Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity.
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PURPOSE: Synovial sarcoma is a high-grade tumor that is associated with poor prognosis. Previous studies analyzing prognostic factors are limited because of inclusion of heterogeneous cohorts of patients with nonextremity and recurrent tumors. The objective of this study was to determine independent prognostic factors of primary synovial sarcoma localized to the extremity. PATIENTS AND METHODS: Between July 1, 1982, and June 30, 1996, 112 patients underwent surgical resection for cure at our institution and then were followed-up prospectively. Clinical and pathologic factors examined for prognostic value included age, sex, tumor site and location, depth, size, microscopic status of surgical margins, invasion of bone or neurovascular structures, and monophasic or biphasic histology. The end points analyzed were the time to first local recurrence that was not preceded by a distant recurrence, time to any distant recurrence, and time to disease-related mortality. These end points were modeled using the method of Kaplan and Meier and analyzed by the log-rank test and Cox regression. RESULTS: The median duration of follow-up among survivors in this cohort of 112 patients was 72 months. The 5-year local-recurrence, distant-recurrence, and mortality rates were 12%, 39%, and 25%, respectively. Tumor size > or = 5 cm (P =.001; relative risk [RR] = 2. 7; 95% confidence interval [CI], 1.5 to 5.2) and the presence of bone or neurovascular invasion (P =.04; RR = 2.3; 95% CI, 1.0 to 5. 3) were independent adverse predictors of distant recurrence. Tumor size > or= 5 cm (P =.003; RR = 2.3; 95% CI, 1.4 to 6.3) and the presence of bone or neurovascular invasion (P =.03; RR = 2.7; 95% CI, 1.0 to 6.5) were also independent adverse predictors of mortality. CONCLUSION: The natural history of primary synovial sarcoma of the extremity is related to tumor size and invasion of bone and neurovascular structures. (+info)
Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome.
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The clinicopathologic features of 48 tumors that were histologically similar to gastrointestinal stromal tumors but occurred in the soft tissues of the abdomen were analyzed to determine their overall similarity to their gastrointestinal counterpart, their biologic behavior, and the parameters that predict risk for adverse outcome. Classic leiomyomas and leiomyosarcomas were specifically excluded. The tumors occurred in 32 women and 16 men, who ranged in age from 31 to 82 years (mean, 58 years). Forty tumors arose from the soft tissue of the abdominal cavity, and the remainder arose from the retroperitoneum. They ranged in size from 2.1 to 32.0 cm and varied from tumors composed purely of rounded epithelioid cells to those composed of short fusiform cells set in a fine fibrillary collagenous background with some cases showing a mixed pattern. Tumors displayed variable amounts of stromal hyalinization, myxoid change, and cyst formation. The tumors expressed CD117 (c-kit receptor) (100%), CD34 (50%), neuron-specific enolase (44%), smooth muscle actin (26%), desmin (4%), and S-100 protein (4%). Tumors were evaluated with respect to several parameters: size (<10 cm or >10 cm), cellularity (low or high), mitoses (0 to 2 per 50 high-power fields, >2 per 50 high-power fields), nuclear atypia (1 to 3+), cell type (epithelioid, spindled, or mixed), and necrosis (absent or present). These parameters were then evaluated in univariate and multivariate analysis with respect to adverse or nonadverse outcome, the former defined as metastasis or death from tumor. Follow-up information was obtained for 31 patients (range, 4 to 84 months; median, 24 months). One patient presented with an adverse event and, therefore, was excluded from subsequent analysis. Twelve patients (39%) developed metastases or died of tumor. In univariate analyses, cellularity, mitotic activity (>2 per 50 high-power fields), and necrosis were associated with statistically significant increases in the risk for adverse outcome. Despite the relatively small sample size, in a multivariable analysis mitotic activity (relative risk, 7.46; P = .09) and necrosis (relative risk, 3.75; P = .07) displayed trends toward independent predictive value. No association was noted between histologic pattern and outcome. Although only 39% of tumors behaved in a malignant fashion, this figure probably represents a conservative estimate because long-term follow-up (>5 years) was available for only a limited number of patients. Stratification of patients who have extragastrointestinal stromal tumor into those with 0 to 1 adverse histologic factors versus those with 2 to 3 offers the advantage of separating patients into two groups that have a markedly different risk for adverse outcome in the short term (0.02 events versus 0.54 events per person-year; P < .001, respectively). Extragastrointestinal (soft tissue) stromal tumors are histologically and immunophenotypically similar to their gastrointestinal counterpart but have an aggressive course more akin to small intestinal than gastric stromal tumors. (+info)
Case report: paraarticular soft-tissue osteoma of the hip.
