Flavoxate: present and future.

OBJECTIVE: This non-systematic review discusses the available evidence on the use of flavoxate in the treatment of overactive bladder (OAB). METHODS: Medline was searched for inclusion of relevant studies. No limitations in time were considered. RESULTS: Flavoxate hydrochloride is an antispasmodic agent which exerts an inhibition of the phosphodiesterases, a moderate calcium antagonistic activity, and a local anesthetic effect. Results from preclinical and clinical studies show that flavoxate significantly increases bladder volume capacity (BVC), with greater results if compared to other drugs such as emepronium bromide and propantheline. Moreover in clinical trials, both versus placebo or versus active comparators, flavoxate treatment was associated with a significant improvement in different low urinary tract symptoms, such as diurnal and night frequency, urgency and urinary incontinence, suprapubic pain, dysuria, hesitancy and burning. In addition flavoxate was associated with an overall more favourable safety profile than competitors. CONCLUSIONS: Several researches and a number of years of clinical practice have proven the efficacy and tolerability of flavoxate administration in the treatment of OAB and associated symptoms. However, new studies are necessary to collect more evidence on the role of this molecule in the treatment of OAB and to further explore its use in other indications such as symptomatic treatment of lower urinary tract infections.

Detection of Y chromosome microdeletions and mitochondrial DNA mutations in male infertility patients.

Infertility affects about 10-15% of all couples attempting pregnancy with infertility attributed to the male partner in approximately half of the cases. Proposed causes of male infertility include sperm motility disturbances, Y chromosome microdeletions, chromosomal abnormalities, single gene mutations, and sperm mitochondrial DNA (mtDNA) rearrangements. To investigate the etiology of decreased sperm fertility and motility of sperm and to develop an appropriate therapeutic strategy, the molecular basis of these defects must be elucidated. In this study, we aimed to reveal the relationships between the genetic factors including sperm mtDNA mutations, Y chromosome microdeletions, and sperm parameters that can be regarded as candidate factors for male infertility. Thirty men with a history of infertility and 30 fertile men were recruited to the study. Y chromosome microdeletions were analyzed by multiplex PCR. Mitochondrial genes ATPase6, Cytb, and ND1, were amplified by PCR and then analyzed by direct sequencing. No Y chromosome microdeletions were detected in either group. However, a total of 38 different nucleotide substitutions were identified in the examined mitochondrial genes in both groups, all of which are statistically non-significant. Fifteen substitutions caused an amino acid change and 12 were considered novel mutations. As a conclusion, mtDNA mutations and Y chromosome microdeletions in male infertility should be examined in larger numbers in order to clarify the effect of genetic factors.

The efficacy of Tc99m dimercaptosuccinic acid (Tc-DMSA) scintigraphy and ultrasonography in detecting renal scars in children with primary vesicoureteral reflux (VUR).

INTRODUCTION: Pyelonephritis-induced renal scarring in children is a major predisposing factor for proteinuria, hypertension, and ultimate renal failure. The aim of this study was to investigate and compare the efficacy of Tc99m dimercaptosuccinic acid (Tc-DMSA) renal scintigraphy and renal ultrasonography (USG) in detecting renal scars in children with primary vesicoureteral reflux (VUR). MATERIALS AND METHODS: Tc-DMSA scan and USG studies were done in 62 children who were admitted to our clinic between 1997 and 2003 because of documented urinary tract infection (UTI) and diagnosed with primary VUR. Renal scarring detection rates of Tc-DMSA scan and USG were compared according to reflux grades. RESULTS: In the whole group, renal scars were detected by Tc-DMSA scan and USG in 55% and 38% of refluxing units, respectively. Detection rates of Tc-DMSA and USG according to reflux grades were as follows: 47% and 29 % in low-grade VUR (grades 1 and 2), 46 % and 25% in mid-grade VUR (grade 3), 76% and 65% in high-grade VUR (grades 4 and 5), respectively. CONCLUSION: USG was found to be an inappropriate study in the detection of renal parenchymal scars, irrespective of the reflux grade. In this study, Tc-DMSA scan detected scars in 35% of kidneys reported to be normal on USG.

