Transrectal periprostatic lidocaine injection anesthesia for transrectal prostate biopsy: a prospective study.

Transrectal ultrasound (TRUS)-guided biopsy remains the mainstay of the diagnosis of prostate cancer. Although this diagnostic method is a safe procedure and well tolerated by most patients a significant number of patients report discomfort and pain during prostate biopsy. In order to define the best method of anesthesia, many studies, in which different methods were compared, have been performed. To determine the effectiveness of local injection anesthesia in TRUS-guided prostate biopsy, we designed and performed this prospective study in order to evaluate the utility of periprostatic nerve block for pain management. A total of 100 patients who had elevated total prostate-specific antigen (tPSA) and/or abnormal digital rectal examination (DRE) were included in this study. Half of the patients received periprostatic injection anesthesia (group I) and the remaining half received placebo (group II). Patients received 10 cm3 (5 cm3 each side) 1% lidocaine injected into the periprostatic nerve plexus under transrectal ultrasonic guidance. Pain during biopsy was assessed using a 10-point modified visual analog scale (VAS). In groups I and II, mean patient age was 66.8+2.5 and 65.6+11.5 y, mean tPSA was 7.87+/-3.6 and 11.3+/-1.7 ng/ml, mean biopsy duration was 6.5+/-2.5 and 6.6+/-2.2 min and mean pain score during TRUS-guided biopsy was 1.46+/-2.2 and 4.5+/-2.1, respectively. No statistically significant difference was observed with respect to age, tPSA and mean biopsy duration between these groups. Mean pain VAS score was statistically or significantly better (P=0.0001) in the lidocaine injection group (group I), and furthermore no patient had a VAS pain score > or =5 in this group. Only minor and transient complications occurred in both groups. This study reinforces the usage of periprostatic nerve block as a standard method of pain management during TRUS-guided prostate biopsy, because it is simple, safe, uncostly and significantly effective without requiring additional time.

The efficacy of neoadjuvant chemotherapy in invasive bladder cancer.

Radical cystectomy is the gold standard in the treatment of invasive bladder cancer. However, five-year disease-free survival is low most probably due to micrometastatic disease at the time of surgery. The neoadjuvant chemotherapy may be performed as the first line management for invasive bladder tumors in order to treat micrometastases found at the diagnosis and improve resectability of larger neoplasms. A total of 43 patients diagnosed with invasive bladder tumors and 11 patients received neoadjuvant chemotherapy. The mean age of patients was 64 (43-74) years, and mean follow-up period was 52 months (12-114). Neoadjuvant chemotherapy protocol consisted of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or cisplatin, methotrexate, and cisplatin (CMV). All patients in neoadjuvant chemotherapy group underwent radical cystectomy. There was no significant difference between the groups with respect to disease-free survival time and overall survival time. In patients who received neoadjuvant chemotherapy, the respective disease-free and overall survival times were 31 months and 36 months versus 30 months and 35 months in patients who were treated with surgery only (p > 0.05). Five-year survival rates were 36% and 31% in the chemotherapy and no-chemotherapy groups, respectively. In the present study, 5-year survival rate was not affected by neoadjuvant chemotherapy in invasive bladder tumor. Complete pathological remission (stage p0) was found in 28% and pathological downstaging (stage < T2) was seen in 9% of patients in the neoadjuvant chemotherapy group. Five-year survival rates were 75% and 14.2% in patients who responded to chemotherapy, and in patients with no response, respectively (p < 0.05). The most favorable prognostic factor in this study was the response to neoadjuvant chemotherapy revealed as complete remission or pathological downstaging. The most important issue remains the prediction of patients who would respond and benefit from neoadjuvant chemotherapy.

Effect of propylthiouracil on adenosine deaminase activity and thyroid function in patients with psoriasis.

