History of treated hypertension and diabetes mellitus and risk of renal cell cancer.

BACKGROUND: An increased risk of renal cell cancer (RCC) has been reported in subjects with hypertension. Whether this association may vary according to sex, smoking, obesity, or RCC clinical presentation is unclear. Results on the link between diabetes mellitus and RCC are inconclusive. PATIENTS AND METHODS: We conducted an Italian multicenter case-control study, including 767 (494 men, 273 women) incident cases of RCC, under 80 years of age, and 1534 hospital controls, frequency-matched to cases. Multiple logistic regression models, conditioned to center, sex, and age, and adjusted for period of interview, education, smoking, and body mass were used to estimate odds ratios (OR). RESULTS: Compared with subjects never treated, patients with a history of treated hypertension [OR = 1.7, 95% confidence interval (CI) 1.4-2.1] reported an excess risk of RCC. This pattern was confirmed in different strata of sex, education, smoking habits, body mass, tumor histological type, stage, or grade. The attributable risk of RCC for treated hypertension in this population was 16%. A slight, nonsignificant increased risk was found for history of diabetes mellitus (OR = 1.3, 95% CI 0.9-1.7). CONCLUSION: A possible causal role of hypertension in renal cell carcinogenesis is supported by the consistency of the direct association.

Prostate cancer and body size at different ages: an Italian multicentre case-control study.

We investigated the influence of anthropometric measures at diagnosis and at different ages on prostate cancer risk using an Italian multicentre case-control study conducted between 1991 and 2002 of 1294 histologically confirmed cases and 1451 controls admitted to the same network of hospitals for acute non-neoplastic conditions. Height, weight, body mass index (BMI), waist-to-hip ratio, lean body mass 1 year before diagnosis/interview were not significantly associated with risk. However, a positive association with high BMI at age 30 years was found (odds ratio=1.2 for BMI> or =24.7 vs <22.7) and: for less differentiated prostate cancer, with BMI 1 year before diagnosis/interview. This study supports possible relationships between high body mass in young adulthood, and a tendency to high weight throughout adult life, and the risk of prostate cancer.

[Color Doppler and ultrasound-guided prostate biopsy in the diagnosis of prostatic neoplasm]. / Color Doppler e biopsie prostatiche ecoguidate nella diagnosi di neoplasia prostatica.

The diagnosis of prostate neoplasm is still limited today by the variable power of prediction of the three main surveys used: prostate-specific antigen (PSA), digito rectal exploration (DRE) and ultrasound transrectal (TRUS). The study aimed to estimate the benefits and the diagnostic impact of the color Doppler ultrasonography on the diagnosis of prostate neoplasm through biopsies targeted on areas with abnormal flow. With this purpose, 222 biopsies performed on 71 patients between 1997 and 1999 were considered, which led to a diagnosis of neoplasm in 36 patients. Of the 84 biopsies that revealed prostate adenocarcinoma, 74 (64.3%) were correlated to hypoechoic lesions with abnormal flow signals while 41 (35.6%) showed a benign pathology (prostatitis or benign prostatic hyperplasia) (p < 0.0011). In five patients (13%) who did not present any evident lesions at a first transrectal ultrasound, the diagnosis of neoplasm was made only through biopsies targeted on areas with abnormal flow. Therefore, the color Doppler exam can be used during prostate ultrasonography either to consolidate the diagnosis or to give a useful target in case of isoechoic lesions.

Is stage pT4a (D1) reliable in assessing transitional cell carcinoma involvement of the prostate in patients with a concurrent bladder cancer? A necessary distinction for contiguous or noncontiguous involvement.

PURPOSE: A series of patients with concurrent transitional cell carcinoma involvement of the prostate and bladder is reviewed to define the impact of prostate involvement pathways and the degree of prostate invasion on survival rate. MATERIALS AND METHODS: A total of 72 patients who underwent radical cystectomy for pathological stage pT4a (D1) cancer was divided into contiguous--stage pT4a, transitional cell carcinoma of the bladder extended into the prostate through the bladder wall and noncontiguous--stage pT4a simultaneous transitional cell carcinoma of the prostate and bladder carcinoma that did not directly infiltrate into the prostate through the bladder wall. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement, stromal invasion and extracapsular extension. The survival rate was estimated by the Kaplan-Meier and Cox proportional hazards methods. Comparisons between curves were performed by univariate log rank and multivariate L-ratio tests. RESULTS: The overall 5-year survival rate for stage pT4a was 21.5% (median followup 64 months). Furthermore, 46% and 7% of patients in noncontiguous and contiguous pT4a groups, respectively, were estimated to be alive (p < 0.000). Those with positive nodes experienced a poor outcome in both groups. Of patients with noncontiguous pT4a stage 100% with urethral mucosal involvement, 50% with ductal/acinar involvement and 40% with stromal invasion were estimated to be alive. The major prognostic factors were bladder tumor stage, nodal involvement and degree of prostate invasion. CONCLUSIONS: The invasion pathways of the prostate in patients with transitional cell bladder carcinoma have a statistically significant prognostic role. Contiguous and noncontiguous involvements are 2 distinct clinicopathological features and they should not be included in the same stage. In the noncontiguous stage pT4a group bladder and prostate transitional cell carcinoma should be separately staged, and prostate involvement also should be staged according to invasion degree.

