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Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas.

OBJECTIVE: To define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. METHODS: The authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and disease-specific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. CONCLUSIONS: Positive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.

Adolescent↗

Comparative antitumor activities of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) and mitomycin C.

The antitumor activity of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) against 7 kinds of ascitic tumors and 4 kinds of solid tumors was compared with that of mitomycin C (MMC). M-83 showed more potent activities than MMC against ascites sarcoma 180, fibrosarcoma Meth 1, sarcoma Meth A, melanoma B-16, leukemia P388 and lymphoma EL4, by a single intraperitoneal injection. Furthermore, M-83 gave markedly higher chemotherapeutic ratio than MMC in these tumor systems. M-83 was also markedly effective against solid tumors of sarcoma 180, Meth 1, Meth A and Lewis lung carcinoma, by a single intravenous injection. M-83 gave lower myelo-suppression than MMC at the doses which gave almost equal inhibition on the tumor growth of solid Meth 1. M-83 and MMC significantly inhibited the growth of HeLa S3 cells. Cell growth was observed at 24 hours after addition of 3 X 10(-3) mM of drugs, but no growth was shown thereafter. M-83 inhibited more strongly the incorporation of the radioactive precursor into DNA than that into RNA or protein at the concentration of 3 X 10(-3) mM.

Animals↗

NEUROGENIC sarcoma.

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Fibrosarcoma↗

Bioassay of aniline hydrochloride for possible carcinogenicity.

A bioassay of aniline hydrochloride for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Aniline hydrochloride was administered in the feed, at either of two concentrations, to groups of 50 male and female animals of each species, with the exception of 49 female mice in the high dose group. The high and low dietary concentrations of aniline hydrochloride were, respectively, 0.6 and 0.3 percent for rats and 1.2 and 0.6 percent for mice. After a 103-week period of compound administration, observation of the rats and mice continued for up to an additional 5 weeks. For rats and mice, respectively, 25 and 50 animals of each sex were placed on test as controls and fed only the basal diet. In male rats there were several types of mesenchymal tumors, primarily of the spleen, associated with administration of the compound. Hemangiosarcomas of the spleen and the combined incidence of fibrosarcomas and sarcomas NOS of the spleen were each statistically significant in male rats. The combined incidence of fibrosarcomas and sarcomas NOS of multiple body organs was also significant in male rats. The number of female rats having fibrosarcomas or sarcomas NOS of either the spleen alone or multiple organs of the body cavity was significantly associated with increased dietary concentration of aniline hydrochloride. This result was not supported by the Fischer exact tests, but because of the rarity of these tumors, the observed incidences (0/24 in the control group, 1/50 [2 percent] in the low dose group, 7/50 [14 percent] in the high dose group) were considered indicative of a compound-related carcinogenic effect. In mice of both sexes no tumors occurred in statistically significant increased incidences among dosed groups when compared to controls. Under the conditions of this bioassay, dietary administration of aniline hydrochloride was carcinogenic to male and female Fischer 344 rats, inducing hemangiosarcomas and a combination of fibrosarcomas and sarcomas NOS of the spleen and a combination of fibrosarcomas and sarcomas NOS of multiple body organs. There was no evidence of compound-induced carcinogenicity in B6C3F1 mice of either sex.

Journal Article↗

Frequent occurrence of p53 mutations in rhabdomyosarcoma and leiomyosarcoma, but not in fibrosarcoma and malignant neural tumors.

We have analyzed soft-tissue sarcomas (STS) molecularly for mutations in the tumor-suppressor gene p53 and immunohisto-chemically for expression of p53 and mdm2 proteins. In this study, tumor samples from 3 groups of soft-tissue sarcomas, i.e., fibrosarcomas, myogenic sarcomas and malignant neural tumors (MNT), were investigated. The methods applied encompass immunohistochemistry on 198 tumor samples using p53 antibodies (DO-1 and DO-7) and an mdm2 antibody (IF-2). Out of these, 100 samples were subjected to non-radioactive PCR-SSCP-sequencing analysis. Immunohistochemical detection rate for p53 (range of 57% to 67%) and for mdm2 proteins (range of 19 to 44%) was similar in all 3 groups. In higher tumor grades, an increased rate of immunopositivity was found for p53 but not for mdm2. Investigation of p53 mutational status revealed 6 mutations in myogenic sarcomas but none in malignant neural tumors or fibrosarcomas, suggesting different roles of p53 in the 3 STS groups. Interestingly, a G-->A transition in codon 245 (a CpG site) was found in 3 myogenic sarcomas. Our results and those of others suggest p53 codon 245 as a mutational hotspot in sarcomas, as recognized in carcinomas.

Base Sequence↗

[Malignant fibrous histiocytoma: pleomorphic sarcoma NOS or pleomorphic fibrosarcoma].