BACKGROUND: T-cell activation has been implicated in the pathogenesis of psoriasis; adenosine deaminase (ADA) activity has been considered as a marker of T-cell activation. The antithyroid drug propylthiouracil (PTU) has recently been shown to have beneficial effects on psoriatic lesions, probably by acting on the immune system. OBJECTIVES: To investigate whether ADA activity may be related to psoriasis and whether oral PTU affects ADA activity and gives clinical improvement in psoriatic patients. METHODS: ADA activities were measured in plasma, erythrocyte and tissue samples of patients with psoriasis before and after 2 months of treatment with either PTU 100 mg three times daily or PTU plus thyroxine 25 microg once daily (to prevent possible hypothyroidism, which may be induced by PTU) as well as in healthy controls. The severity of the disease was evaluated before and after treatment according to Psoriasis Area and Severity Index (PASI) scores. Routine analyses and thyroid function tests were also carried out during the study. RESULTS: All patients showed significant clinical improvement in their lesions and decreased PASI scores after the treatments. Elevated baseline ADA activities in skin and plasma were found to be lower, and decreased baseline erythrocyte ADA was higher, after the treatments in all patients, and they were not different from control values. Although thyroid function tests were not affected by the treatments, serum thyroid-stimulating hormone levels were found to be higher after the treatments, and there was a larger increase in patients treated with PTU alone. However, none of the patients had clinical hypothyroidism or cytopenia. CONCLUSIONS: ADA activity may be clinically useful for indicating T-cell activation in psoriasis. Because of its antiproliferative and immunomodulatory effects, antioxidant potential and low toxicity, PTU may be an effective agent in the treatment of psoriasis.

Apoptotic regression of prostatic tissue induced by short-term doxazosin treatment in benign prostatic hyperplasia.

OBJECTIVES: Benign enlargement of the prostate comprises both hypertrophy and in particular hyperplasia of prostatic stromal and glandular compartments. Alpha adrenergic blockade has been shown to be effective in the management of BPH. Recent investigations have shown that this effect may in part be due to apoptosis. METHODS: A total of 29 patients who were symptomatic due to BPH were enrolled into this prospective placebo controlled, double-blind randomized study and underwent prostatectomy at the end of the 4th week. Clinical efficacy was evaluated by a set of detailed investigations. Surgical specimens were analyzed by immunohistochemistry and tissue components of stroma, smooth muscle and glandular epithelium were calculated by a software on a computer after representative areas were scanned and captured as high resolution images. Apoptosis in each tissue specimen was analyzed by Terminal Deoxynucleotidyl Transferase End Labelling (TUNEL) method utilizing Biotin-16-dUTP. RESULTS: Both groups were similar in terms of baseline evaluation in all aspects. There was a steady decline in patients' urinary complaints as evidenced by International Prostate Symptom Score System (IPSS) in the doxazosin group compared to placebo. Uroflowmetric investigations on patients revealed that maximum flow rates in the active drug group increased throughout the study. Mean PSA levels decreased by 14% at the end of the study in the doxazosin group, while it increased by 11% in the placebo group. Average stroma to epithelial ratio in the doxazosin group was 2:1 in comparison to a value of 1:1 in the placebo group. The rate of apoptosis was 2.2% and 3.2% for the epithelial and stromal compartments, respectively, in the doxazosin group, and 1.2% and 2.7% for the placebo arm. CONCLUSIONS: These data suggest apoptosis as the possible underlying molecular mechanism partly responsible for the clinical efficacy and morphological changes induced by doxazosin treatment in BPH.

Use of double J stent in a case of spontaneous ureteral extravasation of urine.

OBJECTIVES: Although there are numerous case reports of spontaneous rupture of the collecting system, especially including the calyceal fornix or the renal pelvis, spontaneous rupture of the ureter is a rare condition. METHODS: Herein, we present a case of a patient who suffered symptoms of acute abdomen due to rupture of the proximal ureter. Extensive assessment revealed no etiological factor as to the extravasation. RESULTS/CONCLUSIONS: The condition was managed conservatively by insertion of a double-J catheter. The double-J ureteral stent was removed on the first postoperative month under local anesthesia uneventfully. One year after the spontaneous ureteral extravasation, the patient remained without clinical problems. The diagnosis, pathogenesis and complications of this unusual condition are reviewed.

