Anti-programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1) drugs have been used clinically, including those for skin cancer, with reasonable efficacy. Despite extensive ongoing research on bone and soft tissue sarcomas, there is a paucity of reviews that present a coherent picture. The present article is a comprehensive narrative review on the role of the PD-1/PD-L1 immune checkpoint in bone and soft tissue tumors. The review outlines the biological functions and mechanisms of action of PD-1/PD-L1 and its expression and clinical significance in various tumor types, including osteosarcoma and soft tissue sarcoma. Clinical trial results of immune checkpoint inhibitors, their association with prognosis, mechanisms of resistance to therapy, immune-related adverse events, and their potential in combination therapies, were also discussed.

Pathological fractures of benign bone tumors can be difficult to treat, and the underlying pathogenesis remains unclear. Herein, we aimed to determine preventive measures for pathological fractures in patients with benign bone tumors based on fracture outcomes. Between April 2015 and July 2023, we enrolled 18 consecutive patients with oncological pathological fractures treated at our department. Age, sex, histopathological diagnosis, site of origin, whether incisional or pathological fracture, treatment, operative time, blood loss, recurrence, and characteristics of impending and pathological fractures were examined. The median patient age was 22 years, comprising 9 males and 9 females. The pathology included bone cysts (n = 6), enchondromas (n = 5), fibrous dysplasia (n = 4), giant cell tumors (n = 2), and aneurysm bone cysts (n = 1). Six cases involved the humerus, 5 the femur, 3 the phalanges, 2 the toes, 1 the ribs, and 1 the tibia. Five and 13 cases were impending and pathological fractures, respectively. Thirteen patients underwent surgery, whereas 5 were treated conservatively. Surgical methods included curettage and artificial bone graft (n = 6); curettage and artificial bone graft plus compression hip screw fixation (n = 3); and curettage and artificial bone graft plus plate fixation, intramedullary nail, artificial head replacement, and plate fixation (n = 1 case each). The mean operative time and blood loss were 76 ± 56 minutes and 10 ± 80.1 mL, respectively. Recurrence occurred in 1 case. All impending fractures had onset in the lower extremity bones. Pathological fractures due to benign bone tumors of the lower extremities should not be overlooked as symptoms of pain.

BACKGROUND/AIM: This study aimed to assess the status of medical collaboration between our hospital and affiliated institutions based on referral letters for patients with osteosarcoma. PATIENTS AND METHODS: A single-center retrospective analysis of osteosarcoma referrals was conducted between September 1, 2012, and March 31, 2023. Fourteen patients were included (eight males, six females; mean age=28 years, range=8-74 years) each with a pathologically confirmed diagnosis of a malignant soft-tissue tumor and available referral documentation from previous physicians. Survey parameters included type of referral hospital, geographical area, and medical department of the referral hospital, as well as imaging and blood tests conducted and the corresponding findings. RESULTS: Patients were referred from various medical institutions: Six from general hospitals, six from clinics, one from a university hospital, and one from a clinic with beds. Most patients (n=10) were from southern Osaka. Among the referrals, 11 patients were referred to orthopedics, two to surgery, and one to pediatrics. Analysis of imaging studies showed eight patients with only radiographs; three patients with radiographs, computed tomography (CT), and magnetic resonance imaging (MRI); one patient with only CT; one patient with only MRI; and one patient with both radiographs and CT. Imaging findings included indications of suspected malignancy in 12 patients and suspected bone tumors in two. Blood tests were conducted in two patients, namely alkaline phosphatase and C-reactive protein, and alkaline phosphatase and lactate dehydrogenase, respectively. Blood tests were not performed in the remaining 12 patients. CONCLUSION: Referrals for patients with osteosarcoma at our facility and related facilities were well documented, ensuring informative content and adequate medical coordination.

Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited.

Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%-70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care.

BACKGROUND: We conduct a retrospective analysis of patients with pathological fractures resulting from upper extremity malignancies, focusing on the evaluation of treatment strategies employed. MATERIALS AND METHODS: We retrospectively studied 10 patients with metastatic bone tumors of the upper extremities. The study variables included tumor site, primary pathology, duration from the first diagnosis of the primary lesion to the occurrence of the pathological fracture, use of bone-modifying drugs, surgical technique, adjuvant therapy, postoperative functional assessment, Katagiri's score, American Society of Anesthesiologists physical status (ASA-PS), outcome, and correlations between the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and Musculoskeletal Tumor Society (MSTS) score. RESULTS: The sites involved were the humerus and radius in eight and two patients, respectively. Primary pathologies were liver cancer in three patients, lung cancer and renal cancer in two patients each, and one patient each with multiple myeloma, plasmacytoma, and Hodgkin's lymphoma. Nine patients experienced pathological fractures, and one had an impending fracture. The median time from primary tumor diagnosis to fracture was 12.5 months. Bone-modifying drugs were administered in all cases. Surgical procedures included intramedullary nails in seven patients and plate fixation in two. Chemotherapy served as adjuvant therapy in nine cases. The mean MSTS score was 26.5, and Katagiri's score averaged 6. The median ASA-PS stood at 2. Outcomes showed seven patients alive with disease and three dead from disease. A significant association between the ECOG-PS and MSTS score was not observed. CONCLUSION: Pathological fractures caused by malignant bone tumors of the upper extremity should be treated proactively with surgery regardless of prognosis.

