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PubMed1998

Adjuvant chemotherapy for primary cardiac sarcomas: the IGR experience.

The effect of additional treatments after surgery in patients with primary cardiac sarcoma (PCS) remains unknown. The present study aims to evaluate the benefit of chemotherapy in patients with non-metastatic cardiac sarcomas after optimal resection. Between October 1979 and December 1995, 15 patients with a median age of 45 (range 16-66) and a resected primary cardiac sarcoma [angiosarcoma (six), malignant fibrous histiocytoma (three), leiomyosarcoma (two), rhabdomyosarcoma (two), liposarcoma (one) and synoviosarcoma (one)] received a doxorubicin-containing regimen within 6 weeks of surgery. Adjuvant chemotherapy combinations included cyclophosphamide, vincristine and dacarbazine in four patients; ifosfamide in nine; methotrexate and vincristine in one; and doxorubicin alone in one patient. At present, 13 patients have relapsed (five during therapy), with a median time to progression of 10 months. Twelve patients developed local relapse, in four cases without metastatic disease. Two patients remain in complete remission 27 and 25 months after surgery. The median time to progression was shorter in patients presenting a cardiac angiosarcoma than other histological types (3 vs 14 months, P < 0.01). Twelve patients have died, with a median overall survival of 12 months. The 2-year survival rate is 26%. Survival was significantly longer for patients with completely resected tumours (22 vs 7 months; P = 0.02) and those who did not have angiosarcoma (18 vs 7 months; P = 0.04). In conclusion, post-operative conventional doxorubicin-based chemotherapy failed to modify the natural history of patients with resected cardiac sarcomas. Locoregional failure remains the main problem even after histologically complete resection. New approaches must be tested in patients with primary cardiac sarcoma.

Adolescent↗
PubMed2005

Gene expression profiling of human sarcomas: insights into sarcoma biology.

Sarcomas are a biologically complex group of tumors of mesenchymal origin. By using gene expression microarray analysis, we aimed to find clues into the cellular differentiation and oncogenic pathways active in these tumors as well as potential biomarkers and therapeutic targets. We examined 181 tumors representing 16 classes of human bone and soft tissue sarcomas on a 12,601-feature cDNA microarray. Remarkably, 2,766 probes differentially expressed across this sample set clearly delineated the various tumor classes. Several genes of potential biological and therapeutic interest were associated with each sarcoma type, including specific tyrosine kinases, transcription factors, and homeobox genes. We also identified subgroups of tumors within the liposarcomas, leiomyosarcomas, and malignant fibrous histiocytomas. We found significant gene ontology correlates for each tumor group and identified similarity to normal tissues by Gene Set Enrichment Analysis. Mutation analysis done on 275 tumor samples revealed that the high expression of epidermal growth factor receptor (EGFR) in certain tumors was not associated with gene mutations. Finally, to further the investigation of human sarcoma biology, we have created an online, publicly available, searchable database housing the data from the gene expression profiles of these tumors (http://watson.nhgri.nih.gov/sarcoma), allowing the user to interactively explore this data set in depth.

Cluster Analysis↗
PubMedDate not supplied

Bullous change by CT heralding metastatic sarcoma.

The association of spontaneous pneumothorax with metastatic osteosarcoma is well known. Small blebs and bullous change can be easily detected in the lungs by computed tomography. In patients with known sarcomas, blebs and bullae may appear as the first or early manifestation of metastatic disease (or concurrent with the disease) as illustrated by the three patients presented here with three different types of sarcomas. The literature has been reviewed as to the etiology of spontaneous pneumothoraces occurring in metastatic sarcomas and the relationship of bleb and bullae formation to these spontaneous pneumothoraces is discussed.

Adolescent↗
PubMed2005

Dedifferentiated liposarcoma of the oral cavity with angiosarcomatous dedifferentiation.

We report a unique case of a 42-year-old woman with a dedifferentiated liposarcoma of the soft tissue of the oral cavity with angiosarcomatous dedifferentiation. Liposarcomas compromising the head and neck region are very unusual, and most of the cases in oral cavity show a well-differentiated pattern. Dedifferentiation in liposarcomas occurs in about 10% of the cases and, when it occurs, the dedifferentiated areas usually resemble high-grade fibrosarcoma or pleomorphic sarcoma. Divergent differentiation might also occur. To the best of our knowledge, there are only nine cases of dedifferentiated liposarcoma of the oral cavity, none of which show an angiosarcomatous dedifferentiation.

Adult↗
PubMedDate not supplied

Long-term results of aggressive surgical treatment of primary and recurrent retroperitoneal liposarcomas.

