ABSTRACT
BACKGROUND: As angiogenesis represents one of the hallmarks of cancer we investigated whether intravesically administered interferon-a (IFN-a2b) reduces neo-angiogenesis in the 'normal' urothelium adjacent to the tumor in patients with superficial bladder carcinoma after complete transurethral resection (TUR) of the tumor. PATIENTS AND METHODS: In the present study 47 patients after TUR of the tumor were examined. 10 patients (group A) received no further treatment (control group); 37 patients (group B) received intravesical treatment with IFN-a2b. The instillations started within 7 days after TUR, were performed weekly for 2 months, twice a month for the next 4 months, and thereafter monthly for 6 more months. Cold cup biopsies were taken before TUR of the transitional cell carcinoma (TCC): from the tumor (T), near tumor (NT) and from normal epithelium (N). Cold cup biopsies 'near tumor', were also taken during follow-up cystoscopy (C1, C2, and C3) 2, 6, and 12 months after TUR, respectively. Angiogenesis was estimated by counting the microvessels detected with CD31 immunostaining. RESULTS: Significant differences of microvascular density (MVD) between patients of group A and B appear after TUR (p < 0.005, Kruskal-Wallis and Wilcoxon test). The MVD difference was maximal 6 months after TUR (C2(A)-C2(B), second cystoscopy) and measured at 12.17 microvessels/ mm(2) (26.2%). CONCLUSION: Our results show that the intravesical administration of IFN-a2b after TUR significantly decreases the angiogenic potential of the 'healthy' urothelium adjacent to the tumor in patients with TCC. This observation could possibly explain, to a certain extent, the mechanism by which IFN-a2b reduces the recurrence rate of primary TCC.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/surgery , Interferon-alpha/therapeutic use , Neovascularization, Pathologic/drug therapy , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Urothelium/blood supply , Administration, Intravesical , Aged , Biopsy , Carcinoma, Transitional Cell/blood supply , Carcinoma, Transitional Cell/pathology , Chemotherapy, Adjuvant , Cystoscopy , Female , Humans , Interferon alpha-2 , Male , Microcirculation/drug effects , Microcirculation/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Neovascularization, Pathologic/pathology , Prospective Studies , Recombinant Proteins , Treatment Outcome , Urinary Bladder Neoplasms/blood supply , Urinary Bladder Neoplasms/pathologyABSTRACT
A new "bone seeking" agent, namely the organic compound diphosphonate labeled with Tc99m was tried in 21 patients for skeletal scanning. In 3 cases, although the clinical and roentgenographic evidence of bone lesions was absent, bone metastases were found, and these were confirmed histologically. The organic diphosphonate is more stable compared to the inorganic polyphosphates and the images obtained are excellent.
