Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats.

To evaluate the protective role of bosentan (BOS), an endothelin-1 (ET-1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg-1 streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg-1 and 100 mg kg-1 , respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET-1, eNOS, iNOS, tumour necrosis factor (TNF)-α, ET-RA and ET-RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET-1, TNF-α and iNOS gene expressions increased, eNOS, ET-RA and ET-RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF-α expressions in a dose-dependent manner.

Robotic-assisted laparoscopic nephroureterectomy and bladder cuff excision.

BACKGROUND AND OBJECTIVES: Our aim was to show that bladder cuff excision and distal ureterectomy can be safely performed by using the LigaSure device during robotic-assisted laparoscopic nephroureterectomy. METHODS: A 60-year-old man presented with gross hematuria. He was diagnosed with upper urinary tract transitional cell carcinoma (TCC) on the left side and was scheduled for robot-assisted laparoscopic surgery. Without changing the patient's position, sealing with the LigaSure atlas for bladder cuff excision and distal ureterectomy was performed. RESULTS: The operating time was 140 minutes from the initial incision to skin closure of all incisions. The estimated blood loss during the surgery was 120 mL. There were no intraoperative or postoperative complications. The Foley drain was removed on day 3 after normal cystographic findings, and the patient was discharged from the hospital on the fourth postoperative day. CONCLUSION: Robot-assisted nephroureterectomy with distal ureterectomy in the same position using a LigaSure device is a safe alternative for upper tract transitional cell carcinoma.

The actual incidence of papaverine-induced priapism in patients with erectile dysfunction following penile colour Doppler ultrasonography.

Penile color Doppler sonography is a valuable method for evaluating erectile dysfunction. However, there are some concerns about the safety of this method due to the intracorporeal pharmacological injection, which may cause priapism as a complication, resulting in penile fibrosis. To evaluate the actual incidence of papaverine-induced priapism in patients with erectile dysfunction (ED) who underwent penile colour Doppler sonography and to determine the safety of this diagnostic tool, a retrospective study was conducted using the database of our institution. A total of 672 men with ED underwent penile color Doppler ultrasonography with the intracorporeal injection of 60 mg papaverine hydrochloride. The patient characteristics of priapism cases were retrospectively evaluated. Priapism in 18 of the 672 patients (2.68%) was successfully treated with blood aspiration, irrigation and injection of an alpha-agonist medication, when needed. Patients with priapism were younger compared with those without priapism; mean age 45 +/- 12.51 (20-68) versus 50.93 +/- 12.04 (17-78) (P < 0.001). Penile Doppler ultrasound is a safe procedure in evaluating erectile dysfunction. The incidence of priapism, which is the most important complication of this procedure, is low and can be managed successfully with conservative approaches.

Suppression of angiogenesis, tumorigenicity, and metastasis by human prostate cancer cells engineered to produce interferon-beta.

We determined whether the IFN-beta gene can be used to suppress angiogenesis, tumor growth, and metastasis of human prostate cancer cells growing in the prostate of nude mice. Highly metastatic PC-3M human prostate cancer cells were engineered to constitutively produce murine IFN-beta subsequent to infection with a retroviral vector containing murine IFN-beta cDNA. Parental (PC-3M-P), control vector-transduced (PC-3M-Neo), and IFN-beta-transduced (PC-3M-IFN-beta) cells were injected into the prostate (orthotopic) or subcutis (ectopic) of nude mice. PC-3M-P and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node metastases, whereas PC-3M-IFN-beta cells did not. PC-3M-IFN-beta cells also suppressed the tumorigenicity of bystander nontransduced prostate cancer cells. PC-3M-IFN-beta cells produced small tumors (3-5 mm in diameter) in nude mice treated with anti-asialo GM1 antibodies and in severe combined immunodeficient/Beige mice. Immunohistochemical staining revealed that PC-3M-IFN-beta tumors were homogeneously infiltrated by macrophages, whereas control tumors contained fewer macrophages at their periphery. Most tumor cells in the control tumors were stained positive by an antibody to proliferative cell nuclear antigen; very few were positively stained by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, PC-3M-IFN-beta tumors contained fewer proliferative cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells. Staining with antibody against CD31 showed that control tumors contained more blood vessels than PC-3M-IFN-beta tumors. PC-3M-IFN-beta cells were more sensitive to lysis mediated by natural killer cells in vitro or to cytostasis mediated by macrophages than control transduced cells. Conditioned medium from PC-3M-IFN-beta cells augmented splenic cell-mediated cytolysis to control tumor cells, which could be neutralized by antibody against IFN-beta. Collectively, the data suggest that the suppression of tumorigenicity and metastasis of PC-3M-IFN-beta cells is due to inhibition of angiogenesis and activation of host effector cells.

Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor.

