Underlying synovial sarcoma undiagnosed for more than 20 years in a patient with regional pain: a case report.

Synovial sarcoma (SS) is a malignant tumor comprising 5-10% of all soft tissue sarcomas. SS has distinct characteristics, such as a predilection for young adults and relatively slow growth compared to other soft tissue sarcomas. Some patients with SS experience long-standing pain at the tumor site before the development of a palpable mass. Herein, we report the case of a 39-year-old woman with SS in the upper arm who presented with pain for > 20 years. The tumor detected on magnetic resonance imaging at 17 years was an SS. To the best of our knowledge, no English-language reports on imaging study-based identification of SS, which was undiagnosed for > 20 years, are known in the literature. This report discusses the imaging features of this latent lesion and the volume-doubling time of this unusual tumor.

Japanese orthopaedic association (JOA) clinical practice guidelines on the management of malignant bone tumors - Secondary publication.

BACKGROUND: In Japan, there are currently no general guidelines for the treatment of primary malignant bone tumors. Therefore, the Japanese Orthopaedic Association established a committee to develop guidelines for the appropriate diagnosis and treatment of primary malignant bone tumors for medical professionals in clinical practice. METHODS: The guidelines were developed in accordance with "Minds Clinical Practice Guideline Development Handbook 2014″ and "Minds Clinical Practice Guideline Development Manual 2017". The Japanese Orthopaedic Association's Bone and Soft Tissue Tumor Committee established guideline development and systematic review committees, drawing members from orthopedic specialists leading the diagnosis and treatment of bone and soft tissue tumors. Pediatricians, radiologists, and diagnostic pathologists were added to both committees because of the importance of multidisciplinary treatment. Based on the diagnosis and treatment algorithm for primary malignant bone tumors, important decision-making points were selected, and clinical questions (CQ) were determined. The strength of recommendation was rated on two levels and the strength of evidence was rated on four levels. The recommendations published were selected based on agreement by 70% or more of the voters. RESULTS: The guideline development committee examined the important clinical issues in the clinical algorithm and selected 22 CQs. The systematic review committee reviewed the evidence concerning each CQ and a clinical value judgment was added by experts. Eventually, 25 questions were published and the text of each recommendation was determined. CONCLUSION: Since primary malignant bone tumors are rare, there is a dearth of strong evidence based on randomized controlled trials, and recommendations cannot be applied to all the patients. In clinical practice, appropriate treatment of patients with primary malignant bone tumors should be based on the histopathological diagnosis and degree of progression of each case, using these guidelines as a reference.

Significantly earlier ambulation and reduced risk of near-falls with continuous infusion nerve blocks: a retrospective pilot study of adductor canal block compared to femoral nerve block in total knee arthroplasty.

BACKGROUND: Near-falls should be detected to prevent falls related to the earlier ambulation after Total knee arthroplasty (TKA). The quadriceps weakness with femoral nerve block (FNB) has led to a focus on adductor canal block (ACB). We purposed to examine the risk of falls and the earlier ambulation in each continuous infusion nerve block. METHODS: Continuous infusion nerve block (FNB or ACB) was performed until postoperative day (POD) 2 or 3. Pain levels and falls/near-falls with knee-buckling were monitored from POD 1 to POD 3. The score on the manual muscle test, MMT (0 to 5, 5 being normal), of the patients who could ambulate on POD 1, was investigated. RESULTS: A total of 73 TKA cases, 36 FNB and 37 ACB, met the inclusion criteria. No falls were noted. But episodes of near-falls with knee-buckling were witnessed in 14 (39%) cases in the FNB group and in 4 (11%) in the ACB group (p = 0.0068). In the ACB group, 81.1% of patients could ambulate with parallel bars on POD 1, while only 44.4% of FNB patients could do so (p = 0.0019). The quadriceps MMT values in the ACB group was 2.82, significantly higher than 1.97 in the FNB group (p = 0.0035). There were no significant differences in pain as measured with a numerical rating scale (NRS) and rescue analgesia through POD 3. CONCLUSION: ACB was associated with significantly less knee-buckling and earlier ambulation post-TKA, with better quadriceps strength. Our study indicated the incidence of falls and near-falls with continuous infusion nerve blocks, and support the use of ACB to reduce the risk of falls after TKA. It is suggested that a certain number of the patients even with continuous ACB infusion should be considered with the effect of motor branch to prevent falls.

