Comparison of Oncologic Outcomes Between Two Alternative Sequences with Abiraterone Acetate and Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Sequential treatment of androgen receptor axis targeted agents (ARAT), abiraterone acetate (ABI) and enzalutamide (ENZA), in metastatic castration-resistant prostate cancer (mCRPC) demonstrated some positive effects, but cross-resistances between ABI and ENZA that reduce activity have been suggested. Therefore, we conducted a meta-analysis to compare oncologic outcomes between the treatment sequences of ABI-ENZA and ENZA-ABI in patients with mCRPC. The primary endpoint was a combined progression-free survival (PFS), and the secondary endpoint was overall survival (OS). A total of five trials on 553 patients were included in this study. Each of the included studies was retrospective. In two studies including both chemo-naïve and post-chemotherapy mCRPC patients, for ABI-ENZA compared with ENZA-ABI, pooled hazard ratios (HRs) for PFS and OS were 0.37 (p < 0.0001; 95% confidence intervals (CIs), 0.23-0.60) and 0.64 (p = 0.10; 95% CIs, 0.37-1.10), respectively. In three studies with chemo-naïve mCRPC patients only, for ABI-ENZA compared with ENZA-ABI, pooled HRs for PFS and OS were 0.57 (p = 0.02; 95% CIs, 0.35-0.92) and 0.86 (p = 0.39; 95% CIs, 0.61-1.21), respectively. The current meta-analysis revealed that ABI-ENZA had a significantly more favorable oncological outcome, but the level of evidence was low. Therefore, large-scale randomized trials may be needed.ope

Comparison of single and multiple sessions of percutaneous sclerotherapy for simple renal cyst

OBJECTIVE: To compare the results of single and repeated percutaneous sclerotherapy in patients with simple renal cysts. PATIENTS AND METHODS: Eighty-two patients with simple renal cysts underwent needle aspiration andsclerotherapy under ultrasonographic guidance. Forty-two patients (group 1) underwent one session of sclerotherapy with 99% ethanol immediately after aspiration and 40 patients (group 2) underwent sclerotherapy at least twice. The patients were followed up using ultrasonography at 3-month intervals. The complete disappearance or a reduction of more than half in the diameter of the renal cyst was considered a successful treatment. RESULTS: The mean diameter of the renal cysts was not significantly different in group 1 (6.12 cm) and 2 (6.75 cm). There was complete or partial regression in eight (19%) and 16 (38%) in group 1, and in 29 (73%) and nine (23%) in group 2, respectively. The overall success rate was significantly better in group 2 (95%) than in group 1 (57%; P < 0.001). CONCLUSIONS: These results suggest that multiple sclerotherapy is better than a single injection of sclerosant for reducing the recurrence of simple renal cysts.ope

Does an Alternative Sunitinib Dosing Schedule Really Improve Survival Outcomes over a Conventional Dosing Schedule in Patients with Metastatic Renal Cell Carcinoma? An Updated Systematic Review and Meta-Analysis

Treatment-related adverse events (AEs) can obfuscate the maintenance of a conventional schedule of sunitinib in patients with metastatic renal cell carcinoma. Accordingly, alternative schedules seeking to improve the safety profile of sunitinib have been tested. Recently, two meta-analyses similarly described improved safety profiles favoring a two weeks on and one week off (2/1) schedule, but with conflicting results for survival outcomes. Therefore, we conducted an updated systematic review and meta-analysis, including all recently published studies and using complementary statistical methods. Endpoints included progression-free survival, overall survival, and AEs of 15 types. Eleven articles were included in this meta-analysis. Using adjusted findings, we noted statistically better results in progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; p = 0.005), but no difference in overall survival (hazard ratio, 0.66; 95% confidence interval, 0.42-1.04; p = 0.08). Moreover, the 2/1 schedule was beneficial for reducing the incidence of several AEs. Conclusively, our meta-analysis suggests that the 2/1 schedule holds promise as an alternative means of reducing AEs and maintaining patient quality of life. While the survival outcomes of the 2/1 schedule seem also to be favorable, the level of evidence for this was low, and the interpretation of these findings should warrant caution. Large scale randomized trials are needed to support these results.ope

Application and Treatment Result of an Enuresis Alarm Based on a Questionnaire in Children with Enuresis?.