Early cystic relapse of embryonal carcinoma of testis in obturator fossa.

OBJECTIVE: We report a case of embryonal carcinoma stage IIB arising from the right testis that subsequently underwent chemotherapy and retroperitoneal lymph node dissection and presented with an early cystic recurrence in the obturator fossa. METHODS: This case is reanalyzed retrospectively and literature is reevaluated for the early recurrences of testicular tumors at atypical locations. We discuss the rarity of obturator fossa as a location for early recurrences of testis tumors. RESULTS: Only one case of recurrence in obturator fossa has been reported. CONCLUSIONS: This case provides an example of the possibility of recurrence in an unpredictable short interval subsequent to proper therapies and underscores the importance of close follow-up.

Effect of urinary stone disease and extracorporeal shockwave lithotripsy on excretion of glycosaminoglycans.

BACKGROUND AND PURPOSE: The effect of glycosaminoglycans (GAGs) in urinary crystal inhibition has been shown in vitro, but their inhibitor role in vivo has not been precisely determined in stone-forming patients. The aim of this study was to compare the levels of total GAGs and their components in primary stone-forming patients and a healthy control group and to investigate the impact of shockwave lithotripsy (SWL). PATIENTS AND METHODS: Thirty-eight patients with primary kidney stones and 31 healthy controls were included in this prospective study. Total urinary GAG concentrations were determined by the dimethylene blue assay (DMB), and GAG fractions (chondroitin sulfate, heparan sulfate, and dermatan sulfate) were studied by cellulose acetate electrophoresis. Analysis was repeated after SWL in the stone patients. RESULTS: Chondroitin sulfate was the major component secreted in the urine of the control subjects. Heparan sulfate was the major component in the urine of the stone patients with less chondroitin sulfate and dermatan sulfate (48%, 35%, 16.5%, respectively). Our study showed a significant increase in total urinary GAGs (4.75 v. 7.43 microg/mg of creatinine; P<0.0001) after SWL. Dermatan sulfate was the main component in this group (P<0.0001). The total urinary GAG concentrations remained high for at least 2 days after SWL. CONCLUSION: The elevation in total GAGs after SWL indicates the presence of tissue injury, which also renders dermatan sulfate the principal excreted component. Studies with longer follow-up periods are needed to determine whether these changes in the excretion of GAG components persist.

Effects of single-shot and twin-shot shockwaves on urinary enzyme concentrations.

BACKGROUND AND OBJECTIVE: Extracorporeal shockwave lithotripsy (SWL) remains the first-line treatment of urinary calculi. However, a number of studies have shown that adverse effects on the kidneys and the surrounding tissues may be encountered in short- and long-term follow-up. The aim of this study was to compare the effects of single-shot and twin-shot SWL techniques to identify the safest modality in terms of urinary enzyme excretion. PATIENTS AND METHODS: In this prospective, investigator-blinded, randomized study, urinary enzymes, beta2-microglobulin, microalbumin, Na, K, Ca, and creatinine concentrations were analyzed in 59 consecutive patients. Measurements were performed in urine specimens collected immediately before and after the SWL procedure and also on the 3rd and 7th days after treatment, which was performed on a Dornier MFL-5000 lithotripter utilizing the twin-shot technique (Group 1; N = 30) or the single-shot technique (Group 2; N = 29) with 3000 shockwaves at 18 kV per treatment. RESULTS: Although there was no statistically significant difference in the results between the groups, urinary levels of microalbumin, alanine and aspartate aminotransferases, beta-2-microalbumin, gamma-glutamyltranspeptidase, Na, K, and Ca rose acutely after SWL, reaching maximum levels on the 3rd day, and returned to the baseline by the 7th day following the treatment in both groups. CONCLUSION: This study demonstrates that SWL performed by either a single-shot or twin-shot shockwave technique has a transient detrimental effect on renal function, as assessed by urine enzyme concentrations. It is recommended that the twin-shot shockwave technique be used in routine lithotripsy in consideration of the cost-effectiveness provided by the shorter treatment time.