Long-term followup of newborns with myelodysplasia and normal urodynamic findings: Is followup necessary?

PURPOSE: A subset of newborns with myelodysplasia have normal bladder function on urodynamic assessment. We analyzed long-term followup in this population to determine the necessity for subsequent urological surveillance. MATERIALS AND METHODS: We retrospectively analyzed the records of 25 of 204 newborns (12%) with myelodysplasia in whom neurourological evaluation was normal after surgical repair of the spinal defect. Initial assessment included complete urodynamic study, renal ultrasound, urinalysis and urine culture. These patients were reevaluated every 3 months until age 3 years, semiannually until age 6 years and yearly thereafter. The longest followup was 18.6 years. RESULTS: Of the 25 newborns 22 had myelomeningocele and 3 had meningocele. During a mean followup of 9.1 years urodynamics subsequently showed neurourological deterioration in 8 children (32%). No changes in urodynamics were observed in any patient older than 6 years. All children with neurourological deterioration underwent magnetic resonance imaging, which confirmed a tethered spinal cord that was then surgically corrected. After the untethering procedure 2 patients (25%) regained normal voiding function, whereas in 6 (75%) mild or moderate neurogenic bladder dysfunction persisted. CONCLUSIONS: Newborns with myelodysplasia and initially normal urodynamic studies are at risk for neurological deterioration secondary to spinal cord tethering, especially during the first 6 years of life. Close followup of these children is important for the early diagnosis and timely surgical correction of tethered spinal cord, and for the prevention of progressive urinary tract deterioration.

Systemic administration of apomorphine improves the hemodynamic mechanism of clitoral and vaginal engorgement in the rabbit.

Clitoral and vaginal engorgement during sexual stimulation depend in part on the increase of arterial inflow. It has been shown that apomorphine (APO), a non-selective dopamine receptor agonist, produces penile erection by activating dopaminergic receptors in the central nervous system. Our aim was to study whether systemic administration of APO improves the hemodynamic mechanism of clitoral and vaginal engorgement in the rabbit. Female New Zealand white rabbits (3.5-4 kg, n=6) were anesthetized. To examine sexual arousal function, the vaginal/clitoral branch of the pelvic nerve was stimulated electrically and maximal increases in clitoral intracavernosal and vaginal wall blood flows and pressures were recorded. After this APO was injected intravenously in a dose-response manner (0.05, 0.1, 0.2, 0.3 and 0.4 mg/kg) and nerve stimulation was performed after each dose. Changes in nerve-stimulated increase of clitoral intracavernosal and vaginal blood flows and pressures after APO was compared to those recorded before APO. Electrical stimulation of the vaginal/clitoral branch of the pelvic nerve significantly increased clitoral intracavernosal and vaginal wall blood flows in the rabbit. Intravenous administration of APO caused concentration dependent increase in nerve stimulation-induced peak clitoral intracavernosal and vaginal wall blood flows reaching to statistically significant at the concentration of 0.1 and 0.2 mg/kg. Inravenous administration of APO greater than 0.2 mg/kg (0.3 and 0.4 mg/kg) were less effective or produced adverse effects on clitoral intracavernosal and vaginal wall blood flows. Intravenous APO also tended to increase nerve-stimulated increase of clitoral intracavernosal and vaginal wall pressures, but the effect was not statistically significant. In conclusion, our studies suggest that systemic administration of APO may improve clitoral and vaginal engorgement by increasing clitoral intracavernosal and vaginal wall arterial inflow.

Atherosclerosis-induced chronic arterial insufficiency causes clitoral cavernosal fibrosis in the rabbit.

