Military service and health-related quality of life among gay and bisexual prostate cancer survivors: Results from the Restore -2 study.

INTRODUCTION: There are notable disparities in health-related quality of life (HRQOL) between gay and bisexual men (GBM) and heterosexual patients with prostate cancer (PCa); however, the role of past military service is unclear. This study examines HRQOL differences in GBM PCa survivors based on reported military service history. METHODS: We used data from the 24-month follow-up survey of the Restore-2 study, a clinical trial which evaluated a rehabilitation programme for GBM PCa survivors. PCa HRQOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC-50) and the Functional Assessment of Cancer Treatment-Prostate (FACT-P). Mental health quality of life was assessed using the Brief Symptom Inventory-18 (BSI-18) scale, while sexual functioning was measured using the Sexual Minorities and Prostate Cancer Scale (SMACS). Multivariable linear regression was used to estimate unadjusted and adjusted mean differences in HRQOL between GBM with and without a reported history of military service. RESULTS: In this cross-sectional study of 351 GBM PCa survivors, 47 (13.4%) reported a history of US military service. After adjusting for covariates, participants who reported a history of military service (compared with those with no military service) had clinically better scores on the FACT-P physical, social and emotional well-being domains, as well as higher total FACT-General, EPIC urinary bother and hormonal function scores. Additionally, men with a history of military service reported significantly fewer sexual problems, more sexual confidence and less urinary incontinence in sex. CONCLUSION: This exploratory study provides the first evidence that GBM PCa survivors with a military background may have clinically better outcomes than those without military service. Potential reasons may include the structured support and healthcare access associated with military service, fostering resilience and well-being. These findings underscore the need for further research to elucidate how military service influences PCa HRQOL.

Nonandrogenic mediators of prostatic growth.

Prostate growth and development are primarily under the control of androgens; however, other factors can also influence prostatic growth through alternative pathways. This article discusses some of the major nonandrogenic mediators of prostate growth. Information on the pathways by which these factors exert their effects is also reviewed.

Urine based markers of urological malignancy.

PURPOSE: A number of urine based markers have been and are being investigated for the diagnosis and prognostication of urological conditions. A majority of these markers have been evaluated in urological neoplasms, particularly bladder cancer. The diagnosis of bladder cancer currently relies on identifying malignant cells in the urine and subsequently visualizing the tumor on cystoscopy. This diagnosis is further confirmed by transurethral resection or biopsy. While urine cytology is specific, it is not sensitive, especially for detecting low grade disease. This characteristic has prompted the search for more accurate markers of bladder cancer. In this review we critically examine the results of studies evaluating various markers for bladder cancer. MATERIALS AND METHODS: The published literature on urine based markers for all urological diseases, particularly bladder cancer, was identified using a MEDLINE search and critically analyzed. The sensitivity, specificity, positive and negative predictive values of the various markers were compared. The benefit of using combined markers rather than a single marker was also analyzed from published reports. RESULTS: Most published literature on urine based markers for urological malignancies involve such markers for diagnosing and prognosticating bladder cancer. Hence, we focused mainly on urine based markers in bladder cancer. Most markers appear to have an advantage over urine cytology in terms of sensitivity, especially for detecting low grade, superficial tumors. However, most markers tend to be less specific than cytology, yielding more false-positive results. This scenario is more common in patients with concurrent bladder inflammation or other benign bladder conditions. However, there is reason to be optimistic about several new markers that appear to provide better specificity. Few urine based markers have been identified and investigated in other urological tumors. CONCLUSIONS: Detecting bladder cancer using diagnostic markers still presents a challenge. A number of new markers are currently available that appear to be significantly more accurate than cytology. However, further studies involving a larger number of patients are required to determine their accuracy and widespread applicability for diagnosing bladder cancer. Urine based markers do not appear to have a significant role in the diagnosis or prognosis of other urological malignancies, such as prostate, kidney or testicular cancer.

Effects of vitamin D (calcitriol) on transitional cell carcinoma of the bladder in vitro and in vivo.

