Tolterodine extended release is well tolerated in older subjects.

OBJECTIVES: To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB). METHODS: This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8-12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65-74 (n = 1059) and > or = 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms. RESULTS: Discontinuation rates were slightly higher among subjects > or = 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65-74 or > or = 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment x age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65-74 years, 16%; > or = 75 years, 15%). The occurrence of all other AEs was < or = 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts. CONCLUSION: The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.

Comparison of cystoscopic and histological findings in patients with suspected interstitial cystitis.

PURPOSE: Although the exact etiology of interstitial cystitis remains elusive, bladder inflammation appears to be common in many patients. The National Institutes of Health (NIH) have established diagnostic criteria for interstitial cystitis based on the presence of irritative voiding symptoms in the absence of other identifiable pathology. Cystoscopic examination with hydrodistention performed in patients under anesthesia is part of the NIH diagnostic criteria. We determine if the severity of cystoscopic findings correlated with histological evidence of inflammation in patients with suspected interstitial cystitis. MATERIALS AND METHODS: A total of 69 patients who met NIH symptom criteria for interstitial cystitis and underwent cystoscopy, hydrodistention and bladder biopsy under anesthesia were reviewed. There were 2 investigators blinded to the histological data who independently reviewed operative reports. A urological pathologist blinded to the clinical data reviewed biopsies for inflammation severity. Cystoscopic and histological findings were then converted to a numeric scale. Numeric data were analyzed using the Pearson correlation coefficient. RESULTS: Cystoscopic examination revealed no evidence of interstitial cystitis in 6 patients (9%), mild changes in 27 (39%), moderate changes in 23 (33%) and severe changes in 13 (19%). Histological examination revealed no inflammation in 21 patients (30%), mild inflammation in 28 (41%), moderate inflammation in 11 (16%) and severe inflammation in 9 (13%). Histological scores correlated poorly with total and scaled cystoscopic severity scores (r = 0.295 and 0.349, respectively). CONCLUSIONS: Severity of cystoscopic findings observed during hydrodistention with anesthesia does not appear to correlate with the degree of inflammation identified histologically in patients with suspected interstitial cystitis.

Resolution of urge symptoms following sling cystourethropexy.

PURPOSE: Persistence of urinary urge symptoms in women after pubovaginal sling cystourethropexy is a distressing problem. We assess the ability of preoperative video urodynamics to identify patients in whom urinary urge symptoms failed to resolve postoperatively. MATERIALS AND METHODS: The records of 84 consecutive women who had undergone pubovaginal sling cystourethropexy were reviewed. Preoperative video urodynamics revealed stress urinary incontinence in all cases and concomitant detrusor instability in some. Cases of motor urge, defined as urge symptoms plus detrusor instability, were divided into low and high pressure categories. Patients with urge symptoms but no demonstrable detrusor instability on video urodynamics were diagnosed with sensory urge. Postoperatively complete urge resolution was defined as total absence of symptoms without pharmacological therapy. Mean followup was 26.7 months (range 2 to 62). RESULTS: Of the 84 patients 41 with motor urge and 28 with sensory urge had preoperative urge symptoms. Complete resolution or improvement in urge symptoms occurred in 24 (58.5%) and 7 (17.1%) of the motor urge, and 11 (39.3%) and 9 (32.1%) of sensory urge cases, respectively. Of the 41 patients with motor urge 23 had low pressure instability, which completely resolved in 21 (91.3%) and improved in 2 (8.7%). Of the 18 remaining patients with high pressure motor urge only 5 (27. 8%) had complete resolution of urge and 5 (27.8%) had improvement. CONCLUSIONS: Our results suggest that patients with low pressure motor urge are significantly more likely to experience resolution of urinary urge symptoms after pubovaginal sling cystourethropexy than those with high pressure motor urge or sensory urge.

Fascia lata sling cystourethropexy for the management of female urinary incontinence.

Pubovaginal sling cystourethropexy has rapidly become one of the primary surgical treatment options for women with urinary incontinence. The procedure has evolved over time with regard to clinical indications, patient selection criteria and surgical techniques. This article reviews the historical development of pubovaginal sling cystourethropexy, including recent technical advances. The selection of graft materials is considered and the utility of fascia lata emphasized. Clinical results and potential complications of the procedure are also reviewed.