In our previous studies we found that aging-associated fibrosis of clitoral cavernosal tissue correlated with the prevalence of cardiovascular disease in elderly women. The aim of this study was to determine specifically, arterial insufficiency-related structural changes of clitoral cavernosal tissue in a rabbit model. New Zealand white female rabbits were divided into clitoral cavernosal ischemia (CCI, n = 5) and control (n = 5) groups. The CCI group underwent balloon endothelial injury of the iliac arteries and received 0.5% cholesterol diet. The control group received a regular diet. After 16 weeks, arteriography was performed then the animals were sacrificed. The iliac arteries and the entire clitoris were removed. Cross-sections of the iliac arteries and clitoris were processed for histologic evaluation The percentage of smooth muscle and connective tissue in trichrome stained sections of clitoral cavernosal tissue was determined by computer-assisted histomorphometry. Arteriography revealed diffused occlusive disease in the common iliac, internal iliac and pudendal arteries in the CCI group. Histology showed that arterial occlusive disease spreads from the site of balloon injury to the smaller branches involving the clitoral cavernosal arteries. Diffuse fibrosis was observed in the clitoral cross-sections of the CCI group. The percentage of clitoral cavernosal smooth muscle (mean +/- standard error) in the CCI group (53% +/- 0.9%) was significantly decreased compared with the control group (62% +/- 0.8%) (P = 0.0001). Chronic clitoral cavernosal ischemia causes significant fibrosis and loss of smooth muscle in the clitoral cavernosal tissue. These findings suggest that chronic clitoral cavernosal arterial insufficiency may play a role in the pathophysiology of female sexual arousal disorders.

Isoprostane 8-epi PGF2alpha, a product of oxidative stress, is synthesized in the bladder and causes detrusor smooth muscle contraction.

Isoprostane 8-epi PGF2alpha is a product of oxidative stress that causes potent smooth muscle contraction. Its production increases in conditions associated with oxidative stress such as in diabetes, smoking, and aging. The aim was to study whether the urinary bladder synthesizes isoprostane 8-epi PGF2alpha and releases to the urine and whether isoprostane 8-epi PGF2alpha causes bladder smooth muscle contraction. Urine samples were obtained transurethrally from 12 male New Zealand white rabbits for measurement of isoprostane 8-epi PGF2alpha levels. To examine whether bladder synthesizes isoprostane 8-epi PGF2alpha, both ureters were ligated, then the bladder was washed 5 times by filling and emptying with normal saline. Bladder was refilled with normal saline, and at 5 minutes a bladder washout sample was taken. After this, the bladder was contracted by nerve stimulation periodically for 30 minutes, and then another washout sample was taken. Strips of bladder tissues were processed for study of isoprostane 8-epi PGF2alpha production in tissue culture chambers and for isometric tension measurements in the organ bath. Enzyme immunoassay (EIA) revealed a remarkable amount of isoprostane 8-epi PGF2alpha in the rabbit urine. EIA of washout samples showed that the bladder synthesizes isoprostane 8-epi PGF2alpha and its production increases with nerve stimulation-induced contractions. EIA of samples from the tissue culture media showed that bladder strips synthesize isoprostane 8-epi PGF2alpha in vitro. Electrical field stimulation (EFS) significantly increased the synthesis and release of isoprostane 8-epi PGF2alpha by the bladder strips. In the organ bath, isoprostane 8-epi PGF2alpha caused concentration-dependent contraction of bladder tissue. While the threshold contraction required smaller concentration of isoprostane 8-epi PGF2alpha (3 nmol) than carbachol (10 nmol), the amplitude of contraction to carbachol was greater than isoprostane 8-epi PGF2alpha. Our studies show that the rabbit bladder synthesizes isoprostane 8-epi PGF2alpha and releases it to the urine. Production of isoprostane 8-epi PGF2alpha in the bladder increases with nerve stimulation-induced contraction. Exogenous isoprostane 8-epi PGF2alpha causes significant bladder smooth muscle contraction. Our findings necessitate further studies to evaluate the possible role of oxidative stress and increased isoprostane 8-epi PGF2alpha production in bladder dysfunction. Neurourol. Urodynam. 19:43-51, 2000.