PURPOSE: Vitamin D (calcitriol) has significant antiproliferative effects on various tumor cells in vitro and in vivo. In the clinical situation a major impediment to systemic administration of calcitriol is the side effect of hypercalcemia. To test the potential usefulness of calcitriol for bladder cancer treatment, we studied the antiproliferative effect of vitamin D on 2 human bladder cancer cell lines, 253j and T-24, in vitro. We also examined the in vivo effects of calcitriol in an animal model of bladder cancer using intravesical administration to avoid the toxicity of systemic calcitriol therapy. MATERIALS AND METHODS: The presence of vitamin D receptors in normal and neoplastic human bladder tissue, and tumor cells T-24 and 253j was determined by immunoblot analysis. Tumor cell proliferation in the presence or absence of calcitriol was determined using a crystal violet assay. Calcitriol induced apoptosis was determined by morphology, polyadenosine diphosphate ribose polymerase cleavage and annexin V binding. In vivo studies were performed by weekly intravesical instillation of calcitriol in female Fischer 344 rats after induction of tumors by N-methyl nitrosourea. Calcitriol administration was started 3 weeks after tumor induction for 7 doses at weekly intervals. RESULTS: Normal and neoplastic human bladder tissue, and the cell lines expressed vitamin D receptors. In the 253j and T-24 cell lines proliferation was significantly inhibited by calcitriol. Progressive cleavage of full length polyadenosine diphosphate ribose polymerase was observed in calcitriol treated cells starting as early as 4 hours after exposure. Similar changes were not observed in the control cells treated with vehicle (ethanol) alone. After 24 hours of treatment with calcitriol 45.8% of 253j cells bound annexin compared to 16.5% of control cells (chi-square p <0.001). Of the control animals 66% developed bladder tumors and 55% of the animals treated with calcitriol early (3 weeks) after tumor induction developed bladder tumors. Almost all of the tumors that developed in the calcitriol group were unifocal, and only 20% were invasive compared to 50% of those in the control animals. CONCLUSIONS: These results demonstrate that calcitriol inhibits proliferation and induces apoptosis in human bladder tumor cells in vitro, and may have therapeutic potential in bladder cancer. In vivo studies using an N-methylnitrosourea induced model of bladder cancer demonstrate that early institution of intravesical calcitriol therapy after carcinogen exposure results in fewer tumors, which are also less likely to be multifocal, high grade or invasive. With our protocol a short course of intravesical calcitriol administration did not result in any significant toxicity.

In vitro and in vivo effects of vitamin D (calcitriol) administration on the normal neonatal and prepubertal prostate.

PURPOSE: Although many studies have investigated the role of calcitriol in the growth regulation of normal and cancerous prostates, little is known about its role in early prostatic development. The interactions between calcitriol and androgens, and their actions on the normal prostate have similarly been proposed but not evaluated. Previous studies in our laboratory have revealed that in utero administration of 1,25-dihydroxycholecalciferol or calcitriol can influence prostate growth and differentiation throughout the life of the animal. We further examined the influence of calcitriol on the normal prostate in vitro and in vivo by focusing on early stages of prostatic development. MATERIALS AND METHODS: The effects of calcitriol on the growth of the normal human neonatal prostatic epithelial cell line 267B-1 was determined in the presence and absence of dihydrotestosterone (DHT). We also examined the effect of calcitriol on the growth of maturing rat prostates in vivo. Before puberty 4 groups of rats 27 to 38 days old were treated with vehicle (controls) or calcitriol. When the rats reached adulthood at age 100 to 110 days a control group and a calcitriol group were sacrificed. The other 2 groups were given exogenous DHT for 5 days. For the animals to become adapted to DHT they were kept alive for 1 additional week and sacrificed at about age 120 days. RESULTS: In vitro studies demonstrated that 267B-1 cells possess vitamin D receptors and their growth was inhibited by calcitriol with an IC50 (concentration resulting in 50% cytotoxicity) of 30 microM. Proliferation of these neonatal prostate cells was also inhibited by calcitriol in the presence of DHT in vitro. Our studies indicate that, although calcitriol was administered at the apparently important prepubertal period, there was no difference in prostatic weights between the control and calcitriol treated rats. Exogenous administration of DHT decreased prostatic weight of control rats but in rats treated with 1,25-dihydroxycholecalciferol DHT did not have any significant effect on prostatic weight. No statistically significant differences were observed in seminal vesicle weights among the different groups of animals. Analysis of the nuclear matrix protein composition of the prostatic tissue showed differences in composition between the DHT, and calcitriol and DHT treated rat prostates. CONCLUSIONS: These studies indicate that calcitriol administered just before puberty does not significantly influence prostatic growth in the presence of endogenous or exogenous administered DHT, and has an inhibitory effect on neonatal prostate epithelial cell growth in vitro in the presence and absence of DHT. Treatment with calcitriol and DHT also results in differences in nuclear matrix protein composition. Prepubertal administration of calcitriol may inhibit the exogenous DHT action in decreasing epithelial growth and stimulating stromal proliferation in the rat prostate.

