Extended Use of The Spanner® Temporary Prostatic Stent in Catheter-Dependent Men with Comorbidities.

PURPOSE: This US FDA investigational device exemption (IDE) study evaluated the extended use of The Spanner® Temporary Prostatic Stent in catheter-dependent men with urinary retention who were not deemed candidates for corrective surgery but demonstrated bladder contractility. MATERIALS AND METHODS: The Spanner was placed for 3 cycles of 30 days in catheter-dependent men with comorbid conditions, confirmed detrusor contractility, and catheter-associated discomfort. At each visit, postvoid residual, maximum flow rate, international prostate symptom score, quality of life, and adverse events were assessed. Voiding success was defined as PVR ≤ 150 ml at all visits. RESULTS: One hundred seven men were enrolled at 8 US sites; 82/107 (76.6%) completed the trial, and 79/107 (73.8%) successfully maintained PVR ≤ 150 ml for the trial duration. Patients were 77.1 ± 10.6 years old; 63/107 (58.9%) were dependent on Foley and 40/107 (37.4%) on intermittent catheterization for 36.0 ± 39.3 days and 30.2 ± 45.8 days, respectively. 25/107 (23.4%) discontinuations were primarily due to voluntary patient withdrawal 9/107 (8.4%), investigator-initiated withdrawal 8/107 (7.5%), or lack of effectiveness 4/107 (3.7%). During Spanner use, the mean Q max was 11.2 ± 6.6, mean IPSS was 7.5 ± 6.4, and mean QOL was 2.0 ± 1.6. The most prevalent device-related adverse events were asymptomatic bacteriuria 25/107 (23.4%), discomfort 10/107 (9.4%), and urinary urgency 8/107 (7.5%). No device-related serious AEs were reported. CONCLUSIONS: This study demonstrates that catheter-dependent men with sufficient bladder contractility can achieve volitional voiding and successful bladder drainage using The Spanner Temporary Prostatic Stent for extended periods of time.

The impact of HMG-CoA reductase therapy on serum PSA.

BACKGROUND: 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, otherwise known as statins, inhibit the enzyme that controls the conversion of HMG-CoA to mevalonate, a precursor for cholesterol. Statins may be important to prostate cancer biology by inhibiting cell growth, inflammation, and oxidative stress. The purpose of this study was to assess the influence of statin therapy on serum prostate-specific antigen (PSA) levels. METHODS: The computerized medical records at the University of Rochester Medical Center were used to identify men who filled statin prescriptions between May 31st, 2008 and September 30th, 2008. Men with at least one PSA assay performed within 2 years before and at least one PSA assay performed within 1 year after starting a statin medication were included. The primary endpoint was the change in PSA concentration computed as the difference between PSA levels before and after starting a statin medication. Paired t-tests were used to analyze the mean differences in PSA values. RESULTS: A total of 962 patients were identified. The mean difference in serum PSA level after statin administration was -0.29 ng/ml (-8.04%). Subgroup analyses for mean PSA concentration change before and after statin administration by age group revealed: 50-59 years old (-0.1609, 95% CI: -0.2444, -0.0775, P < 0.0002), 60-69 years old (-0.3393, 95% CI: -0.4641, -0.2145, P < 0.0001), and >70 years old (-0.351, 95% CI: -0.490, -0.212, P < 0.0001). CONCLUSIONS: These observations suggest a statistically significant reduction in serum PSA level that is associated with the onset of statin therapy.

Development and validation of the fecal incontinence and constipation quality of life measure in children with spina bifida.