Overactivity and structural changes in the chronically ischemic bladder.

PURPOSE: Our aim was to study the effect of chronic ischemia on bladder contraction and detrusor smooth muscle reactivity. The relationship between structural damage and functional changes in the chronically ischemic bladder was also investigated. MATERIAL AND METHODS: Male New Zealand White rabbits were divided into arterial injury (AI), hypercholesterolemia (Hch) and control groups. The AI group (n = 18) underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet. The Hch group (n = 8) received a 0.5% cholesterol diet alone. The control group (n = 8) received a regular diet. After 16 weeks, iliac artery and bladder wall blood flows were recorded. Cystometrograms and arteriography were obtained and bladder tissues were processed for isometric tension measurement in the organ bath and for histological evaluation. RESULTS: At 16 weeks, blood flow through the iliac arteries was significantly reduced in the AI group compared with the Hch and control groups. In the AI group, 8 animals developed severe bladder ischemia (SBI) defined as greater than 60% decrease in bladder blood flow, 7 animals developed moderate bladder ischemia (MBI) defined as 40 to 60% decrease in bladder blood flow, and 3 animals failed to develop significant bladder ischemia (<40% decrease in bladder blood flow). In the control animals, bladder blood flow increased prior to contraction, decreased during contraction and rebounded to baseline levels after contraction. In animals with MBI and SBI, the increase in bladder blood flow prior to contraction and the rebound of blood flow after contraction, both seen in control animals, were diminished. Detrusor overactivity (significant increase in the frequency of spontaneous bladder contractions) was observed in the MBI group and impaired bladder contraction in the SBI group. In the organ bath, bladder strips from the MBI group demonstrated increased contractile response to carbachol and electrical field stimulation (EFS) while bladder strips from the SBI group showed impaired contractility. Hch alone produced only short-lived ischemia during bladder contraction and caused significantly lesser functional changes compared with those seen in MBI. Histological examination showed atherosclerotic occlusion in the iliac arteries and bladder microcirculation and marked disruption of urothelium in the MBI and SBI groups. Severe fibrosis was seen in bladder tissue from the SBI group, moderate fibrosis in tissue from the MBI group and mild fibrosis in tissue from the Hch group. CONCLUSIONS: Our studies show that chronic MBI is associated with detrusor overactivity and increased smooth muscle contractility to carbachol and EFS while chronic SBI is associated with impaired detrusor contraction. The mechanism of chronic ischemia-induced bladder dysfunction is not known and may involve multiple physiologic and structural changes in the bladder nerves, receptors and contractile components. Our studies suggest that ischemia-induced structural damage in the urothelium and possible chronic exposure of the underlying tissue and nerves to the urine may also play a role in MBI-induced detrusor overactivity. SBI-induced impairment of bladder contraction may involve, in part, extensive fibrosis and loss of bladder smooth muscle. Histopathophysiologic changes in bladder tissue from our MBI model are similar to those seen in patients with detrusor instability, suggesting that chronic ischemia may play a role in the development of idiopathic detrusor instability.

Atherosclerosis-induced chronic ischemia causes bladder fibrosis and non-compliance in the rabbit.