As managing pathological fractures of the extremities can be difficult, the present study aimed to present a treatment algorithm for lower extremity bone malignancies. A total of 38 patients with impending and pathological fractures were treated at the Department of Orthopedic Surgery in Kindai University Hospital. Age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcomes, follow-up period and the MSTS scores and ECOG-PS were compared in cases of primary malignant tumors and those cases of metastatic malignant tumors were retrospectively surveyed. Post-treatment MSTS scores in cases of impending and pathological fractures were compared between intramedullary nail fixation and non-intramedullary nail fixation procedures. Disease sites included the sub-trochanteric femur in 10 patients, trochanteric femur in 8, femoral diaphysis in 7, femoral neck in 5, bilateral trochanteric femur in 3, proximal tibia in 3 and distal femur in 2 patients. A total of 10 patients had metastases between 3-20 sites. The median pre-fracture ECOG-PS score was 1. Adjuvant radiotherapy was administered to 5, chemotherapy to 8 and radiotherapy with chemotherapy to 10 patients. Surgical procedures included intramedullary nails in 18 patients, tumor arthroplasty in 4, plate fixation in 3, artificial head replacement in three, compression hip screw (CHS) in 3, conservative treatment in 2, bilateral intramedullary nail fixation in 2 and artificial bone stem with combined intramedullary nail and plate fixation, right-sided artificial head replacement and left-sided CHS in 1 patient each. The MSTS score was 19.9±8.95 for intramedullary nail fixation and 24.3±7.45 for other procedures, with a negative association between the MSTS score and pre-fracture ECOG-PS. The median follow-up period was 8 months. The outcomes were as follows: Alive with disease, 23 patients; continued disease-free, 1 patient; and dead due to disease, 14 patients. The 1-year postoperative overall survival rate was 60.5%. Moreover, the group with metastatic malignant tumors, which had significantly worse ECOG-PS, had significantly lower MSTS scores than the group with primary malignant tumors. The authors' treatment algorithm for malignant bone tumors of the lower extremity was shown to be useful.

BACKGROUND: Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient's demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review. METHODS: A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up. RESULTS: Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome. CONCLUSION: Long-term monitoring for potential complications remains necessary.

BACKGROUND: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan. METHODS: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients). RESULTS: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis. CONCLUSIONS: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group.

A high prevalence of proximal femoral metastases persists in patients with cancer, particularly regarding lower extremity fractures. This study offers a detailed analysis of clinical characteristics of patients undergoing surgical treatment for pathological or impending fractures, enhancing treatment strategies for metastatic malignancies. A total of thirty patients who underwent treatment of impending and pathological fractures at Kindai University Hospital (Osakasayama, Japan) were included. The retrospective study comprised parameters including age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcome and follow-up period. Post-treatment MSTS scores were compared in cases of impending and pathological fractures, and between intramedullary nailing and other surgical procedures. In addition, one-year postoperative survival rates were calculated. Furthermore, operative time, blood loss and survival rates were compared between impending and pathological fractures. The participants' median age was 70.5 years, with disease sites primarily in the subtrochanteric femur, trochanteric femur, femoral diaphysis, femoral neck and other locations. Pathologies included multiple myeloma and unknown primary, lung, breast, kidney, liver, gastric, esophageal and uterine cancers. The median ECOG-PS score pre-fracture was 2. Treatment approaches involved radiotherapy, chemotherapy and a combination of both. Surgical interventions included intramedullary nailing (16 cases), endoprosthesis (1 case), bipolar head replacement (3 cases) and compression hip screw (3 cases), among others. A negative correlation (R=-0.63) existed between MSTS and pre-fracture ECOG-PS scores. The operative time was significantly shorter in impending than in pathological fractures, with impending fractures showing significantly lower blood loss. The treatment algorithm for malignant bone tumors of the lower extremity provided in the present study was efficient, potentially optimizing treatment strategies for such cases, and contributing to improved patient care and outcomes in oncology and orthopedic surgery.

An eight-year-old female presenting with posterior neck pain and torticollis who had been diagnosed with coronavirus disease 2019 (COVID-19) three weeks earlier was radiographed and diagnosed with atlantoaxial rotatory fixation (AARF). Following treatment with non-steroidal anti-inflammatory drugs (NSAIDs), the posterior neck pain improved, and the torticollis was cured. Symptoms returned after two weeks, and computed tomography showed a 3.94 mm atlantodental interval and axis rotation. The patient was diagnosed with AARF relapse; symptoms resolved spontaneously prior to subsequent examination, and no further relapses were observed. This case highlights the need for clinicians to be aware that AARF may develop after COVID-19. Treatment options should be carefully considered.

The involvement of New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma-associated antigen A4 (MAGE-A4) in soft-tissue sarcoma pathogenesis has recently been reported; however, their involvement in desmoid tumors (DTs) remains unknown. This study aimed to determine the involvement of NY-ESO-1 and MAGE-A4 in DTs. Immunostaining for β-catenin, NY-ESO-1, and MAGE-A4 was performed on DT biopsy specimens harvested at our institution. The positivity rate for each immune component was calculated. In addition, the correlations between the positivity rates for the immune molecules were investigated. The correlation between the positivity rate and age or longest diameter of each immune molecule was also investigated. β-catenin showed staining mainly in the tumor cell nuclei of DTs. Both NY-ESO-1 and MAGE-A4 showed staining in the nucleus, cytoplasm, and infiltrating lymphocytes of DT cells. The mean positive cell rates for β-catenin, NY-ESO-1, and MAGE-A4 were 43.9 ± 21.7, 30 ± 21.6, and 68.9 ± 20.8, respectively. A strong negative correlation was observed between β-catenin and MAGE-A4 positivity rates (r = -0.64). The positivity rates for NY-ESO-1 and MAGE-A4 showed a moderate positive correlation (r = -0.42). A very strong negative correlation was observed between age and the NY-ESO-1 positivity rate (r = -0.72). A weak negative correlation was observed between age and the MAGE-A4 positivity rate (r = -0.28). A medium negative correlation was observed between the longest tumor diameter and NY-ESO-1 positivity (r = -0.37). NY-ESO-1 and MAGE-A4 may be involved in the DT microenvironment. Thus, NY-ESO-1 and MAGE-A4 may be useful in the diagnosis of DT.

