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Noriyoshi Kawaguchi

Publications and source records attributed to Noriyoshi Kawaguchi.

At least 19 recordsLinked to original sources
PubMed2006

Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation.

Ewing's family tumors (EFTs) are highly malignant tumors arising from bone and soft tissues that exhibit EWS-FLI1 or variant EWS-ETS gene fusions in more than 85% of the cases. Here we show that CIC, a human homolog of Drosophila capicua which encodes a high mobility group box transcription factor, is fused to a double homeodomain gene DUX4 as a result of a recurrent chromosomal translocation t(4;19)(q35;q13). This translocation was seen in two cases of soft tissue sarcoma diagnosed as Ewing-like sarcoma. CIC-DUX4 exhibits a transforming potential for NIH 3T3 fibroblasts, and as a consequence of fusion with a C-terminal fragment of DUX4, CIC acquires an enhanced transcriptional activity, suggesting that expression of its downstream targets might be deregulated. Gene expression analysis identified the ETS family genes, ERM/ETV5 and ETV1, as potential targets for the gene product of CIC-DUX4. Indeed, CIC-DUX4 directly binds the ERM promoter by recognizing a novel target sequence and significantly up-regulates its expression. This study clarifies the function of CIC and its role in tumorigenesis, as well as the importance of the PEA3 subclass of ETS family proteins in the development of EFTs arising through mechanisms different from those involving EWS-ETS chimeras. Moreover, the study identifies the role of DUX4 that is closely linked to facioscapulohumeral muscular dystrophy in transcriptional regulation.

Adult↗
PubMed2006

Report of four cases with high-grade surface osteosarcoma.

High-grade surface osteosarcoma is the rarest of the three types of surface osteosarcoma. Four cases with high-grade surface osteosarcoma arising from the distal femur and tibia are reported in this study. One patient was previously diagnosed with Turner's syndrome. Radiologically, three cases presented characteristic appearances suggesting high-grade bone-forming sarcoma arising from the bone surface; however, one case was similar to other juxtacortical lesions such as periosteal and parosteal osteosarcoma, which typically have a better prognosis than high-grade surface osteosarcoma. Therefore, all cases underwent biopsy to determine a definitive diagnosis. Our strategy of treatment for high-grade surface osteosarcoma was a combination of wide resection and pre-/post-operative chemotherapy, equivalent to the treatment for conventional intramedullary osteosarcoma. At the last follow-up, two cases were still undergoing chemotherapy, one case was continuously disease free during the follow-up period of 81 months, and one patient was living with no evidence of disease 60 months after surgery. The aim of this study is to report the clinical information, oncological outcome and appropriate treatment for high-grade surface osteosarcoma.

Adolescent↗
PubMed2006

Oncologic outcome of parosteal osteosarcoma.

BACKGROUND: This retrospective review evaluated the clinical features and surgical outcomes of parosteal osteosarcoma (POS). METHODS: Nine patients were surgically treated and followed up. Their mean age was 30.8 years. Clinical information and oncologic outcomes of each case were analyzed. RESULTS: Sites of involvement were all in the femur, and all tumors arose from the metaphyseal area of the distal femur. Biopsies for definite diagnoses were performed in just two of the nine cases. Wide resection was applied for all tumors. Surgical evaluations were a 1-cm-wide procedure in six cases and a 2-cm-wide procedure (or more) in three cases. All patients were found to be continuously disease free during the follow-up period of 115.1 months. CONCLUSION: POS showed characteristic findings on radiographic images. Therefore, wide resection without biopsy could be performed in 77.8% (7/9) of the cases. This procedure may contribute to attaining better limb function, because of preventing contamination of healthy surrounding tissue and minimizing the extent of resection. The safety margin was evaluated as a 1-cm-wide procedure. For the choice of reconstruction, indication of autobone grafting (3/9) or total knee replacement (TKR) (6/9) depended on tumor size, location, and shape. With no adjuvant treatments, all cases have shown good clinical courses during the entire follow-up period of about 10 years.

