C. Dimopoulos

Nitric oxide synthase and xanthine oxidase activities in the spermatic vein of patients with varicocele : A potential role for nitric oxide and peroxynitrite in sperm dysfunction

PURPOSE The oxidative and reductive stresses within the varicocele veins were estimated. Nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, S-nitrosothiols and superoxide release within the spermatic vein in patients with varicocele, and the role of the noxious oxidant peroxynitrite formed from nitric oxide and superoxide in sperm dysfunction were determined. MATERIALS AND METHODS Whole blood samples were drawn from a peripheral vein and a dilated varicocele vein before ligation. Nitric oxide synthase, xanthine oxidase, nitric oxide and peroxynitrite were measured by novel spectro-fluorophotometric methods. S-nitrosothiols were estimated by a luminol-chemiluminescence method. Serum and red blood cell antioxidant capacity was determined by a chemiluminescence reaction. RESULTS Serum nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, peroxynitrite and S-nitrosothiol levels were greater in the spermatic vein compared to the peripheral vein. Serum antioxidant capacity was greater in varicocele veins compared to peripheral veins. In contrast, the antioxidant capacity of red blood cells was less in the varicocele veins, which was consistent with an increased rate of peroxynitrite production. CONCLUSIONS Our data suggest a high oxidative stress due to the release of nitric oxide synthase and xanthine oxidase within the dilated spermatic vein. The reaction resulted in dramatic formation of nitric oxide, peroxynitrite and S-nitrosothiols, which are biologically active. Formation of peroxynitrite from the reaction of nitric oxide with superoxide could be a causative factor for impaired sperm function in patients with varicocele.

Oral estramustine and oral etoposide for hormone-refractory prostate cancer

OBJECTIVES Estramustine and etoposide have been shown to inhibit the growth of prostate cancer cells in experimental models. An in vivo synergism of the two agents, when administered to patients with metastatic prostate cancer refractory to hormone therapy, has been reported. To confirm these results, we administered this combination to a large number of patients with hormone-refractory prostate cancer (HRPC). METHODS Fifty-six patients with metastatic HRPC were treated with oral estramustine 140 mg three times a day and oral etoposide 50 mg/m2/day for 21 days. Therapy was discontinued for 7 days and the cycle was then repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. To control for the possible interference of an antiandrogen withdrawal effect, all patients discontinued antiandrogen therapy and were not enrolled in the study unless there was evidence of disease progression. RESULTS Forty-five percent of 33 patients with measurable soft tissue disease demonstrated an objective response, which included five complete and ten partial responses. Among 52 patients with osseous disease 17% showed improvement and 50% showed stability of bone scan. Thirty patients (58%) demonstrated a decrease of more than 50% in pretreatment prostate-specific antigen (PSA) levels. The median survival of all patients was 13 months. Good pretreatment performance status, measurable disease response, improvement or stability of bone scan, and PSA response were important predictors of longer survival. CONCLUSIONS We conclude that the combination of estramustine and etoposide is an active and well-tolerated oral regimen in HRPC.

Comparative evaluation of the diagnostic performance of the BTA stat test, NMP22 and urinary bladder cancer antigen for primary and recurrent bladder tumors

PURPOSE We compared overall sensitivity and specificity of the urinary bladder cancer antigen enzyme-linked immunosorbent assay (UBC, IDL Biotech, Sollentuna, Sweden), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and NMP22 test kit (Matritech, Newton, Massachusetts), and the differential sensitivity regarding the histological pattern of tumors. MATERIALS AND METHODS A total of 213 patients with clinical and/or imaging signs of bladder cancer provided a single voided urine sample for the bladder cancer antigen, BTA stat test and NMP22 before cystoscopy. Of these patients 95 were monitored for superficial bladder cancer, while the remaining 118 had no history of bladder cancer. All detected bladder tumors or suspicious lesions were resected transurethrally. A group of 21 age and sex matched healthy volunteers were also evaluated with the same tests. RESULTS Bladder cancer was confirmed histologically in 118 patients, of whom primary and recurrent tumors were in 68 and 50, respectively. The optimal cutoffs calculated with receiver operating characteristics curves were 8 units per ml. for NMP22 and 12 microg./l. for bladder cancer antigen. Overall sensitivity and specificity were 72.9% and 64.6% for the BTA stat test, 63.5% and 75.0% for NMP22, and 80.5% and 80.2%, respectively, for bladder cancer antigen. Bladder cancer antigen proved significantly more sensitive than NMP22 for detecting bladder cancer (p = 0.001) but not more than the BTA stat test, while the specificity of it was significantly higher than that of the BTA stat test (p = 0.009). Bladder cancer antigen had a sensitivity of 80.7% for stage Ta tumors, which was significantly higher than NMP22 (52.6%, p = 0.001) and the BTA stat test (57.9%, p = 0.01). In grade I tumors the sensitivity of bladder cancer antigen (70%) did not differ significantly than that of the BTA stat test (50%) and NMP22 (50%, p = 0.14). Bladder cancer antigen had the least false-positive results in patients with a history of bladder cancer and negative cystoscopy, and those with urological disease other than bladder cancer. CONCLUSIONS Our data indicate that bladder cancer antigen may be a more potent diagnostic marker for bladder cancer than NMP22 and the BTA stat test based on the higher sensitivity for detecting low stage and low grade tumors, and the higher specificity. The contribution of these tests for detection of bladder cancer should still be considered adjunctive to cystoscopy.