The details of immune molecules' expression in desmoid tumors (DTs) remain unclear. This study aimed to determine the expression status of the programmed death-1/programmed death ligand 1 (PD1/PD-L1) immune checkpoint mechanism in DTs. The study included patients with DTs (n=9) treated at our institution between April 2006 and December 2012. Immunostaining for CD4, CD8, PD-1, PD-L1, interleukin-2 (IL-2), and interferon-gamma (IFN-γ) was performed on pathological specimens harvested during the biopsy. The positivity rate of each immune component was calculated as the number of positive cells/total cells. The positivity rate was quantified and correlations between the positivity rates of each immune molecule were also investigated. Immune molecules other than PD-1 were stained in tumor cells and intra-tumor infiltrating lymphocytes. The mean ± SD expression rates of β-catenin, CD4, CD8, PD-1, PD-L1, IL-2, and IFN-ɤ were 43.9±18.9, 14.6±6.80, 0.75±4.70, 0±0, 5.1±6.73, 8.75±6.38, and 7.03±12.1, respectively. The correlation between β-catenin and CD4 was positively moderate (r=0.49); β-catenin and PD-L1, positively weak (r=0.25); CD4 and PD-L1, positively medium (r=0.36); CD8 and IL-2, positively medium (r=0.38); CD8 and IFN-ɤ, positively weak (r=0.28); and IL-2 and IFN-ɤ, positively medium (r=0.36). Our findings suggest that PD-L1-centered immune checkpoint mechanisms may be involved in the tumor microenvironment of DTs.

To introduce wrapping vancomycin-containing cement around a mega-prosthesis (MP) as a novel method to prevent prosthetic joint infection after reconstruction surgery for malignant bone and soft tissue tumors. Five patients with malignant bone and soft tissue tumors treated at our hospital from April 2009 to December 2019 were included. The average age was 71.4 years. Four males and one female were included. Three patients had a bone tumor, and two had a soft tissue tumor. Three right thighs and two left femurs were affected. These tumors were identified histologically as undifferentiated pleomorphic sarcoma, spindle cell sarcoma, diffuse large cell B-cell lymphoma, metastasis of renal cancer, and metastasis of lung cancer. All patients underwent tumor resection and reconstruction with a MP. In all cases, vancomycin-containing cement (2 g/40 g) was wrapped around the implant at the extension. The average follow-up period was 30.4 months. We surveyed whether infection occurred after surgical treatment. We also investigated the Musculoskeletal Tumor Society score and clinical outcome. We observed no postoperative infection. One case of local recurrence was observed, and a hip dissection was performed. The Musculoskeletal Tumor Society score was 79.26 ± 1.26 (mean ± standard deviation) (range: 76-80.3). Three patients remained disease-free, one survived but with disease, and one died of disease. Wrapping vancomycin-containing cement around the MP may be a useful method of preventing postoperative joint infections.

The prognosis for soft tissue sarcomas (STSs) is poor, especially for highly aggressive STSs, and the details of prognostic factors are unknown. This study aimed to investigate the prognostic factors for STSs in hematologic inflammatory markers. We included 22 patients with STSs treated at our institution. The STSs were histologically classified as follows: undifferentiated pleomorphic sarcoma, 7 cases; myxofibrosarcoma, 6 cases; and malignant peripheral nerve sheath tumor, 2 cases. The average patient age was 72.06 years. The numbers of patients who underwent each procedure were as follows: wide resection, 7; wide resection and flap, 2; marginal resection, 2; wide resection and radiation, 1; additional wide resection with flap, 1; wide resection and skin graft, 1; and radiotherapy only, 1. The median follow-up period was 26 months (3-92 months). The outcomes were as follows: continuous disease free, 6 cases; no evidence of disease, 6 cases; alive with disease, 1 case; and died of disease, 2 cases. Pretreatment blood examinations for C-reactive protein (CRP) and albumin levels; neutrophil, lymphocyte, and white blood cell (WBC) counts; and neutrophil/lymphocyte (N/L) ratio were investigated and correlated with tumor size, tissue grade, and maximum standardized uptake value (SUVmax). CRP level and neutrophil and WBC counts were positively correlated with tissue grade and SUVmax. N/L ratio was positively correlated with tumor size and SUVmax. CRP level, WBC and neutrophil counts, and N/L ratio may be poor prognostic factors for highly aggressive STSs.

There is no consensus on a treatment strategy for spinal giant cell tumor of bone (GCTB) because of the difficulty in their treatment. Treatment options often include the use of the controversial denosumab, an antibody therapy aimed at tumor shrinkage, different curettage techniques, resection, or a combination of these therapies. The current study aimed to identify treatment methods associated with favorable outcomes in patients with spinal GCTB. We retrospectively reviewed 5 patients with spinal GCTB, including patients with tumors of the sacrum, treated at our hospital between September 2011 and November 2020. Two men and 3 women were included in the study. The median follow-up period was 74 months (range: 14-108 months). We surveyed the tumor site, treatment method, denosumab use, and outcomes. The median age was 17 years (range: 17-42 years). There were 2 cases of sacral GCTB and 1 case each of lumbar, cervical, and thoracic vertebral GCTB. The comorbidities observed included hepatitis, malignant lymphoma, atopic dermatitis, and asthma. The treatment method included zoledronic acid after embolization and denosumab, denosumab only, curettage and posterior fusion, and curettage resection after embolization and anterior and posterior fusion. Denosumab was used in all cases. Three patients were continuously disease-free, 1 patient with no evidence of disease, and 1 patient alive with disease. Aggressive treatment, especially surgical treatment, may lead to good results in spinal GCTB.

Secondary osteosarcoma is a rare complication of primary malignancies and benign bone lesions. There are various types of diseases that cause secondary osteosarcoma. A 15-year-old male presented at our medical center complaining of pain and redness in the right lower leg. He had been diagnosed with osteofibrous dysplasia in the right tibia when he was 2 years old and since then had been followed up. Although he had a pathological fracture of the right tibia at the age of 7, his fracture healed with a plaster cast and did not require surgery. At the time of the patient's last visit, a radiograph revealed a periosteal reaction as well as erosion of the bone cortex. Magnetic resonance imaging revealed an infiltrative area in the soft tissue surrounding the osteofibrous dysplasia lesion in the tibia. Consequent to pathological examination (through bone biopsy), the patient was diagnosed with secondary osteosarcoma. The patient underwent chemotherapy and extensive resection with liquid nitrogen. He has been progressing satisfactorily after the operation. The present case is the first report of secondary osteosarcoma associated with osteofibrous dysplasia. During the long-term follow-up of osteofibrous dysplasia, oncologists should be aware of the possibility of secondary osteosarcoma.