Clinical value of pathologic changes after intravesical BCG therapy of superficial bladder cancer.

Bladder pathologic features related to intravesical bacillus Calmette-Guerin (BCG) therapy in superficial bladder cancer (Ta, T1, Tis) were evaluated and related to clinical outcome. A total of 105 patients were treated with 75 mg Pasteur BCG weekly for six consecutive weeks. When tumor was not demonstrated a maintenance course was given. An additional six-week course was given when tumor recurrence or persistence, without progression, was observed after the induction course. An inflammatory change in the bladder was the most common pathologic finding. Granuloma was the only specific BCG-related feature and did not appear to be a prognostic factor because of low incidence (24%) and lack of correlation with clinical course. Dysplasia occurred more frequently (57%) in nonresponder patients and (26%) in responder patients, often heralding recurrence of tumor. All patients showing concurrent squamous and/or glandular metaplasia were unresponsive to BCG therapy. Histology and cytology did not correlate perfectly: cytology was ineffective in low-grade tumors and improved diagnostic accuracy, particularly when dysplasia was histologically evident.

BCG in superficial bladder cancer: a review of phase III European trials.

Shortly after Morales' original report, several phase II trials confirmed the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in superficial bladder cancer therapy. Concerns have been expressed about the toxicity related to this new therapeutic modality. These phase II trial data led European urologists to try to answer some questions related to BCG therapy, such as the optimal schedule and dose, the most effective BCG strain and the value of BCG compared with current chemotherapeutic drugs. To date, phase III trials have shown that BCG is more effective than thiotepa and doxorubicin in reducing tumour recurrences and progression and that BCG seems to be as effective as mitomycin C. Toxicity is significantly higher with BCG compared to chemotherapeutic drugs; no strain of BCG seems to be superior in this respect. Further studies are required to identify the optimal schedule and dose, as well as the best therapeutic efficacy/toxicity ratio.

Preoperative and postoperative evaluation of prostate-specific antigen in localized prostatic cancer treated by radical prostatectomy.

Preoperative prostate-specific antigen (PSA) values were determined in 73 patients with clinically localized prostatic cancer and candidates for a radical procedure. Correlation of preoperative PSA with a final pathological stage was attempted. Only in 44.8% of our 22 patients with organ-confined disease was the PSA value within the normal range; in 17.3% of cases PSA values were higher than 20 ng/ml. 18.2% of the patients with locally advanced disease showed normal PSA values, while 45.5% had concentrations above 20 ng/ml. In the case of lymph node involvement, PSA values were normal in 22.7% of the cases. Our data indicate that no strict relationship can be suggested between PSA and the final pathological stage and grading of the tumor in patients who underwent radical prostatectomy.

Mitomycin C in multiple superficial bladder tumors: short-term therapy, long-term results.

At the Institute of Urology, University of Padova, 125 patients with multifocal superficial bladder cancer underwent treatment with intravesical Mitomycin C (MMC; 1 weekly instillation of 40 mg for 8 consecutive weeks) between January 1982 and December 1988. Eighty-four patients had multifocal papillary tumors (stages Ta-T1) and 41 patients had carcinoma in situ of the bladder. At 6 and 36 months the tumor free percentage in the group with papillary tumors was 69 and 36%, respectively; for carcinoma in situ the complete response percentage at the same intervals was 80 and 36%. Thirty-one patients previously unsuccessfully treated with adriamycin did not show any difference compared to untreated ones. The authors emphasize the efficacy and low toxicity of intravesical MMC in multiple superficial bladder cancer. The possibility of long-term relapse suggests maintenance therapy.

A low dose bacillus Calmette-Guerin regimen in superficial bladder cancer therapy: is it effective?

