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2.  Multicenter study evaluating the clinical performance of the OSNA assay for the molecular detection of lymph node metastases in gastric cancer patients 
Gastric Cancer  2013;17(2):273-280.
The accurate diagnosis of lymph node (LN) metastasis is important for making treatment decisions for gastric cancer patients. This multicenter study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay (Sysmex Corp.), an automated system that detects cytokeratin 19 (CK19) mRNA, in detecting LN metastases in gastric cancer patients.
LNs retrieved from patients who had undergone gastric cancer surgery at one of the four Japanese hospitals involved in this study were divided into blocks at 2-mm intervals. Alternate blocks were examined with the OSNA assay and the remaining blocks were assessed histologically.
A total of 394 LNs from 61 patients were examined. The concordance rate between the OSNA assay and the histological examination was 0.942 (95 % CI, 0.914–0.963). Sensitivity and specificity of the OSNA assay compared to the histological examination were 0.833 (95 % CI, 0.707–0.921) and 0.959 (95 % CI, 0.932–0.977), respectively. Discordant results were observed in 23 LNs (5.8 %), and these were mainly the result of tissue allocation bias and/or low CK19 protein expression.
The OSNA assay can detect lymph node metastases in gastric cancer patients as accurately as the histological examination of blocks sectioned at 2-mm intervals. The OSNA assay is a useful tool for the intraoperative diagnosis of LN metastasis in gastric cancer patients.
PMCID: PMC3973934  PMID: 23743877
Stomach neoplasm; Lymphatic metastasis; Intraoperative period; Nucleic acid amplification techniques; Keratin-19
3.  Overexpression of miR-142-5p and miR-155 in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Resistant to Helicobacter pylori Eradication 
PLoS ONE  2012;7(11):e47396.
microRNAs (miRNAs) are small non-coding RNAs that can function as endogenous silencers of target genes and play critical roles in human malignancies. To investigate the molecular pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the miRNA expression profile was analyzed. miRNA microarray analysis with tissue specimens from gastric MALT lymphomas and surrounding non-tumor mucosae revealed that a hematopoietic-specific miRNA miR-142 and an oncogenic miRNA miR-155 were overexpressed in MALT lymphoma lesions. The expression levels of miR-142-5p and miR-155 were significantly increased in MALT lymphomas which do not respond to Helicobacter pylori (H. pylori) eradication. The expression levels of miR-142-5p and miR-155 were associated with the clinical courses of gastric MALT lymphoma cases. Overexpression of miR-142-5p and miR-155 was also observed in Helicobacter heilmannii-infected C57BL/6 mice, an animal model of gastric MALT lymphoma. In addition, miR-142-5p and miR-155 suppress the proapoptotic gene TP53INP1 as their target. The results of this study indicate that overexpression of miR-142-5p and miR-155 plays a critical role in the pathogenesis of gastric MALT lymphoma. These miRNAs might have potential application as therapeutic targets and novel biomarkers for gastric MALT lymphoma.
PMCID: PMC3509063  PMID: 23209550
4.  Large liposarcoma developing in the ischiorectal fossa: Report of a rare case 
We herein report an extremely rare case of a liposarcoma developing in the ischiorectal fossa that was completely resected using a transsacral approach.
A 74-year-old man was admitted to our institute because of a large perianal tumor. A pelvic magnetic resonance imaging (MRI) revealed an 8 cm × 7 cm × 5 cm sized encapsulated heterogeneous tumor on the right side of the ischiorectal fossa. Transsacral excision was performed under a diagnosis of liposarcoma. The tumor was partially fixed to the external sphincter and puborectalis. Therefore, the muscles were partially resected to ensure sufficient margins. Histopathological examination revealed a well differentiated liposarcoma and negative surgical margins.
The basic treatment strategy of liposarcoma is surgical resection, whereas the effects of chemotherapy or radiotherapy remain limited. Although no postoperative adjuvant therapy has been performed in our case, no recurrences have occurred for 1 year after surgery.
Although the curative resection of large tumors located in the ischiorectal fossa is usually difficult, the complete resection of liposarcoma is the main potentially curative treatment. A transsacral approach is useful for a complete resection.
PMCID: PMC3537958  PMID: 23123415
Liposarcoma; Ischiorectal fossa; Soft tissue tumor
5.  Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy 
BMC Cancer  2012;12:444.
Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy.
Case presentation
The patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10.
This case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.
PMCID: PMC3488581  PMID: 23031740
Li-Fraumeni syndrome (LFS); cancer stem cells (CSCs); CD44 variant isoforms
6.  Metastatic Patterns of Myxoid/Round Cell Liposarcoma: A Review of a 25-Year Experience 
Sarcoma  2012;2012:345161.
Myxoid/round cell liposarcoma (MRCL), unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81%) had no metastases, whereas 11 patients (11%) had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73%) had extrapulmonary metastases and 3 patients (27%) had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P = 0.028). The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P = 0.027). 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.
