A. Giannopoulos

PURPOSE: Adiponectin, an adipocyte-secreted hormone with insulin-sensitizing effects, has been inversely associated with several hormonally dependent malignancies, including breast, endometrial, and colorectal cancer. Few studies have examined serum adiponectin in relation to prostate cancer, and expression of adiponectin receptors has previously not been assessed in prostate tumors. EXPERIMENTAL DESIGN: We collected plasma samples and covariate data in the context of a case-control study of 300 Greek men, including 75 prostate cancer cases, 75 patients with benign prostatic hyperplasia (BPH), and 150 healthy controls. Prostate tissue samples were taken from 72 cases and 27 noncases and examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry. RESULTS: Prostate cancer patients had significantly lower plasma adiponectin concentrations as compared with men with BPH and healthy controls (7.4 +/- 5.0 versus 11.5 +/- 6.4 and 12.8 +/- 8.0 ng/mL, respectively). Men in the top two quartiles of adiponectin had a 71% to 73% reduced risk of prostate cancer as compared with men in the lowest quartile after adjusting for age, body mass index, and additional potential confounders. We found no similar relationship between adiponectin and risk of BPH. Results from immunohistochemistry experiments show weaker expression of adiponectin receptors AdipoR1 and AdipoR2 in cancerous versus healthy prostate tissue. CONCLUSIONS: Higher serum adiponectin is associated with a marked reduction in risk of prostate cancer, but not BPH, independently of other risk factors. Malignant prostate tissue samples have reduced expression of adiponectin receptors as compared with benign prostate tissue. These results support a role for adiponectin in the pathogenesis of prostate cancer.

OBJECTIVES: To assess the effect of bladder instillations of hyaluronic acid (HA) on the rate of recurrence of urinary tract infection (UTI). PATIENTS AND METHODS: Forty women (mean age 35 years) with a history of recurrent UTI received intravesical instillations of HA (40 mg in 50 mL phosphate-buffered saline) once weekly for 4 weeks then once monthly for 4 months. The UTI status was assessed over a prospective follow-up of 12.4 months and compared with the rates of UTI before instillation, determined by a retrospective review of patient charts covering 15.8 months. RESULTS: After HA treatment no patients had a UTI during the 5-month treatment phase and 28 (70%) were recurrence-free at the end of the follow-up. The mean (sd) rate of UTI per patient-year was 4.3 (1.55) before treatment and 0.3 (0.55) afterward (P < 0.001). The median time to recurrence after HA treatment was 498 days, compared with 96 days beforehand (P < 0.001). The tolerability was excellent, as side-effects were limited to nine patients who reported mild bladder irritation; no patient interrupted the treatment. CONCLUSIONS: In this preliminary study, bladder instillations of HA had a significant effect on the rate of UTI in women with a history of recurrent UTIs. The bladder instillation of HA is an acceptable and promising therapeutic alternative in patients with recurrent UTI. Expanded placebo controlled clinical trials examining this application of HA are currently underway.

PURPOSE: We compared overall sensitivity and specificity of the urinary bladder cancer antigen enzyme-linked immunosorbent assay (UBC, IDL Biotech, Sollentuna, Sweden), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and NMP22 test kit (Matritech, Newton, Massachusetts), and the differential sensitivity regarding the histological pattern of tumors. MATERIALS AND METHODS: A total of 213 patients with clinical and/or imaging signs of bladder cancer provided a single voided urine sample for the bladder cancer antigen, BTA stat test and NMP22 before cystoscopy. Of these patients 95 were monitored for superficial bladder cancer, while the remaining 118 had no history of bladder cancer. All detected bladder tumors or suspicious lesions were resected transurethrally. A group of 21 age and sex matched healthy volunteers were also evaluated with the same tests. RESULTS: Bladder cancer was confirmed histologically in 118 patients, of whom primary and recurrent tumors were in 68 and 50, respectively. The optimal cutoffs calculated with receiver operating characteristics curves were 8 units per ml. for NMP22 and 12 microg./l. for bladder cancer antigen. Overall sensitivity and specificity were 72.9% and 64.6% for the BTA stat test, 63.5% and 75.0% for NMP22, and 80.5% and 80.2%, respectively, for bladder cancer antigen. Bladder cancer antigen proved significantly more sensitive than NMP22 for detecting bladder cancer (p = 0.001) but not more than the BTA stat test, while the specificity of it was significantly higher than that of the BTA stat test (p = 0.009). Bladder cancer antigen had a sensitivity of 80.7% for stage Ta tumors, which was significantly higher than NMP22 (52.6%, p = 0.001) and the BTA stat test (57.9%, p = 0.01). In grade I tumors the sensitivity of bladder cancer antigen (70%) did not differ significantly than that of the BTA stat test (50%) and NMP22 (50%, p = 0.14). Bladder cancer antigen had the least false-positive results in patients with a history of bladder cancer and negative cystoscopy, and those with urological disease other than bladder cancer. CONCLUSIONS: Our data indicate that bladder cancer antigen may be a more potent diagnostic marker for bladder cancer than NMP22 and the BTA stat test based on the higher sensitivity for detecting low stage and low grade tumors, and the higher specificity. The contribution of these tests for detection of bladder cancer should still be considered adjunctive to cystoscopy.

PURPOSE: The purpose is to investigate the prophylactic effect of intravesically instillated recombinant IFN-gamma against recurrence of superficial transitional cell carcinoma of the bladder and to evaluate its effect in local immune response, presumably mediating its therapeutic efficacy. EXPERIMENTAL DESIGN: We prospectively randomized in two groups 123 patients with initially diagnosed superficial transitional cell carcinoma and stage Ta, T1, grade 2 tumors, who underwent transurethral tumor resection (TUR). In group A, 60 patients received IFN-gamma (1.5 x 10(7) IU/instillation), whereas 63 patients, consisting of the control group B, received mitomycin C (40 mg/instillation). The annual administration schedule consisted of eight weekly followed by four biweekly and then by eight monthly instillations for both regimens. We also analyzed the immunophenotype of the intratumoral and intramural leukocytes by immunohistochemical and flow-cytometric techniques. To this purpose, tumor samples were obtained at TUR and random biopsies at TUR and during cystoscopy at 6 and 12 months, and bladder washings were collected before TUR and at preselected time points. RESULTS: In group A, 44 of 60 (73.4%) patients, and in group B, 36 of 63 (57.2%) patients, were tumor free during the median follow-up period of 26.5 months (range, 3-49 months). IFN-gamma was well tolerated. Six months after starting treatment, follicular cystitis was detected in patients responding to IFN-gamma. After IFN-gamma instillations, statistically significant increases in T cells, T-helper cells, T-cytotoxic cells, natural killer cells, and total leukocytes, as well as in the number of B cells expressing intercellular adhesion molecule-1 and total leukocytes expressing HLA-DR, were observed by flow cytometry in tissue specimens and bladder washings. CONCLUSIONS: Recombinant IFN-gamma appears to be effective against stage Ta, T1, grade 2 bladder tumors' recurrence. Recruitment and activation of intramural leukocytes seem to be involved in the mechanism of IFN-gamma action.