Joel W Slaton — Page 2

PubMed2002

The prognostic value of angiogenesis and metastasis-related genes for progression of transitional cell carcinoma of the renal pelvis and ureter.

PURPOSE: We reported previously that angiogenesis evaluated by intratumor microvessel density (MVD), expression of such angiogenic factors as vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF), and the matrix metalloproteinase-9:E-cadherin ratio (M:E ratio) could identify patients with advanced transitional cell carcinoma (TCC) of the bladder for whom chemotherapy and cystectomy will be unsuccessful. In the present study, we evaluated the significance of the M:E ratio as a predictor for prognosis for patients with TCC in the upper urinary tract (TCC-UUT). EXPERIMENTAL DESIGN: We evaluated MVD by immunohistochemistry and the expression of angiogenic and metastasis-related factors by in situ hybridization in 55 nephroureterectomy specimens from patients who received no neoadjuvant therapy. The expression of angiogenesis, angiogenic and metastasis-related factors, and clinicopathological characteristics were evaluated for their correlation with metastasis, recurrence, and disease prognosis. RESULTS: We found that tumor grade and pathological stage were important predictors for metastasis and survival in these patients. The expression level of matrix metalloproteinase type 9 (MMP-9) and type 2 (MMP-2) and the M:E ratio correlated with MVD. Increased MVD, elevated expression levels of MMP-9 and MMP-2, and a higher M:E ratio were associated with poor prognosis. Moreover, lower expression levels of E-cadherin were associated with fewer recurrences in the urinary bladder. Multivariate analysis indicated that the M:E ratio and E-cadherin expression were independent prognostic factors for disease progression and intravesical recurrence, respectively. CONCLUSION: We suggest that the M:E ratio and E-cadherin expression may be targets for novel therapeutic strategies.

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PubMedDate not supplied

Surgical management of renal cell carcinoma associated with complex inferior vena caval thrombi.

The operative morbidity and mortality of radical nephrectomy are considerably higher when the vena cava is involved by the tumor. The prognostic significance of vena caval extension in this setting remains controversial. We reviewed our experience of vena caval thrombectomy specifically addressing prognostic factors. We retrospectively studied 96 patients treated at our institution between 1985 and 2001. The study population included 28 women and 68 men; (37 left- and 59 right-sided tumors). Twenty-seven patients had metastatic disease at presentation. Prognostic features (age, sex, race, side of tumor, embolization, tumor grade, tumor confinement by renal capsule, cephalic extent of thrombus, nodal status, and presence of distant metastasis) were evaluated using a Cox proportional hazards model (univariate and multivariate). These prognostic features were analyzed in the group as a whole and in the subgroup of patients who did not have metastatic disease at presentation and did not die perioperatively. There were 5 perioperative deaths. Extracapsular tumor extension and regional node involvement were present in 64% and 17% of the patients, respectively. Level of tumor thrombus were as follows: level I (41%), II (29%), III (7%), IV (15%). Fuhrman's grade was 2 in 17%, 3 in 45%, and 4 in 30% of the patients. For all 96 patients, median overall survival (OS) was 35 months. Five-year OS was 35%. The presence of distant metastasis at presentation did not significantly alter median OS (20 months with metastasis vs. 38 months without, P = 0.3), although this finding may have been confounded by selection. The presence of nodal metastasis was associated with decreased OS by multivariate analysis (P < 0.01). After exclusion of patients dying perioperatively and patients with metastasis at presentation, median OS and progression-free survival were 40 and 18 months, respectively (5-year OS was 40%). In the multivariate model, none of the factors examined were associated with OS, but age <58 years, and the presence of extracapsular tumor extension were associated with an increased risk of recurrence. In patients with renal tumors and extension of tumor thrombus into the vena cava, the level of propagation of the thrombus does not predict for OS. Selected patients with metastatic renal cancer may benefit from aggressive surgical resection of the primary tumor and associated tumor thrombus.

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