PMCID: PMC3329861  PMID: 22550416
7.  Spontaneous Remission of Solitary-Type Infantile Myofibromatosis 
Case Reports in Dermatology  2011;3(2):181-185.
Infantile myofibromatosis is a rare fibrous tumor of infancy. The cutaneous solitary type has typically an excellent prognosis. However, histologically, it is important to rule out leiomyosarcoma, which has a poor prognosis. The low frequency of mitosis was definitive for a diagnosis of infantile myofibromatosis. We present a cutaneous solitary-type case of infantile myofibromatosis. Following incisional biopsy, the tumor remitted spontaneously.
PMCID: PMC3177839  PMID: 21941483
Infantile myofibromatosis; Leiomyosarcoma; Solitary type
8.  Natural evolution of desmoplastic fibroblastoma on magnetic resonance imaging: a case report 
Desmoplastic fibroblastoma (collagenous fibroma) is a recently described tumor thought to arise predominantly from subcutaneous tissue or skeletal muscle. The natural evolution of this tumor on magnetic resonance imaging has never been described, to the best of our knowledge. We herein report a case of desmoplastic fibroblastoma arising in the thigh and show the longitudinal magnetic resonance imaging findings.
Case presentation
A 60-year-old Japanese man presented with swelling of the medial side of his right thigh, and he complained of nighttime pain and slight tenderness. Magnetic resonance imaging demonstrated a 4 × 4 cm mass in the right thigh. Open biopsy was performed. The mass was diagnosed histologically as a benign fibrous tumor, and we maintained follow-up without surgical therapy. After one year, magnetic resonance imaging showed an increase in tumor size to 4 × 5 cm, but the histologic findings were the same as those obtained one year earlier. Resection was performed with narrow surgical margins. Pathologic diagnosis was desmoplastic fibroblastoma. Two years after surgery, the patient is free from pain and shows no signs or symptoms of recurrence.
The natural evolution of desmoplastic fibroblastoma is characterized by no changes in patterns on magnetic resonance imaging despite increasing size. This finding is clinically helpful for distinguishing desmoplastic fibroblastoma with increasing pain from the desmoid tumor.
PMCID: PMC3083363  PMID: 21470431
10.  Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents 
The Journal of Clinical Investigation  2010;120(7):2292-2306.
Valvular heart disease (VHD) is the term given to any disease process involving one or more of the heart valves. The condition can be congenital or acquired, for example as a result of atherosclerosis or rheumatic fever. Despite its clinical importance, the molecular mechanisms underlying VHD remain unknown. We investigated the pathophysiologic role and molecular mechanism of periostin, a protein that plays critical roles in cardiac valve development, in degenerative VHD. Unexpectedly, we found that periostin levels were drastically increased in infiltrated inflammatory cells and myofibroblasts in areas of angiogenesis in human atherosclerotic and rheumatic VHD, whereas periostin was localized to the subendothelial layer in normal valves. The expression patterns of periostin and chondromodulin I, an angioinhibitory factor that maintains cardiac valvular function, were mutually exclusive. In WT mice, a high-fat diet markedly increased aortic valve thickening, annular fibrosis, and MMP-2 and MMP-13 expression levels, concomitant with increased periostin expression; these changes were attenuated in periostin-knockout mice. In vitro and ex vivo studies revealed that periostin promoted tube formation and mobilization of ECs. Furthermore, periostin prominently increased MMP secretion from cultured valvular interstitial cells, ECs, and macrophages in a cell type–specific manner. These findings indicate that, in contrast to chondromodulin I, periostin plays an essential role in the progression of cardiac valve complex degeneration by inducing angiogenesis and MMP production.
PMCID: PMC2898587  PMID: 20551517
11.  Ileal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with a Large-Cell Component That Regressed Spontaneously 
Gut and Liver  2010;4(1):117-121.
Reported herein is a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the terminal ileum with a large-cell component, which regressed spontaneously. To the best of our knowledge, only five cases of spontaneously regressing MALT lymphoma have been reported in the English-language literature, and all of these cases were low-grade lymphomas. Spontaneous regression of a MALT lymphoma with a high-grade component is very rare. The present case suggests that MALT lymphoma cells have a reversible nature, even in the presence of a high-grade component.
PMCID: PMC2871597  PMID: 20479924
Mucosa-associated lymphoid tissue lymphoma; Large cell component; Regression; Ileum, Low grade
12.  Primary intratesticular leiomyosarcoma 
This report presents a case of primary intratesticular leiomyosarcoma. A 73-year-old male presented with a 6-year history of left scrotal swelling. A radiological examination revealed a left testicular tumour with multiple metastases in the lung, para-aortic lymph node and other organs. A radical orchiectomy was carried out and the pathology revealed an intratesticular leiomyosarcoma. The patient received additional chemotherapy. Cases of primary intratesticular leiomyosarcoma are rare. This is, to the best of our knowledge, only the tenth case of leiomyisaocoma in an adult reported in the literature, and the first case involving multiple metastases.
PMCID: PMC2792427  PMID: 20019958

Results 1-12 (12)