Bacillus Calmette-Guerin (BCG) intravesical therapy represents a major advance in the treatment of superficial transitional cell carcinoma of the bladder. To date, however, the optimal treatment schedule must be defined and the toxicity related to the treatment is significant. The preliminary results of a randomized ongoing study performed to evaluate the effectiveness and relative toxicity of a low dose (75 mg.) BCG regimen in the treatment of superficial bladder cancer therapy are reported. A total of 126 patients (70 for prophylaxis of recurrent stages Ta and T1 papillary tumors and 56 for treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue) underwent a 6-week course of 75 mg. BCG (Pasteur vaccine). An additional course was given in patients who failed to respond to the induction course. Maintenance therapy was administered in complete responders monthly for 1 year and then quarterly for 1 year. The prophylaxis group (transurethral resection plus BCG) was randomized versus transurethral resection alone (63 patients, control group). A complete response in the prophylaxis, control and therapy groups was observed in 74, 17 and 57% of the patients, respectively, while 4, 17 and 12.5%, respectively, experienced tumor progression. The additional course of therapy increased the response rate. On the contrary, previous unsuccessful intravesical chemotherapy did not affect the response rate. In regard to toxicity, irritative disturbances (27%) and fever (17%) appeared to be significantly decreased compared with the rates reported in the literature. No major complications were experienced. In conclusion, a low dose (75 mg.) Pasteur strain BCG regimen was effective as prophylaxis against recurrent superficial papillary tumors and as treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue. Toxicity related to the treatment appeared to be low.

Results of contemporary radical cystectomy for invasive bladder cancer: a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification.

We reviewed 261 patients who underwent a radical operation at a single institution as definitive treatment of invasive bladder cancer to evaluate the survival and accuracy of the tumor, nodes and metastasis system in characterizing the prognosis. Between January 1979 and June 1987 the 261 evaluable patients underwent 1-stage radical cystectomy with pelvic node dissection and urinary diversion. No chemotherapy and/or radiation therapy was given before or after the operation. The postoperative mortality rate was 1.8%. The over-all staging error between clinical and pathological stages was as high as 44%. The over-all actuarial 5-year survival rate was 54.5%. The 5-year survival rates were 75% for stage pT1, 63% for stage pT2, 31% for stage pT3 and 21% for stage pT4 disease. A significant difference in the survival (p less than 0.002) was observed in stage pT3 by dividing tumors confined within the bladder wall (pT3a, 50%) from those extending throughout the bladder wall (pT3b, 15%). A careful evaluation of transitional cell involvement of the prostate in stage pT4a cancer led to the identification of 2 different patterns: 1) contiguous when a bladder tumor extended directly into the prostate through the bladder wall and 2) noncontiguous when a bladder tumor and a transitional cell carcinoma of the prostate were found simultaneously. These patterns had completely different (p less than 0.05) survival rates (6 versus 37%). The patients with high grade tumors had a worse prognosis in comparison with those with grades 1 and 2 tumors (41 versus 56%, p less than 0.005). The over-all 5-year survival of patients with positive nodes was 4% in comparison with 60% of those without nodal involvement (p less than 0.001). Despite current optimal surgical treatment, nearly 50% of all patients with invasive bladder cancer continue to die. The need for a modification of the current tumor, nodes and metastasis tumor classification to provide the clinician a more reliable staging system for planning treatment modalities is indeed mandatory.

[Low-dose BCG in the therapy of superficial neoplasms of the bladder]. / BCG a baja dosis en la terapia de las neoplasias superficiales vesicales.

The preliminary results of a randomized ongoing study performed in order to evaluate the efficacy and the relative toxicity of a low dose (75 mg). BCG regimen in the treatment of superficial bladder cancer were considered. Ninety-eight patients (58 patients for prophylaxis of the recurrences of Ta-T1 papillary tumors; 40 patients for therapy of carcinoma in situ) received a 6-weeks course of 75 mg. BCG Pasteur vaccine. An additional course was given to non-responders. A maintenance therapy was administered in complete responders monthly for the first year and quarterly for the second. The prophylaxis group (TUR + BCG) was randomized vs TUR alone (40 patients = control group). Complete response in evaluated patients of the prophylaxis, control and therapy groups achieved 86%, 17% and 78%, respectively, after 18 months; 5%, 20% and 9% of patients, respectively, experienced tumor progression. As regards the toxicity, irritative disturbances (27%) and fever (16%) appeared significantly decreased in comparison with those reported in the literature. No major complications were experienced. In conclusion, the low dose (75 mg.) Pasteur BCG regimen used in our trial was effective as a prophylaxis against recurrent superficial papillary tumors and as a treatment of carcinoma in situ, with a significant decrease in toxicity.

Vescica Ileale Padovana: a technique for total bladder replacement.