Adolescent↗
PubMed2006

Malignant change secondary to fibrous dysplasia.

BACKGROUND: Malignant change in fibrous dysplasia (FD) is very rare. This study was carried out to establish some characteristic clinical information about this disorder. METHODS: Four cases with a malignant change in FD out of 128 cases with FD were surgically treated and followed up for a median period of 61.3 months. The mean age of the patients was 39.8 years. Clinical features, radiological findings, and the outcome were analyzed for each of the four cases. RESULTS AND CONCLUSION: The sites of the lesions were tibia (2 cases), femur (1 case), and rib (1 case). The forms of FD were monostotic in one case and polyostotic in three cases. Radiologically, plain films and computed tomography (CT) showed osteolytic lesions with poorly delineated margins within and/or near areas having a ground-glass appearance. In the osteolytic lesions, simple cystic changes associated with old FD could be excluded by enhanced magnetic resonance imaging (MRI). Histopathologically, two cases were osteosarcoma, one case was malignant fibrous histiocytoma (MFH), and one case was fibrosarcoma. The management of this disease should be decided according to the type of primary high-grade bone sarcoma. One patient, with MFH, was dead of lung metastasis 13 months after surgery. The others are alive without disease.

Adult↗
PubMed2006

Surgery for dedifferentiated liposarcoma, presenting two radiologically and pathologically distinctive patterns.

In this paper, we report three cases with dedifferentiated liposarcoma in the lower extremities, presenting two patterns that are distinctively different radiologically and pathologically. The first case was a 67-year-old male who had discovered a mass in his left thigh, which was shown as a low and iso density mass between the muscles on computed tomography (CT). The second case was a 61-year-old male who had suffered from an intramuscular tumor with a non-fatty sarcomatous area within the fatty components as shown on magenetic resonance imaging (MRI). The third case was a 52-year-old female who had presented with an intramuscular tumor of the left thigh, consisting of a mass with fat and another soft tissue tumor adjacent to the lipomatous component as detected with CT and MRI. The final pathological diagnoses of the resected specimens in all three cases were concluded to be dedifferentiated liposarcoma, composed of well-differentiated liposarcomas and spindle and/or pleomorphic sarcomas, compatible with malignant fibrous histiocytoma. In all three cases, wide resection of the tumor was successfully carried out, and all patients have been continuously disease-free up to the most recent follow-up. Evaluation of the surgical margins for the resected specimens indicated that the safety margin for a dedifferentiated lesion should be accomplished as an adequate margin or more, and a marginal margin or more could be considered as safe only for the confined part of a well-differentiated liposarcoma.

Aged↗
PubMed2005

EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12).

POU5F1(OCT3/4) is a sequence-specific transcription factor that is essential for keeping germ cells and embryonic stem cells in an immature and pluripotent status. In this article, we report that POU5F1 was fused to EWSR1 in a case of undifferentiated sarcoma derived from pelvic bone with chromosomal translocation t(6;22)(p21;q12). The EWSR1-POU5F1 chimera consists of exons 1-6 of EWSR1 and exons 2-5 and a part of exon 1 of POU5F1. The predicted amino acid sequence indicates that the chimera is composed of the N-terminal QSY domain of EWS that functions as a transcriptional activation domain and the C-terminal POU DNA-binding domains derived from POU5F1. The t(6;22) tumor does not belong to any known categories of bone and soft-tissue tumors (BSTs). It is suggested that EWS-POU5F1 may act as an oncogenic transcription factor and that its expression may contribute to undifferentiated and immature phenotypes of BST.

Artificial Gene Fusion↗
PubMed2005

Surgical treatment of bone metastasis: indications and outcomes.