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A case of paraarticular soft-tissue osteoma of the hip is presented. The patient is a 30-year-old white male with a two year history of progressive left hip pain. Plain film and cross-sectional imaging in conjunction with pathologic correlation are used to make the diagnosis. The lesion lacks the typical zoning pattern of myositis ossificans, shows no direct communication with native bone, and is extraarticular in location as opposed to synovial osteochondromatosis. Soft tissue osteomas most commonly occur around the knee, the foot, and the ankle. Soft tissue osteomas are rare tumors and this case is unusual in that it occurs around the hip. (+info)
Evaluation of the autoinduction of ifosfamide metabolism by a population pharmacokinetic approach using NONMEM.
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AIMS: This study investigated the population pharmacokinetics of ifosfamide in 15 patients treated for soft tissue sarcoma with 9 or 12 g m-2 ifosfamide by means of a 72 h continuous i.v. infusion. METHODS: A model was developed using nonlinear mixed effects modelling (NONMEM) to describe the nonlinear pharmacokinetics of ifosfamide by linking the ifosfamide plasma concentrations to the extent of the autoinduction. RESULTS: The proposed model revealed the effect of autoinduction on the disposition of ifosfamide. The initial clearance, volume of distribution, rate constant for enzyme degradation, induction half-life of the enzyme and the ifosfamide concentration at 50% of the maximum inhibition of enzyme degradation were estimated at 2.94 +/- 0.27 l h-1, 43.5 +/- 2.9 l, 0.0546 +/- 0. 0078 h-1, 12.7 h and 30.7 +/- 4.8 microM, respectively. Interindividual variabilities of initial clearance, volume of distribution, rate constant for enzyme degradation were 24.5, 23.4 and 22.7%, respectively. Proportional and additive variability not explained by the model were 13.6% and 0.0763 microM, respectively. CONCLUSIONS: The absence of a lag time for the autoinduction of ifosfamide metabolism could be the result of an immediate inhibition of the enzymatic degradation of CYP3A4 by ifosfamide. By application of the autoinduction model individual pharmacokinetic profiles of patients were described with adequate precision. This model may therefore be used in the future development of a model to individualize dose selection in patients. (+info)
Malignant fibrous histiocytoma in a Djungarian hamster.
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A subcutaneous malignant fibrous histiocytoma (MFH) was observed in the region between the right posterior trunk and right hind limb of a 2-year-old male Djungarian hamster weighing 45 g. Histologically, the tumor consisted of bizarre multinucleated giant cells, histiocytic cells, and fibroblastic cells with a storiform pattern, and was considered to be of the storiform-pleomorphic type of MFH. Severe nuclear atypia with prominent nucleoli and many mitotic figures was also observed. Electron microscopy demonstrated fibroblastic cells and histiocytic cells. The fibroblastic cells were spindle-shaped, and sometimes had an invaginated nucleus. The histiocytic cells were polygonal with an oval or kidney-shaped nucleus. The cytoplasm of both cells contained numerous free ribosomes, small amounts of rough endoplasmic reticulum, and round mitochondria. Tumor cells were immunohistochemically positive for vimentin, and were thought to be of undifferentiated mesenchymal cell origin. This is the first report of spontaneous MFH in a hamster. (+info)
Involvement of cyclins in cell proliferation and their clinical implications in soft tissue smooth muscle tumors.