The entity and nosology of pleomorphic malignant fibrous histiocytoma (MFH) is still ambiguous. The actual WHO-Classification uses pleomorphic malignant fibrous histiocytoma (MFH) and pleomorphic sarcoma NOS (not otherwise specified) synonymously. On the other hand text and illustrations convey the impression, that these tumors also could be pleomorphic lipo-, leio- or rhabdomyosarcomas etc. It would have been more informative to emphasize, that with the above mentioned specific sarcoma types MFH-like appearance may occur. Furthermore it would have been more up to date to consider pleomorphic sarcomas NOS as pleomorphic fibrosarcomas and include them in the chapter of fibroblastic and myofibroblastic tumors. This concept already has been carried out for the former myxoid variant of MFH, nowadays preferentially called myxofibrosarcoma. There is controversial discussion about the clinical significance of exact typing of pleomorphic sarcomas. Problems may also occur due to the lack of standards, which degree of desmin expression signifies leiomyosarcoma or just indicates myofibroblasts in MFH. The requirement of exclusion of other tumor-types before diagnosing pleomorphic fibrosarcoma still remains obligatory. After verification of the diagnosis pleomorphic sarcoma NOS or pleomorphic fibrosarcoma, grading e.g. according to criteria of the FFCCS can be carried out. Most cases of pleomorphic fibrosarcoma will qualify as high grade malignant.

Diagnosis, Differential↗

Infantile rhabdomyofibrosarcoma: a high-grade sarcoma distinguishable from infantile fibrosarcoma and rhabdomyosarcoma.

Three patients with a predominantly fibrosarcomatous, desmoplastic, and fascicular spindle-cell sarcoma, resembling that of infantile fibrosarcoma but with ultrastructural and immunocytochemical evidence of rhabdomyoblastic differentiation, are described. The tumors were compared light and electron microscopically and immunocytochemically with six classical cases of infantile fibrosarcoma of the desmoplastic type. The three tumors occurred in two girls and one boy who were between 1 and 3 years of age. Ultrastructurally, the tumor cells primarily demonstrated fibroblastic and myofibroblastic features, but there were also tumor cells with sarcomere-like structures. The spindle-shaped, fibroblast-like tumor cells expressed vimentin, desmin, and smooth muscle-specific and sarcomere-specific actins. In one tumor peculiar intracytoplasmic inclusions were observed by light and electron microscopy. The immunocytochemical analysis indicated that these bodies contained all types of thin and intermediate filaments. In short-term cell cultures the tumor cells of two examined tumors revealed immunoreactivity for vimentin, smooth muscle-specific actin, and desmin. Cytogenetically, both tumors displayed a similar chromosomal pattern. One tumor contained two abnormal clones with monosomy 19 and monosomy 22, respectively, and the other tumor revealed a single clone with monosomy 19. In addition, both tumors contained clones with a normal karyotype. Two of the patients with metastatic spread died within 2 years of the primary operation. The third patient is alive with a local recurrence. The three tumors described here deviate from infantile fibrosarcoma in terms of their clinical, ultrastructural, immunocytochemical, and cytogenetic characteristics. The descriptive term "infantile rhabdomyofibrosarcoma" is suggested. The present investigation calls for detailed studies of tumors diagnosed as infantile fibrosarcomas that have metastasized and followed a fatal course.

Child, Preschool↗

Experimentally induced synovial sarcoma.

Synovial sarcoma has been induced in the knee joints of rats by intra-articular injection of 9-10-dimethyl-1-2-benzanthracene. Tumours developed from three to six months after the last injection. The neoplasms obtained were classified as synovial sarcoma (50%), fibrosarcoma (25%), giant cell sarcoma (15%), malignant fibrous histiocytoma (10%). The synovial membrane in the treated knee joints presented a chronic synovitis associated with fibrosis and proliferation of the lining cells. The primitive tumour spread locally infiltrating muscle and the adjacent bones. Metastases occurred most frequently to the lungs (70%) and liver (20%); lymph nodes were involved in 10%.

9,10-Dimethyl-1,2-benzanthracene↗

Primary pure intratesticular fibrosarcoma.

Testicular sarcoma appears to be a rare stromal tumor usually of indolent course with potential for distant metastases. A pure primary intratesticular fibrosarcoma in a 71-year-old male is presented. By the time the tumor became evident metastases had already occurred widely. The course was rapidly fatal. A review of the literature yielded only one case reported previously. The present case illustrates that pure fibrosarcoma occurs occasionally as a stromal tumor and may be associated with a dismal prognosis. The diagnosis of pure fibrosarcoma should be made only after extensive sampling of the testicular tumor to rule out an associated germ cell component. The differential diagnosis also includes the fibroma of gonadal stroma origin and the unclassified sex cord-stromal tumor with a predominance of spindle cells.

