Kazumasa Nishimoto

Association study of TRAF1-C5 polymorphisms with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese

Objective: The primary aim of this study was to investigate the association of polymorphisms of TRAF1-C5, a newly identified rheumatoid arthritis (RA) risk locus in Caucasians, with susceptibility to RA and systemic lupus erythematosus (SLE) in Japanese populations. Gene expression levels of TRAF1 and C5 to assess the functional significance of genotypes were also analysed. Methods: A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay. Results: Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio  = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04). Conclusion: Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.

Intramuscular spindle cell lipoma: Case report and review of the literature

Spindle cell lipoma (SCL) is a relatively rare adipocytic neoplasm and is histologically characterized by a mixture of uniform spindle cells and mature fat cells. It occurs predominantly in male patients aged 45–65 years, and in most cases it arises in the subcutaneous tissue of the neck or shoulder. Although the neoplasm sometimes affects unusual sites, only three cases have been reported in which the lesion was intramuscular. Here we present a case of SCL arising in skeletal muscle; to our knowledge, the first report in 10 years. The tumor occurred in the neck of a 50‐year‐old male patient. Magnetic resonance imaging (MRI) revealed a lipomatous tumor within the right trapezius muscle. The tumor was localized beneath the fascia and was excised completely at surgery. Histologically, the tumor was typical of a spindle cell lipoma with no evidence of malignancy. An immunohistochemical study revealed all spindle cells were strongly positive for CD34. Differential diagnosis is discussed with a review of the literature.

Osteosarcoma with metastasis to the stomach

We herein present a case of osteosarcoma metastasizing to the stomach. An 18-year-old man who underwent amputation of the right arm for osteosarcoma developed persistent pain in the lower abdomen the following year. Endoscopy revealed a tumor that was highly suspicious of Bormann type III gastric cancer; however, based on histopathological studies, the fi nal diagnosis of metastatic osteosarcoma was made. Osteosarcoma rarely metastasizes to the digestive organs, and the stomach is one of the most unlikely destinations. In general, metastatic gastric cancer is regarded as a sign of an extremely poor prognosis with a low 1-year survival rate. The patient also demonstrated multiple metastatic lesions in the lung and died 6 months after the diagnosis of gastric metastasis.

Growth suppression and apoptosis induction in synovial sarcoma cell lines by a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ)

Synovial sarcoma is a relatively common soft tissue sarcoma with an aggressive clinical course. Although surgery is currently the first treatment modality, improvement of adjuvant chemotherapy is deemed essential to improve the clinical outcome. Nuclear factor-kappaB (NF-kappaB) is constitutively activated in various cancer cells and has emerged as a potential therapeutic molecular target; however, the possible involvement of NF-kappaB in the pathology of sarcomas remains to be clarified. Herein we examined the effects of a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) on two synovial sarcoma-derived cell lines, HS-SY-II and SYO-1. The growth of both cell lines was completely inhibited by DHMEQ and apoptosis was induced at 10 microg/ml. Additionally, we found that DHMEQ showed additive effects when used in combination with other cytotoxic agents. These observations indicate that inhibition of NF-kappaB activity may serve as a potential therapeutic target for synovial sarcoma.

Lack of association between PADI4 and functional severity in Japanese rheumatoid arthritis patients

Clinical presentation of rheumatoid arthritis (RA) varies from mild deformity of small joints to mutilating severe arthritis causing remarkable functional disorder and restriction of daily life activities. Prediction of disease outcome may allow better targeting of aggressive treatment. Recently, anti-cyclic citrullinated peptide antibody (anti-CCP) has been reported to be associated with disease outcomes.1–5 Peptidylarginine deiminase type 4 ( PADI4 ), encoding citrullinating enzyme, was identified as one of the RA susceptibility genes and was also reported to be associated with the level of anti-CCP in RA patients.6 These findings suggest the hypothesis that PADI4 determines disease severity of RA as well as its susceptibility. Our aim was to investigate the association between …

Association of EMCN with susceptibility to rheumatoid arthritis in a Japanese population

Objective. Endomucin, an endothelial-specific sialomucin, is thought to facilitate “lymphocyte homing” to synovial tissues, resulting in the major histopathologies of rheumatoid arthritis (RA). We examined the association between RA susceptibility and the gene coding endomucin, EMCN. Methods. Association studies were conducted with 2 DNA sample sets (initial set of 1504 patients, 752 controls; and validation set, 1113 patients, 940 controls) using 6 tag single-nucleotide polymorphisms (SNP) from the Japanese HapMap database. Immunohistochemistry for the expression of endomucin was conducted with synovial tissues from 4 patients with RA during total knee arthroplasty. Electromobility shift assays were performed for the functional study of identified polymorphisms. Results. Within the initial sample set, the strongest evidence of an association with RA susceptibility was SNP rs3775369 (OR 1.20, p = 0.0075). While the subsequent replication study did not initially confirm the observed significant association (OR 1.13, p = 0.062), an in-depth stratified analysis revealed significant association in patients testing positive to anti-cyclic citrullinated peptide (anti-CCP) antibody in the replication data set (OR 1.15, p = 0.044). Investigating 2 sample sets, significant associations were detected in overall and stratified samples with anti-CCP antibody status (OR 1.17, p = 0.0015). Positive staining for endomucin was detected in all patients. The allele associated with RA susceptibility had a higher binding affinity for HEK298-derived nuclear factors compared to the nonsusceptible allelic variant of rs3775369. Conclusion. A significant association between EMCN and RA susceptibility was detected in our Japanese study population. The EMCN allele conferring RA susceptibility may also contribute to the pathogenesis of RA.

