Local dissemination of osteosarcoma observed after massage therapy: a case report.

BACKGROUND: Limited evidence is available regarding the dissemination of tumor tissues due to compression during massage therapy, a routine procedure in patients with various symptoms in Asian countries. CASE PRESENTATION: A 12-year-old male presented at a massage clinic with pain and swelling of his left knee, which worsened the same night. Consistent with conventional osteosarcoma, radiography revealed cortical bone destruction, osteoblastic changes, and periosteal reactions. Magnetic resonance imaging revealed a tumor in the distal femur, an extraskeletal mass, and an infiltrative lesion in the intramuscular and neurovascular areas surrounding the distal femur; this was considered as hemorrhage and dissemination of the tumor tissue. 18Fluorine-labelled fluorodeoxyglucose-positron emission tomography and computed tomography revealed multiple metastases in the spine, liver, and lung. Consistent with osteosarcoma, histopathological examination revealed tumor cell proliferation with extensive pleomorphism and mitoses. Despite undergoing chemotherapy, radiation therapy, and hip disarticulation, the patient died due to multiple metastases 13 months after the initial diagnosis. CONCLUSIONS: The present case suggests association of massage therapy with the local dissemination of tumor tissues, although influence of massage therapy on metastatic lesions remains unclear. Massage therapists should be aware of the possibility for dissemination of hidden malignancies due to the procedure.

Preoperative evaluation of the efficacy of radio-hyperthermo-chemotherapy for soft tissue sarcoma in a case series.

PURPOSE: Radio-hyperthermo-chemo (RHC) therapy, which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft tissue tumors has been introduced with the aim of decreasing the possibility of local recurrence after surgery. To avoid unnecessary neoadjuvant therapy and to plan the appropriate surgical treatment, surveillance of RHC therapeutic efficacy during treatment is necessary. In this study, we determined the optimal response criteria to evaluate the efficacy of RHC by comparing preoperative images before and after RHC with pathological evaluation of necrosis in the resected tumor. PATIENTS AND METHODS: From 2004 to 2014, 20 patients were enrolled into this study. Needle biopsy revealed 6 cases of myxoid liposarcoma, 6 cases of undifferentiated pleomorphic sarcoma, 4 cases of myxofibrosarcoma, and 4 cases of synovial sarcoma. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST, we calculated the responses to RHC therapy by comparing pre- and post-RHC therapy images. In addition, resected specimens underwent pathological analysis to evaluate response based on tumor necrosis. The correlation between assessment based on preoperative images and resected tumors were evaluated by the Spearman's rank-order correlation coefficient. RESULT: From the surgical specimens, pathological assessment of necrosis in resected tumor were assessed as less than 50% (2 cases), 50-90% (9 cases), 90-99% (6 cases), and total necrosis (3 cases). Use of the RECIST 1.1 underestimated good responders as stable disease (SD) or progressive disease (PD) in 5 out of 15 cases; on the other hand, use of the modified RECIST did not underestimate the pathological assessment of necrosis. The correlations between responses based on preoperative images and those based on histological assessments were 0.23 (RECIST 1.1) and 0.76 (modified RECIST). CONCLUSION: Because pathological responses can be underestimated using the RECIST 1.1, the modified RECIST, which take into consideration tumor viability, as assessed by contrast MRI, should also be considered when evaluating the efficacy of RHC.

Clinical outcomes of radio-hyperthermo-chemotherapy for soft tissue sarcoma compared to a soft tissue sarcoma registry in Japan: a retrospective matched-pair cohort study.

Regional hyperthermia is considered to enhance the antitumor effects of chemotherapy and radiotherapy. In this study, we confirmed the efficacy of concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for neoadjuvant treatment of malignant soft tissue sarcoma (STS). From 1994 to 2013, we performed RHC in 150 patients. This study was limited to 60 patients using the following exclusion criteria: salvage for recurrence or unplanned excision, trunk location, metastasis at initiation, non-STS, and no definitive surgery. As a control group, we collected data from 11,031 patients in the Bone and Soft Tissue Tumor Registry in Japan (BSTT). We performed multivariate logistic regression analysis, and propensity scores were created for comparisons between groups. The primary outcome of this study was to compare oncologic outcomes (5-year local control rate [LC] and overall survival rate [OS]). In the RHC group, two local recurrences (3.3%) occurred, and no patients underwent amputation. Margins of definitive surgery were not identical between groups [wide margins (60.0% vs. 85.3%), marginal margins (28.3% vs. 10.5%), and intralesional margins (7.4% vs. 4.2%), RHC and BSTT groups, respectively, P < 0.001]. After adjustment, the difference in OS was not significant between groups (HR = 1.26, P = 0.532); however, a statistically significant difference in LC was observed (HR = 4.82, P = 0.037). RHC resulted in a high LC at 5 years compared to the BSTT group, and amputation was averted in the RHC group, despite the wider margins in the BSTT group. This indicates that less invasive surgery might be achieved with effective neoadjuvant therapy.