Alteration of epidermal growth factor receptor expression following ischaemia of renal tissue.

This study was aimed to investigate Epidermal Growth Factor Receptor (EGF-R) expression after ischaemic injury in renal tissue and the effects of calcium channel blockers in the prevention of damage due to ischaemic insult. Simple nephrectomy was performed in a group of Sprague-Dawley rats, and kidneys were grouped according to cold ischaemia time (1, 6, 12, 24 and 48 hours, respectively) and to the type of calcium channel blockers (diltiazem and verapamil) used. EGF-R expression status was investigated in each group by immunohistochemistry on paraffin sections. Overall expression of EGF-receptor was detected in 8 (22.8%) kidneys. In terms of localization of EGF-receptor expression cortical tubular staining was detected in 8 (100%) kidneys, medullar tubular staining in (62.5%) kidneys and glomerular mesangial staining in 5 (62.5%) kidneys. There was no difference between various ischaemia times and different calcium channel blockers used. It has been concluded that hypoxia and cold ischaemia causes widespread down-regulation of EGF-receptor expression in renal tissue regardless of treatment with calcium channel blockers.

Clinical significance of nuclear p53 protein accumulation in bladder cancer.

OBJECTIVES: To investigate the correlation of nuclear p53 accumulation with disease outcome in a cohort of patients with transitional cell carcinoma of the bladder. METHODS: A total of 90 patients (11 female, 79 male) with transitional cell carcinoma of the bladder were included in this study. Tumour samples from the primary tumour were analysed by immunohistochemistry for nuclear accumulation of p53 protein. Outcome of each patient was recorded and investigated for a possible relation with p53 status. RESULTS: Nuclear p53 deposition was determined in 22 specimens. The nuclear p53 deposition was seen in less than 20% of the nuclei examined in 13 and more than 20% in 9 cases. No stromal staining was observed. Nuclear p53 deposition was present in 15.2% (7/46) of grade 2 tumours, and 34% (15/44) of grade 3 tumours (p=0.037). Stage distribution revealed 15.5% (5/33) positivity in stage pTa, 25.8% (8/31) in pT1 and 34% (9/26) in stage pT2-3 tumours. Tumours with p53 nuclear accumulation had a higher rate of recurrence and progression and shorter survival. CONCLUSION: Results of the current study indicate p53 as an important factor in determination of biological behaviour of bladder cancer.

Prognostic significance of p53 protein accumulation in stage pT1 transitional cell carcinoma of the bladder.

OBJECTIVE: Mutations in the tumour suppressor gene p53 results in the production of a mutant type, dysfunctional p53 protein which can readily be detected in the cell nucleus by immunohistochemical staining. This study aims to investigate the association of nuclear p53 protein accumulation with the clinical outcome of stage pT1 transitional cell carcinoma of the bladder which is renowned for high rates of recurrence and progression. METHODS: TUR samples of the tumours from fifty-two patients with primary stage T1 bladder cancer were analyzed immunohistochemically using the standard avidin-biotin peroxidase method for nuclear p53 accumulation. Status of p53 immunostaining was correlated with tumour recurrence, disease progression and three-year survival of each patient. RESULTS: The rate of tumour recurrence in pT1 bladder cancer was 36% in patients with tumours stained negatively for p53 protein and 78% in patients with tumours stained positively for p53 protein. Disease progression was seen in 15% of p53 (-) patients and in 56% of p53 (+) patients. CONCLUSIONS: In stage pT1 bladder tumours p53 nuclear accumulation indicates higher rates of tumour recurrence and disease progression. Accordingly, in patients who have pT1 bladder tumours with nuclear p53 accumulation, institution of more aggressive therapy should be considered and early radical therapeutic modalities should be offered to these patients.

Bcl-2 and p53 overexpression as associated risk factors in transitional cell carcinoma of the bladder.

