Open Access Journal of Urology最新文献

Purpose: Pooled results from 2 randomized, placebo-controlled, US phase III studies (NCT00224107, NCT00224120) showed that silodosin, a uroselective α-blocker, significantly improved International Prostate Symptom Scores (IPSS) in men with symptomatic benign prostatic hyperplasia (BPH). This analysis evaluated the effect of silodosin on each symptom assessed by IPSS questionnaire.

Materials and methods: Study participants (N = 923) were men aged ≥50 years with IPSS ≥13 and Qmax 4-15 mL/s. They received silodosin 8 mg or placebo once daily for 12 weeks. Patient responses to 7 IPSS questions were collected at weeks 0 (baseline), 0.5, 1, 2, 4, and 12 and scored on a 6-point scale. Efficacy of silodosin versus placebo was assessed by analysis of covariance.

Results: For each symptom, the 2 treatment groups had similar mean baseline scores. Decrease in score from baseline (mean ± standard deviation) to last observation was significantly greater with silodosin than with placebo for all symptoms (P < 0.005); symptom improvement with silodosin (versus placebo) was greatest for weak stream (silodosin, -1.1 ± 1.4 versus placebo, -0.5 ± 1.2; P < 0.0001) and smallest for nocturia (silodosin, -0.6 ± 1.1 versus placebo, -0.4 ± 1.2; P = 0.0037). Compared with placebo, silodosin significantly improved nocturia within 1 week (silodosin, -0.5 ± 1.07 versus placebo, -0.3 ± 1.05; P = 0.009) and all other symptoms within 3 to 4 days (P < 0.01).

Conclusions: Silodosin significantly improved all BPH-associated symptoms assessed by IPSS questionnaire within the first week of treatment. All improvements were maintained over the 12-week study period.

Objective: Second-line treatment options in advanced urothelial cancer are limited. We investigated the efficacy of a methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) combination after failure of gemcitabine/platinum chemotherapy.

Patients and methods: Twenty-five patients with advanced urothelial cancer, who received second-line MVAC after first-line gemcitabine/cisplatin (n = 9) or gemcitabine/carboplatin (n = 16), were included in this retrospective analysis.

Results: Twenty-two patients (88%) relapsed within 6 months after first-line treatment. Following MVAC, there were 5 (20%) objective responses. Median follow-up was 20.2 months. Median progression-free survival (PFS) was 3.8 months (95% CI: 2.3-5.2), and median overall survival (OS) was 9 months (95% CI: 6.6-11.4). Eastern Cooperative Oncology Group performance status 0.1 versus 2 was associated with longer PFS (5 months versus 3.3 months, P = 0.049). Response or stabilization of disease during second-line chemotherapy predicted for a significantly longer PFS and OS (7.4 versus 3.5, P = 0.005; 15.5 versus 7, P = 0.046).

Conclusions: Second-line MVAC chemotherapy may result in prolonged survival in some patients with refractory disease. Further research in this field is necessary.

Overactive bladder is a prevalent condition which negatively impacts quality of life and puts a significant economical burden on society. First-line therapy often includes pharmacotherapy with antimuscarinic medications, and numerous research studies have demonstrated that tolterodine extended-release (ER) is an efficacious and tolerable formulation of this class of medication. This review provides an update on the clinical use of tolterodine ER, detailing the current literature on its efficacy, tolerability, adverse effects, and comparability with other commonly prescribed medications for the treatment of overactive bladder.

Unlabelled: This paper analyzes the statistical correlation of urinary serotonin and dopamine data in subjects not suffering from monoamine-secreting tumors such as pheochromocytoma or carcinoid syndrome. Peer-reviewed literature and statistical analyses were searched and monoamine (serotonin and dopamine) assays defined in order to facilitate their proper interpretation. Many research findings in the literature are novel. Baseline assays completed with no monoamine precursors differ from baseline assays performed on a different day in the same subject. There is currently no scientific basis, value, or predictability in obtaining baseline monoamine assays. Urinary assays performed while taking precursors can demonstrate a lack of correlation or unexpected correlations such as inverse relationships. The only valid model for interpretation of urinary monoamine assays is the "three-phase model" which leads to predictability between monoamine assays and precursor administration in varied amounts.

Purpose: This paper reviews the basic science of urinary monoamine assays. Results of statistical analysis correlating baseline and nonbaseline assays are reported and provide valid methods for interpretation of urinary serotonin and dopamine results.