PURPOSE: Fecal incontinence and constipation in children with spina bifida are recognized to impact quality of life. Most disease specific quality of life instruments on fecal incontinence target adults and/or children without neuropathic bowel. We developed an instrument to evaluate bowel function and its impact on quality of life in children with spina bifida and their caregivers. MATERIALS AND METHODS: A 51-item questionnaire termed the FIC QOL (Fecal Incontinence and Constipation Quality of Life) survey was developed from expert opinion, patient interviews, and modification of previously published adult and pediatric studies for nonneuropathic bowel dysfunction. The items are divided into 7 quality of life factor groupings, including bowel program, dietary management, symptoms, travel and socialization, family relationships, caregiver emotional impact and financial impact. The questionnaire was given to caregivers of children with and without spina bifida. Discriminant validity was evaluated by comparing the spina bifida and control groups. Test-retest reliability was evaluated by having 41 patients complete 2 surveys within 4 to 6 weeks. RESULTS: Comparing questionnaires from 92 index patients and 52 controls showed a statistically significant difference for all 7 quality of life factor groupings. The FIC QOL instrument objectively demonstrated the negative impact of fecal incontinence and constipation on quality of life in these families. Comparing 82 questionnaires at 2 time points demonstrated the reliability of all FIC QOL questions. CONCLUSIONS: The FIC QOL instrument provides a valid and reliable measure of the effect of fecal incontinence and constipation on the quality of life of caregivers and their children with spina bifida.

Non-surgical management of multicystic dysplastic kidney.

OBJECTIVES: To better define the outcome and association of multicystic dysplastic kidney (MCDK) with hypertension, vesico-ureteric reflux (VUR), infection and cancer, as there is no consensus on the management of patients born with MCDK. The risk of cancer has dictated the surgical management of the disease in the past. METHODS: The Medline database was searched for articles published between 1965 and 2006 and written in the English language, and containing the keywords 'multicystic dysplastic kidney'. RESULTS: The inclusion criteria were met by 105 reports that were subsequently analysed. Of MCDK, 60% regress or involute within 3 years. About 25% of patients will have VUR into the contralateral kidney, of which 90% is grade

Cost-benefit and outcome analysis: effect of prostate biopsy undergrading.

OBJECTIVES: Brachytherapy is a widely used treatment for localized prostate cancer (CaP) and is only appropriate as monotherapy for low-risk cancer. The predicted response to therapy is defined by the pretreatment parameters, of which the biopsy Gleason grade is central. However, the biopsy grade often misrepresents the true pathologic grade. We examined the impact of incorrect biopsy grading on brachytherapy outcomes. METHODS: We constructed a decision analytic model to assess the theoretical performance of brachytherapy for a theoretical cohort of men with Gleason score 6 CaP who underwent radical prostatectomy. The variables regarding biopsy Gleason scores and the correlation with the surgical specimen findings were generated from the institutional data. The ranges for these variables, biochemical performance of brachytherapy, costs, and disease state utilities, were obtained from a data review. RESULTS: For the base case, 67% of biopsy grades correlated with the pathologic grade. With this concordance, 8% of failures could be attributed, in part, to undergrading. On the basis of the model assumptions, as concordance worsened to 50%, the rate of undergraded failures increased to 12%. After adjusting for the quality of life associated with higher-grade disease and the risk of biochemical failure, the aggregate cost of treatment of biopsy grade 6 disease was increased by 8% because of undergrading ($75,700 versus $81,500 per case). The bulk of this effect was the cost of failure among patients with undergraded disease. CONCLUSIONS: Brachytherapy for Gleason score 6 disease is reported to have excellent results. Undergrading of prostate biopsies can negatively affect clinical outcomes and increase treatment costs. Although the risk is low, it should be considered when counseling patients with CaP.

Renal cell carcinoma metastatic to gallbladder: a survival advantage to simultaneous nephrectomy and cholecystectomy.

Renal cell carcinoma is a relatively uncommon cancer. Patients presenting with a renal adenocarcinoma are often found to have evidence of metastatic disease at the time of diagnosis. Herein, we describe the case of a 39-year-old male with renal cell carcinoma and a synchronous metastatic focus to the gallbladder. The patient underwent a successful simultaneous nephrectomy and cholecystectomy and is doing well 30 months after surgery without evidence of disease recurrence. A thorough metastatic work-up along with aggressive surgical intervention in patients with renal cell carcinoma and unusual metastatic foci can provide a long-term favorable outcome.

Biologic agents as adjunctive therapy for prostate cancer: a rationale for use with androgen deprivation.

The prevalence of prostate cancer emphasizes the need for improved therapeutic options, particularly for metastatic disease. Current treatment includes medical or surgical castration, which initially induces apoptosis of prostate cancer cells, but ultimately an androgen-independent subpopulation emerges. In addition to a transient therapeutic effect, androgen-deprivation therapy (ADT) can initiate biochemical events that may contribute to the development of and progression to an androgen-independent state. This transition involves multiple signal transduction pathways that are accompanied by many biochemical changes resulting from ADT. These molecular events themselves are therapeutic targets and serve as a rationale for adjunctive treatment at the time of ADT.