RATIONALE: The genomic alteration of cutaneous angiosarcoma (cAS) is complex. Treatment efficacy of immunotherapy for cAS remains controversial and prognosis remains poor. Herein, we report a case of cAS with programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4. PATIENT CONCERNS: A 69-year-old man presented with a chief complaint of left thumb pain, with a soft tissue mass in the palmar side of the thumb. He had no past medical history. Three months prior, the man experienced the pain while scuba diving. He visited a nearby clinic, and magnetic resonance imaging revealed a soft tissue tumor on the palmar side of the thumb. He was referred to our hospital and a marginal excisional biopsy was performed. DIAGNOSIS: Pathological findings revealed an angiosarcoma with high-flow serpentine vessels. INTERVENTIONS: An excision was performed from the base of the thumb to achieve a wide margin. OUTCOMES: One year after the treatment, the patient has not experienced recurrence, metastasis, or complications. LESSONS: Histopathology of the excised specimen was positive for programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4; their expression may be a therapeutic target for cAS. Combining immunotherapy with surgical treatment may be effective for cAS.

The cancer/testis antigens (CTAs), New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen gene (MAGE)-A4 are normally restricted to male germ cells but are aberrantly expressed in several cancers. Considering the limited information regarding their significance in osteosarcoma (OS), the purpose of this study was to determine the clinical significance of NY-ESO-1 and MAGE-A4 expression in OS. Nine patients with OS treated at Kindai University Hospital were included in the study. The median age was 27 years, and median follow-up period was 40 months. The specimens obtained at the time of biopsy were used to perform immunostaining for NY-ESO, MAGE-A4, p53, and Ki-67. The positive cell rates and positive case rates of NY-ESO, MAGE-A4, p53, and Ki-67 were calculated. The correlation between the positive cell rate of immunohistochemical markers was also calculated. The correlation between the positive cell rate of NY-ESO-1 or MAGE-A4 and tumor size or maximum standardized uptake (SUV-max) was also determined. The positive cell rates of NY-ESO-1 or MAGE-A4 in continuous disease-free (CDF) cases were also compared with those in alive with disease (AWD) or dead of disease (DOD) cases. The average positive cell rates of NY-ESO, MAGEA4, p53, and Ki-67 were 71.7%, 85.1%, 16.2%, and 14.7%, and their positive case rates were 33.3%, 100%, 44.4%, and 100%, respectively. The positivity rates of NY-ESO-1 and p53 were strongly correlated, whereas those of NY-ESO-1 and Ki-67 were moderately correlated. The MAGE-A4 and p53 positivity rates and the MAGE-A4 and Ki-67 positive cell rates were both strongly correlated. The NY-ESO-1 and MAGE-A4 positivity rates were moderately correlated. The positive correlation between the NY-ESO-1 positive cell rate and tumor size was medium, and that between the MAGE-A4 positivity rate and SUV-max was very strong. There was no significant difference in the positive cell rates of NY-ESO-1 or MAGE-A4 between CDF cases and AWD or DOD cases. Overall, our results suggest that NY-ESO-1 and MAGE-A4 may be involved in the aggressiveness of OS.

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

INTRODUCTION: A giant cell tumor of soft tissue (GCST) is a benign soft tissue tumor that often occurs subcutaneously in the extremities. Rare cases of malignant GCST have been reported, but its pathogenesis remains unclear. PATIENTS CONCERNS: We report a case of a 68-year-old man who noticed a painless mass on his second toe one and a half years ago. He visited the Department of Dermatology at our hospital. Magnetic resonance imaging revealed a soft tissue tumor, surrounding the distal aspect of the second toe. DIAGNOSIS: A biopsy of the tumor was performed by a dermatologist, and it revealed a malignant giant cell tumor of the toe. INTERVENTIONS: He was referred to our department and underwent lay amputation for wide-margin resection. OUTCOMES: No recurrence or metastasis was observed 5 years after treatment. CONCLUSION: : Malignant GCST should be treated with wide-margin resection immediately after its diagnosis.

Immunotherapy has altered the treatment paradigm for soft tissue sarcomas (STSs). Considering the limited information regarding the clinical significance of immunohistochemical markers in STS, the purpose of this study was to determine the clinical significance of programmed cell death-1 (PD-1), PD ligand-1 (PD-L1), New York esophageal squamous cell carcinoma-1 (NY-ESO-1), and melanoma-associated antigen-A4 (MAGE-A4) expression in STSs. Twenty-two patients (median age, 72.5 years) with STSs treated at our hospital were included in this study. The specimens obtained at the time of biopsy were used to perform immunostaining for PD-1, PD-L1, NY-ESO, and MAGE-A4. The rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells and cases were calculated. The correlations among the positive cell rates of the immunohistochemical markers as well as their correlations with the histological grade, tumor size, or maximum standardized uptake (SUVmax) value were also determined. The average rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells were 4.39%, 28.0%, 18.2%, and 39.4%, respectively. Although the PD-1-positive cell rate showed no correlation with the rates of NY-ESO-1- and MAGE-A4-positive cells, the PD-L1-positive cell rates showed strong positive correlations with the rates of NY-ESO-1- and MAGE-A4-positive cells. PD-1-, PD-L1-, NY-ESO-1-, and MAGE-A4-positive cell rates showed weak to moderate correlations with histological grade or tumor size, while the PD-1-, PD-L1-, and MAGE-A4-positive cell rates showed strong to very strong positive correlations with the SUVmax value. Thus, PD-1, PD-L1, NY-ESO, and MAGE-A4 expressions are correlated and may be involved in the aggressive elements of STSs.

We aimed to investigate the clinical significance of the expression of NY-ESO-1 and MAGE-A4 in soft tissue sarcoma (STS). Immunostaining for NY-ESO-1, MAGE-A4, and Ki67 was performed using pathological specimens harvested from 10 undifferentiated pleomorphic sarcoma (UPS), nine myxofibrosarcoma (MFS), and three malignant peripheral nerve sheath tumor (MPNST) patients treated at our hospital. We examined the correlation of NY-ESO-1 and MAGE-A4 expression levels with tumor size, histological grade, and SUVmax values. Positive cell rates of various markers were also compared between patients in remission and those who were not in remission. The rates of cases positive for NY-ESO, MAGE-A4, and Ki67 were 50%, 63.6%, and 90.9%, respectively. The average rates of cells positive for NY-ESO, MAGE-A4, and Ki67 in all STS types were 18.2%, 39.4%, and 16.8%, respectively. A positive correlation was observed between rates of cells positive for NY-ESO-1 and MAGE-A4 and between NY-ESO-1 and MAGE-A4 expression levels and clinical features. There was no significant difference in the positive cell rate of NY-ESO-1 or MAGE-A4 between remission and non-remission cases. Our results suggest that NY-ESO-1 and MAGE-A4 expression may be useful for the diagnosis and prognostication of UPS, MFS, and MPNST.

