A case of emphysematous cystitis caused by mechanical stimulation of pelvic fracture nonunion.

Emphysematous cystitis is a rare condition that develops due to tissue hyperglycemia and urinary tract infection by gas-producing bacteria. We report a case of emphysematous cystitis caused by mechanical stimulation of a pelvic fracture nonunion. An 80-year-old man was injured in a motorcycle accident and diagnosed with pelvic fracture. Seven days later, he had high fever and computed tomography (CT) revealed gas in the hematoma around the pelvic fracture and the abscess. Therefore, infection following the pelvic fracture was diagnosed. Despite multiple operations and antibiotics treatment, malformation and nonunion of the pelvis occurred. One month after starting weight bearing, emphysema of the bladder wall adjacent to the pubic fracture were found and spread throughout the bladder wall. With stopping of weight bearing, antibiotics treatment and a urinary catheter, emphysema disappeared after 2 months. It was considered that the pubic fracture fragment irritated the bladder wall due to weight bearing and emphysematous cystitis consequently developed.

Circulating MicroRNA-92b-3p as a Novel Biomarker for Monitoring of Synovial Sarcoma.

The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.

Second primary osteosarcomas in patients with retinoblastoma.

OBJECTIVE: Second primary malignancies have become the leading cause of death in retinoblastoma survivors. Although osteosarcoma is the most common second malignancy, little is known about its clinical and therapeutic features. METHODS: We retrospectively reviewed a database of patients with retinoblastoma and osteosarcoma occurring as a second malignancy between 1964 and 2010 at the National Cancer Center Hospital of Japan. RESULTS: Among 857 patients with retinoblastoma registered in the database, 10 (1.1%) developed osteosarcoma as a second malignancy. The median age at the onset of retinoblastoma was 3 months, being bilateral in nine patients and unilateral in one. Systemic chemoreduction was performed in three patients and intra-arterial chemotherapy in six; all patients received external beam radiotherapy. The median age at the onset of second primary osteosarcoma was 11.2 years; four were radiation-related and six were located in an extremity. Among five patients treated at our institute, four patients with tumors on an extremity were treated by wide resection with neoadjuvant and adjuvant chemotherapy. Three of these four patients (75%) were good responders to high-dose methotrexate-based multi-agent chemotherapy and survived with no evidence of disease (median follow-up period, 17.3 years). One patient whose temporal bone was affected underwent radiotherapy with chemotherapy but died after local recurrence. CONCLUSIONS: The clinical outcomes of second primary osteosarcoma in an extremity occurring in retinoblastoma survivors may be more favorable than those of conventional osteosarcoma. Early diagnosis of radiation-related osteosarcoma arising in the craniofacial region should be made at a stage where complete resection is possible.

The Values and Limitations of FDG-PET/CT for Diagnosis of Hibernoma.

Hibernoma is a rare benign lipogenic tumor of brown fat that develops in a wide variety of locations. Although the features of hibernoma demonstrated by MRI resemble those of liposarcoma, recent FDG-PET/CT studies have documented higher radiotracer uptake than liposarcoma, suggesting that FDG/PET/CT is useful for differentiating hibernoma from liposarcoma. Here we report two cases of hibernoma that showed relatively lower SUVs than those reported previously, lying within the range for liposarcoma. Our findings emphasize that hibernoma needs to be included in the differential diagnosis of any fat-containing tumor showing intense accumulation by FDG-PET/CT. Although it is unlikely that such a rare condition could be reasonably diagnosed on the basis of MRI and FDG-PET/CT alone due to possible SUV overlap between hibernoma and liposarcoma, it is important to recognize this extremely rare lipogenic tumor for accurate diagnosis and appropriate management.

Analysis of microRNAs expressions in chondrosarcoma.

MicroRNAs (miRNAs) are small non-coding RNAs capable of inhibiting gene expression post-transcriptionally and expression profiling can provide therapeutic targets and tools for cancer diagnosis. Chondrosarcoma is a mesenchymal tumor with unknown cause and differentiation status. Here, we profiled miRNA expression of chondrosarcoma, namely clinical samples from human conventional chondrosarcoma tissue, established chondrosarcoma cell lines, and primary non-tumorous adult articular chondrocytes, by miRNA array and quantitative real-time PCR. A wide variety of miRNAs were differently downregulated in chondrosarcoma compared to non-tumorous articular chondrocytes; 27 miRNAs: miR-10b, 23b, 24-1*, 27b, 100, 134, 136, 136*, 138, 181d, 186, 193b, 221*, 222, 335, 337-5p, 376a, 376a*, 376b, 376c, 377, 454, 495, 497, 505, 574-3p, and 660, were significantly downregulated in chondrosarcoma and only 2: miR-96 and 183, were upregulated. We further validated the expression levels of miRNAs by quantitative real-time PCR for miR-181a, let-7a, 100, 222, 136, 376a, and 335 in extended number of chondrosarcoma clinical samples. Among them, all except miR-181a were found to be significantly downregulated in chondrosarcoma derived samples. The findings provide potential diagnostic value and new molecular understanding of chondrosarcoma.

Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2'-deoxycytidine against synovial sarcoma cell lines.