PURPOSE: The overall goal was to determine whether chronic ischemia and hypercholesterolemia interfere with bladder function and structure. The roles of atherosclerosis-induced chronic ischemia and hypercholesterolemia in bladder fibrosis and non-compliance were studied in the rabbit. The relationship between ischemia-induced changes in the expression of transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) and the severity of bladder fibrosis was also investigated. MATERIALS AND METHODS: Male New Zealand White rabbits were divided into chronic bladder ischemia (CBI, n = 11), hypercholesterolemia (Hch, n = 8) and control (n = 8) groups. The CBI group underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet. The Hch group received a 0.5% cholesterol diet alone. The control group was placed on a regular diet. After 16 weeks, iliac artery and bladder wall blood flow measurements, cystometrograms (CMG) and aorto-iliac arteriograms were obtained in all animals. Iliac arteries and bladder tissues were processed for histological staining and computer-assisted histomorphometric image analysis. The expressions of TGF-beta1 and bFGF in bladder tissue were determined by immunohistochemical staining utilizing monoclonal antibodies. RESULTS: At 16 weeks, arteriography and histology showed significant diffuse atherosclerotic occlusive disease of the aorto-iliac arteries in the CBI group. Iliac artery and bladder wall blood flows were significantly decreased in the CBI group compared with the Hch and control groups. Atherosclerosis-induced CBI shifted the volume-pressure curve to the left and caused severe bladder fibrosis. Hypercholesterolemia also caused fibrosis and non-compliance but to a much lesser extent compared with those caused by CBI. In histomorphometry, the percentage of detrusor smooth muscle was moderately decreased in the Hch group and severely decreased in the CBI group compared with the control group. In immunohistochemical stains of bladder tissues, bFGF expression was similar in the three groups of animals. TGF-beta1 expression was significantly greater in bladder tissues from the CBI group compared with the Hch and control groups. CONCLUSIONS: Our studies show that atherosclerosis-induced chronic ischemia increases TGF-beta1 expression in the bladder leading to fibrosis, smooth muscle atrophy and non-compliance. Hypercholesterolemia also interferes with bladder structure and compliance but to a significantly lesser extent compared with CBI. Our studies suggest that arterial insufficiency and hypercholesterolemia, common aging-associated disorders, may play important roles in the pathophysiology of voiding dysfunction in the elderly.

Histomorphometric analysis of age-related structural changes in human clitoral cavernosal tissue.

PURPOSE: To characterize age-associated histological changes of human clitoral cavernosal tissue and to determine whether age-related histological changes of clitoral cavernosal tissue correlate with vascular disease-related mortality. MATERIALS AND METHODS: Human clitorises were obtained from 15 fresh cadavers (age: 11 to 90 years) and from 3 patients undergoing clitoral surgery (age: 6 months to 15 years). Cross sections of the clitorises were stained with Masson's trichrome and utilized for computer assisted histomorphometric image analysis to determine the clitoral cavernosal content of smooth muscle and connective tissue. RESULTS: These studies revealed a strong link between increase in age and decreased clitoral cavernosal smooth muscle fibers. In histomorphometry, the percentage of clitoral cavernosal smooth muscle (mean +/- standard error) in an age group of 6 months to 15 years (n = 4) was 65+/-1.5, in 44 to 54 years (n = 7) was 50+/-1.2, and in 55 to 90 years (n = 7) was 37+/-1.3 (ANOVA, p = 0.0001). In the 18 tissues studied, decrease in the percentage of clitoral cavernosal smooth muscle significantly correlated with increase in age (simple regression, r = 0.61). In the age group of 44 to 90 years, clitoral cavernosal fibrosis was significantly greater in the presence of cardiovascular disease-related mortality compared with those without cardiovascular disease-related mortality. CONCLUSION: This study shows that aging women undergo histological changes in clitoral cavernosal erectile tissue. Vascular risk factors may adversely affect the structure of clitoral cavernosal tissue. These findings may be of importance in the pathophysiology of age-associated female sexual arousal disorders.

Evaluation of prostate specific antigen density and transrectal ultrasonography-guided biopsies in 100 consecutive patients with a negative digital rectal examination and intermediate serum prostate specific antigen levels.