Due to advances in cancer treatment that prolong survival, there has been a noticeable increase in the prevalence of bone metastasis. Consequently, the likelihood of orthopedic surgeons encountering such tumors and the need for effective surgical treatment are also expanding. Although bone metastasis constitutes only one possible type of metastatic lesion, and while local control at a bone metastatic site alone may have little effect on total curability, the quality of life (QOL) of the patient cannot be ensured if local control is ignored. Therefore, it is important to achieve local control through multidisciplinary treatments aimed at both reduced surgery and at conservation of limb function. Surgical treatment may be indicated after a series of more conservative treatments. Among the main indications are pathologic fracture or a high risk of fracture of limb bones. Acute spinal cord injury caused by acute compression fracture from spinal metastasis is a relative indication. The occurrence of a solitary metastasis, for which extended survival may be anticipated, is also an indication for surgery to achieve local control. Appropriate local control is required to realize a predicted survival period. As well, the surgical method, resection margin, and supplementary treatments, and immediately effective reconstruction method should be selected accordingly.

Bone Neoplasms↗
PubMed2004

Clinico-molecular study of dedifferentiation in well-differentiated liposarcoma.

Well-differentiated liposarcoma (WD) acquires fully malignant potential when the histological progression named dedifferentiation occurs. This progression is supposed to occur in a time-dependent manner but this is still a debated issue. Clinically, the prediction of dedifferentiation for WD is very important from the therapeutic point of view. To identify genes that are predictive of dedifferentiation and to understand the mechanism of dedifferentiation, we investigated clinical information of 50 cases and studied the gene expression profiles of 36 lipomatous tumors using cDNA microarray. The clinical study showed that the dedifferentiation did not always seem to occur in a time-dependent manner. Interestingly, from the gene expression study, unsupervised hierarchical clustering analysis of well-differentiated lesions obtained from dedifferentiated liposarcoma (DD) cases that were indistinguishable from WD pathologically showed a clearly distinct gene expression pattern from WD. Using the pattern-matching program, 1687 genes including 487 known genes were identified, which discriminated WD cases from well-differentiated lipomatous lesions obtained from DD cases. These results suggest that the dedifferentiation may arise from different types of WD that could be distinguished from gene expression profiling but could hardly be classified by the pathological studies.

Base Sequence↗
PubMed2004

Postradiation soft tissue sarcoma: a multiinstitutional analysis of 14 cases in Japan.

Radiation therapy (RT) is commonly used to treat malignant tumors, but it leads to side effects and complications. Postradiation sarcomas developing from a previously irradiated area are especially vicious to deal with, though their occurrence is rare. This article focuses on the clinical manifestations, pathological characteristics, and therapeutic effects concerning postradiation soft tissue sarcomas (PRSTSs). A series of 14 PRSTSs treated between 1979 and 2000 in five hospitals in Japan were analyzed. Their histological types were malignant fibrous histiocytoma (eight cases), extraskeletal osteosarcoma (four cases), fibrosarcoma (one case), and leiomyosarcoma (one case). The primary diagnoses, RT history, latent period, and outcome of treatment were studied retrospectively. The original tumors included uterine cancer (seven cases), breast cancer (four cases), synovial sarcoma (one case), squamous cell carcinoma (one case), and Hodgkin's disease (one case). There were 13 women and 1 man, with ages ranging from 23 to 77 years (mean 58 years) at the time of the appearance of the PRSTS. RT doses ranged from 48 to 91 Gy (mean 62 Gy). The latent period from RT to the occurrence of the PRSTS varied from 4 to 27 years (mean 12.6 years). Altogether, 4 of 13 patients (31%) had recurrence of the sarcoma after resection. Of the 10 patients whose tumors were removed with a wide margin, one had a local recurrence; 3 cases were performed with a marginal margin and all 3 had a local recurrence. One of three who underwent RT and one of five who underwent chemotherapy (CT) responded. Of the 14 patients, 6 (42.9 %) survived continuously disease free, 2 (14.3%) died from other causes, 2 (14.3%) has an unknown outcome, and 4 (28.6 %) died of the disease during the follow-up period of 16-36 months (mean 24 months). The deaths due to other causes included an esophageal cancer and a wound infection. The prognosis of the PRSTS patients was not poor if the tumor could be removed with a wide surgical margin. Because adjuvant therapies including RT and CT had a poor effect on PRSTSs, the primary treatment of PRSTSs should be radical resection with a wide margin.