Successful Treatment with Pazopanib for Multiple Lung Metastases of Inguinal Epithelioid Sarcoma: A Case Report.

Epithelioid sarcoma is a rare soft tissue sarcoma and usually resistant to chemotherapy. It has high rates of local recurrence and distant metastasis, and the prognosis after metastasis is poor. We report a case of multiple lung metastases of an epithelioid sarcoma originating in the inguinal area that we treated with the multikinase inhibitor pazopanib. The patient was a 38-year-old male who began to experience discomfort in his left inguinal area. Magnetic resonance imaging showed a tumor extended from the medial aspect of the wing of the left ilium along the iliopsoas muscle to its site of insertion on the femur. The histopathological diagnosis with a biopsy was proximal-type epithelioid sarcoma. Although a positron emission tomography examination showed fluorodeoxyglucose accumulation in the left inguinal tumor, there was no distant metastasis. Wide resection by a combined iliac resection procedure was performed. Twelve months after surgery, computed tomography revealed multiple nodules and a diagnosis of bilateral multiple lung metastases was made. Treatment with pazopanib 800 mg was started. After 2.5 months of treatment, a clear reduction in the size of the pulmonary metastases was shown. Thirty months after the start of pazopanib treatment, most of the metastases have disappeared, and no development of new lesions has been seen. Therefore, it appeared that pazopanib was capable of serving as one of the choices of therapeutic agents that should be taken into consideration for the treatment of advanced epithelioid sarcoma.

Computed tomography-guided resection of osteoid osteoma of the sacrum: a case report

IntroductionOsteoid osteoma is a benign tumor that usually occurs in the long bones of young adults. Its symptoms can be diverse depending on the location of the tumor and especially difficult to diagnose when occurring in an atypical location. Osteoid osteoma arising in the sacrum is extremely rare, and here, we present a case that was treated successfully in a minimally invasive fashion under computed tomography guidance.Case presentationA 25-year-old Asian man was referred to our institution due to persistent pain in the buttock after 12 months of conservative treatment. Computed tomography and magnetic resonance imaging scans revealed a ring-shaped radiolucency consistent with a nidus of osteoid osteoma in the sacrum. The lesion was subsequently resected under computed tomography guidance and the histological diagnosis was compatible with osteoid osteoma. His postoperative course was uneventful, and at two years after surgery our patient is symptom-free with no evidence of recurrence.ConclusionsComputed tomography-guided resection of osteoid osteoma in the spinal column is feasible and accurate if there is adequate margin from vital organs. Although rare, it is important to always bear in mind the possibility of osteoid osteoma occurring in the sacrum when no other apparent lesion is detected.

Extraskeletal Chondroma of the Index Finger: A Case Report

Extraskeletal chondroma is defined as a rare, benign, cartilaginous tumor arising from soft tissues such as tendons, tendon sheath synovia, and joint capsules with no continuity to the periosteum or bone cortex. In histopathologic findings, the tumor exhibits many lobular structures and some parts similar to hyaline cartilage. Therefore, it is sometimes difficult to differentiate this tumor from low-grade chondrosarcoma because of their similar histopathologic findings. In order to prevent recurrence, it is necessary to remove the tumor as a whole, including the capsule, so as not to leave any remnants of the tumor. In this article, we report our treatment experience with a case of extraskeletal chondroma in the index finger of a 63-year-old patient.

Hibernoma Showing High Uniform Accumulation on an 18F-Fluorodeoxyglucose Positron Emission Tomography Scan: A Case Report

Background: Hibernoma is a rare, benign, soft tissue tumor arising from brown fat that cannot be distinguished from other lipogenic tumors on computed tomography and magnetic resonance imaging (MRI) scans. On the other hand, the image of hibernoma on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is different from that of other lipogenic tumors. However, fewer studies have investigated the typical features of hibernoma on PET scans. We present the case of a hibernoma that was incidentally detected on 18F-FDG-PET. Case Presentation: A 48-year-old Asian man underwent 18F-FDG-PET for routine follow-up of gastric cancer. The patient reported a painless soft mass on the upper arm that had persisted for several years. On 18F-FDG-PET, the mass showed a maximum standardized uptake value of 9.6. The mass showed high intensity on T1- and T2-weighted MRI scans, and showed focally enhanced septa after gadolinium administration. The mass was surgically resected. Histopathologically, the mass was composed of brown adipose cells characteristic of hibernoma. His postoperative course was uneventful, and there was no local recurrence at the final 24-month follow-up. Conclusion: Hibernoma showed strong uniform accumulation on 18F-FDG-PET, suggesting that 18F-FDG-PET would be a useful modality for the differential diagnosis of hibernoma versus other lipogenic tumors.