Myxoid liposarcoma (MLPS) is known to have a variety of metastatic manifestations. We report a MLPS originating in the pelvis with metastasis to the calcaneus. The patient was a 72-year-old man who developed lumbar pain and right lower extremity pain 2 years ago. He visited a nearby clinic and underwent a radiographic examination. Computed tomography (CT) revealed a tumor in the right retroperitoneum. A CT-guided needle biopsy was performed, and pathological examination revealed myxoid liposarcoma. Wide surgical resection was not performed due to the patients' wishes, technical difficulties, and magnitude of the invasion, and the patient received heavy particle radiation therapy (HPRT) of 70.4 Gy. After HPRT, the tumor mass was slightly reduced. However, 11 months after HPRT, a recurrent lesion in the liver was observed. Although HPRT was performed again for the metastatic liver lesion (70.4 Gy), the tumor increased in size. Furthermore, 1 month later, the patient complained of pain in the left foot, and CT and magnetic resonance imaging revealed an osteolytic lesion in the calcaneus. A biopsy was performed, and pathological examination showed a metastatic lesion of myxoid-type liposarcoma. The patient wore a short lower limb orthosis and was able to walk but died 1 month later. Oncologists should note that MLPS can metastasize to the calcaneus.

ABSTRACT: Recent data suggest that programmed cell death -1 (PD-1) and programmed cell death ligand-1 (PD-L1) are involved in the pathogenesis of Langerhans cell histiocytoma (LCH); however, their contributions are not well established. Also, the involvement of PD-1/PD-L1 molecules in musculoskeletal LCH remains particularly unclear. The current study aims to characterize the involvement of PD-1/PD-L1 immune checkpoint system in the pathogenesis of musculoskeletal LCH. PD-1/PD-L1 expression was evaluated in 6 patients, 3 men and 3 women with a mean age of 13.5 years, with musculoskeletal LCH who were treated at Kindai University Hospital and Osaka Women's and Children's Hospital between November 2005 and December 2020. The median follow-up period for all patients with musculoskeletal LCH was 41 months. We surveyed symptoms, number of lesions, treatment modality, and outcomes. Immunostaining for CD4, CD8, PD-1, and PD-L1 was also performed on pathological specimens obtained by biopsy. Multiple lesions were observed in 5 cases, and a single lesion was observed in 1 case. The chief complaint in 5 cases was pain. Four patients underwent spontaneous regression. The other 2 patients received chemotherapy. The outcomes included continuous disease-free (n = 5) and alive with the disease (n = 1). The CD4-, CD8-, PD-1-, and PD-L1-positive rates among all specimens were 100%, 100%, 16.6%, and 83.3%, respectively. The CD4/PD-L1, CD8/PD-L1, and PD-1/PD-L1 positive rates in all the specimens were 83.3%, 83.3%, and 16.6%, respectively. We believe that the PD-1/PD-L1 immune checkpoint molecules may play some role in the microenvironment of musculoskeletal LCH.

Background: Biopsies are widely used for diagnosing metastatic tumors in the bone and soft tissues; however, their usefulness and limitations remain unclear. Patients and methods: Biopsies of patients (13 men, 8 women, mean age 76 years) with metastatic tumors in the bone (19 patients) and soft tissues (2 patients) were reviewed retrospectively. Investigators surveyed the lesion sites, medical histories, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), biopsy sites, methods, comorbidities, diagnoses, treatments, and outcomes. Results: Five patients had multiple lesions, and 16 patients had one lesion. The ECOG PS scores were PS0 (11 patients), PS1 (7 patients), PS2 (2 patients), and PS3 (1 patient). Biopsy sites included pelvic bone (6 cases), rib bone (5 cases), spinal vertebra (7 cases), soft tissue of the shoulder (2 cases), and inner retroperitoneum (1 case). Diagnostic methods included open biopsy (8 patients), core needle biopsy under general (7 patients) or local (3 patients) anesthesia, and computed tomography-guided core needle biopsy under local anesthesia (3 patients). Histology indicated hematological malignancies (9 cases); breast cancer (3 patients); lung cancer, renal cell cancer, cancer of unknown primary (2 cases each); prostate cancer, endometrial (uterine) cancer, and myxoid liposarcoma (1 case each). The primary site identification rate was 90.5%. Outcomes included three patients "dead of disease." Conclusion: Biopsies are useful for early diagnosis and for the scrutiny of primary lesions of metastatic bone and soft tissue tumors. If the primary tumor is still unknown after biopsy, evidence-based treatment should be initiated promptly.

Inhibitors of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint system are used for treating various malignancies. However, evidence on their use in soft tissue sarcomas (STS) is limited. This study aimed to retrospectively investigate the relationship between the expression of PD-1/PD-L1 and related antigens in STS, and their association with clinical characteristics. Immunostaining for CD4, CD8, PD-1, PD-L1, IL-2, and IFN-γ was performed using pathological specimens harvested at the time of biopsy from 10 patients with undifferentiated pleomorphic sarcoma (UPS), nine with myxofibrosarcoma (MFS), and three with malignant peripheral nerve sheath tumor (MPNST) who were treated at our hospital. Subsequently, the positive immunostaining cell rates were calculated. We also examined the correlation between each immune positive cell rate and age, tissue grade, size, and maximum standardized uptake (SUV-max) values. The 3-year event-free survival (EFS) and overall survival (OS) rates were compared between the positive and negative groups (positive rate >10%; negative <10%) for various immune stains. The positive rates were also compared between the presence and absence of events groups. There was positive staining for the immune checkpoint molecules in every STS type except for PD-1 in MPNST. CD4, CD8, and PD-1 stained lymphocytes in close proximity to the tumor in adjacent tissue sections. A positive correlation was observed between the positive cell rates of each immune component including inflammatory cytokines such as IL-2 and IFN-γ. Additionally, the clinical features positively correlated with the positive PD-1/PD-L1 expression rates. No significant differences in the 3-EFS and OS rates was observed between the PD-1/PD-L1 positive and negative groups. Our results suggest that an inducible immune checkpoint mechanism may be involved in UPS, MFS, and MPNST.

