ki-67, and cytoplasmic expression of COX-2. All clinicopathological characteristics including the intensity of immunohistochemical staining were analyzed with respect to their prognostic value for meloxicam treatment. Of the 31 patients with meloxicam treatment, there was 1 with complete remission (CR), 7 with partial remission (PR), 12 with stable disease (SD), and 11 with progressive disease (PD). Higher nuclear expression of ß-catenin was significantly associated with a poor response (PD/SD) (p = 0.017). The positivity of COX-2 and Ki-67 and none of the other clinical variables were associated with prognosis. The nuclear expression of ß-catenin can predict the efficacy of meloxicam treatment for patients with sporadic DTs.

Potential drug interactions between pazopanib and proton pump inhibitors/potassium-competitive acid blockers in patients with soft tissue sarcoma.

Because absorption of the oral drug pazopanib depends on gastric pH, concomitant use of proton pump inhibitors (PPIs)/potassium-competitive acid blockers (P-CABs) may inhibit pazopanib absorption by elevating the gastric pH. This study investigated to what extent the concomitant use of PPIs/P-CABs affects treatment with pazopanib in patients with soft tissue sarcoma. We retrospectively reviewed the medical records of patients with soft tissue sarcoma who had received at least one dose of pazopanib at our institution, among which those who had received concomitant PPIs/P-CABs were included in this analysis. Using paired sample t tests, the frequency of dose reduction or interruption of pazopanib and the major adverse events (AEs) were compared in each patient between periods with and without PPIs/P-CABs. Between January 2018 and December 2022, eight patients were eligible. The median time to treatment failure (TTF) was 3.9 months (2.1-38.2 months). Two patients received concomitant PPIs/P-CABs throughout their treatment with pazopanib. Among the other six patients, dose reduction or interruption of pazopanib occurred less frequently (P = 0.021), and neutropenia tended to be milder (P = 0.155) with the concomitant use of PPIs/P-CABs. Although the concomitant use of PPIs/P-CABs had no apparent effect on TTF in patients undergoing pazopanib treatment, dose reduction or interruption of pazopanib occurred less frequently, and neutropenia was milder, suggesting that concomitant use of PPIs/P-CABs might decrease the pharmacological activity of pazopanib. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-023-00638-2.

Clinical results of active surveillance for extra-abdominal desmoid-type fibromatosis.

BACKGROUND: The treatment of choice for desmoid-type fibromatosis (DF) has been changed to active surveillance (AS). However, few studies have reported clinical outcomes of AS modality in Asian countries. This study aimed to clarify the significance of AS as a DF treatment modality. METHODS: A total of 168 lesions from 162 patients with extra-abdominal DF were included. The mean age at diagnosis was 39 years (1-88 years), and the median maximum tumor diameter at the first visit was 64.1 mm (13.2-255.8 mm). The clinical outcomes of AS and the risk factors requiring active treatment (AT) (defined as an event) from AS modality were investigated. RESULTS: Of the 168 lesions, 94 (56%) were able to continue AS, with a 5-year event-free survival of 54.8%. Of the 68 lesions with PD, 21 (30.9%) lesions were able to continue AS. Neck location (p = 0.043) and CTNNB1 S45F mutation (p = 0.003) were significantly associated with the transition to AT, and S45F mutation was a significant factor associated with the transition to AT by multivariate analysis (hazard ratio: 1.96, p = 0.048). AT outcomes after AS were evaluable in 65 lesions, and 49 (75%) lesions did not require a transition to a second AT. CONCLUSIONS: AS was revealed as an effective treatment modality. The transition to AT needs to be considered for neck location and CTNNB1 S45F mutation DF. Good results can be obtained by selecting a treatment method that considers the tumor location even in cases that require intervention.

Hyaluronan in articular cartilage: Analysis of hip osteoarthritis and osteonecrosis of femoral head.

Hyaluronan (HA) plays crucial roles in the maintenance of high-quality cartilage extracellular matrix. Several studies have reported the HA in synovial fluid in patients with osteoarthritis (OA), but few have described the changes of HA in articular cartilage of OA or idiopathic osteonecrosis of the femoral head (ONFH). KIAA1199 was recently reported to have strong hyaluronidase activity. The aim of this study was to clarify the HA metabolism in OA and ONFH, particularly the involvement of KIAA1199. Immunohistochemical analysis of KIAA1199 and HA deposition was performed for human OA (n = 10), ONFH (n = 10), and control cartilage (n = 7). The concentration and molecular weight (MW) of HA were determined by competitive HA ELISA and Chromatography, respectively. Regarding HA metabolism-related molecules, HAS1, HAS2, HAS3, HYAL1, HYAL2, and KIAA1199 gene expression was assessed by reverse transcriptase polymerase chain reaction. Histological analysis showed the overexpression of KIAA1199 in OA cartilage, which was accompanied by decreased hyaluronic acid binding protein (HABP) staining compared with ONFH and control. Little KIAA1199 expression was observed in cartilage at the collapsed area of ONFH, which was accompanied by a slight decrease in HABP staining. The messenger RNA (​​​​​mRNA) expression of HAS2 and KIAA1199 was upregulated in OA cartilage, while the mRNA expression of genes related to HA catabolism in ONFH cartilage showed mostly a downward trend. The MW of HA in OA cartilage increased while that in ONFH cartilage decreased. HA metabolism in ONFH is suggested to be generally indolent, and is activated in OA including high expression of KIAA1199. Interestingly, MW of HA in OA cartilage was not reduced.