Salvage method for unplanned excision of soft tissue sarcoma: long-term results of second-look surgery following radio-hyperthermo-chemotherapy.

We have established a "second-look operation" protocol that consists of whole biopsy of surgical scar tissue following radio-hyperthermo-chemotherapy (RHC) after unplanned excision of soft tissue sarcoma. Out of 30 patients who underwent RHC for soft tissue sarcoma at our Institution, 6 were enrolled into this study to undergo a second-look operation for unplanned excision. Radiotherapy was given to a total dose of 32 Gy. Hyperthermia was conducted once a week, for a total of five sessions. Chemotherapy was performed at weekly intervals. Surgery was performed to excise the scar tissue that was enhanced on preoperative MRI. In all six cases, no residual tumors were identified in resected scar tissue; thus, no additional wide excision was performed. The average follow-up period was 10.9 years. There were no local recurrences, and all patients were alive at their final follow-up. Long-term follow-up confirmed that RHC can replace additional wide excision for unplanned excision of soft tissue sarcoma.

TNF-alpha-induced aquaporin 9 in synoviocytes from patients with OA and RA.

OBJECTIVES: To determine whether aquaporins (AQPs) are expressed in the synovial tissues of patients with OA and RA, and to examine the patterns of expression in patients with and without hydrarthrosis. METHODS: AQPs were detected in synovial tissue samples from patients with OA and RA using RT-PCR and immunohistochemistry. Fibroblast-like synoviocytes (FLSs) from patients with OA and RA were cultured and stimulated with TNF-alpha. The expression of AQPs in FLSs was examined using RT-PCR and western blot analyses and the function of aquaglyceroporins was examined by a glycerol uptake assay. RESULTS: AQP1, -3 and -9 mRNAs were expressed in synovial tissues from patients with OA and RA. AQP1, -3 and -9 proteins were also detected by immunohistochemistry. AQP9 mRNA was expressed more strongly in the synovial tissues of OA patients with hydrarthrosis than those without. AQP9 mRNA and protein expression were strongly induced with TNF-alpha treatment in FLSs, whereas the expression of AQP1 and -3 mRNAs was not induced with TNF-alpha treatment. AQP9 as an aquaglyceroporin was induced by TNF-alpha. CONCLUSIONS: AQP9 mRNA was detected in synovial tissues from OA and RA patients with hydrarthrosis. AQP9 expression was strongly induced in FLSs with TNF-alpha. Although the functions of AQP1, -3 and -9 in synovial tissues remain to be elucidated, it suggested that AQP9 might be related to the pathogenesis of hydrarthrosis and inflammatory synovitis.

Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis.

Genetic susceptibility to rheumatoid arthritis (RA) is associated with certain MHC class II molecules. To clarify the role of these determinants in RA, we generated the D1CC transgenic mouse that expressed genes involved in antigen processing and presentation by the MHC class II pathway in joints. The class II transactivator, which was transcribed from the rat collagen type II promoter and enhancer, directed the expression of these genes. In D1CC mice congenic for the H-2(q) (DBA/1) background, small amounts of bovine collagen type II in adjuvant induced reproducibly an inflammatory arthritis resembling RA. Importantly, these stimuli had no effect in DBA/1 mice. Eighty-nine percent of D1CC mice developed chronic disease with joint swelling, redness, and heat in association with synovial proliferation as well as pannus formation and mononuclear infiltration of synovial membranes. Granulomatous lesions resembling rheumatoid nodules and interstitial pneumonitis also were observed. As in patients with RA, anticyclic citrullinated peptide antibodies were detected during the inflammatory stage. Finally, joints in D1CC mice displayed juxtaarticular demineralization, severe joint space narrowing, and erosions, which led to ankylosis, but without the appearance of osteophytes. Thus, aberrant expression of MHC class II in joints facilitates the development of severe erosive inflammatory polyarthritis, which is very similar to RA.