PURPOSE: Alarm interventions are effective and safe treatments for nocturnal enuresis when compared with the other treatments. However, the rate of doctors prescribing enuresis alarms is quite low in Korea. This study evaluated the application conditions and treatment results of an enuresis alarm in children with enuresis in Korea. MATERIALS AND METHODS: 147 out of 316 patients who purchased an enuresis alarm through a alarm sales agency in Korea were evaluated retrospectively. The questionnaire had two main categories: items of enuresis(number of episodes during the night, enuresis frequency during a week, etc.) and the items of the enuresis alarm(previous treatment history, a motivation of using enuresis alarm treatment, the period of using the enuresis alarm, initial success, continued success, dropout of using enuresis alarm, nocturia after treatment, etc.). RESULTS: A total 147 children participated in this study. The initial success rate was 30.6% whereas the continued success rate was 34.0%. In addition, the dropout rate was 27.2%. 46.2% of patients purchased the enuresis alarm with a doctor's prescription and 53.8% purchased the alarm without a prescription. Among the factors, the success and dropout rate were affected by only whether the patient visited the hospital. Thirty five patients who took combination therapy with medicine had a significantly lower initial success rate. CONCLUSIONS: In Korea, without a doctor's prescription, 53.7% patients attempt to treat enuresis alarm directly. The initial and continued success rate with the enuresis alarm was approximately 30% and the dropout rate was approximately 30%.ope

Diagnosis and treatment of nocturnal enuresis in children

Nocturnal enuresis is a heterogeneous disorder with various underlying pathophysiological mechanisms and causes a mismatch between the nocturnal bladder capacity and the amount of urine produced during sleep at night. It is associated with a simultaneous failure of conscious arousal in response to the sensation of bladder fullness. Generally, a complete history and physical examination, with a specific focus on the genitourinary, gastrointestinal, and neurologic systems, is sufficient to evaluate a patient with enuresis. The therapeutic focus is directed toward a differential approach based on the underlying mechanism and toward combination therapies such as alarm devices and desmopressin as well as anticholinergic agents and desmopressin. Children with increased nocturnal urine production usually have a good response to desmopressin therapy. Patients with a small bladder generally show a poor response to desmopressin treatment, but they would benefit more from combination therapy with enuretic alarm, urotherapy, and antimuscarinic agents in addition to desmopressin. Different types of bladder dysfunction, which result in a small nocturnal bladder capacity, probably contribute significantly to the pathogenesis of nocturnal enuresis, particularly in those with treatment failure and refractory symptoms. Because different clinical subgroups may show different responses to treatment, it is necessary to distinguish these subgroups before a decision on the specific treatment protocol can be madeope

Neurologic Mechanisms Underlying Voiding Dysfunction due to Prostatitis in a Rat Model of Nonbacterial Prostatic Inflammation.

PURPOSE: The neurological molecular mechanisms underlying the voiding dysfunction associated with nonbacterial chronic prostatitis/chronic pelvic pain syndrome remain poorly understood. In this study, we assessed whether prostate inflammation activated bladder afferent neurons, leading to bladder dysfunction, and sought to elucidate the underlying mechanisms. METHODS: Thirty male Sprague-Dawley rats were divided into 3 groups: sham-saline, formalin-injected, and capsaicin-pretreated and formalin-injected. Chemical prostatitis was induced by 0.1 mL of 10% buffered formalin injected into the ventral prostate. Capsaicin was injected subcutaneously to desensitize capsaicin-sensitive nerves. In each group, conscious cystometry was performed, and c-fos expression within the spinal cord was determined immunocytochemically. Double immunofluorescent staining with c-fos and choline acetyltransferase (ChAT) was performed. On the third day after pseudorabies virus (PRV) infection, c-fos and PRV double-staining was performed. RESULTS: Intraprostatic formalin significantly increased the maximal voiding pressure and decreased the intercontraction interval, compared with controls. Pretreatment with capsaicin significantly reversed these effects. More c-fos-positive cells were observed in the sacral parasympathetic nucleus (SPN) and dorsal gray commissure (DCM) in the prostatitis group than in the sham group. c-fos-positive cells decreased in the capsaicin-pretreated group. Preganglionic neurons labeled by c-fos and ChAT were observed in the SPN in rats with prostatitis. Interneurons labeled by c-fos and PRV were identified in the DCM after PRV infection. Conclusions: Our results suggest that prostate inflammation activates afferent nerve fibers projecting to the lumbosacral spinal cord, producing reflex activation of spinal neurons innervating the bladder and bladder hyperreflexia. This is mediated by capsaicin-sensitive prostate afferent neurons.ope

Usefulness of Rapid PSA Kit®

Purpose: The incidence rate of prostate cancer has increased remarkably in Korea. The serum prostate specific antigen (PSA) value has been used for screening, although its clinical significance in prostate cancer screening is still inconclusive. However, if the measurement time was short and the cost was low, such an assay kit should be sufficient for prostate cancer screening. Materials and Methods: We developed pared monoclonal antibodies against PSA which could be used in assay kits for PSA. The Rapid PSA Kit used an immunochromatographic method to qualitatively judge a positive or negative result. Serum specimens from 78 men with benign prostate hyperplasia or prostate cancer were tested using the kit. Results: The sensitivity of the kit was determined to be 4ng/ml. 33 samples had a value of greater than 5ng/ml, so were considered positive. 5 samples had values between 4ng/ml and 5ng/ml, of which 3 were positive. The other 40 samples had values less than 4ng/ml, and 11 of these were judged positive. These results indicated that the sensitivity and specificity of the Rapid PSA Kit were 94.7 and 72.5%, respectively. Conclusions: Tests using the Rapid PSA Kit can be easily performed at outpatient clinics or elsewhere. This kit is useful in the initial screening of prostate cancer as the results can be obtained within 15 minutes and the cost is lower than with ordinary serum PSA tests.ope