BACKGROUND: This study was undertaken to assess the importance of prostate biopsies in patients with a negative digital rectal examination (DRE) and elevated prostate specific antigen (PSA) levels and to investigate the role of PSA density (PSAD) and hypoechoic lesions on transrectal ultrasound (TRUS) in increasing the diagnostic sensitivity and specificity for prostate cancer (PCa). METHODS: One hundred patients with varied initial symptoms who had a negative DRE and a PSA level between 4 and 20 ng/mL underwent TRUS-guided systematic and, if present, lesion-directed biopsies. RESULTS: PCa was detected in 11 patients (11%). TRUS examinations revealed hypoechoic lesions in 31 patients. Lesion-directed biopsies revealed PCa in 13% (4/31) of patients with abnormal TRUS whereas, 7% (5/69) of patients with negative TRUS findings had PCa. Additional systematic biopsies detected PCa in 2 patients where lesion-directed biopsies were negative. None (0/19) of the lesions smaller than 0.2 mL on TRUS had PCa whereas, 33% (4/12) of patients with lesions greater than 0.2 mL had PCa. When the subgroup of patients with negative TRUS and PSA levels between 4 and 10 ng/mL were considered, 25% (1/4) of cases with PCa would have been missed if 0.15 was used as the cut-off point for PSAD, however, this would save 61% (30/49) of unnecessary biopsies. The positive predictive value of PSA (cut-off level 10 ng/mL), PSAD (cut-off level 0.15), and hypoechoic lesions on TRUS were found to be 11.5%, 33%, and 13%, respectively. When hypoechoic lesions greater than 0.2 mL were taken as the positive finding, the positive predictive value and specificity rates of TRUS increased to 33% and 91%, respectively, without any change in the sensitivity. CONCLUSIONS: In patients with a negative DRE and intermediate PSA levels, the application of PSAD would have saved 49% of study patients with BPH from a biopsy, but would have missed 27% of PCa cases. By ignoring lesions smaller than 0.2 mL on TRUS, a very high specificity of 91% was achieved with a sensitivity of 36%. Thus, further investigations aimed at defining a better mode of diagnosis of PCa are warranted.

The role of free prostate-specific antigen in the diagnosis of prostate cancer.

OBJECTIVE: To determine whether the free/total prostate-specific antigen (PSA) ratio can discriminate between patients with prostate cancer or benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A prospective study was conducted using free and total PSA assays in patients who underwent transrectal-ultrasound guided biopsies indicated by a total serum PSA level of > 4 ng/mL and/or a positive digital rectal examination. Sixty-nine men (median age 68 years, range 57-86) who presented to our out-patient department with symptoms of prostatism were included in the study. Blood samples were drawn from all patients before biopsy. RESULTS: Histopathological examination detected prostate cancer in 17 of 69 (25%) patients and 13 of these 17 patients had a free/total PSA ratio of < 0.15; only 12 of 52 (23%) patients with BPH had a ratio of < 0.15. Receiver operating characteristic analysis indicated a threshold free/total PSA ratio of < or = 0.15 was the optimum discriminatory level. In the whole study group, this threshold had sensitivity, specificity, positive- and negative-predictive values of 76%, 77%, 52% and 91%, respectively. There were 40 patients with serum PSA levels of 4-10 ng/mL and 17.5% (7/40) of these were diagnosed with cancer. Using a free/total PSA ratio of 0.15 would have failed to diagnose two patients of seven with prostate cancer but 30 patients would have avoided a biopsy. In this subgroup, the threshold ratio of 0.15 had sensitivity, specificity, positive- and negative-predictive values of 71%, 85%, 50% and 93%, respectively. The rates for a PSA density (PSAD) at a threshold of > or = 0.15 were 71%, 76%, 38%, 93%, respectively. CONCLUSION: These results indicate that using the free/total PSA ratio gives a significant improvement over PSAD and total PSA values alone in the diagnosis of prostate cancer: its use may also enhance the diagnostic accuracy in patients with intermediate PSA levels.

The impact of prostate-specific antigen, its density and the Gleason score in the prediction of extracapsular disease in prostate carcinoma.