Clinical usefulness of the novel marker BLCA-4 for the detection of bladder cancer.

PURPOSE: Previous studies at our laboratory identified 6 bladder cancer specific nuclear matrix proteins termed BLCA-1 to 6. We recently developed an immunoassay that detects the bladder cancer specific nuclear matrix protein BLCA-4. We analyzed urine samples from patients with bladder cancer, those with spinal cord injury and normal volunteers to determine the BLCA-4 level in these 3 groups. MATERIALS AND METHODS: Urine samples obtained from 51 normal controls, and 54 patients with bladder cancer and 202 with spinal cord injury were tested for BLCA-4. We evaluated the association of BLCA-4 level with tumor grade and stage, urine cytology and bladder cancer history in the nonspinal cord injured population. Similarly we compared parameters associated with BLCA-4, such as spinal cord injury duration, catheterization, history of urinary tract infection, smoking and urine culture, in spinal cord injured patients. RESULTS: We established a normal cutoff point of 13 optical density units per microg. protein for the BLCA-4 assay. The BLCA-4 level was less than the cutoff in all 51 normal controls, while in 53 of the 55 urine samples (96.4%) of patients with bladder cancer and 38 of the 202 (19%) of spinal cord injured patients urinary BLCA-4 was greater than the cutoff. There was no correlation of any individual factors studied in these cases, including urinary tract infection and urinary BLCA-4. CONCLUSIONS: Elevated urinary BLCA-4 levels may accurately identify bladder cancer and distinguish these patients from normal individuals. There is no correlation of urinary BLCA-4 with a history of urinary tract infection, smoking, catheterization or cystitis considered independently. Urinary BLCA-4 determination appears to have high potential as a test for screening and monitoring bladder cancer in the general population and in groups at high risk for the disease, such as those with spinal cord injury.

Detection of bladder cancer using a novel nuclear matrix protein, BLCA-4.

We have identified previously six nuclear matrix proteins (NMPs) that are bladder cancer specific. In this study, we analyzed the expression of one of these proteins, BLCA-4, in bladder tumors and normal bladder tissue. We also examined the appearance of BLCA-4 in the urine as a biomarker for bladder cancer. BLCA-4 was isolated from nuclear matrix preparations of bladder tumors, and its peptide sequence was determined. The antibodies generated against the resulting BLCA-4 peptides were then used to detect its presence in immunoblots and in urine samples by immunoassay. We analyzed tissue samples of bladder tumor and normal donor bladders and urine obtained from 51 normal individuals and 54 patients with pathologically confirmed bladder cancer. The BLCA-4 peptide sequences do not resemble any known human protein sequences. On immunoblot analysis, BLCA-4 expression was detectable in tumor and normal tissues from patients with bladder cancer but not in any of the normal bladder tissue obtained from organ donors. Using a prospectively determined cutoff level of 13 A (absorbance) units/microg protein, all 51 normal individuals tested were negative for BLCA-4 expression, whereas 53 of 55 samples from patients with bladder cancer were positive. These results suggest that BLCA-4 is present throughout the bladder in both the tumor and morphologically normal areas in bladder cancer patients. BLCA-4 is a very sensitive (96.4%) and specific (100%) marker for bladder cancer. BLCA-4 is a bladder cancer-specific marker that can be detected using a urine-based assay and can be used in the diagnosis of bladder cancer.

Evaluation of the effect of spinal cord injury on serum PSA levels.