Patients and methods: Key scientific claims promoting the validity of the urinary neurotransmitter testing (UNT) model applications are discussed. Many of these claims were not supported by the scientific literature. Matched-pairs t-tests were performed on several groupings. Results of all statistical tests were compared with peer-reviewed literature.

Results: The statistical analysis failed to support the UNT model. Peer-reviewed literature search failed to verify scientific clams made in support of applications of the UNT model in many cases.

Introduction: We report a case of a vesico-vaginal fistula (VVF) post cold cup biopsy; to our knowledge this is the only reported case. We present the clinical history/presentation, investigation and the outcome of the treatment. VVFs are among the most distressing complications of gynecologic and obstetric procedures. The risk of developing a VVF is more than 1% after radical surgery and radiotherapy for malignancies. Management of these fistulas has been better defined and standardized over the last decade.

Methods and results: A case of low grade superficial bladder cancer was treated with multiple resections of bladder tumor and a single installation of mitomycin post initial resection which successfully cleared her bladder cancer, but nevertheless led to a small size and scarred bladder. In addition there was a long history of smoking with its effects on tissue integrity and healing. VVFs are very rare and are an unpleasant outcome post a cold cup biopsy, adding to the psychological and social effects of the surgical treatment.

Conclusion: Although cold cup biopsy is a normal day procedure performed by both residents and consultants, consensus should exist on how to treat a patient who has a bladder with defective integrity and small capacity. The rate of successful fistula repair reported in the literature varies between 70% and 100% in nonradiated patients, with similar results when a vaginal or abdominal approach is performed, the mean success rates being 91% and 97%, respectively.

Purpose: Reports on clinical measurements of bone mineral density (BMD) in prostate cancer patients undergoing intermittent androgen suppression therapy (IAS) that allows for hormonal recovery between treatment cycles indicate decreased osteoporosis compared to continuous androgen suppression therapy (CAS). In the present study the effect of IAS on bone metabolism by determinations of CrossLaps, a biochemical marker of collagen degradation, were examined.

Method: In total 100 IAS treatment cycles of 75 patients with prostate cancer stages ≥ pT2 were studied. Clinical data and monthly laboratory tests (testosterone, prostate-specific antigen; PSA) of these patients were monitored together with measurements of C-terminal telopeptide collagen fragments using CrossLaps® ELISA assays.

Results: During phases of androgen suppression (AS) lasting for 9 months serum testosterone (<1 ng/mL) and PSA (<2 ng/mL) levels were reversibly reduced, indicating partial growth arrest and apoptotic regression of the prostatic tumors. Serum CrossLaps concentrations peaked at the last 2 months of the AS phases (0.91 ± 0.25 μg/L; mean ± SEM) and were reduced below initial values (0.21 ± 0.43 versus baseline of 0.43 ± 0.06 μg/L) during therapy cessation periods until tumor progression-related increases.

Conclusion: Measurements of the serum concentration of CrossLaps in prostate cancer patients receiving IAS indicated that treatment cessation phases rapidly reversed increased bone degradation associated with AS phases, in strong agreement with the clinical observations reporting reduced loss of BMD in IAS when compared to CAS. In terms of clinical outcomes, IAS seems to be as effective as CAS while showing reduced side effects, as demonstrated here by the reduction of androgen-induced bone matrix degradation.

Sevelamer (Renagel and Renvela), is an orally administered weakly basic anion exchange resin that binds dietary phosphate in the gastrointestinal tract, and is approved for use in the US, Europe and many other countries for the treatment of hyperphosphatemia in adult patients on hemodialysis or peritoneal dialysis. Clinical evidence shows that sevelamer is at least as effective as calcium-based oral phosphate binders in controlling serum phosphate, but with a lower incidence of hypercalcemia. Whilst sevelamer hydrochloride is associated with mild acidosis, sevelamer carbonate does not have this drawback. Use of sevelamer and avoidance of calcium-based binders may slow the progression of vascular calcification in hemodialysis patients, and it also reduces serum low-density lipoprotein-cholesterol levels. There was no between-group difference in all-cause mortality between sevelamer and calcium-based phosphate binder therapy in the primary efficacy analysis of the large (n >2100), 3-year DCOR trial. In the smaller (n = 109) nonblind RIND trial in patients new to hemodialysis, data suggest there may be an overall survival benefit with sevelamer versus calcium-based phosphate binder treatment but the evidence on the efficacy of sevelamer in reducing mortality and hospitalization is not strong. The balance of evidence, however, does not strongly support the use of sevelamer over the much less costly calcium-based binders except in patients at risk of hypercalcemic episodes. Further research into cardiovascular and all-cause mortality over a longer time period would be needed to settle this issue, and the relative survival benefits and cost effectiveness of all phosphate binder therapies remains to be fully determined. Despite the relative paucity of data available, sevelamer has established itself as the most widely used binder in the United States and the most widely used noncalcium-based binder worldwide. However, affordability is a major issue for most health economies and in the light of recent economic events is likely to become more prominent.