OBJECTIVE: To evaluate the effectiveness of serum prostate-specific antigen (PSA). PSA density (PSAD), the preoperative Gleason score of transrectal-ultrasonography (TRUS)-guided needle biopsies and the Gleason score of the final histological examination in predicting extracapsular disease in prostate cancer (PCa). MATERIAL AND METHODS: We retrospectively analyzed 32 patients who underwent radical retropubic prostatectomy as the primary treatment for their clinically localized disease. RESULTS: Extracapsular extension was found in 21 patients. In a comparison of different cutoff levels, the best positive predictive values were found for PSA of 20 ng/ml, PSAD of 0.2 and 0.3, a Gleason score of TRUS-guided biopsies of 5 and one of the prostatectomy specimens of 7 with 100, 80 (both), 74 and 95%, respectively, A PSA value higher than 20 ng/ml and a preoperative Gleason score of 7 or higher predicted extracapsular disease with specificity rates of 100 and 91%, respectively. It was noteworthy that there was a statistically significant undergrading in the extracapsular group in the Gleason scores of TRUS-guided biopsies compared to the prostatectomy specimens. CONCLUSION: PSA levels above 20 ng/ ml and/or Gleason scores of 7 or higher in TRUS-guided biopsies are strong indicators of extracapsular extension of PCa.

Correlation of transrectal ultrasonography and core biopsies with pathology results in radical prostatectomy specimens.

BACKGROUND: We compared preoperative tumor location, as identified by transrectal ultrasonography (TRUS), and TRUS-guided core biopsies with the final histopathological examination of radical prostatectomy specimens. METHODS: Thirty patients who had radical retropubic prostatectomy after evaluation with TRUS are included in the study. Diagnosis of prostate cancer was established with TRUS-guided systematic (3 cores from base, mid and apex of the peripheral zone, and 1 core from the transition zone of each side of the prostate) and lesion-directed core biopsies in all cases. Each prostate gland was halved for histopathological examination and results are reported in terms of "sides". RESULTS: Histopathological examination of the prostatectomy specimens revealed prostate cancer bilaterally in 29 glands (58 sides) and unilaterally in 1 gland. Preprostatectomy TRUS examinations missed cancer in 29 sides, and core biopsies were negative for cancer in 14 sides. CONCLUSION: This study revealed that 49% of prostate cancer lesions (n = 29 sides) were not recognized on TRUS and 52% of those (n = 15 sides) were diagnosed only by additional systematic biopsies. Furthermore, even with TRUS-guided systematic core biopsies, failure to detect the prostate cancer lesions may be as high as 24% (n = 14 sides).

Glutathione S-transferase and multidrug-resistant phenotype in transitional cell carcinoma of the bladder.

OBJECTIVE: To asses the role of expression of resistance phenotypes in treatment failure in patients with invasive transitional cell carcinoma of the urinary bladder, since P-glycoprotein and glutathione S-transferase pi (GST) expression are implicated in resistance to various chemotherapy agents in different tumors. METHODS: Tumor samples from P-glycoprotein and GST-pi were analyzed by immunohistochemistry. RESULTS: P-glycoprotein and GST-pi were found in 35.7 and 42.9% of the samples, respectively. In 21.4% of the samples there was simultaneous expression of both proteins. No significant impact on prediction of tumor behavior was evident on statistical analysis by any one of the protein expressions. CONCLUSION: Drug resistance in transitional cell carcinoma may be through different mechanisms. Although the small sample size of this study precludes firm conclusions, the assessment of P-glycoprotein or GST-pi expression appears to be of little value as a predictor of response to chemotherapy in this group of tumors.

The impact of prostate-specific antigen density in predicting prostate cancer when serum prostate-specific antigen levels are less than 10 ng/ml.