OBJECTIVES: Prostatic structure and secretory activity are thought to be influenced by autonomic innervation of the prostate. Prostatic denervation is especially likely in patients with spinal cord injury (SCI) at the level of the cauda equina or the conus medullaris, where the peripheral nerve supply to the prostate may be specifically damaged. This may result in changes in serum prostate-specific antigen (PSA) levels, either directly or indirectly. Therefore, we measured serum PSA levels and also studied the influence of factors such as age, catheterization, duration of SCI, urinary tract infection, and history of cystitis on serum PSA values in men with SCI. METHODS: Serum PSA levels were determined in 79 men with SCI (age older than 40 years) using banked sera by the Abbott MEIA PSA assay. Variables such as age, catheterization, duration of SCI, urine culture results, and history of cystitis were obtained from a review of patient records. Comparisons were made with a randomly selected, non-SCI control population of 501 men, 40 to 89 years old, who underwent serum PSA determination at our institution. Statistical comparisons were performed using the Mann-Whitney U test (nonparametric), since the populations were not normally distributed. Multivariate logistic regression analysis was used to assess the correlation between the various factors and the serum PSA levels in men with SCI. RESULTS: No statistically significant differences were found in the median serum PSA values between the SCI group and the non-SCI control population. The age-specific PSA values obtained in the SCI group were also comparable to those reported for the general population at large. Age (P <0.03) and the presence of a catheter (P <0.0002) were the only two factors that were correlated with higher serum PSA values in the SCI group by regression analysis. CONCLUSIONS: Men with SCI tended to have serum PSA value distributions that were similar to those of the general population. However, those in the SCI group who had indwelling catheters were more likely to have higher PSA values at baseline, as were older men with SCI.

Urolume stent placement for the treatment of postbrachytherapy bladder outlet obstruction.

OBJECTIVES: Transurethral resection (TURP) or incision of the prostate is generally not effective for treating bladder outlet obstruction after transperineal brachytherapy for prostate cancer. Furthermore, TURP could compromise full-dose effective radiation delivery to the prostate. We analyzed the efficacy of the UroLume stent in treating the urinary outflow obstruction in such patients. METHODS: Five patients who had undergone brachytherapy (3 with (192)Ir high-dose radiation and 2 with (125)I) subsequently developed one or more episodes of urinary retention 2 weeks to 4 years after treatment. The patients failed or could not tolerate alpha-blockers or clean intermittent catheterization. Three patients subsequently underwent urethral dilation/optical internal urethrotomy for strictures, and 1 patient underwent suprapubic tube placement. Following the failure of these interventions, each of these patients had a UroLume stent placement. A single UroLume stent (2 cm in 3 patients and 2.5 cm in 2 patients) was placed under local/spinal anesthesia. RESULTS: All patients were able to void spontaneously immediately after stent placement. Of the patients with previous urethral strictures, 1 remained continent and 1 had persistent incontinence. Neither of the patients with early postbrachytherapy retention developed incontinence after stent placement. The main complaints following stent placement were referred pain to the head of the penis and dysuria. Stent-related symptoms necessitated stent removal in 2 of 5 patients, 4 to 6 weeks after placement. CONCLUSIONS: The UroLume stent can be used as an alternative form of therapy for managing postbrachytherapy bladder outlet obstruction. The treatment is easily reversible by removing the stent when obstruction resolves.

Positive predictive value (PPV) of prostate specific antigen (> ng/ml) and abnormal digital rectal exam for prostate cancer on the Caribbean island of Tobago

OBJECTIVE: To establish and compare the positive predictive values (PPV) for elevated (4 ng/ml) prostate specific antigen (PSA) and abnormal digital rectal exam (DRE) in an Afro-Caribbean population. DESIGN AND METHODS: We screened 728 men aged 40-79 years, recruited from the general population on the Caribbean island of Tobago. Ninety-five percent reported African ancestry. This population had not previously undergone screening for prostate cancer. RESULTS: PSA was elevated (> or = 4 ng/ml) and/or DRE was abnormal in 291 (40 percent) men. Pathological diagnosis of random sextant biopsies was completed in 191 (66 percent) of men. Ninety-two (13 percent) of the screened men were diagnosed with prostate cancer. Among men biopsied for abnormal DRE in the presence of normal PSA, PPV for abnormal DRE was 26 percent (11/43), range 9-50 percent across age groups. Among men with elevated PSA and normal DRE, the PPV for PSA was 46 percent (29/63), range 42-54 percent (no men aged 40-49 years (n=105) fell into this category). When all men with elevated PSA were considered, ignoring DRE status, PPV for PSA was 55 percent (79/144), range 50-60 percent. If both PSA and DRE were abnormal, the PPV was 63 percent. CONCLUSIONS: The PPV of abnormal DRE was similar to that observed in other populations undergoing screening for the first time. We speculate that a lower PSA cut-off point may be appropriate for optima ascertainment of cases in this high-risk population.(Au)