The aim of this study was to establish the role of surgery in the treatment of retroperitoneal liposarcomas. Data concerning 28 patients submitted to surgery for retroperitoneal liposarcoma in our department over the period from 1972 to 1999 were reviewed retrospectively and analysed. Seventy-four operations were performed; in 54% of the operations it was necessary to resect contiguous organs (kidney 60%, colon 50%, adrenal gland 35%). In 89%, grossly curative resection was achieved at the first operation; 20 patients had at least one local recurrence after first operation (median time interval: 22 months). The mean follow-up was 80 months; median survival time was 51 months and 5-year actuarial survival time 51%. Patients with low-grade liposarcoma showed a statistically significant improvement (P < 0.001) in median survival (153 months) versus those with medium- (37 months) and high-grade sarcomas (8 months). At present surgery is still the treatment of choice in the treatment of primary and recurrent liposarcoma; in the case of low-grade liposarcomas especially, an aggressive surgical approach can result in long-term survival.

Adolescent↗
PubMed1994

Histological necrosis in soft tissue sarcoma following preoperative irradiation.

Forty-eight patients with soft tissue sarcomas that presented adverse features for treatment by limb salvage surgery and postoperative irradiation were treated by preoperative irradiation and surgery using a consistent protocol. Following resection, the extent of histological necrosis in the specimen was scored according to the criteria of Willet et al. Of the 48 cases, 16 (34%) demonstrated Grade 1 response (< 50% necrosis), 15 (31%) Grade 2 (50-80% necrosis), and 17 (35%) Grade 3 (> 80% necrosis). There was a trend toward more extensive necrosis in liposarcoma tumors (53% showing Grade 3 response compared to 26% of other sarcomas). Logistic regression analysis demonstrated a significant relationship between necrosis and tumor size (P < 0.001) with larger tumors having higher grades of necrosis. Tumor grade did not seem to affect the extent of necrosis. In comparison to the previous report of necrosis in soft tissue sarcoma following irradiation, the current analysis revealed a smaller proportion of tumors with Grade 3 necrosis.

Adult↗
PubMed2004

Lessons from genetic profiling in soft tissue sarcomas.

Soft tissue sarcomas represent a heterogeneous group of tumors and include over 50 histotypes. Some of these tumor types are characterized by specific chromosomal translocations, whereas other types show complex genetic aberrations. The recent developments within gene expression technologies have now been applied to studies of soft tissue sarcomas (STS) and the first results indicate that genetic signatures are useful for classification and diagnosis. Distinctive expression profiles have been found in e.g. gastrointestinal stromal tumors (GISTs), synovial sarcomas, malignant peripheral nerve sheath tumors (MPNSTs), and in subsets of liposarcomas. The more pleomorphic tumor types, such as high-grade variants of leiomyosarcomas, malignant fibrous histiocytomas (MFHs), fibrosarcomas, and subtypes of liposarcomas, show a greater variability among the expression profiles, but interestingly subsets with distinctive expression profiles can be identified also among these tumors. The data available place many of the genes hypothesized to be involved in the development of a certain type of STS, such as the KIT gene in GIST development, among the top discriminating genes. Thereby expression profiling provides novel insights into the pathogenesis of STS. Although much work remains to be done to validate the data and to define optimal discriminating gene lists, the current lessons from gene expression studies in STS are encouraging and imply that genetic signatures may serve as diagnostic and prognostic markers and may help identify novel therapeutic strategies.

Chromosome Aberrations↗
PubMed1998

Retroperitoneal tumors: do the satellite tumors mean something?

BACKGROUND AND OBJECTIVES: Primary retroperitoneal tumors constitute a rather uncommon disease with an incidence of 2 in 100,000. Local recurrence after surgical resection is reported between 60% and 90% at 10 yr. The aim of this study was to present the problem of satellite tumors around the main tumor mass and their possible relation to local recurrence. METHODS: Twenty-nine patients with retroperitoneal tumors underwent surgical resection in our department during an 8-yr period. We reviewed their records including their preoperative computed tomography (CT) scans. RESULTS: Twenty patients had "complete" resections requiring seven nephrectomies, four colectomies, two splenectomies, and one appendectomy. In nine cases the resection was incomplete because of tumor invasion to vital structures. Histopathology revealed that the resected tumors were: liposarcomas (12), leiomyosarcomas (4), paragangliomas (5), malignant fibrous histiocytomas (3), other sarcomas (3), schwannoma (1), myelolipoma (1), and the malignancy grade was I in 6, grade II in 11, and grade III in 12 cases. Two patients died within 30 d of the operation. The I year recurrence rate was 41.4% (12/29) and the total recurrence rate 55.2% (16/29). Survival at 5 yr was 31% (9/29), whereas the disease-free survival was 20.7% (6/29). Four patients required reoperations. In seven cases (24,1%) preoperative CT scans revealed small nodular lesions around the main tumor that were removed en bloc and were of the same histopathological type as the main tumor. We called these "satellite" tumors. All seven patients had local recurrence within 1 yr. CONCLUSIONS: There seems to be a close relationship between the finding of satellite tumors and the recurrence of the disease. The existence of satellite tumors on the preoperative CT scan may be used as a guide for the extent of the resection, and further investigations are necessary before they are used as a prognostic sign.