Extracorporeal shock wave lithotripsy for renal stones in children.

The aim of our study is to determine the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) as a method of treatment of nephrolithiasis in childhood. Between 1986 and 1994, 50 children with renal calculi were treated by ESWL in our department. The age of the children ranged from 8 months to 14 years. Thirty-three of them were boys and 17 girls. The stone location was in the renal pelvis in 38 cases, in the upper renal calyx in 4 cases, in the lower calyx in 2, while 6 children had staghorn calculi. The stone size ranged between 3 and 39 mm. All treatments were performed with Dornier HM4 except 12 children, all older than 10 years, who underwent ESWL with Dornier HM3. All ESWL procedures took place under general anesthesia or sedation with ketamine. The number of shock waves varied between 400 and 2,000 per treatment and the standard maximum generator voltage was 18 kV. The overall stone clearance rate at 1 month was 66%. Fourteen children with large residual fragments underwent a second ESWL procedure 3 months later. With a mean follow-up of 33 months, 41 children (82%) are stone-free. Ten children developed urinary tract infection and 5 Steinstrasse. Twelve children had a pre- and post-ESWL DMSA scan and no permanent impairment of renal function was observed. We conclude that ESWL is the treatment of choice for urinary tract lithiasis in childhood. It is a low-risk method, without serious complications, which yields as high a success rate in children as in adults. We believe that as the stone fragmentation and clearance is much higher in children that in adults, the method must be the initial approach and may be the monotherapy even in staghorn or complex stones.

Treatment of patients with metastatic urothelial carcinoma and impaired renal function with single-agent docetaxel

OBJECTIVES To evaluate the efficacy and toxicity of single-agent docetaxel in patients with metastatic urothelial carcinoma and impaired renal function. METHODS Eleven consecutive patients previously untreated for metastatic disease with renal impairment (median serum creatinine level of 2.6 mg/dL) were treated with intravenous docetaxel 100 mg/m2 for 1 hour every 21 days. Granulocyte colony-stimulating factor was administered at a dose of 5 microg/kg/day subcutaneously from days 5 to 14. RESULTS Five of 11 patients achieved a partial response, with time to progression of responding patients ranging from 5 to 22 months or more. The median overall survival rate was 11 months. Renal function improved in 5 of 8 patients with tumor-related renal impairment. Toxicity was primarily hematologic, with 5 patients developing grade 3 or 4 neutropenia; nonhematologic toxicities were manageable. CONCLUSIONS Our preliminary data indicate that single-agent docetaxel therapy may represent an effective therapeutic alternative for patients with advanced urothelial carcinoma and renal insufficiency precluding cisplatin-based combination chemotherapy.

Extracorporeal Shock Wave Lithotripsy in 5 Patients with Aortic Aneurysm

PURPOSE The safety and efficacy of extracorporeal shock wave lithotripsy (ESWL*) in patients with an aortic aneurysm were assessed. MATERIALS AND METHODS Five patients with an aortic aneurysm and symptomatic renal (4) or upper ureteral (1) lithiasis underwent ESWL with either an HM3 or HM4 lithotriptor. RESULTS The procedure was well tolerated in all patients. The stone was fragmented completely in the 4 patients with renal lithiasis, while 1 with ureteral lithiasis also required ureteroscopic extraction of the stone fragments. CONCLUSIONS For patients with symptomatic renal stones and an aortic aneurysm ESWL may be the treatment of choice.