Prognostic implications of extracapsular extension of lymph node metastases in prostate cancer.

We performed a retrospective review of surgical pathology specimens and clinical data for all patients with node-positive prostate cancer diagnosed in our institutions between 1985 and 1994. We used adjusted actuarial survival analyses and univariate and multivariate analyses to evaluate the clinical significance of extracapsular perinodal tumor extension. Sixty patients with histologically confirmed prostate cancer metastatic to regional lymph nodes were reviewed. Forty-two patients (70%) had evidence of extracapsular extension of the tumor into perinodal tissue. The 5-year adjusted cumulative survival rates for patients with extracapsular nodal extension was 54.6%, compared with 71.4% for patients with histologically confined nodal metastases (P < .05). Univariate and multivariate analyses revealed the presence of extracapsular nodal tumor extension to be an independent predictor of patient survival. In this study, only the histologic grade (Gleason score) of the primary tumor was a stronger predictive factor. These data suggest that histologic evidence of extracapsular tumor extension from lymph node metastases into perinodal tissue might be an important prognostic factor in patients with node-positive adenocarcinoma of the prostate. Development of a pathologic substage to include this feature might be warranted.

Transurethral collagen injection for treatment of postprostatectomy urinary incontinence in men.

OBJECTIVES: Transurethral injection of glutaraldehyde cross-linked bovine collagen has recently been advocated as a potentially useful treatment modality for management of urinary incontinence. The reported clinical experience with urethral collagen injection in adult males has been limited. METHODS: This study summarizes the current literature and reviews the clinical results of collagen injection in a group of 25 men with incontinence after either transurethral or radical prostatectomy. RESULTS: The overall results in this series were disappointing. Only 2 patients (8%) achieved significant improvement with this treatment. Eight patients (32%) experienced minimal improvement in symptoms, and 15 (60%) remained incontinent with no improvement in symptoms after collagen injection. The number of injection procedures and volume of collagen material implanted did not correlate with clinical outcome. Five patients (20%) have subsequently required placement of an artificial urinary sphincter to control their incontinence. CONCLUSIONS: We conclude that transurethral injection of glutaraldehyde cross-linked bovine collagen has a limited role in the management of urinary incontinence in adult men after prostatectomy.

The role of estrogen replacement therapy in the management of urinary incontinence and urinary tract infection in postmenopausal women.

The hormonal changes associated with normal aging and menopause may contribute to the development of urinary disorders including both urinary incontinence and urinary tract infections. Estrogen replacement therapy has been used successfully in the treatment of both of these disorders in postmenopausal women. Although the selection of specific treatment modalities should be tailored to the individual patient, hormonal replacement should be considered a viable conservative treatment option for many older women with urinary complaints. Future research will help to delineate the most effective route of administration and type of estrogen used in treating these complaints.

Cellular adhesion molecules in urologic malignancies.

Cell adhesion molecules (CAMs) are important in cell-cell interaction and interactions between cells and components of the extracellular matrix. CAMs have been associated with invasion and metastasis in a wide variety of human malignancies, including tumors of the genitourinary tract. Cadherins are transmembrane glycoproteins that bind cells by homophilic, homotypic interactions. Loss of expression of E-cadherin has been associated with dedifferentiation, invasion, and metastasis in prostate cancer and transitional cell neoplasia of the urinary bladder. CD44, a family of transmembrane glycoproteins principally involved in cell-extracellular matrix interactions, also has been associated with invasion and metastasis in urologic malignancies. Through alternative splicing, a variety of CD44 isoforms can be expressed that can undergo extensive posttranslational modification. CD44 variants have been associated with metastasis in a variety of human malignancies, particularly in the gastrointestinal system. Although loss of expression of CD44 standard form has been associated with aggressive prostate gland and bladder cancers, no specific isoform has been associated with metastasis of these neoplasms. Integrins are transmembrane glycoproteins with wide cellular distribution that bind a variety of extracellular matrix components. Integrins have been studied extensively in prostate cancer in which altered integrin expression has been associated with malignant prostatic epithelium. Additional adhesion molecules that have been studied to a variable degree in urologic malignancies include selectins and the immunoglobulin super-family. CAMs are fundamental to diverse biologic processes and appear capable of regulating intracellular signaling events that appear to have significant importance in human malignancy, including cancers of the urogenital tract.