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Expression of cyclins A and E and cyclin-dependent kinase 2 (cdk2) was examined immunohistochemically in 55 cases of soft tissue smooth muscle tumors, including vascular leiomyoma, and compared to expression of Ki-67 and proliferating cell nuclear antigen. Cyclin A was expressed in 70% of the leiomyoma cases, but with much lower labeling indexes than in leiomyosarcoma. Cyclin E was expressed exclusively in leiomyosarcoma. Although the differences of cyclin A- and cyclin E-labeling indexes between leiomyoma and leiomyosarcoma were statistically significant, no significant differences were found in the other markers. Furthermore, cyclin A- and/or E-positivity predicted a poor prognosis in recurrence- or metastasis-free survivals and overall survival. Immunoblotting revealed that cyclins A and E were expressed, in complex with cdk2, exclusively in tumors. In addition, not only leiomyosarcoma, but also leiomyoma specimens that exhibited negligible levels of complex expression, manifested detectable cdk2 activity. These results suggest 1) up-regulation of active cyclin A/cdk2 expression and associated kinase activity is critical for unrestrained cell proliferation; 2) cyclin E/cdk2 complexes may play a crucial role in leiomyosarcoma; 3) immunohistochemical detection of cyclins can be a more reliable tool for differential diagnosis between leiomyoma versus leiomyosarcoma than that of Ki-67 or proliferating cell nuclear antigen, and be a possible prognostic indicator. (+info)
Imaging of soft-tissue tumors using L-3-[iodine-123]iodo-alpha-methyl-tyrosine single photon emission computed tomography: comparison with proliferative and mitotic activity, cellularity, and vascularity.
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The radiolabeled amino acid L-3-[123I]-iodo-alpha-methyltyrosine (IMT) is a new tumor tracer that accumulates in many tumors and is suitable for single photon emission computed tomography (SPECT) imaging. Using IMT SPECT, we studied 32 patients with a soft-tissue tumor suspected to be a soft-tissue sarcoma to determine whether: (a) tumors can be visualized; (b) benign and malignant lesions can be distinguished; and (c) IMT uptake is related to tumor grade and proliferation. Whole-body imaging was performed 15 min after administration of 300 MBq IMT, biopsy, or resection 1-2 weeks later. IMT uptake was quantified using a region-of-interest method resulting in tumor:background (T:B) ratios. These were compared with tumor grade, mitotic index, tumor cellularity, vascularity, and the Ki-67 proliferation index. Eleven patients had a benign tumor, and 21 patients had a soft-tissue sarcoma. Six benign tumors demonstrated minor IMT uptake, and five lipomas had no uptake. All malignant tumors had high uptake and were clearly visualized. T:B ratios in malignant tumors (3.83 +/- 1.16) were higher (P < 0.001) than in benign tumors (1.52 +/- 0.60). Small (<5 mm) metastases in two patients were not detected. Taking the T:B ratio 2.0 as the cutoff level, the sensitivity for detection of malignancy was 100%, and specificity was 88%. IMT uptake correlated with histological grade (r = 0.82; P < 0.001), mitotic index (r = 0.75; P < 0.001), tumor cellularity (r = 0.73; P < 0.01), and with the Ki-67 proliferation index (r = 0.63; P < 0.01). In conclusion, IMT SPECT visualized all soft-tissue sarcomas. Uptake in sarcomas was clearly higher than in benign lesions, yielding 100% sensitivity for detection of malignancy at 88% specificity. Uptake increased with higher tumor grade and higher proliferation rate. (+info)
The relationship between intracellular and extracellular pH in spontaneous canine tumors.
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Recently, it has been suggested that the cellular uptake of chemotherapeutic drugs may be dependent on the pH gradient between the intracellular (pHi) and extracellular (pHe) compartments. It has been demonstrated in murine tumor models that the extracellular environment is acidic, relative to the intracellular environment, thus favoring preferential accumulation of drugs that are weak acids into cells. However, concomitant measurements of pHi and pHe in spontaneous tumors have not been reported, so it is not certain how well the murine results translate to the clinical scenario. In this study, both types of measurements were performed in dogs with spontaneous malignant soft tissue tumors. On average, pHe was more acidic than pHi, with maintenance of a more physiologically balanced intracellular tumor environment. However, the magnitude of the gradient varied widely, and individual tumors had both positive and negative pH gradients (pHi - pHe). These data suggest that the magnitude and direction of the pH gradient may need to be measured for individual patient tumors and/or that manipulation of pHe may be required if exploitation of the pH gradient is to be achieved for tumor-selective augmentation of intracellular drug delivery. (+info)