Expression of transforming growth factor β in renal cell carcinoma and matched non-involved renal tissue

TGFβ1 is one of several cytokines produced by proximal tubular and renal cancer cells. Previous studies have been mainly focused on determining plasma or serum TGFβ levels, its effect on RCC cultures, and the expression of TGFβ mRNA. Cancerous and autologous normal kidney samples were obtained from 24 patients treated by radical nephrectomy. TGFβ1 expression was determined using a semi quantitative Western blot analysis and immunohistochemistry. Blot densities and immunohistochemical expression intensities in normal and neoplastic tissue were compared, and subsequently correlated to tumor stage, histological type and nuclear grade. All tissue samples examined expressed TGFβ1; mean tumor to non-involved kidney spot density ratio correlated with advancing stage and higher nuclear grade. The overexpression of TGFβ1 in certain RCCs may partially explain their resistance to the growth suppression action of TGFβ. The correlation with tumor stage and grade indicates a possible role in the development of metastatic potential as well as in host’s immune response modulation.

BACK PROPAGATION NEURAL NETWORK IN THE DISCRIMINATION OF BENIGN FROM MALIGNANT LOWER URINARY TRACT LESIONS

PURPOSE We investigated the potential value of morphometry and artificial intelligence tools to discriminate between benign and malignant lower urinary tract lesions. MATERIALS AND METHODS The lesions included lithiasis in 50 cases, inflammation in 61, benign prostatic hyperplasia in 99, carcinoma in situ in 5, and grade I and grades II and III transitional cell carcinoma of the bladder in 71 and 184, respectively. Images of routine processed voided urine smears stained by the Giemsa technique were analyzed using a custom image analysis system, providing a data set of 45,452 cells. A neural net model of the back propagation type was used to discriminate benign from malignant cells based on the extracted morphometric and textural features. Data from 13,636 randomly selected cells (30% of the total data) were used as a training set and the data from the remaining 31,816 cells comprised the test set. In a similar attempt to discriminate at the patient level data on 30% of those randomly selected were used to train a back propagation neural net and data on the remaining 329 were used for testing. RESULTS Application of the back propagation neural net enabled the correct classification of 95.34% of benign and 86.71% of malignant cells with overall 90.57% accuracy. At the patient level the back propagation neural net enabled the correct classification of 100% of those with benign and 94.51% of those with malignant disease with overall 96.96% accuracy. CONCLUSIONS The use of neural nets and image morphometry may increase the speed of cytological diagnosis and the diagnostic accuracy of voided urine cytology.

Influence of Digital Examination, Cystoscopy, Transrectal Ultrasonography and Needle Biopsy on the Concentration of Prostate-Specific Antigen

The influence of various prostatic manipulations, including digital rectal examination, cystoscopy, transrectal ultrasonography and transrectal needle biopsy, on the serum prostatic-specific antigen (PSA) levels in 170 men, were examined. We found that digital rectal examination, cystoscopy and transrectal ultrasonography had no significant effect on PSA levels, except for transrectal needle biopsy, which caused an immediate increase of serum PSA in 96.2% of the patients lasting more than 2 weeks in 42.3% of the cases. In conclusion, serum PSA determination after digital rectal examination, after cystoscopy and after transrectal ultrasonography is accurate and reliable. On the other hand, we must wait about 6 weeks after needle biopsy before measuring PSA in the serum of patients with prostatic diseases.

One-session bilateral ureteroscopy: Is it safe in selected patients?

The aim of this study was to investigate the possibility to perform bilateral ureteroscopy in one session and to determine the procedures indications and complication rate.Twenty-two patients underwent bilateral ureteroscopy in one session. Eighteen patients had bilateral lithiasis of the lower ureteral third, three patients had unexplained haematuria and one had unexplained bilateral hydronephrosis. The rigid ureteoroscope was used in cases with stones and the flexible one in cases with haematuria and hydronephrosis. Ureteral catheters were placed in all patients.The overall stone-free rate was 83.3%. The procedure failed to confirm a diagnosis in 2 patients with unexplained haematuria. Follow-up included IVU and retrograde cystogram 3 months after the procedure and a renal scan one year later. No major complication was observed.It is concluded that bilateral ureteroscopy in one session can be performed safely in selected patients. The method does not yield major complications and saves patients from a second procedure and a second anaesthesia.