Adolescent↗
PubMed2000

Expression of telomerase activity and telomerase RNA in human soft tissue sarcomas.

OBJECTIVE: To investigate whether telomerase is reactivated in soft tissue tumor and whether telomerase activity is regulated at the transcriptional level. DESIGN: Fresh tissue samples of 24 soft tissue sarcomas were analyzed for telomerase activity by a radioactive polymerase chain reaction-based telomeric repeat amplification protocol assay and for human telomerase RNA (hTR) by an in situ hybridization assay. SETTING: Tertiary care teaching hospital. PATIENTS: Twenty-four patients with soft tissue tumor were surgically treated. Twelve patients had malignant fibrous histiocytoma, 5 had liposarcoma, 6 had leiomyosarcoma, and 1 had rhabdomyosarcoma. RESULTS: Telomerase activity was detected in 4 sarcoma samples (17%), all of which were positive for hTR. Expression of hTR was demonstrated in 13 sarcomas (54%), 4 of which were positive for telomerase and 9 of which were negative for telomerase. One (50%) of 2 grade 1 tumors, 9 (50%) of 18 grade 2 tumors, and 3 (75%) of 4 grade 3 tumors showed hTR expression. CONCLUSIONS: The relatively low frequency of telomerase activity in soft tissue sarcomas suggests that telomerase may not play an important role in tumorigenesis in these tumors. Telomerase ladders were demonstrated only in association with tumors expressing hTR. It is noteworthy that half of the patients with grade 1 and 2 tumors expressed hTR, suggesting that telomerase RNA may be useful as a marker for identifying tumor aggressiveness earlier than the conventional histopathologic grading scale.

Adult↗
PubMed2000

Clinico-pathological data and prognostic factors in completely resected AJCC stage I-III liposarcomas.

BACKGROUND: In general, although biological behavior and prognosis of liposarcomas (LPS) are more favorable compared with most other soft tissue sarcomas (STS), prognosis can vary widely depending on tumor characteristics, especially histological subtype and tumor grade. PATIENTS AND METHODS: All consecutive, completely resected stage I-III LPS (as determined by the American Joint Committee on Cancer staging guidelines), treated at the Groningen University Hospital from 1977-2000, were analyzed. RESULTS: A total of 69 patients, 35 males and 34 females, median age 51 (range 11-80) years, were reviewed. After a median follow-up of 71 (range 5-231) months, the overall local recurrence and metastasis rate at five years after diagnosis were 27% and 16%, respectively. Retroperitoneal localization was a significant negative prognostic factor regarding local recurrence; dedifferentiation, grade II-III, and deep location regarding distant metastasis; and dedifferentiation, grade II-III, stage II-III, size >20 cm and non-radical resection regarding survival. CONCLUSIONS: LPS have a relatively mild biologic behavior, with the exception of very large, deeply located, dedifferentiated and/or grade II-III LPS. Radical resection is important for disease-specific survival. LPS have a relatively mild biologic behavior, with the exception of very large, deeply located, dedifferentiated and/or grade II-III LPS.

Adolescent↗
PubMed1987

Immunohistochemical staining for apolipoprotein B in human sarcomas.

A study of immunocytochemical staining for apolipoprotein B (apo B) in 52 human sarcomas and eight benign soft-tissue tumors is described. A peroxidase-antiperoxidase technique was employed using a rabbit anti-apo B antiserum. All 27 liposarcomas examined were positive for apo B, and 23 of these tumors showed at least 2-plus staining on a scale of 0 to 3 plus. Of the ten myxoid liposarcomas within this group, seven showed 2-plus or 3-plus staining, while the other three stained 1 plus. By contrast, 11 of 13 malignant fibrous histiocytomas were negative for apo B; the remainder showed 1-plus staining. Myxoid areas present in three of these cases were negative for apo B. Five of seven rhabdomyosarcomas stained at least 2 plus for apo B. Both benign and malignant peripheral nerve sheath tumors showed no consistent pattern of staining. We conclude that apo B immunocytochemical staining tends to be high in tumors whose normal tissue counterparts exhibit relatively large numbers of low-density lipoprotein receptors. Furthermore, immunoperoxidase staining for apo B should be a useful adjunct in the evaluation of soft-tissue sarcomas, particularly in cases with myxoid differentiation.