Adult↗
PubMed2004

The concept of curative margin in surgery for bone and soft tissue sarcoma.

To clarify the safety margin in excision of bone and soft tissue sarcomas, a new evaluation method for surgical margins was drafted by the Bone and Soft Tissue Committee of the Japanese Orthopaedic Association in 1989. This new evaluation system was applied to 1329 patients with bone and soft tissue sarcomas, of whom 492 were excluded because of insufficient details, leaving 837 patients (901 surgeries) for the current study. Based on the results derived from analyzing these registered surgical margins, predictable safety margins under different conditions could be determined. When preoperative treatment is not done or is ineffective in high-grade sarcoma, a margin greater than 3 cm wide is necessary. When the preoperative modality is effective, a 2-cm wide margin is permissible. However, for recurrent sarcoma, whether low-grade or high-grade, a curative procedure is necessary. For low-grade sarcoma, obtaining an adequate wide margin is essential but partial marginal margins are acceptable at sites where barriers exist. When the margin is insufficient, radiotherapy should be used regardless of the tumor grade. Making a safety margin definitive through this system, an optimum treatment can be obtained and unnecessary adjunctive modalities can be avoided.

Bone Neoplasms↗
PubMed2004

Pasteurized autologous bone graft in surgery for bone and soft tissue sarcoma.

For skeletal reconstruction in surgery for bone tumors, pasteurization of bone has been used with favorable results over autoclaving or boiling. Twenty-three patients with primary malignant bone tumors and two patients with soft tissue sarcoma invading bone reconstruction surgery with pasteurized autologous bone graft comprised the study group. There were 16 females and nine males, between 7 and 77 years of age who were followed up for at least 3 years (mean, 52 months). The International Society of Limb Salvage graft evaluation method was used for evaluation of the radiographs. Fifteen patients (60%) had complete incorporation of the graft and eight patients (32%) had partial incorporation. Viability of the grafts was evaluated by bone scintigraphy. Of 22 patients evaluated, uptake was detected in 17 patients from approximately 6 months postoperatively after which it increased gradually. The functional results were assessed by the system of the Musculoskeletal Tumor Society, and the mean functional rating was 86%. Eighteen patients have been disease-free and seven have died of disease. Fracture (12%) and infection (20%) were the main complications. No local recurrence was detected. These results indicate that pasteurization of bone may be a useful option for reconstruction after resection of malignant bone tumors. The advantages of extracorporeal pasteurization include convenience of use, avoidance of intraspecies infection and allogenic reactions, and satisfactory bone remodeling.

Adolescent↗
PubMed2004

[Surgical treatment for bone and soft tissue sarcoma].

There are many kinds of wide excision or wide resection, which are methods to remove the tumor with surrounding tissues. The curability of wide resection depends on the range and characteristics of the normal surrounding tissues. The fascia, periosteum and perivascular sheath act as barriers against invasion of tumors. Therefore, evaluation of the surgical margin is essential in surgery for malignancy. Some sarcomas characteristically show invasive growth patterns while others have a discrete border. Causes of the local recurrence are 1) insufficient surgical margin, 2) skip metastasis, 3) tumor thrombus, and 4) lymph node metastasis. The so-called "Safety surgical margin" is the margin that prevents local recurrence due to insufficient surgical treatment. Local recurrence due to other causes can not be treated by surgery alone as chemotherapy is also required. For example, the infiltrative type of malignant fibrous histiocytoma requires a curative procedure. On the other hand, non-infiltrative types of sarcoma or high-grade sarcoma, which are good responders to preoperative treatment, are locally controlled by an adequate wide margin procedure. When the tumor is close to the bone, main vessels and/or nerves, it is sometimes very difficult to preoperatively decide whether or not to sacrifice these important organs. A new surgical method, "In Situ Preparation (ISP)," is a useful method to solve such problems. ISP makes it possible to evaluate the surgical margin without contamination. And additional procedures including alcohol soaking or pasteurization can be achieved according to the surgical margin. Because ISP can prevent overtreatment, the number of our cases that require resection of the nerves or vessels have decreased. After a wide resection, there have been many possible complications, including infection, deep venous thrombosis, loosening of prosthesis, skin necrosis, and arterial occlusion. Once postoperative complications occur, patients must remain in the hospital for a long time. To prevent this, the preservation of normal tissue, meaning reduction of surgical margin, is important.