Use of urine-based markers for detection and monitoring of bladder cancer.

Diagnosis and monitoring of bladder cancer present a difficult clinical problem. Urine cytology with confirmatory cystoscopy form the cornerstone of diagnosis at the present time. The subjectivity and low sensitivity of cytology led to the development of numerous tests as adjuncts to cystoscopy for the diagnosis and follow-up of bladder cancer patients. These tests usually are objective, quantitative (NMP-22, BTA TRAK, BLCA-4, telomerase activity, etc.), or qualitative (BTA Stat and FDP) and have higher sensitivity than cytology, but some have lower specificity. We review the different, new urine-based tests that were developed recently for the diagnosis and monitoring of patients with bladder cancer. The advantages and disadvantages of these tests are discussed, as well as their possible future role in the management of patients with bladder cancer.

Update on urine-based markers for bladder cancer. How sensitive and specific are the new noninvasive tests?

Urine cytology is still the most commonly used noninvasive test to diagnose bladder cancer. However, cytology's ability to detect low-grade bladder tumors is limited, and its results require interpretation by a pathologist, are not available immediately, and are subjective. Several noninvasive urine-based tests are now available for detection and follow-up of bladder cancer. At least two of these new tests (BTA stat and AuraTek FDP) can easily be performed in the office, and the results are available in about 10 minutes. When choosing a test, physicians should keep in mind that none of the currently available tests is 100% accurate. However, the new urine-based tests are more sensitive than urine cytology and hence more reliable in detecting low-grade bladder cancer. They are useful tools in patients with urinary symptoms or microscopic hematuria or as office-based adjuncts to diagnostic procedures. Some of the markers that are being developed could significantly improve and simplify workup, diagnosis, and follow-up, and they may allow for detection of disease at an earlier stage, thus improving the chances of curative therapy.

Advantages and risks of ileovesicostomy for the management of neuropathic bladder.

OBJECTIVES: To evaluate the efficacy and complications of ileovesicostomy in patients with neurogenic bladder dysfunction. METHODS: Fifteen consecutive neurologically impaired patients (8 from multiple sclerosis, 4 from spinal cord injury, 3 from other causes) with complications of previous bladder management underwent ileovesicostomy. There were 10 women and 5 men. All patients were either poor candidates for or refused continent urinary diversion or bladder augmentation cystoplasty. RESULTS: At a mean follow-up of 23.2 months, 14 of 15 patients had low-pressure urine drainage through their ileovesicostomy. Four women with documented preoperative detrusor hyperreflexia had postoperative intermittent mild urge incontinence per native urethra. They did not require any further treatment, except for oral anticholinergic drugs (oxybutynin and tolterodine). Because of persistent severe urge incontinence, 1 woman required conversion of her ileovesicostomy to an ileal conduit with concurrent cystectomy. The ileovesicostomy of another myelodysplastic man who had four failed artificial urinary sphincters in the past was also converted to an ileal conduit because of persistent urethroperineal fistula despite perineal urethral closure. Renal function was preserved in all patients. Long-term complications were stomal stenosis in 2 patients, bladder and kidney stone formation in 5, and symptomatic urinary tract infections in 3. CONCLUSIONS: Ileovesicostomy can be safely performed in neurologically impaired women and men. Severe preoperative detrusor hyperreflexia with urge incontinence appears to be a risk factor for persistent urge incontinence postoperatively in women. Continued routine urologic surveillance for infection and stones is mandatory. Ileovesicostomy is a versatile procedure for neurologically impaired patients, because it can be converted to a conventional ileal conduit if necessary. In addition, in cases of neural recovery, the ileal "chimney" can be excised and the patient's original lower urinary tract would be preserved.

