These, and other data, suggest that ingestion of low to moderate arsenic levels may affect bladder cancer incidence, and that cigarette smoking may act as a co-carcinogen.

Initial results of this combined chemoradiotherapy program show that bladder preservation can be achieved in the majority of patients, and that overall survival is similar to that reported with aggressive surgical approaches. Long-term survival and quality-of-life assessments require longer follow-up study.

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Purpose To evaluate the clinical and immunologic outcomes of DC (dendritic cell) vaccine with interleukin (IL)-2 and IFN-α 2a in metastatic renal cell carcinoma patients. Experimental Design Eighteen consented and eligible patients were treated. Peripheral blood monocytes were cultured ex vivo into mature DCs and loaded with autologous tumor lysate. Treatment consisted of five cycles of intranodal vaccination of DCs (1 × 107 cells/1 mL Lactated Ringer’s solution), 5-day continuous i.v. infusion of IL-2 (18MiU/m2), and three s.c. injections of IFN-α 2a (6MiU) every other day. Response Evaluation Criteria in Solid Tumors criteria were used for disease assessment. Correlative immunologic end points included peripheral blood lymphocyte cell phenotype and function as well as peripheral blood anti–renal cell carcinoma antibody and cytokine levels. Results All patients received between two and five treatment cycles. Toxicities consisted of known and expected cytokine side effects. Overall objective clinical response rate was 50% with three complete responses. Median time to progression for all patients was 8 months, and median survival has not been reached (median follow up of 37+ months). Treatment-related changes in correlative immunologic end points were noted and the level of circulating CD4+ T regulatory cells had a strong association with outcome. Pre–IP-10 serum levels approached significance for predicting outcome. Conclusions The clinical and immunologic responses observed in this trial suggest an interaction between DC vaccination and cytokine therapy. Our data support the hypothesis that modulation of inflammatory, regulatory, and angiogenic pathways are necessary to optimize therapeutic benefit in renal cell carcinoma patients. Further exploration of this approach is warranted.

Many studies that have calculated prostate cancer volumes from microscopic slides have used correction factors, ranging from 1.22 to 1.5, to compensate for tissue shrinkage during tissue processing. We undertook a study to measure tissue shrinkage directly because our experience suggested less shrinkage than that reported by others. Ten prostatectomy specimens were processed in a uniform manner. Multiple identical linear measurements were taken at four stages of processing: in the fresh state, following fixation, following processing, and from the microscopic slide. Linear shrinkage following fixation was minimal (4.1%) but increased to 14.5% following tissue processing. With rehydration and expansion on the flotation bath, tissues swelled so that net linear tissue shrinkage was 4.3%, and net volumetric tissue shrinkage was 12.4%, which translates into a correction factor for tissue shrinkage of 1.14. The following variables had no statistically significant effect on shrinkage: concentration of formalin, whole-mount versus quadrant sections, thickness of tissue slices, length of time in the alcohol dehydration steps, and temperature of the flotation bath over a range of 35 to 45 degrees C. This study suggests that (a) tissue-shrinkage correction factors that have been used in some previous studies may not be applicable for all laboratories because of interlaboratory variations in tissue-processing procedures or differences in measuring shrinkage; and (b) some calculated tumor volumes that have been used for prognostic thresholds may be high because of inflated tissue-shrinkage correction factors.

Purpose Electrical properties of the prostate may provide sufficient contrast for distinguishing malignant and benign formations in the gland. We evaluated how well these electrical properties discriminate cancer from noncancer tissues in the prostate. Materials and Methods Electrical admittivity (conductivity and permittivity) was recorded at 31 discrete frequencies of 0.1 to 100 kHz from each of 50 ex vivo human prostates. A specifically designed admittivity probe was used to gauge these electrical properties from sectioned prostate specimens. The specific tissue area probed was marked to provide precise colocalization between tissue histological assessment and recorded admittivity spectra. Results Adenocarcinoma, benign prostatic hyperplasia, nonhyperplastic glandular tissue and stromal tissue were the primary tissue types probed. Mean cancer conductivity was significantly less than that of glandular and stromal tissues at all frequencies (p <0.05), while mean cancer permittivity was significantly greater than that of all benign tissues at 100 kHz (p <0.0001). ROC curves showed that permittivity at 100 kHz was optimal for discriminating cancer from all benign tissues. This parameter had 77% specificity at 70% sensitivity and an ROC AUC of 0.798. Conclusions The contrast in electrical admittivity properties of different prostate tissues shows promise for distinguishing cancer from benign tissues. Sensitivity and specificity exceed those reported for current prostate specific antigen screening practices at low prostate specific antigen, making this an attractive addition to the clinical armamentarium for identifying prostate cancer.

Tissue electrical impedance is a function of its architecture and has been used to differentiate normal and cancer tissues in a variety of organs including breast, cervix, skin, and bladder. This paper investigates the possibility of differentiating normal and malignant prostate tissue using bioimpedance spectra. A probe was designed to measure impedance spectra over the range of 10 kHz to 1 MHz. The probe was fully characterized using discrete loads and saline solutions of different concentrations. Impedance spectra of five ex vivo prostates were measured in the operating room immediately following radical prostatectomy. Wilcoxon signed-rank tests were used to compare the normal and malignant findings. The impedance probe had a signal-to-noise ratio (SNR) > 84 dB across the entire spectrum and measured a tissue volume of approximately 46 mm(3). At 10 kHz, prostate conductivity (or) ranged from 0.232 S/m to 0.310 S/m for tumor and from 0.238 S/m to 0.901 S/m for normal tissue. At 1 MHz the ranges were 0.301 S/m to 0.488 S/m for tumor and 0.337 S/m to 1.149 S/m for normal. Prostate permittivity (epsilonr) ranged from 6.64 x10(4) to 1.25 x 10(5) for tumor and from 9.08 x 10(4) to 4.49 x 10(5) for normal tissues at 10 kHz. And, at 1 MHz the er ranges were 9.23 x 10(2) to 1.88 x 10(3) for tumor and 1.16 x 10(3) to 2.18 x 10(3) for normal tissue. Both sigma and epsilonr of tumor tissue were found to be significantly lower than that of normal tissue (P < 0.0001). Conductivity and permittivity are both higher in normal prostate tissues than they are in malignant tissue making them suitable parameters for tissue differentiation. This is in agreement with trends observed in other tissues reported in much of the literature. Expanded studies are needed to further validate this finding and to explore the biological mechanism responsible for generating the results.

Hospital volumes inversely related to in-hospital mortality, length of stay and total hospital charges after radical prostatectomy. Further study is necessary to examine the association of hospital volume with other important outcomes, including incontinence, impotence and long-term patient survival after radical prostatectomy.