Germ-cell cancer is the most common solid tumor in men aged 15 to 35 years and has become the model for curable neoplasm. Over the last 3 decades, the cure rate has increased from 15% to 85%. This improved cure rate has been largely attributed to the introduction of cisplatin-based chemotherapy. In stage I seminoma and nonseminoma, cure rates approach 100% and treatment is governed by patient choice based on the perceived morbidities of each therapy and personal preferences. For seminoma, treatments include surveillance, radiotherapy, and single course carboplatin. For nonseminoma, treatments include surveillance, retroperitoneal lymph node dissection (RPLND), and adjuvant chemotherapy. Low volume (<3 cm) stage II seminoma is typically managed with radiotherapy while higher volume (>3 cm) stage II and stage III disease treated with chemotherapy. Positron emission tomography (PET) imaging can differentiate active cancer versus necrosis for postchemotherapy residual masses. PET-positive masses are managed with either surgery or second-line chemotherapy. Low volume (<5 cm) stage II nonseminoma with normal serum tumor markers may be managed with either RPLND or chemotherapy. Patients with persistently elevated serum tumor markers and larger volume stage II and stage III disease are managed with systemic chemotherapy. As with seminoma, good risk patients are typically treated with 3 courses of bleomycin, etoposide, and cisplatin (BEP) and intermediate and poor risk patients are treated with 4 courses. Residual postchemotherapy masses should be resected due to the uncertainty of the histology with 50% to 60% harboring residual teratoma or active cancer. The majority of patients completing initial therapy who relapse do so within 2 years. A minority of patients (2%-3%) recur after 2 years and this phenomenon is termed late relapse. Excluding chemonaïve patients, late relapse disease is typically managed surgically with 50% being cured of disease. Current therapeutic challenges in testis cancer include the accurate prediction of postchemotherapy histology to avoid surgery in patients harboring fibrosis only, improved therapy in platinum-resistant and platinum-refractory disease, and the understanding of the biology of late relapse.

Renal cell carcinoma (RCC) remains a significant health concern that frequently presents as metastatic disease at the time of initial diagnosis. Current first-line therapeutics for the advanced-stage RCC include antiangiogenic drugs that have yielded high rates of objective clinical response; however, these tend to be transient in nature, with many patients becoming refractory to chronic treatment with these agents. Adjuvant immunotherapies remain viable candidates to sustain disease-free and overall patient survival. In particular, vaccines designed to optimize the activation, maintenance, and recruitment of specific immunity within or into the tumor site continue to evolve. Based on the integration of increasingly refined immunomonitoring systems in both translational models and clinical trials, allowing for the improved understanding of treatment mechanism(s) of action, further refined (combinational) vaccine protocols are currently being developed and evaluated. This review provides a brief history of RCC vaccine development, discusses the successes and limitations in such approaches, and provides a rationale for developing combinational vaccine approaches that may provide improved clinical benefits to patients with RCC.

Neuroendocrine (NE) differentiation is a common feature in prostate cancer (PC). The clinical significance of this phenomenon is controversial; however preclinical and clinical data are in favor of an association with poor prognosis and early onset of a castrate resistant status. NE PC cells do not proliferate, but they can stimulate the proliferation of the exocrine component through the production of paracrine growth factors. The same paracrine signals may favor the outgrowth of castrate adapted tumors through androgen receptor dependent or independent mechanisms. Noteworthy, NE differentiation in PC is not a stable phenotype, being stimulated by several agents including androgen deprivation therapy, radiation therapy, and chemotherapy. The proportion of NE positive PC, therefore, is destined to increase during the natural history of the disease. This may complicate the assessment of the prognostic significance of this phenomenon. The majority of clinical studies have shown a significant correlation between NE differentiation and disease prognosis, confirming the preclinical rationale. In conclusion the NE phenotype is a prognostic parameter in PC. Whether this phenomenon is a pure prognostic factor or whether it can influence the prognosis by favoring the onset of a castrate resistance status is a matter of future research.