What Causes Bladder Fibrosis?: Abnormal Innervation or Abnormal Bladder Dynamics

Purpose: Bladder tissue fibrosis is characterized by the abnormal deposition of connective tissue within different layers of the bladder wall, resulting in "non-compliance". The different etiologies of bladder fibrosis are, either neurogenic, which encompasses myelodysplasia and spinal cord injury, or nonneurogenic, due to bladder outlet obstruction. In this study, we examined whether bladder fibrosis is due to the effect of abnormal innervation or to abnormal bladder dynamics. Materials and Methods: Thirty-five Sprague-Dawley male rats (250-300g) were divided into four groups; normal (n=5), bilateral pelvic nerve transection; denervation (n=10), vesicostomy (n=10), and vesicostomy after denervation (n=10) groups. After 4 weeks, the bladders of animals in each group were obtained. In the histologic study, the collagen to muscle ratio in Masson's trichrome stain and the elastin density (%) in Van Gieson stain were determined using a Metamorph ver 4.6r5 image analyzer. TGF-beta1 and collagen III protein expressions were detected by Western blotting. Results: The collagen to muscle ratios of the normal group, vesicostomy, denervation and vesicostomy after denervation group were; 0.67+/-0.04*, 0.67+/-0.04*, 1.25+/-0.03* and 0.96+/-0.02, respectively (*p>0.001), and the elastin densities were 14.73+/-1.09**, 16.38+/-2.27, 23.6+/-1.93** and 18.35+/-1.27, respectively (**p>0.01). By Western blotting, the denervation group showed significantly increased TGF-beta1 and collagen III protein expressions compared with the normal group and the vesicostomy group. Conclusions: The orders of the collagen to muscle ratio and of the deposition of elastin were; denervation > vesicostomy after denervation > vesicostomy > normal group by histologic study. The levels of TGF-beta1 and of collagen III in the denervation group were higher than in the vesicostomy after denervation group. The above findings show that both pressure and nerve innervation in the bladder, have significant effects on the process of bladder fibrosis. Meanwhile, vesicostomy could reduce the fibrotic effect caused by denervation, although it is not complete.ope

Hematologic Toxicity of Gemcitabine and Cisplatin Combination Therapy in Advanced Urothelial Cancer

PURPOSE: To evaluate the hematologic toxicity of gemcitabine and cisplatin (GC) in patients with advanced transitional cell carcinomas. MATERIALS AND METHODS: From 25 patients, with advanced transitional cell carcinomas, 8 had previously received M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy for a metastatic disease, and were scheduled to receive gemcitabine, 1,000mg/m2, intravenously, over 30 minutes, on days 1, 8 and 15, and cisplatin, 70mg/m2, over 1 hour, on day 2 of a 28-day cycle. The hematological toxicities of each cycle were evaluated. RESULTS: The main hematological toxicities were thrombocytopenia (grade 3 in 24% and grade 4 in 16% of patients), leukopenia (grade 3 in 14% of patients) and anemia (grade 3 in 12% of patients). Four of the patients that experienced grade 4 thrombocytopenia had a tendency for recurring grade 4 thrombocytopenia during the GC chemotherapy. However, there was no evidence of bleeding. CONCLUSIONS: The most severe hematological toxicity of the GC chemotherapy was thrombocytopenia. The careful observation of the patients that experience grade 4 thrombocytopenia is recommended.ope

Is It Necessary to Repeat Videourodynamic Studies on Spina Bifida Children?.

PURPOSE: A videourodynamic study is useful for examining the functional and structural problems of the urinary tract simultaneously. Due to its invasiveness, however, it is important to obtain as much information as is possible as the study is being conducted. The purpose of this study was to evaluate the results of a repeated videourodynamic examination in spina bifida children. MATERIALS AND METHODS: Between January 2005 and July 2006, a total of 48 patients who were diagnosed with spina bifida and underwent repeated videourodynamic studies were enrolled in this study. We compared variables including compliance, involuntary detrusor contraction (IDC), cystometric bladder capacity (CBC), maximum detrusor pressure, and post-voiding residual urine (PVR) between the initial and repeated studies. RESULTS: During the repeated studies, cases of IDC decreased significantly (p<0.05) compared with the initial studies. No other significant differences were found in terms of compliance, CBC, maximum detrusor pressure, and PVR. CONCLUSIONS: There were no significant differences in terms of compliance, CBC, maximum detrusor pressure, and PVR between initial and repeated studies. However, the number of patients who had IDC decreased significantly in the second study. Nevertheless, we conclude that the first examination in this study was enough to evaluate the overall function and structure of the urinary tract. We believe that repeat studies are not necessary in children with spina bifida.ope