Effect of prenatal vitamin D (calcitriol) exposure on the growth and development of the prostate.

BACKGROUND: We previously found that in the absence of testosterone (T), calcitriol promotes proliferation of normal prostatic stroma, while in the presence of T, it has a differentiating effect on prostatic epithelium. The present study was conducted to determine the effect of calcitriol exposure in utero on the postnatal development of the normal prostate. METHODS: Pregnant rats were injected subcutaneously with either 1.25 microg of calcitriol or vehicle alone on alternate days till delivery. Calcitriol-exposed and control pups were sacrificed at age 25 days (prepuberty), 63 days (postpuberty), or 102 days (adults), and their prostates and seminal vesicles were harvested and weighed. RESULTS: Pups prenatally exposed to calcitriol and sacrificed before puberty (25 days) had a 35% greater mean prostatic weight than controls (0.0314 vs. 0.0422 g, P < 0.007), and calcitriol-exposed adult rats (102 days) had a 68% greater mean prostatic weight than controls (0.1365 vs. 0.2304 g, P < 0.005). No differences were observed in seminal vesicle weights, and in serum calcium and testosterone levels. A disproportionately high mortality rate from sudden death (71%) was observed at puberty in uncastrated male rats prenatally exposed to calcitriol. CONCLUSIONS: These findings suggest that high-dose calcitriol exposure in utero may uniquely influence subsequent prostatic growth. Nonandrogenic steroids such as calcitriol may also be involved in genetic imprinting of the prostate.

Diagnostic value of voided urine and bladder barbotage cytology in detecting transitional cell carcinoma of the urinary tract.

In this article we report on our experience with the use of urine cytology for the screening and diagnosis of transitional cell carcinoma (TCC) of the bladder and upper urinary tracts at our institution between January 1987 and December 1995. A total of 76 patients were included in the study. All patients had voided urine cytology studies read as positive or highly suspicious for malignancy and no prior history of TCC of the urinary tract. All these patients subsequently underwent cystoscopy, bladder/ureteral barbotage cytology, random bladder biopsies, and radiographic studies of the upper tracts. Of the 76 patients with positive urine cytology, 53 also had barbotage urine cytologies which were positive. Six of these patients were found to have cystoscopically evident TCC of the bladder, and 1 patient had upper tract TCC. Three other patients subsequently went on to develop TCC of the bladder at 52, 89 and 111 months of follow-up. An additional patient was diagnosed with upper tract TCC at 12 months of follow-up. Among the 23 patients with negative bladder/ureteral barbotage cytology, 3 patients, 2 at the time of initial cystoscopy, and one 15 months later, showed evidence of TCC. Median patient follow-up was 97 (range 35-132) months. Thus of 76 patients with initial positive voided urine cytology studies, only 9 proved to have TCC at initial work-up, while 5 other patients were diagnosed with TCC during a median follow-up of 97 months. The statistical diagnostic values of the bladder/ureteral barbotage urine cytology studies at the time of cystoscopic work-up were: sensitivity 77%; specificity 31%; positive predictive value 13%, and negative predictive value 91%. Our data suggest that in patients without a previous history of TCC, the diagnostic value of bladder barbotage urine cytology is insignificant, and therefore not cost effective to be included as part of the routine work-up of TCC. Moreover, in patients with initially positive voided urine cytology and negative work-up, if the cytology subsequently becomes negative, the likelihood of the development of TCC is low. However, if the initially positive cytology continues to remain positive, there is a much higher probability of TCC being detected in this population.

Tolterodine for overactive bladder: time to onset of action, preferred dosage, and 9-month follow-up.