Staging of incidentally detected prostate cancer: role of repeat resection, prostate-specific antigen, needle biopsy, and imaging.

Numerous studies have confirmed the distinct biological behavior of two subsets of prostate cancer diagnosed incidentally after either transurethral resection (TURP) or open prostatectomy for presumed benign prostatic hyperplasia (BPH). Focal, low-grade lesions are associated with a low risk for clinical progression and are designated as stage T1a or A1. These cases have traditionally been managed conservatively with close clinical observation. In contrast, multifocal, high-volume, or high-grade tumors are associated with a more aggressive clinical course and are designated as stage T1b or A2. Early definitive intervention is usually advocated for these latter patients. Therefore, accurate pathological assignment to either stage T1a or T1b is crucial for selection of appropriate management options. A variety of methods for staging patients with incidentally detected prostate cancer have been proposed, including detailed histological analysis, repeat TURP or transurethral biopsy, serial prostate-specific antigen (PSA) analysis, and imaging with either transrectal ultrasound (TRUS) or magnetic resonance (MRI) techniques. This article critically examines the clinical utility of these staging modalities for patients with incidentally detected prostate cancer.

Expression of CD44 isoforms in human prostate tumor cell lines.

We have examined the expression of the transmembrane glycoproteins CD44 in four human prostate tumor cell lines. Expression was examined at the protein level by flow cytometric analysis and Western blot, and at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR). All four cell lines (DU145, LNCaP, PC3, and ND1) expressed the standard CD44 isoform (CD44s) at the mRNA level and all cell lines except LNCaP expressed CD44s at the protein level. All four cell lines contained one or more isoforms containing the v6 region (exon 10) at the mRNA level, which has been associated with metastatic potential. However, a subpopulation of LNCaP and ND1 cells showed protein expression of v6. In addition, soluble CD44 isoforms were identified in cultured supernatants from all cell lines except LNCaP. These results show that CD44 isoforms are expressed on human prostate tumor cell lines, including the expression of variant isoforms containing the v6 region, and provide a rationale for the further study of this cellular adhesion molecule in prostate cancer. In addition, preliminary results indicate altered expression of CD44 in human prostatic adenocarcinomas examined immunohistochemically.

Human prostate carcinoma cell lines secrete GM-CSF and express GM-CSF-receptor on their cell surface.

Using specific ELISA kits, we investigated the secretion of cytokines in five human prostate carcinoma cell lines: ALVA 31, DU145, LNCaP, ND1 and PC3. Three of the five cell lines investigated secreted granulocyte-macrophage colony-stimulating factor (GM-CSF); GM-CSF was not identified in ALVA31 or LNCaP. In addition, we have shown that conditioned media of DU145, ND1 and PC3 stimulated proliferation of the GM-CSF-dependent cell line MO7e indicating that these cells secrete biologically active GM-CSF. By flow cytometric analysis we determined that all five cell lines expressed the alpha-subunit of the GM-CSF receptor on the cell surface but only ALVA31 expressed both the alpha- and beta-subunits of the GM-CSF receptor. Varying concentrations of GM-CSF did not stimulate the proliferation rate of any of the prostate carcinoma cell lines. Thus, there does not appear to be autocrine loop of GM-CSF-induced proliferation. However, the expression of E-cadherin and endoglin (CD105) was modulated under GM-CSF treatment in ALVA31. In addition, GM-CSF decreased the level of soluble CD44 in ND1. These results suggest that the GM-CSF receptor alpha-subunit may play a role in metabolic activity of prostate cancer.

Urethral reconstruction after pelvic fracture with urethral disruption: the gold standard.

Traumatic injuries with disruption of the posterior urethra frequently occur in patients who sustain pelvic fracture. Several endoscopic and open reconstructive techniques have been proposed for management of such urethral injuries. Treatment objectives include restoration of physiological urethral voiding with preservation of urinary continence and sexual function. This article summarizes the current recommendations for evaluation and treatment of patients with traumatic posterior urethral injuries. The various reconstructive techniques are reviewed and selection criteria and clinical outcomes are evaluated.