Background and Objectives: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells. LCH often involves the bone, and its clinical evidence is limited. The purpose of this study is to report on the treatment of LCH at our institution and to add to the evidence for LCH. Materials and Methods: We reviewed six cases of LCH treated in our hospital between November 2005 and February 2016. Patient age at the first visit, sex, site of origin, symptoms, image tools used for diagnosis, biopsy site, complications, treatment, and final clinical outcome were evaluated. The median follow-up period was 41 months. Results: The median patient age at the first visit was 13.5 years. Three male and three female individuals were enrolled. Multiple lesions were observed in five cases, and a solitary lesion was observed in one case. Pain was the chief complaint in five cases. Radiography was the most commonly used imaging tool. Bone scintigraphy or magnetic resonance imaging and positron emission tomography-computed tomography were also used to diagnose systematic LCH. Biopsy of the femur was performed in two cases, and biopsy of the tibia, lumbar vertebrae, rib, and radius was performed in one case each. Regarding comorbidities, one case of hepatitis B and one case of autism were observed. Chemotherapy was initiated in two patients. The other four patients were observed naturally. Continuous disease-free survival was observed in five patients. One patient remained alive but not without disease during the final follow-up examination. Conclusion: LCH should be diagnosed as early as possible to treat it appropriately.

Background: Metastasis to soft tissue is rare, and the pathogenesis remains unclear. Soft tissue metastases (STMs) have varied presentations; existing reports are few. Herein, we report a case of STMs of the shoulder with a rich characterization. Case presentation: A 93-year-old man presented to our hospital with pain and swelling of the left shoulder for one week. Magnetic resonance imaging (MRI) showed a T1 low-intensity and T2 high-intensity mass. We suspected a primary sarcoma and performed a needle biopsy. However, on histopathological examination, the findings were suggestive of lung adenocarcinoma. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography also revealed FDG accumulation in the right lung, thus confirming the diagnosis. Conclusion: Oncologists should keep in mind that STMs of lung cancer may resemble soft-tissue sarcomas at the time of initial diagnosis.

Undifferentiated pleomorphic sarcoma (UPS) is major type of soft tissue sarcomas. UPS presenting with inflammation is rare, and its pathophysiology remains unclear. Herein, we report a rare case of UPS with prolonged fever. A 91-year-old female complaining of high fever was referred to our hospital because of a high C-reactive protein (CRP) level of 12.51 mg/dL. She had been experiencing intermittent fevers for approximately 10 years. The fever of unknown origin worsened with time and went into remission with repeated antimicrobial therapy. She also had a mass on her central lower back over the sacral region for 6 years, which showed a gradual increase in size. The blood tests showed that the leukocyte count and neutrophils were 6.51 × 103 /µL and 70.3%, respectively. She had a 10 × 10 cm mass on her buttock that showed 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) accumulation on FDG-positron emission tomography-computed tomography examination (standardized uptake value-max value: 5.4). A blood culture examination was performed to rule out bacteremia, however, no bacteria were identified. We then performed a needle biopsy and confirmed the diagnosis of UPS; subsequently, the patient underwent a wide-margin resection. A few days after the surgery, her CRP, leukocyte, and neutrophil levels decreased to 0.305 mg/dL, 2.83 × 103/uL, and 50.1%, respectively. This case demonstrated that UPS with inflammation should be treated surgically as soon as possible after ruling out other sources of infection to achieve a favorable prognosis.

Soft tissue myoepitheliomas are often misdiagnosed due to their rarity. Herein, we describe a case of soft tissue myoepithelioma of the shoulder. A 72-year-old woman had a suspected sarcoma on her shoulder and under-went open biopsy. She was referred to our hospital, where the tumor was widely resected and the diagnosis of myoepithelioma was histologically confirmed. No recurrence has been observed in the 3 years since the sur-gery. Careful and prompt planning is necessary for the effective treatment of myoepithelioma.

Osteosarcoma (OS) is the most common malignant bone tumor and a leading cause of cancer-related deaths in children and adolescents. Current standard treatments for OS are a combination of preoperative chemotherapy, surgical resection, and adjuvant chemotherapy. Cisplatin is used as the standard chemotherapeutic for OS treatment, but it induces various adverse effects, limiting its clinical application. Improving treatment efficacy without increasing the cisplatin dosage is desirable. In the present study, we assessed the combined effect of ascorbate on cisplatin treatment using cultured human OS cells. Co-treatment with ascorbate induced greater suppression of OS cell but not nonmalignant cell proliferation. The chemosensitizing effect of ascorbate on cisplatin treatment was tightly linked to ROS production. Altered cellular redox state due to increased ROS production modified glycolysis and mitochondrial function in OS cells. In addition, OS cell sphere formation was markedly decreased, suggesting that ascorbate increased the treatment efficacy of cisplatin against stem-like cells in the cancer cell population. We also found that enhanced MYC signaling, ribosomal biogenesis, glycolysis, and mitochondrial respiration are key signatures in OS cells with cisplatin resistance. Furthermore, cisplatin resistance was reversed by ascorbate. Taken together, our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.