This is a prospective study of 28 patients who had urinary frequency (>8 times/day) and either urgency or urge incontinence (>1 time/day). After a 2-week run-in period (visit 1), the patients were started on tolterodine 1 mg twice a day (bid) (visit 2). They were followed at 4 and 8 weeks (visits 3 and 4). The patients were contacted by telephone 1 week after visit 2. Tolterodine was increased to 2 mg bid if the patient had incomplete improvement at either the initial phone call or during visit 3. Evaluation criteria were daily micturition charts including urinary frequency, nocturia, leakage episodes, average urine volume per day, and average voided volume. Tolterodine was well tolerated without side effects in 20 (80%) of 28 patients. Eight patients (20%) dropped out after enrollment because of side effects in 3, no improvement in 2, and missing visits (>1) in 3. Drug dosage in the 20 patients who tolerated tolterodine was 1 mg bid in 3 and 2 mg bid in 17 (85%). According to micturition charts, urinary frequency, nocturia, and leakage episodes decreased significantly after tolterodine treatment, whereas average urine volume per day and average voided volume did not change significantly. There were no electrocardiographic or biochemical abnormalities due to tolterodine treatment. Mean follow-up was 9.4 months. All 20 patients who tolerated tolterodine continue to take the medication without significant side effects. We conclude that tolterodine is well tolerated and effective for overactive bladders. Two milligrams bid is the dosage preferred by the majority of patients and the onset of action is seen within 1 week of treatment. Long-term compliance and efficacy are excellent, with no dropout in >9 months of follow-up.

Differential effects of vitamin D on normal human prostate epithelial and stromal cells in primary culture.

OBJECTIVES: Because epidemiologic evidence has demonstrated that vitamin D may play a role in the etiology of prostate cancer, we tested the inhibitory effect of the biologically active form of vitamin D (1,25-D) on the cell proliferation of human prostate epithelial and stromal cells in a chemically defined situation in the presence and absence of dihydrotestosterone (DHT). We also tested the effect of 1,25-D in castrated rats in the presence and absence of flutamide, an androgen receptor blocker. METHODS: Prostate stromal and epithelial cells were isolated from freshly collected human prostatectomy specimens, and cell proliferation was measured with the MTT assay. Immunohistochemistry was performed to detect the presence of 1,25-D receptors, androgen receptors, smooth muscle actin, and E-cadherin. For in vivo analysis of 1,25-D, male Sprague-Dawley rats were castrated, then treated with either 1,25-D, 1,25-D with flutamide, or vehicle control. RESULTS: Incubation of primary cultures of prostate epithelial cells with 1,25-D at a concentration of 10(-8) M reduced cell proliferation by 40% of controls. The inhibition of growth by 1,25-D was maintained in the presence of DHT. Conversely, the effect of a similar dose of 1,25-D on stromal cell exposure was increased proliferation. In vivo, 1,25-D increased the prostatic weight of castrated rats that had serum testosterone levels below the detectable limit. The addition of flutamide did not alter this effect. CONCLUSIONS: These results confirm that vitamin D may be an effective antiproliferative agent of epithelial cells in prostate cancer therapy and support in vivo studies performed in the normal rat prostate.

Vitamin D in the prevention and treatment of prostate cancer.

Current approaches to the management of prostate cancer include surgery, radiation therapy, or hormonal manipulation either individually or in combination. With an increase in understanding of the etiology and natural history of prostate cancer, the influence of dietary factors on the disease is becoming more evident. There have been a number of studies in this regard that have demonstrated a relationship between prostate cancer and numerous dietary constituents including vitamins. The fat-soluble vitamins A and D have both been found to affect the growth of prostate cancer in preclinical experiments. Of the two, vitamin D has been the focus of greater attention in recent years, and there are indications that it may be useful both in the prevention and treatment of prostate cancer. This article reviews the current literature in this area to determine if treatment with vitamin D would be a viable management alternative for the patient described in the case study.

Nuclear structural proteins as biomarkers of cancer.

The regulation of cell processes is integrally connected to cellular and extracellular structure. Studies over the past three decades have demonstrated the complex interactions of cell structure and function. The relationship of cellular structure and function has perhaps been most studied in the transformed cell. The hallmark of transformation is alterations in the shape of the cell and the nucleus. Many of the cellular alterations observed in the cancer process are structural, including changes in extracellular matrix-cytoskeletal interactions, cytoskeletal elements, as well as nuclear structure. This review focuses on the structural components of the nucleus, the nuclear matrix, and their role in the cancer process and the use of these structural components of the nucleus, the nuclear matrix, and their role in the cancer process and the use of these structural components as cancer specific biomarkers. J. Cell. Biochem. Suppls. 32/33:183-191, 1999.