Diagnostic accuracy of fine needle aspiration cytology and core needle biopsy in bone and soft tissue tumor: A comparative study of the image-guided and blindly performed procedure.

INTRODUCTION: Fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) can provide tissue samples for the diagnoses of bone and soft tissue tumors. We evaluated the diagnostic accuracy of FNAC and CNB, the usefulness of the image-guided needle procedures, and assessed whether a discordance can influence the prognosis. PATIENTS AND METHODS: We retrospectively examined the accuracy rates of FNAC and CNB procedures by analyzing results of 405 specimens of 389 patients. We evaluated the diagnostic accuracy of FNAC and CNB, compared the clinical effectiveness between the image-guided procedures and the blind procedures, and also compared survival rates between the true positive and the false negative cases for patients with high-grade malignant tumors. RESULTS: The accuracy rates of FNAC were 86.6% and 93.8% for CNB. In cases with non-palpable masses, there were significantly low sampling error rates in the image-guided procedure. There were no significant differences in progression-free-survival and overall survival rates in patients between the false negative and true positive cases. CONCLUSION: Both FNAC and CNB procedures had high accuracy rates. Limited to cases with no palpable masses, the image-guided procedure had a low sampling error rate and was an effective method for obtaining tissue samples.

Human leukocyte antigen I is significantly downregulated in patients with myxoid liposarcomas.

The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.

Minimally Invasive Spinal Stabilization with Denosumab before Total Spondylectomy for a Collapsing Lower Lumbar Spinal Giant Cell Tumor.

A 21-year-old man consulted our hospital for treatment of a spinal giant cell tumor (GCT) of Enneking stage III. Lower lumbar-spine tumors and severe spinal canal stenosis are associated with high risk for surgical mor-bidity. Stability was temporarily secured with a percutaneous pedicle screw fixation in combination with deno-sumab, which shrank the tumor. Total en bloc spondylectomy was then performed 6 months after initiation of denosumab, and the patient was followed for 3 years. There was no local recurrence, and bony fusion was obtained. Minimally invasive surgery and denosumab allowed safer and easier treatment of a collapsing lower lumbar extra-compartmental GCT.

Risk factors of local recurrence after surgery in extraabdominal desmoid-type fibromatosis: A multicenter study in Japan.

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.

Usefulness of surgical treatment for asymptomatic patients with extra-peritoneal desmoid-type fibromatosis: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review is to assess and compare the efficacy of surgical treatment for patients with asymptomatic extra-peritoneal desmoid-type fibromatosis to the wait-and-see policy by evaluating (1) the exacerbation rate (exacerbation; recurrence after surgery or progressive disease following non-surgical treatment) and (2) treatment-associated complications in extra-peritoneal desmoid-type fibromatosis. METHODS: We evaluated documents published between 1 January 1990 and 31 August 2017. The risk of bias in the selected literature was analyzed using the Cochrane Collaboration Risk of Bias Tool. Quality of evidence was evaluated using Grading of Recommendation, Assessment, Development and Evaluation approach. RESULTS: One prospective cohort study, four case-control studies and five case series studies were identified. Meta-analysis was performed to evaluate the exacerbation rate after treatment on one prospective cohort study and four case-control studies. In comparing surgical and non-surgical treatments, the exacerbation rate was significantly higher in the surgical treatment group (odds ratio: 1.32, 95% confidence interval 1.01-1.73, P = 0.05). However, in the case series study, the recurrence rate was 23.4% for the surgical treatment group, while the progressive disease rate was 28.1% for the non-surgical treatment group. The postoperative complication rates associated with surgical treatment in the two studies were 20.8 and 17.2%, respectively. CONCLUSIONS: When considering the exacerbation rate, non-surgical treatment might be appropriate for asymptomatic patients with extra-peritoneal desmoid-type fibromatosis. However, if patients with tumor-related symptoms opt for surgery, including those who face difficulties due to the presence of tumors, it is important to fully explain to them the possibility that the recurrence rate and treatment-associated functional failures may increase depending on the site of occurrence.