Salmonella infection predominantly causes four clinical syndromes: enteric fever, gastroenteritis, bacteremia, and asymptomatic carrier state. Salmonella osteomyelitis is an extremely rare manifestation of salmonella infection except in children with hemoglobinopathies. Salmonella osteomyelitis has been reported to mostly affect the diaphysis of long bones and lumbar spine. Here, we describe a case of salmonella osteomyelitis of the right 6th rib in a 74-year-old woman who presented with breast pain, swelling, high fever and local heat. Her medical history showed myocardial infarction; namely, at the age of 71, the patient had undergone the drug-eluting stent placement in the left anterior descending artery. A computed tomography (CT) scan at the first visit to another hospital showed a mass in the chest that invaded the ribs. 18F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging showed a lesion suspected to be a mammary malignant tumor. A needle biopsy revealed mesenchymal cells and suspected mammary sarcoma. However, the osteomyelitis of the rib was diagnosed when pyogenic tissue was observed during an open biopsy. The bacterial culture examination identified Salmonella enterica. Surgical drainage and antibiotic treatment were performed. Importantly, there was no evidence for any underlying disease that could lead to an immunocompromised status of the patient. To our knowledge, this is the first report of salmonella osteomyelitis of the rib presenting in an older female that required differentiation from a mammary tumor. Clinicians should consider rib osteomyelitis when they find swelling and local heat in the female's breast tissue and detect no cancerous tissue.

Recent data have suggested that PD-1 and PD-L1 are involved in osteosarcoma (OS) pathogenesis; however, their contributions are not well-established. Here, the PD-1/PD-L1 expression was evaluated in (OS) cases. Preoperative needle biopsy specimens were obtained from 16 patients with OS. Immunostaining for CD4, CD8, PD-1, and PD-L1 was performed on pathological specimens. Clinical parameters, including age, tumor size, preoperative alkaline phosphatase (ALP) level, standardized uptake value (SUV)-max level, and survival rate, were compared between PD-1/PD-L1-positive and -negative groups. CD4-, CD8-, PD-1-, and PD-L1-positive rates among all specimens were 75%, 75%, 18.7%, and 62.5%, respectively. The rates of co-expression of CD4 and CD8 with PD-L1 were 56.2% and 50%, respectively. Tumors were significantly larger in PD-L1-negative cases than in PD-L1-positive cases. Age, size and ALP and SUV-max levels did not differ significantly between PD-1/PD-L1-positive and -negative cases. The 3-year survival rates did not differ significantly between PD-1-positive and -negative cases or between PD-L1-positive and -negative cases. However, the occurrence of cancer-related events, including recurrence, metastasis, and death was associated with the PD-1-negative and PD-L1-positive status. The PD-1/PD-L1 checkpoint is likely involved in the immune microenvironment in OS and may be involved in the occurrence of cancer-related events.

OBJECTIVE: To examine the clinical features and outcomes of adolescent and young adult sarcoma patients who underwent surgical management and clarify important factors associated with prognosis. We reviewed 18 young adult sarcoma patients sarcoma patients treated surgically in our hospital. The tumor site, histology, grade, stage, and American Society of Anesthesiologists-Physical Status before surgery, operation time, intraoperative blood loss, complications, surgical margin, local recurrence, metastasis, and outcomes were investigated. The 3-year survival rate was also calculated. We compared survival based on age, grade, and surveyed features of poor outcome cases. RESULTS: The 3-year survival rate was 61.3%. There was no significant difference in survival based on age, grade, operation time, or intraoperative blood loss. Three of five patients who died of the disease had stage ≥ IV at diagnosis. All patients with R1 surgical margins developed recurrence and all those with an American Society of Anesthesiologists-Physical Status ≥ 2 died. Patients with late-stage sarcomas, R1 tumor margin, or high American Society of Anesthesiologists-Physical Status score had poor prognoses. To achieve a favorable outcome in adolescent and young adult sarcoma patients, early detection and obtaining R0 ≥ surgical margin are essential.

Purpose: This study aimed to evaluate the clinical features and outcomes of osteosarcoma to identify prognostic factors and determine new strategies to improve overall survival. Patients and Methods: We retrospectively analyzed 12 cases of osteosarcoma treated at our hospital from 2012 to 2017. Tumor site, tissue type, stage, treatments, adverse effects, postoperative limb function, surgical margin, and final outcomes were evaluated. Results: All patients received chemotherapy, and 10 underwent wide resection. The Musculoskeletal Tumor Society scores were more than good in all cases, and the 3-year survival rate was 73.3%. Two patients are alive with disease, eight have remained disease-free, and two died of the disease. Three of the four recurrent cases involved the pelvis. Conclusion: The treatment of primary osteosarcoma with wide resection in our department, therefore, yielded favorable outcomes. However, improved treatment strategies are needed for pelvic and advanced cases.

Salmonella osteomyelitis is extremely rare; only a few cases have been reported in healthy adults. We describe a case of salmonella osteomyelitis in an otherwise healthy 20-year-old Japanese woman who presented with distal tibial pain. X-ray and magnetic resonance imaging showed a lesion suspected to be a bone cyst. Osteomyelitis was diagnosed when pus was observed during an open biopsy. The bacterial culture examination yielded salmonella. Surgical drainage and antibiotic treatment were performed, after which no recurrence was observed. To our best knowledge, this is the first report of salmonella osteomyelitis of the distal tibia in an otherwise healthy individual.

Epithelial carcinomas occasionally have sarcomatous components that consist primarily of spindle and cuboidal cells, which often resemble osteoblasts. Sarcomatoid carcinomas consist of similar cells. Recent studies have characterized these phenomena as a manifestation of epithelial-mesenchymal transition in carcinoma cells, but the mesenchymal phenotypes that manifest in sarcomatous cells of epithelial carcinomas are not well understood. Here, we examined the expression profiles of four osteoblastic differentiation biomarkers in the sarcomatous components of multiple carcinoma types, including five renal clear cell, four breast invasive ductal, two esophageal, one maxillary squamous cell, three larynx, three lung, one liver, and one skin sarcomatoid carcinoma. Expression was analyzed by immunohistochemistry using antibodies against cell adhesion molecule 1, a member of the IgCAM superfamily, osterix transcription factor (Osterix), cluster of differentiation 151, a transmembrane 4 superfamily member, and alkaline phosphatase. Immunostaining intensity was rated in scale 0 (negative), 0.5 (weak), and 1 (strong) for each marker, and the four scale values were summed to calculate osteoblastic scores. In all, 10 cases had a osteoblastic score >= 3, and all of these 10 cases were cell adhesion molecule 1- and Osterix-positive. Eight and five of the nine samples with a osteoblastic score < 3 were negative for cell adhesion molecule 1 (p < 0.0001) and Osterix (p = 0.006), respectively. The other markers showed no statistical significance. These results indicate that osteoblastic differentiation can occur in carcinoma cells and that cell adhesion molecule 1 could be a useful marker for identifying this phenomenon in carcinoma tissues.