Bcl-2 and p53 genes are implicated in cell cycle regulation with roles on programmed cell death. Consequently, presence of Bcl-2 and nuclear accumulation of p53 were proposed to confer a growth advantage tumour cells. We have investigated their role as prognostic factors in fresh tumour samples from a cohort of twenty patients with transitional cell carcinoma of the bladder by immunohistochemical analysis in paired specimens. Expression of Bcl-2 was observed in 11 cases (69%) and nuclear p53 accumulation in 9 (45%). In the presence of Bcl-2 protein expression, tumours showed a slightly higher rate of recurrence (55% vs. 40%) and significantly more progression (36% vs. 0%). Recurrence and progression rates were not significantly different in tumours with and without nuclear p53 overexpression (recurrence rates 56% vs. 55% and progression rates 33% vs. 27%, respectively). Grade and stage appeared as important prognosticators since 75% of grade 3 tumours showed recurrence and 50% progressed in contrast to 44% and 13%, respectively, of grades 1 and 2 tumours. Similarly, 50% of Ta-T1 tumours recurred and 20% progressed, while these rates were 75% and 75% for T2-T3 tumours. Also, expression of Bcl-2 and nuclear accumulation of p53 correlated with grade. In grade 3 tumours, 75% showed nuclear p53 overexpression and 80% cytoplasmic Bcl-2 protein. These figures were 25% and 64% for grades 1 and 2 tumours. In conclusion, Bcl-2 protein expression in transitional cell carcinoma appears to be associated with a poorer prognosis and together with nuclear p53 overexpression they are associated with tumour de-differentiation.

The role of in vitro chemosensitivity tests to predict the clinical efficacy of antineoplastic agents in genito-urinary tumors.

OBJECTIVE: To develop an in vitro screening system to predict the response to treatment of common malignancies of the genito-urinary tract. MATERIAL AND METHODS: Flow cytometric analysis and cytotoxicity assays (trypan blue and lactic dehydrogenase colorimetric tests) were performed on hormone resistant prostate cancer cell line PC-3 and primary transitional cell carcinoma samples treated with different antineoplastic agents and their combinations. Apoptosis induced by different agents was also investigated by previously established criteria. RESULTS: There were 9 bladder tumors (47.4%) in the study group that displayed drug resistance to at least one antineoplastic agent. When the drugs were examined individually, there was resistance to cis-platinum in 3 patients (15.8%), methotrexate in 6 (31.6%), vinblastine in 7 (36.8%), epirubicin in 2 and adriamycin in 2 patients (10.5%). Stratification of patients according to the stage of the tumor revealed statistically significant difference between the superficial and invasive tumors in terms of drug resistance (p < 0.05). In prostate cancer cell line vinblastine treatment resulted in a significant increase in S phase fraction. Percent cytotoxicity by trypan blue exclusion test was 26.1% and was significantly higher than the control group (8.7%, p < 0.002). Also, an increase in apoptotic index after the treatment was observed (44.4% and 12.1%, respectively; p < 0.0001). CONCLUSION: Both toxicity assays showed a very good correlation (p < 0.005) and can be used to evaluate the effects of different antineoplastic agents on individual tumors.

Impact of the expression of epidermal growth factor, transforming growth factor alpha, and epidermal growth factor receptor on the prognosis of superficial bladder cancer.

OBJECTIVES: To investigate the correlation of epidermal growth factor receptor (EGFR) expression and its ligands EGF and transforming growth factor-alpha (TGF-alpha) with disease outcome in a cohort of patients with superficial bladder cancer. METHODS: Tumor samples of 21 patients with transitional cell carcinoma of the bladder were analyzed by immunohistochemistry for expression of EGFR, EGF, and TGF-alpha. Disease-related events were recorded during a routine clinical follow-up and analyzed for possible correlation with the expression status of the above-mentioned proteins. RESULTS: All Stage pT1 transitional cell carcinomas expressed EGFR, and 10 of 21 (48%) tumors showed focal areas of strong EGF and/or TGF-alpha expression. Of these, 80% with EGF positivity (8 of 10) had recurrences, whereas only 9% of patients without EGF staining (1 of 11) did so. The same pattern was observed with TGF-alpha. A strong association was confirmed between EGF/TGF-alpha positivity and tumor recurrence (P <0.005). We also found that EGF and TGF-alpha were expressed in stroma and/or around the vessels of tumor tissue in 48% and 38% of the tumors, respectively. No association was found between the recurrence rate/vascular invasion and the stromal/vascular wall expression of the growth factors. CONCLUSIONS: Expression of EGF and TGF-alpha is correlated with tumor recurrence. Also, there is the ability of vessel walls to express EGF and TGF-alpha in superficial bladder cancer. Further clarification of the impact of this expression on angioinvasion of tumor cells may be helpful in understanding the nature of local invasion and metastasis.