Blood Vessel Prosthesis Implantation↗
PubMed2003

Radiographic analysis of pasteurized autologous bone graft.

OBJECTIVE: Local malignant bone tumor excision followed by pasteurization and subsequent reimplantation is a unique technique for reconstruction after resection of primary bone sarcomas. The purpose of this investigation was to assess the normal and abnormal long-term radiographic findings of intercalary and osteo-chondral pasteurized bone graft/implant composite. DESIGN AND PATIENTS: The long-term radiographic findings of pasteurized bone grafts used in reconstruction after resection of bone and soft tissue sarcomas in relation to patients' clinical data were reviewed retrospectively. Thirty-one patients (18 females, 13 males; age range 7-77 years, mean 30 years) who underwent surgery between April 1990 and January 1997 at the authors' institute constituted the material of this study. They were followed up for at least 3 years or until the patient's death (mean 69 months). The International Society of Limb Salvage graft evaluation method that assesses the fusion, resorption, fracture, graft shortening, fixation, subluxation, joint narrowing and subchondral bone was used for evaluation of the radiographs. RESULTS AND CONCLUSIONS: Twenty-one patients (68%) showed complete incorporation of graft and eight patients (26%) had partial incorporation. The overall radiographic evaluation rate was 81%. Fracture (10%) and infection (16%) were the main complications. No local recurrence was detected. These results indicate that pasteurization of bone is a useful option for reconstruction after resection of malignant bone tumors.

Adult↗
PubMed2003

Results of surgery for malignant fibrous histiocytomas of soft tissue.

BACKGROUND: To address the prognosis and the role of surgery in the management of patients with malignant fibrous histiocytoma (MFH), strict definition and accurate evaluation of local recurrence is mandated, together with adequate gross and microscopic evaluation of the achieved surgical margins. METHODS: One hundred and twenty-three patients with MFH were retrospectively analyzed regarding prognostic factors of the disease, which included the following: (1). primary or recurrent, (2). histological grade, (3). adjuvant chemotherapy, (4). size, (5). local recurrence after primary surgery done at the authors' institute, (6). adjuvant radiotherapy, and (7). surgical margin. Initially, all patients were metastasis-free (M0N0). RESULTS: Local recurrence after primary surgery done at the authors' institute was the most significant prognostic factor, where 20 of 123 patients developed local recurrence ( P < 0.0001). The cause of local recurrence were insufficient surgical margin in 16 patients, while in 4, local recurrences were related to lymph node metastasis, skip metastasis, and tumor embolism. The local recurrence rate for each surgical procedure was 75% for intralesional, 44.4% for marginal, 30.8% for inadequate wide, 12.3% for adequate wide, and 5% for curative procedures. In patients with a history of recurrent tumor or infiltrative pattern, local recurrence was not observed after a curative procedure, but occurred even after an adequate wide procedure. CONCLUSION: To improve the prognosis of MFH, surgical prevention of local recurrence is essential. An adequate wide procedure for primary tumors and a curative procedure for recurrent tumors and tumors with an infiltrative pattern provide safe surgical margins.

Adolescent↗