Clinical features and treatment outcome of desmoid-type fibromatosis: based on a bone and soft tissue tumor registry in Japan.

BACKGROUND: Treatment modality of desmoid-type fibromatosis (DF) has changed from surgery with a wide surgical margin to conservative treatment. In this study, tumor characteristics of DF, transition of the treatment modality, and clinical outcome of surgical treatment were analyzed based on data obtained from the bone and soft tissue tumor registry established in Japan. METHODS: Data were collected as registration data and follow-up data. Five hundred and thirty registered cases of DF were identified, including 223 cases with follow-up data with or without surgical treatment. RESULTS: The number of registered patients increased gradually. The frequency of surgical treatment was gradually reduced year by year. The 3-year local recurrence free survival (LRFS) was 77.7%, with tumor location and size tending to correlate with LRFS. Interestingly, there was no significant difference in LRFS between wide and marginal margin (P = 0.34). CONCLUSIONS: The treatment modality has shifted from surgical to conservative treatment, with risk factors for surgical treatment similar to those noted in previous studies. The National registry system is crucial for a rare disease such as DF, and in the future, a population based registry system should be established to better comprehend the actual status of DF.

Expression Profiling of Receptor-Activator of Nuclear Factor-Kappa B Ligand in Soft Tissue Tumors.

Bone and soft tissue tumors are derived from mesenchymal cells, and they are hard to treat. Receptor-activator of nuclear factor-kappa B ligand (RANKL) is an essential cytokine for osteoclast differentiation and activation and is expressed on the surface of osteoblasts or stromal cells. In this study, to explore the potential of denosumab treatment for soft tissue tumors, we analyzed the expression profiles of RANKL mRNA in 425 tumor specimens of 33 histological types by real-time RT-PCR. Denosumab is a monoclonal antibody that prevents the binding of RANKL to receptor-activator of nuclear factor-kappa B (RANK). For comparison, the relative expression levels of RANK and osteoprotegerin (OPG) mRNAs were also measured. OPG functions as a soluble decoy receptor for RANKL. Higher expression levels of RANKL mRNA were detected in calcifying aponeurotic fibroma, fibrosarcoma, calcifying epithelioma, myositis ossificans, heterotopic calcification, giant cell tumor of the tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS), compared with the levels of other tumor types. Moreover, the expression levels of RANK mRNA were highest in GCTTS, followed by myositis ossificans and PVNS, whereas the expression levels of OPG mRNA were greatly varied among these histological types. We then analyzed RANKL protein expression by immunohistochemistry in 57 tumor specimens with higher expression levels of RANKL mRNA. RANKL-positive cells were detected in GCTTS, PVNS, myositis ossificans, heterotopic calcification, and calcifying aponeurotic fibroma. In conclusion, RANKL is expressed in subsets of soft tissue tumors with calcification, and denosumab is a potential therapeutic option for soft tissue tumors expressing RANKL.

Prognostic impact of the tumor immune microenvironment in synovial sarcoma.

The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD-L1) were evaluated by immunohistochemistry. Moreover, we investigated PD-L1 and programmed death ligand 2 (PD-L2) mRNA expression in 19 of the 36 cases, using real-time PCR. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD-L1 expression was observed using immunohistochemistry. Moreover, although PD-L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression-free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD-L1, and PD-L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma.

A malignant solitary fibrous tumour arising from the first lumbar vertebra and mimicking an osteosarcoma: a case report.