[Abstract] Between 1993 and 2010, 10 patients (4 men and 6 women ; 10 hips) underwent proximal femoral replacement secondary to metastatic disease using the Howmedica Modular Resection System. The mean age was 55 years (range : 24-68 years). The most common diagnosis (3 out of 10) was breast cancer. Five pathologic fractures were noted. Eight patients could ambulate with full weight-bearing postoperatively and an abduction brace was not necessary. Six patients died of their diseases at 6-30 months postoperatively. No dislocations, infections, nor reoperations occurred. Proximal femoral replacement provides excellent pain relief and good restoration of function when more simple reconstructive options are not feasible

It has been reported that vascular endothelial growth factor (VEGF) and its receptors play an important role in the destruction of articular cartilage in ostcoarthritis through increased production of matrix metalloproteinases. We investigated whether the oxidized low-density lipoprotein (ox-LDL) binding to lectin-like ox-LDL receptor-1 (LOX-1) upregulates VEGF expression in cultured bovine articular chondrocytes (BACs). Ox-LDL markedly increased VEGF mRNA expression and protein release in time- and dose-dependent manners, which was significantly suppressed by anti-LOX-1 antibody pretreatment. Activation of peroxisome proliferator-activated receptor (PPAR)-gamma was evident in BACs with ox-LDL addition and was attenuated by anti-LOX-1 antibody. The specific PPAR-gamma inhibitor GW9662 suppressed ox-LDL-induced VEGF expression. These results suggest that the ox-LDL/LOX-1 system upregulates VEGF expression in articular cartilage, at least in part, through activation of PPAR-gamma and supports the hypothesis that ox-LDL is involved in cartilage degradation via LOX-1. (c) 2006 Elsevier Inc. All rights reserved.

Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 mu g/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 mu g/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 mu g/mL ox-LDL significantly suppressed chondrocytes viability (84.6% 3.4% and 80.9% 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% 7.1% and 85.7% 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 mu g/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% 4.9% and 48.7% 6.7% of control at 24 h, respectively (n 3; p < 0.01 when compared with individual application of cyclic loading or 10 mu g/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Objective: To examine the effect of oxidized low-density lipoprotein (ox-LDL) on the intracellular production of reactive oxygen species (ROS) in bovine articular chondrocytes (BACs) and to investigate whether this increase occurs through binding to the receptor lectin-like ox-LDL receptor-1 (LOX-1). Furthermore, to ascertain whether the binding of ox-LDL to LOX-1 results in NF-kappaB activation. Design: BACs were preincubated with 2',7'-dichlorofluorescin diacetate (DCFH-DA), a dye that allows the monitoring of intracellular ROS production for DCF by spectrofluorometry. BACs were incubated with native LDL and ox-LDL (10, 50, and 100 mug/ml) for 5 min at 37degreesC and DCF formation was observed. BACs were also preincubated with anti-LOX-1 mAb (40 mug/ml) or ascorbic acid (10 t!V!). Nuclear extracts from BACs treated for the indicated periods with 50 mug/ml ox-LDL, and preincubated with anti-LOX-1 mAb or ascorbic acid, were prepared and analyzed by electrophoretic mobility shift assay (EMSA). Results: ox-LDL induced a significant dose-dependent increase in ROS production after 5-min incubation with BACs (P<0.001). ROS formation was markedly reduced in BACs preincubated with anti-LOX-1 mAb and ascorbic acid (P<0.001). Activation in BACs of the transcription factor NF-κB was evident after 5-min incubation with ox-LDL and was attenuated by anti-LOX-1 mAb and ascorbic acid. Conclusion: ox-LDL binding to LOX-1 in BACs increased the production of intracellular ROS and activated NF-κB. Reduction of NF-κB activation by ascorbic acid indicates that the activation, at least in part, is ROS-dependent. These observations support the hypothesis that hypercholesterolemia is one of several risk factors for arthritis, and that lipid peroxidation products such as ox-LDL are involved in cartilage matrix degradation. © 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

近年,血管内皮における酸化低比重リポ蛋白(ox-LDL)の特異的受容体として同定されたLOX-1(レクチン様酸化LDL受容体1)が軟骨細胞にも発現していることが示され,軟骨変性との関連が示唆されている.そこで本研究では高脂血症負荷が軟骨変性を促進するかどうかをin-vivoにおいて検討することとし,遺伝性高脂血症ウサギ(KHC)とコントロールとして日本白色ウサギ(JW)を用いて膝前十字靭帯と内側半月を切除して実験的変形性膝関節症を作成し,軟骨変性を組織学的に評価し,また免疫染色法によりox-LDLの局在とLOX-1の発現を検討した.その結果,KHCではSham手術側においても軟骨変性の進行を認めた.また手術側においてJWでは軟骨の表層・移行層の繊維化や細胞数増多が特徴的に認められたのに対し,KHCでは軟骨の菲薄化・細胞数減少が顕著であった.免疫染色ではKHC軟骨のSham側と両群の手術側にox-LDL,LOX-1の局在がみられた.塩基性線維芽細胞増殖因子(bFGF)は軟骨細胞の重要な成長因子であるが,免疫染色でbFGF陽性細胞率を検討したところKHCでは手術側,Sham側ともに有意に低下していた.また,JWより採取した培養軟骨細胞で検討したところ酸化LDLは経量的・経時的にbFGFmRNA発現を抑制した.本研究により高脂血症負荷は実験的変形性関節症を促進させることが示され,その増悪にはox-LDLの蓄積とLOX-1の発現,およびそれらによるbFGF発現抑制も関与している可能性が示された.本研究は近年世界的に肥満との関係などが注目されている関節症を,生活習慣病の一つである高脂血症負荷という観点からin-vivoにおいて捉えた報告ということができる.