OBJECTIVE: To evaluate the impact of prostate-specific antigen density (PSAD) when serum levels of prostate-specific antigen (PSA) are less than 10 ng/ml. METHODS: We retrospectively analyzed 134 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsies according to Cooner's algorithm. RESULTS: Histopathological examination revealed prostate cancer (PCa) in 22 (16%) and benign prostatic hypertrophy (BPH) in 112 (84%) patients. Five patients (23%) with PCa had PSAD < 0.15 of whom 3 had PSA < 4 ng/ml and 2 had PSA between 4 and 10 ng/ml. In the BPH group, 60 patients (54%) had PSAD below 0.15 whereas 52 patients (46%) had PSAD over 0.15. With 0.15 as the cutoff level of PSAD, the sensitivity and specificity of PSAD was found as 77 and 54%, respectively. In this patient population, PSA with the cutoff level of 4 ng/ml has sensitivity and specificity levels of 77 and 33%, respectively. According to these results, a statistically significant difference was found between PSA and PSAD only in terms of diagnostic specificity (chi-square, p < 0.05). There were 29 patients with negative digital rectal examination (DRE) and TRUS and PSA 4-10 ng/ml who underwent biopsy because of PSAD > 0.15. No cancer was detected in this group of patients, suggesting that biopsy in this subgroup may be unnecessary. CONCLUSION: Although PSAD seemed to increase the specificity without any decrease in sensitivity in the diagnosis of prostate cancer, it did not bring any practical advantage in our selected population since all PCa cases had abnormal DRE and/or TRUS findings.

The effectiveness of imaging modalities in clinical staging of localized prostatic carcinoma.

Findings on transrectal ultrasonography (TRUS), computerized tomography (CT), and magnetic resonance imaging (MRI) in local staging of prostatic carcinoma (PCa) were compared with the final pathological staging in 30 patients who underwent radical prostatectomy. We found TRUS and MRI to have the same accuracy rate (53%) in local staging, whereas CT revealed a lower accuracy rate with 47%. TRUS revealed the highest accuracy rate in detecting seminal vesicle invasion with 70%, and MRI in invasion of periprostatic tissue with 67%. Although it revealed similar efficiency as MRI, TRUS should be considered as the first line modality in local staging of PCa in light of its relatively high accuracy rate, cost effectiveness and case in performance.

Economics of different treatment options of benign prostatic hyperplasia in Turkey.

Benign prostatic hyperplasia (BPH) has an important impact on the national health economics and can be managed in a large spectrum of modalities from simple follow-up to surgery. In this study, we aimed to compare different treatment options of BPH in terms of cost effectiveness in Turkey. The first evaluation of a BPH patient has a cost of $200. The cost of TURP or open prostatectomy (OP) in our hospital including all the expenses is $740. Finasteride has an annual cost nearly equal to TURP and OP. Considering the expenses of the close follow-up studies and regular visits, one-year lasting Finasteride treatment is two times more expensive than surgery. In comparison with medical treatment options, TURP as the gold standard of treatment of BPH is cost effective when long-term expenses are considered.

When should one perform shockwave lithotripsy for lower caliceal stones?

Extracorporal shockwave lithotripsy of lower caliceal stones is often unrewarding because of the difficulty of passing stone fragments. We report our results in SWL of lower pole stones in 219 patients and compare them with the results of SWL of middle (82 patients) and upper pole (85 patients) stones. The stone-free rate of SWL monotherapy was found to be 59%, 77%, and 64% in lower, middle, and upper caliceal stones, respectively. In lower pole stones, SWL was unsuccessful in 41% of the patients, of whom 9% had minimal residual asymptomatic stones (less than 4 mm in greatest diameter). In comparison with the results of percutaneous nephrolithotomy (PCN) of lower pole urolithiasis in the literature, SWL was unsuccessful in large stones, with stone-free rates of 13% and 0 when the stone size was 3 to 4.9 cm2 and > 5 cm2, respectively. A stone-free rate of 82% when the stone burden was < 1 cm2 is similar to the PCN results of other centers, suggesting that SWL may be the first choice of treatment in lower pole stones of this size. We achieved a stone-free rate of 59% when the stone size was between 1 and 3 cm2, which is lower than the stone-free rates of PCN in the literature. In spite of its lower stone-free rates, SWL, with its lower morbidity, may still be considered an acceptable treatment modality in this range of moderate stone burden, especially when there is a patient desire for conservative treatment.