Aged↗

Interstitial photoradiation therapy for primary solid tumors in pet cats and dogs.

Photoradiation therapy, a new method for treatment of solid malignant tumors, depends upon the tumor localization and retention of hematoporphyrin derivative, which is activated in vivo by light in the red region of the spectrum. As currently applied to cutaneous and s.c. lesions, the light dose is limited by both normal tissue reactions and the effective penetration of the light through the tissues. In this report, primary solid malignant lesions in pet cats and dogs have been treated by interstitial photoradiation therapy by applying the activating light from a laser [635 +/- 5 (S. D.) nm] directly into the tumor masses thrugh a 200-micrometer quartz fiber optic. Twelve of 14 lesions (four osteosarcomas, two squamous cell carcinomas, two malignant melanomas, one mast cell sarcoma, one fibrosarcoma, one sebaceous gland sarcoma, and a metastatic prostatic carcinoma) responded to treatment, and three are currently considered permanently controlled at 1 year or more following treatment. This method has not only allowed photoradiation therapy to be applied to some remote lesions but has also nearly eliminated normal tissue effects, thus greatly extending the applicability of this treatment to a wide range of human tumors.

Adenocarcinoma↗

Post-irradiation pituitary sarcoma.

A fibrosarcoma developed in the pituitary fossa of a patient who had been irradiated 13 years previously for treatment of pituitary adenoma. The tumor was a large aggressively growing spindle cell neoplasm which eroded adjacent structures, causing increased intracranial pressure, and eventual cerebellar tonsillar herniation. In common with previously described post-irradiation sarcoma of the pituitary, this lesion developed in the path of irradiation after a long latent period, did not metastasize, and contained histologically recognizable benign appearing pituitary adenoma interspersed among the spindle cell tumor. The dose of radiation (5000 rads) also lay within the range associated with sarcomatous transformation.

Aged↗

Soft tissue sarcoma of the hand.

The authors report twelve cases of soft tissue sarcoma distal to the flexor crease of the wrist. These were isolated from a total of 414 cases of soft tissue sarcoma treated at the Rizzoli Institute. This case material comprises three epitheloid sarcomas, four fibrosarcomas, two rhabdomyosarcomas, one synovial sarcoma, one myxoid malignant fibrous histiocytoma, and one myxoid chondrosarcoma. The authors deal in detail with the biological behaviour, the criteria of differential diagnosis, and the indications for treatment in each histological type of sarcoma.

Adolescent↗

Heterogeneity of collagen isolated from methylcholanthrene-induced sarcoma.

Rat fibrosarcoma induced by subcutaneous injection of methylcholanthrene was found to contain at least three different types of collagen. Two of them were identified as type I and type III collagens, the third (fraction B) seems to be specific for this tumour. The ratio of type I to type III collagen is lower in fibrosarcoma than in normal rat skin. The number of hydroxyproline residues in alpha 1 (I), alpha 2 (I) and alpha 1 (III) chains of tumour collagen appears to be higher than in the corresponding chains of rat skin collagen. Fraction B is composed of three identical alpha chains connected with disulphide bonds. It contains a relatively low amount of glycine: 234 molecules per 1000 residues. The amount of hydroxyproline and cysteine is similar to that found in the type III collagen.

Alkylation↗

Wide resection of primary tumors of bone and replacement with massive bone grafts: an improved technique for transplanting allogeneic bone grafts.

The treatment by wide resection of 104 local aggressive and low grade malignant bone tumors is presented with results after follow-up for 5.0 years on the average. The series comprises 29 giant cell tumors, most of them malignant or premalignant, 25 cartilaginous tumors (12 verified chondrosarcomas and 13 chondromas suspect of malignancy), 14 cases of sarcoma, 6 of fibrosarcoma, 4 parosseal sarcomas, 3 osteosarcomas and one chordoma. The remaining 36 cases include: aneurysmal bone cysts, fibrous dysplasia, chondroblastomas, osteoblastomas, giant chondromyxoid fibroma, and hemangiomas. After resection of the affected area, the resulting defect was replaced with massive autologous or allogeneic bone or osteoarticular graft in altogether 68 cases (autologous bone transplant in 61 cases and allograft in 7). A metallic endoprosthesis was used in replacement in 8 cases. No replacement of the defect was needed in 28 cases. The technique of the allogeneic bone transplantations consisted of massive bone or bone cartilage grafts which had been stored at a low temperature, and firm osteosynthesis. In every case, allogeneic (stored) bone was supplemented with autologous cancellous bone around the juncture of graft and host bone. This supplement proved to be important for success of the operation. The overall results were good in 81% and fair in 11%. Five cases had to be amputated and 3 patients were lost to follow-up, a possible total of 8% poor results. Extensive resection with massive bone grafting is a worthwhile approach in the treatment of selected cases of aggressive and low grade malignant bone tumors.

Adolescent↗