[Comparison among patients considered candidates for radical prostatectomy in academic institutes in different countries]. / Comparación entre pacientes considerados candidatos para prostatectomía radical en instituciones académicas de distintos países.

OBJECTIVE: Radical prostatectomy is performed in potentially curable prostatic cancers, but surgical indication might somehow depend on the idiosyncrasies of a population. Herein we compare the characteristics of patients undergoing radical prostatectomy in teaching University Hospitals of different countries. METHODS: We conducted a retrospective review on 250 consecutive patients who underwent radical prostatectomy before January 1997 in five teaching University Hospitals in Europe (Spain, Sweden, Switzerland, Turkey) and the United States (Detroit, MI). Clinicopathological data were recorded and compared, and a questionnaire investigated whether patient and physician attitudes towards surgery differed. RESULTS: The number of surgeries per month at each institution ranged from 0.9 to 10 and the proportion of newly diagnosed patients that undergo surgery from 0.14 to 0.36. The Kruskal-Wallis test revealed both median age and preoperative prostate-specific antigen (PSA) levels were different between groups. Similarly, despite standardized surgery and histologic work-up, differences in the detection of extracapsular invasion and the rate of detectable PSA after surgery were observed between institutions. Diagnosis in the Swedish and Swiss groups was more often based on digital rectal examination, while the rest were more confident with transrectal ultrasound. Doctors at some institutions were more inclined to recommend radical surgery, either by not mentioning or disapproving other therapeutic strategies. The proportion of patients who said they would elect surgery again ranged from 72% to 92%, and the proportion of doctors who said they would perform surgery again ranged from 78% to 100%. Patients' and doctors' degree of satisfaction with the decision made were also different. CONCLUSIONS: (i) Candidates for radical prostatectomy in teaching hospitals of several countries are different. Might therefore have practical implications on the design of clinical trials and the interpretation of the results of treatment. (ii) Patient and physician acceptance of surgery varies according to countries and is more established firm in those countries where it is more frequently performed.

Role of apoptosis in testicular tissue damage caused by varicocele.

OBJECTIVE: Histomorphological changes reported in patients with varicocele (so-called stress pattern) have some degree of resemblance to the ones observed during apoptosis of various cell types due to a variety of reasons. In order to further clarify a possible role of apoptosis in impaired spermatogenetic activity associated with varicocele, we have investigated the presence of this specific type of cell death in testicular tissue. MATERIAL AND METHODS: Surgical specimens were obtained after the completion of ligation and division of the spermatic vein(s) in patients with varicocele associated with infertility and testicular tissue obtained by scrotal orchiectomy for hormonal ablation treatment in prostate cancer patients served as the control group. Terminal deoxynucleotidyl transferase end labeling (TUNEL) technique was utilized in paraffin-embedded tissue specimens to demonstrate the presence of apoptosis. RESULTS: Data obtained from 29 samples (varicocele, 24 patients; control, 5 patients) revealed that apoptosis was quite rare in testicular tissue of control group. Mean percentage of apoptotic cells per high power field (x400 magnification) was 2% for the control group and 14.7% for varicocele patients. CONCLUSION: In light of our data, it appears that apoptosis may have a significant role in spermatogenetic dysfunction associated with varicocele.

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.