BACKGROUND: A solitary fibrous tumour (SFT) is an unusual neoplasm typically found in soft tissues. Although SFTs can arise in the bones, they very rarely arise in the vertebral arch. Here, we describe a case of a SFT that arose in the vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked osteosarcoma. CASE PRESENTATION: A 49-year-old woman presented with a 2-month history of lower back pain and a lumbar region mass. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the L1 vertebral arch. The patient received neoadjuvant chemotherapy, followed by a surgical procedure comprising an anterior spinal fusion and en bloc resection. Histologically, our initial diagnosis was osteosarcoma. The postoperative course was uneventful, and the patient received adjuvant chemotherapy. However, the tumour metastasised to the lung 5 years after the first surgery, and a second surgery was performed for lung tumour resection. The histology of the metastatic lung tumour appeared similar to that of the malignant SFT, and the specimen from the first surgery was re-examined. Immunohistochemically, the tumour was positive for STAT6. Reverse transcription-polymerase chain reaction revealed a NAB2-STAT6 fusion gene, thus confirming our final diagnosis of malignant SFT. The patient died of disease progression 8 years after the first surgery; however, there was no evidence of local recurrence. CONCLUSIONS: Malignant SFT in the vertebral arch is extremely rare and very difficult to distinguish histologically an osteoid from lace-like collagen. STAT6 immunostaining is useful for distinguishing malignant SFTs from other neoplasms. Although it is difficult to completely resect a SFT arising from the spine, we demonstrated the feasibility of an en bloc resection of spinal tumours arising from posterior elements, without local recurrence.

Real-time polymerase chain reaction analysis of MDM2 and CDK4 expression using total RNA from core-needle biopsies is useful for diagnosing adipocytic tumors.

BACKGROUND: Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL. METHODS: A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage. RESULTS: In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P < 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P < 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test). CONCLUSION: Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.

Extraskeletal myxoid chondrosarcoma arising in the femoral vein: a case report.

Soft tissue tumors arising in deep veins of the extremities are uncommon, although a few cases of synovial sarcoma or leiomyosarcoma arising in the femoral vein have been documented. However, to the best of our knowledge, an extraskeletal myxoid chondrosarcoma (EMC) arising in the femoral vein has not been reported in the English literature. We report a case of EMC arising in the femoral vein of a 70-year-old man who presented with right leg edema and was diagnosed with a deep venous thrombosis (DVT) by computed tomography (CT). Magnetic resonance imaging (MRI) revealed a mass in the right proximal thigh that was diagnosed as myxomatous sarcoma by aspiration cytology, and anticoagulant therapy was initiated. The mass was surgically resected en bloc, including the femoral vein and surrounding soft tissue, and the femoral artery was preserved. The femoral vein was not reconstructed. The histologic diagnosis was an extraskeletal myxoid chondrosarcoma. The patient received postoperative local radiation treatment, with a total dose of 60 Gy, and is currently doing well with no evidence of local recurrence or metastasis at 8 months after surgery. In summary, this case report shows that EMC can arise in the femoral vein, and that reconstruction of the femoral vein is not always necessary during surgery for soft tissue tumors.

Bladder Cancer Invading the Prostate and Penis and Multiple Bone Metastases Showing Significant Improvement after a Short-Term Pembrolizumab Therapy following Radiation and Gemcitabine and Cisplatin Therapy Leading to a Pathologically Complete Remission.

A 65-year-old man was diagnosed with bladder cancer invading the prostate and penis and multiple bone metastases. He underwent palliative radiation (30 Gy/10 fr) through vertebral bones (Th3 and Th12-L5) and pelvic bones for pain control. The patient received pembrolizumab therapy after three courses of gemcitabine and cisplatin therapy. CT four weeks after starting pembrolizumab therapy showed that both the primary and metastatic lesions had notably reduced in size, and no new lesion was detected. He subsequently fell, resulting in a femoral neck pathological fracture, and underwent hemiarthroplasty. Pathological examination of the pathological fracture site revealed no residual tumor tissue.

Telomelysin shows potent antitumor activity through apoptotic and non-apoptotic cell death in soft tissue sarcoma cells.

This study investigated the pathway underlying the antitumor activity of telomelysin, a telomerase-dependent, replication-selective oncolytic adenovirus, in soft tissue sarcoma cells. Treatment with telomelysin alone resulted in simultaneous induction of apoptosis and autophagy, whereas cotreatment with telomelysin and 3-methyladenine significantly reduced cell viability and increased apoptosis and the cellular ATP level compared to treatment with telomelysin alone, indicating that telomelysin-mediated autophagy is a death-protective but not death-promoting process. Cotreatment with Z-Val-Ala-Asp-CH2F significantly increased cellular ATP depletion compared to telomelysin-alone treatment while inhibiting telomelysin-induced apoptosis and having no significant effect on cell viability, indicating that it promotes transition from apoptotic to necrotic cell death.