A new technique for detubularized and originally reshaped ileal total bladder replacement following radical cystectomy for bladder cancer is described and named 'Vescica Ileale Padovana'. 16 patients have been clinically, radiologically and urodynamically evaluated with a follow-up ranging from 4 to 18 months (mean 10 months). The complication rate was low: 1 ureteroileal stenosis; 2 urethroileal strictures. Daytime continence was perfect in 87% (14 of 16 patients). Nighttime continence was perfect (dry sleep for 6-7 h) in 81% (13 of 16 patients). The reservoir features were: high capacity (400-650 ml); low pressure (mean pressure at capacity 17 cm H2O no pressure waves in 50% of patients 30-50 cm H2O wide pressure waves with 250-ml threshold volume in 50%); absence of reflux; complete voiding by abdominal straining, and perineal relaxation.

[Mitomycin C in the topical treatment of superficial neoplasms of the bladder]. / La mitomicina C en el tratamiento tópico de las neoplasias vesicales superficiales.

From January 1982 to October 1987, 100 patients with multifocal superficial bladder cancer received intravesical MMC at the Institute of Urology, University of Padova. Seventy-three patients had papillary multifocal superficial bladder carcinoma (stages Ta-T1): treatment was divided into therapeutic (18 cases), and prophylactic (55 cases). 27 patients had carcinoma in situ. 39 patients affected by neoplasia relapsed to previous intravesical ADM treatment. All patients received 40 mg. intravesical MMC weekly for 8 consecutive weeks, repeating the cycle in cases of relapse. Complete response rates at 12 months was 53%, 50 to 67% for each group, respectively. Recurrence rate was lower compared to that before treatment; progression rate was also lower compared to a group who received only endoscopic treatment. In patients who relapsed with ADM treatment, the percentage of complete response was 69%. We underscore the efficacy of MMC in lowering relapse and progression in multifocal superficial bladder cancer, which represents the best indication for this kind of treatment.

Prognosis of bladder cancer. III. The value of radical cystectomy in the management of invasive bladder cancer.

From January 1979 to June 1982, 141 consecutive patients with bladder transitional cell carcinoma were treated with a single stage lymphadenectomy plus radical cystectomy. The survival rate observed in our patients, based on the TNM classification, was comparable with that reported for other groups employing contemporary surgery. Survivorship for patients with deep invasive tumors was also estimated by breaking down the pT3 stage, and patients with tumor confined to the bladder wall (pT3a) were separately evaluated from those with tumor extended outside (pT3b). The results obtained with this subdivision showed that pT3a patients have almost the same survival rate as pT2 patients. From these results it is concluded that radical cystectomy is a satisfactory curative treatment of bladder cancer confined to the bladder wall, whatever the extension of the muscular involvement. Such considerations suggest that, in order to achieve a more objective analysis of the results after radical cystectomy for invasive bladder cancer, a modification of clinical staging is necessary. Moreover, a simplification of the classification methods should provide a better identification of the elements required to assess the prognosis and to improve treatment planning.

Prognosis of bladder cancer. II. The fate of patients with T1b transitional cell bladder cancer.

We have reviewed the tumor progress in 46 patients who presented T1b lesions in a previous study on the prognosis of superficial bladder cancer. A group of 12 patients with single or very few localizations was treated by transurethral resection. Five patients progressed and were submitted to cystectomy. Two of these 5 patients died within 3 years of the surgical treatment. Twenty-seven patients with multiple lesions underwent cystectomy soon after the initial diagnosis. Nearly 30% experienced progression; 4 patients died within 4 years after cystectomy. A delayed cystectomy was performed in 7 patients with multifocal disease; in all but one the tumor progressed; 5 patients died between 7 and 28 months after the surgery.

Prognosis of bladder cancer. I. Risk factors in superficial transitional cell carcinoma.

A retrospective study was carried out on 200 consecutive superficial transitional cell carcinomas of the bladder in order to identify which factors could influence the recurrence and/or progression of the tumor. Many parameters were considered, such as stage, grade, number, size, site, tumor-free interval and bladder mucosa mapping. A careful histological study of the initial tumor was employed and the tumors confined to the stromal core of the papillary tumor (T1a) were separated from those with invasion of the lamina propria of the bladder wall (T1b). The behavior of the T1b lesions observed in our study will be discussed in a forthcoming article. Recurrence occurred in 83% of our patients, and it was influenced by number and grade of the tumor and by the presence of dysplasia in normal-appearing mucosa. In 20% of our patients tumor progression occurred. Tumor progression was correlated with invasion of the lamina propria of the bladder wall, high-grade neoplasias, tumor-free interval, dysplasia or carcinoma in situ in normal-appearing mucosa. The results of our study suggest that, by these risk factors, a better prediction of the behavior of superficial transitional cell carcinoma and, as a consequence, more appropriate treatment can be provided.

Bladder herniation through abdominal wall: an exceptional complication of retropubic prostatic adenomectomy.

A case of bladder herniation through the abdominal wall as a late complication of retropubic prostatic adenomectomy is reported. The computed tomographic scan gave the diagnosis and a complete recovery was obtained with herniorraphy.