PURPOSE: In this study, the methylation status of RASSF1A in synovial sarcomas and the effect of demethylation on synovial sarcoma were examined. METHODS: The methylation status in 74 soft tissue sarcomas (STSs) including 21 synovial sarcomas was determined by methylation specific PCR. The effect of the de-methylating agent 5-aza-20-deoxycytidine (5-Aza-dC) on synovial sarcoma was examined using synovial sarcoma cell lines (SYO-1 and HS-SY-II). RESULTS: RASSF1A methylation was observed in 10 (47.6%) of 21 synovial sarcomas and in 10 (18.9%) of 53 the other STSs (P = 0.0295). De-methylation of the cells by treatment with 5-Aza-dC induced re-expression of RASSF1A and growth suppression of the cells. The calculated IC50 of 5-Aza-dC against the SYO-1 and the HS-SYII cells were 0.9 and 1.3 lM (96 h), respectively. With twice weekly administration of 1 or 10 mg/kg 5-Aza-dC, the growth of the mouse xenograft tumors of SYO-1 was significantly suppressed in comparison to the controls (P\0.01). CONCLUSION: This is the first report showing the anti-tumor effect of 5-Aza-dC on synovial sarcoma. 5-Aza-dC is suggested to have a good therapeutic potential against synovial sarcoma.

Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: involvement of cyclin C in osteosarcoma.

The molecular pathogenesis of osteosarcoma is very complicated and associated with chaotic abnormalities on many chromosomal arms. We analyzed 12 cases of osteosarcomas with comparative genomic hybridization (CGH) to identify chromosomal imbalances, and detected highly frequent chromosomal alterations in chromosome 6q, 8p, 10p and 10q. To define the narrow rearranged region on chromosome 6 with higher resolution, loss of heterozygosity (LOH) analysis was performed with 21 microsatellite markers. Out of 31 cases, 23 cases (74%) showed allelic loss at least with one marker on chromosome 6q. We identified two distinct commonly deleted regions on chromosome 6 using markers D6S1565 located at 6q16 and 6q23MS1 at 6q23. The expression analysis of genes located at the deleted region was performed, and the decreased mRNA expression of the CCNC gene, one of the regulators of cell cycle, was detected. Growth of osteosarcoma cell line was significantly suppressed after the CCNC cDNA transfection. Fine mapping of the deleted region containing a possible tumor suppressor gene and the transfection assay suggest that the CCNC is a candidate tumor suppressor gene.

Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization.

PURPOSE: To analyze the relationship between chromosomal instabilities and clinicopathological factors in synovial sarcoma (SS). METHODS: Twenty-two fresh-frozen SS were analyzed by metaphase comparative genomic hybridization (CGH). Additional microarray CGH was performed in 13 cases. RESULTS: Fourteen patients with SYT-SSX1 rearrangements and nine patients with biphasic tumor subtypes had better prognosis than the eight patients with SYT-SSX2 rearrangements and 13 patients with monophasic subtypes, respectively. Gains (average 3.0) were more frequent than losses (average 1.0). Frequent gains were identified on chromosomal regions 2, 6q, 7, 8q, 12, 17q, 18q, and 21q, whereas frequent losses were over-lapped on chromosomes 1p31-p35, 3p, 6q, 16, and 17p. High-level gains were observed on chromosomes 1q21-q31, 7, 8, 12, 17q, 18q, and 21q. Thirteen monophasic and nine biphasic tumors had an average of 5.1 and 2.8 aberrations, respectively. Patients with tumors harboring numerous aberrations (>or=3) had a worse clinical course. Microarray CGH more specifically detected genetic imbalances including gains in MDM2, MSH2, KCNK12, DCC, CDK2, ERBB3, SAS, and CDK4 and losses in HRAS, RASSF1, and CCND1. Gain of SAS was an important prognostic factor of SS. CONCLUSION: We have identified several factors influencing the prognosis of SS patients by metaphase and microarray CGH.

Chromosomal imbalances in malignant peripheral nerve sheath tumor detected by metaphase and microarray comparative genomic hybridization.

Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant tumors affecting adolescents and adults. There have been a few reports on chromosomal aberrations of MPNSTs; however, the tumor-specific alteration remains unknown. We characterized the genomic alterations in 8 MPNSTs and 8 schwannomas by metaphase comparative genomic hybridization (CGH). In 5 of 8 MPNSTs, microarray CGH was added for more detailed analyses. Frequent gains were identified on 3q13-26, 5p13-14, and 12q11-23 and frequent losses were at 1p31, 10p, 11q24-qter, 16, and 17. Microarray CGH revealed frequent gains of EGFR, DAB2, MSH2, KCNK12, DDX15, CDK6, and LAMA3, and losses of CDH1, GLTSCR2, EGR1, CTSB, GATA3, and SULT2A1. These genes seem to be responsible for developing MPNSTs. The concordance rate between metaphase CGH and microarray CGH was 66%. Metaphase CGH was useful for identifying chromosomal alterations before applying microarray CGH.

Amplification of MYCL in Atypical Ewing Tumor. Analysis of Metaphase and Microarray Comparative Genomic Hybridization.

A 20-year-old man developed a soft tissue mass in his right upper arm and, 3 months later, was referred to our hospital. The tumor cells showed brisk mitotic activity and a large amount of cytoplasmic glycogen was demonstrated with periodic acid Schiff stain. A diagnosis of atypical Ewing sarcoma was made. Chemotherapy according to the VACA protocol, comprising vincristine, actinomycin D, cyclophosphamide and doxorubicin was started. The chemotherapy was effective and a limb salvage procedure was performed by implantation of an autoclaved bone after wide tumor excision. During the postoperative chemotherapy, a local recurrence and multiple metastases developed, and the patient died due to disease progression. Fourteen years later, this tumor sample, preserved in a deep-freeze, was analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the fusion gene. This tumor had an EWS exon 7 to FLI1 exon 6 fusion transcript. Moreover, metaphase and microarray comparative genomic hybridization (CGH) was done to detect chromosomal instabilities. Many gains and losses were noted on metaphase CGH, and MYCL amplification was identified on microarray CGH.