Imatinib mesylate inhibits cell growth of malignant peripheral nerve sheath tumors in vitro and in vivo through suppression of PDGFR-ß.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive and associated with poor prognosis. Basic research to develop new treatment regimens is critically needed. METHODS: The effects of imatinib mesylate on MPNSTs were examined in six human MPNST cell lines and in a xenograft mouse model. RESULTS: The results showed expression of platelet-derived growth factor receptor-ß and suppression of its phosphorylation by imatinib mesylate in all six cell lines. Imatinib mesylate effectively suppressed MPNST cell growth in vitro at concentrations similar to those used clinically (1.46 - 4.6 µM) in three of six cell lines. Knockdown of PDGFR-ß by transfection with a specific siRNA also caused significant reduction in cell proliferation in the sensitive cell lines, but not in the resistant cell lines. Furthermore, imatinib mesylate also significantly suppressed colony formation within soft agar and tumor growth in xenograft models using two of the three sensitive MPNST cell lines. There was excellent agreement between in vitro and in vivo sensitivity to imatinib mesylate, suggesting possible selection of imatinib-sensitive tumors by in vitro analysis. CONCLUSIONS: The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo.

Alveolar rhabdomyosarcoma after treatment of osteosarcoma.

Secondary rhabdomyosarcoma (RMS) after treatment of osteosarcoma (OS) is rare. Reported here is the case of a metachronous RMS in the nasal cavity, developing 12 years after successful treatment of non-metastatic OS. The patient was diagnosed as having OS of the femur at 2 years of age. Chemotherapy for OS included doxorubicin (cumulative dose, 488 mg/m(2) ). No radiotherapy was given. There was no family history suggestive of cancer predisposition syndrome. At 14 years of age, alveolar RMS was diagnosed on histopathology. PAX3-FKHR fusion transcripts were detected on reverse transcription-polymerase chain reaction. Germline TP53 mutation was not seen on standard DNA sequencing. The occurrence of secondary sarcomas, in the Children's Cancer Survivor study conducted in North America, has been associated with high cumulative doses of anthracyclines, which may also have played a role in the development of RMS in the present case. In the future, novel molecular technologies might uncover genetic cancer predisposition in patients with metachronous cancers.

SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group.

In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.

Osteoconductive action of alendronate after implantation of beta tricalcium phosphate in rat adjuvant-induced arthritis.

The aim of the study was to determine the effect of alendronate on resorption of ß-tricalcium phosphate (ß-TCP) and bone formation in rats with adjuvant-induced arthritis (AIA). After preparation of a model of AIA in rats (day 0), alendronate or vehicle was injected intraperitoneally once daily five times in a week. Cylindrical ß-TCP was implanted into the rat femoral condyle on day 7. Rats were killed on days 12, 15, and 21, and specimens and serum samples were collected. Specimens were analyzed by tartrate-resistant acid phosphate (TRAP) staining, immunohistochemistry of the ED1 protein, and in situ hybridization with digoxigenin-labeled α1 chain of type I procollagen (COL1A1). Mineralized bone sections were analyzed by Villanueva bone stain. The serum osteocalcin level was measured using an enzyme-linked immunosorbent assay kit. Alendronate decreased the number of TRAP-positive cells attached to ß-TCP, the numbers of ED1-positive multinucleated giant cells, and resorption of ß-TCP. In AIA rats treated with alendronate, COL1A1 mRNA-positive cells adhered to ß-TCP were round or cuboid whereas the cells in untreated AIA rats were fibroblast-like cells. Alendronate increased calcification of newly formed bone whereas it did not restore the bone formation suppressed with inflammation. These results suggest that alendronate has the potential to conduct mature bone after implantation of ß-TCP in AIA. Alendronate may help to reduce insufficiency of newly formed bone after implantation of ß-TCP in diseases characterized by increased bone resorption such as rheumatoid arthritis.