Outcomes and quality of life issues in the pharmacological management of benign prostatic hyperplasia (BPH).

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease of the aging male population. BPH treatment includes a variety of pharmacological and surgical interventions. The goal of this paper is to review the natural history of BPH, outcomes of pharmacological management, effects on quality of life (QoL), future pharmacotherapies, and associated patient-focused perspectives. MATERIALS AND METHODS: Medline searches for the keywords benign prostatic hyperplasia, BPH, alpha blockers, 5 alpha-reductase, and quality of life were performed. Relevant literature was reviewed and analyzed. RESULTS: Alpha blockers, 5 alpha-reductase inhibitors, and phytotherapy are the three categories of pharmaceutical interventions currently available for BPH. Various clinical trials have shown that alpha blockers and 5 alpha-reductase inhibitors are safe, efficacious, and improve QoL in patients with BPH. The evidence for phytotherapeutics is not as convincing. The current armamentarium of pharmaceutical interventions are encompassed in these three classes of medications. New pharmacotherapies based on novel mechanisms are on the horizon. CONCLUSION: There are a variety of safe and efficacious medical therapies available for the management of BPH and it is important for the practicing physician to have an understanding of these pharmacotherapies and their potential impact on the patient. There is not enough evidence to make a recommendation regarding phytotherapy use. New classes of drugs for BPH will likely find their way into routine use.

The AKT inhibitor perifosine in biochemically recurrent prostate cancer: a phase II California/Pittsburgh cancer consortium trial.

BACKGROUND: Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer. PATIENTS AND METHODS: Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy < 9 months in duration (completed >or= 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by >or= 50% from the pretreatment value. Treatment was composed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. RESULTS: Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia. CONCLUSION: Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation.

Minimising postoperative incontinence following radical prostatectomy: considerations and evidence.

OBJECTIVES: To review evidence regarding perioperative predictors of incontinence after radical prostatectomy (RP), related anatomic and patient factors, and surgical techniques used to minimise incontinence. METHODS: A search of the Pubmed, Cancerlit, Cochrane, and ISI Web of Science databases was performed for the key words prostatectomy, incontinence, and continence. Relevant articles were reviewed, summarised, and analysed. RESULTS: Enhanced understanding of pelvic anatomy applied to surgical approaches has improved continence rates following RP; however, incontinence remains a potential adverse outcome. Evidence suggests that increasing patient body weight and prostate volume are not associated with continence outcomes, but increasing patient age may be predictive. Behavioural therapy may aid in early return to continence although the timing of therapy and benefit of biofeedback assistance are unclear. Various surgical techniques are used to improve continence, but no evidence overwhelmingly supports any specific technique. At best, evidence supports early return to continence with some techniques. No technique significantly increased margin positivity solely at the experimental anatomic site. CONCLUSIONS: Despite enhanced knowledge of anatomy and improved surgical approach, incontinence persists as a potential adverse outcome of RP. Urologists may not find an evidence-based rationalisation for any particular surgical technique due to the nature of surgical series, variability in the definition of incontinence, and individual surgical skills, preferences, and techniques. Giving careful consideration to the trial design can potentially improve the resulting level of evidence.

Recent developments in advanced urothelial cancer.

PURPOSE OF REVIEW: Metastatic or unresectable urothelial cancer of the urinary bladder has traditionally been treated with systemic chemotherapy, which is most often platinum-based. The long-term survival data and the associated toxicities from this form of therapy have spurred continuing interest in finding novel treatment options for this malignancy. RECENT FINDINGS: Recently, trials of new chemotherapy combinations, many incorporating platinum analogs or deleting platinum entirely, have been reported. None has yet been shown to be superior to cisplatin-based regimens. In addition, recent advances in imaging and laboratory technologies have provided new avenues to understand urothelial cancer behavior and prognosis. These advances provide optimism for improvements in the diagnosis, staging, and ultimately, selection of therapy for patients with urothelial cancer. SUMMARY: This review will summarize recent developments (circa 2004) in the diagnosis and management of advanced bladder cancer.