Apolipoproteins B↗
PubMed2002

Soft tissue sarcoma brain metastases. Prevalence in a cohort of 3829 patients.

BACKGROUND: Brain metastases from soft tissue sarcoma (STS) are uncommon. To the authors' knowledge limited information is available regarding the influence of the initial STS site, the significance of parenchymal versus leptomeningeal metastases, and the role of surgical resection. METHODS: STS patients evaluated between July 1982 and March 1999 who presented with or developed brain metastases were identified from a prospective database. Association between factors was determined using the Fisher exact test. Survival was estimated using the Kaplan-Meier method. The influence of factors on the endpoint (disease specific survival [DSS]) was analyzed using the log-rank test. Significance was defined at P < or = 0.05. RESULTS: A total of 3829 STS patients were evaluated during the study interval; 21 patients presented with and 19 patients subsequently developed brain metastases, accounting for < 1% (40 of 3829 patients) of the total patient group. The STS presentation status for this group of patients (n = 40) included 15 patients with primary STS, 1 patient with local recurrence, and 24 patients with metastatic disease. The most frequent types of STS metastasizing to the brain were leiomyosarcoma (eight patients), liposarcoma (five patients), rhabdomyosarcoma (four patients), and malignant fibrous histiocytoma (MFH) (four patients). Fourteen other sarcoma types were determined in the remaining 19 patients. Of the 19 patients who developed subsequent brain metastases, 18 had lung metastases as the immediate prior site of disease. The median overall follow-up for the 40 patients was 14 months (range, 1-128 months); for survivors (n = 5), the median overall follow-up was 18 months. During follow-up, 34 patients died of disease and 1 patient died of other causes. Brain metastasectomy was performed in 27 of the 40 patients and was highly associated with the initial site of STS; 20 of the 27 patients who underwent resection versus 2 of the 13 patients who did not undergo resection initially had extremity or trunk STS (P < 0.001). No association was observed between parenchymal versus leptomeningeal site of metastases and any outcome factor. The 1-year and 2-year overall DSS for the 40 patients was 55% and 25%, respectively, with a median survival of 15 months. The 1-year and 2-year postmetastasis survival rates were 34% and 20%, respectively, with a median survival of 7 months. Metastasectomy (n = 27) was associated with an improved median postmetastasis survival (9.6 months vs. 2.7 months for unresected patients; P < 0.01). The 2-year postmetastasis survival was 27% for those patients who underwent resection and 0% for the unresected patients. CONCLUSIONS: Although brain metastases from STS are rare, vigilance is warranted. Symptomatic patients should be examined neurologically and investigated thoroughly for metastases. Surgical resection may be an appropriate treatment for selected patients; however, survival is dismal.

Adolescent↗
PubMed1995

Homozygous deletion frequency and expression levels of the CDKN2 gene in human sarcomas--relationship to amplification and mRNA levels of CDK4 and CCND1.

Homozygous deletions of the putative tumour-suppressor gene CDKN2, which encodes an inhibitor of cdk4, have been detected in a high percentage of cancer cell lines of various histological types. In the present study, 109 human sarcomas were examined for homozygous deletions and for mRNA expression levels of the CDKN2 gene. Altogether, deletions were found in only eight (7%) of the cases, but, interestingly, in two (of eight) malignant Schwannomas and in two (of five) rhabdomyosarcomas. In comparison, such deletions were seen in only one (of 21) osteosarcomas and in none of 20 MFHs and 21 liposarcomas. Notably, highly elevated CDKN2 mRNA levels were found in 33% of the sarcomas, whereas no detectable transcript was present in 12 normal tissues. Amplifications of CDK4 and CCND1 (cyclin D1) were observed in 11% and 4% of the sarcomas respectively, but never in tumours with CDKN2 deletions. The level of CDK4 mRNA expression was increased in nine tumours in addition to the 12 samples with CDK4 amplification. Increased levels of the cyclin D1 transcript was found in 37 cases, four with and 33 without amplification. The data indicate that aberrations of these functionally related genes, or in regulation of the expression of the kinase, the activator or the inhibitor, may participate in sarcoma development. Furthermore, the data suggest that homozygous CDKN2 deletions may be of dissimilar significance in different sarcoma subtypes.

Animals↗