Angiogenesis is essential for tumor progression and metastasis. It is mediated by the release of angiogenic factors by the tumor or host. We analyzed the expression of angiogenic factors by the prostate cancer cell line LNCaP and two derived variants, in vitro and in vivo, to determine whether metastatic cell lines express higher levels of these factors. The production of three angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin 8 (IL-8), by LNCaP and its variants, LNCaP-LN3 (highly metastatic) and LNCaP-Pro5 (slightly metastatic), was measured by ELISA. VEGF, bFGF, and IL-8 mRNA expression was determined in vitro by Northern blot analysis. VEGF mRNA expression was determined in vivo by in situ hybridization. VEGF and flk-1 protein expression and microvessel density of LNCaP cell tumors were quantified by immunohistochemistry. In vitro, VEGF production by LNCaP-LN3 (3.15+/-0.04 pg/ml/10(3) cells) was significantly higher than those of both LNCaP (2.38+/-0.34 pg/ml/10(3) cells) and LNCaP-Pro5 (1.67+/-0.37 pg/ml/10(3) cells; P = 0.049 and 0.001, respectively). None of the three cell lines produced detectable levels of bFGF or IL-8 in vitro. In vivo, LNCaP-LN3 tumors exhibited higher levels of VEGF mRNA and protein (152.2+/-28.5 and 200.5+/-28.3) and of flk-1 protein (156.5+/-20.6) and had higher microvessel density (16.4+/-4.2) than either LNCaP tumors (89+/-17.5, 173.3+/-23.0, 124.6+/-21.6, and 12.4+/-3.5, respectively) or LNCaP-Pro5 tumors (63+/-14.7, 141.2+/-38.1, 126.1+/-20, and 5.8+/-2.2, respectively). In conclusion, metastatic human prostate cancer cells exhibited enhanced VEGF production and tumor vascularity compared with prostate cancer cells of lower metastatic potential. Thus, VEGF may play an important role in prostate cancer metastasis.

Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer.

Interleukin 8 (IL-8) is mitogenic and chemotactic for endothelial cells. Within a neoplasm, IL-8 is secreted by inflammatory and neoplastic cells. The highly metastatic PC-3M-LN4 cell line overexpresses IL-8 relative to the poorly metastatic PC-3P cell line. We evaluated whether IL-8 expression by human prostate cancer growing within the prostate of athymic nude mice regulates tumor angiogenesis, growth, and metastasis. PC-3P cells were transfected with the full-length sense IL-8 cDNA, whereas PC-3M-LN4 cells were transfected with the full-sequence antisense IL-8 cDNA. Control cells were transfected with the neomycin resistance gene (Neo). In vitro, sense-transfected PC-3P cells overexpressed IL-8-specific mRNA and protein, which resulted in up-regulation of matrix metalloproteinase 9 (MMP-9) mRNA, and collagenase activity, resulting in increased invasion through Matrigel. After antisense transfection of the PC-3M-LN4 cells, IL-8 and MMP-9 expression, collagenase activity, and invasion were markedly reduced relative to controls. After orthotopic implantation, the sense-transfected PC-3P cells were highly tumorigenic and metastatic, with significantly increased neovascularity and IL-8 expression compared with either PC-3P cells or controls. Antisense transfection significantly reduced the expression of IL-8 and MMP-9 and tumor-induced neovascularity, resulting in inhibition of tumorigenicity and metastasis. These results demonstrate that IL-8 expression regulates angiogenesis in prostate cancer, in part by induction of MMP-9 expression, and subsequently regulates the growth and metastasis of human prostate cancer.

Correlation of non-random chromosomal aberrations in lymphocytes of prostate cancer patients with specific clinical parameters.

The purpose of this research was to correlate non-random chromosomal aberrations in the peripheral blood lymphocytes (PBLs) of prostate cancer patients with specific clinical parameters. Peripheral blood samples were analyzed from 59 informative prostate cancer patients. Non-random chromosomal alterations detected in the PBLs and their correlation with any specific clinical parameters were analyzed statistically. A comparison was made between specific chromosomal abnormalities in the patients having an early (<65 years) or late (> or =65 years) age at disease onset, low-grade (Gleason grade <7) or high-grade (Gleason grade > or =7) tumors, a low (<10 ng/ml) or high (> or =10 ng/ml) prostate-specific antigen (PSA) level, and androgen-sensitive or -insensitive disease. In examining the specific chromosomal breakpoints, the regions 1p13, 2q21, 3p21, 4q13, 5q31, 6p21, 7p15, 7p13, 7q32, 10p11, 10q26, 11p15, 11p11, 14q12, and 16q12 showed breaks in at least four cases. Chromosome 15 (P=0. 045) was significantly altered in patients having a PSA value greater than or equal to 10, while it (P=0.017) and chromosome 19 (P=0.036) were significantly altered in patients having a PSA value greater than or equal to 20. In addition, chromosomes 5 (P=0.032), 8 (P=0.020), 16 (P=0.009), and 20 (P=0.047) were significantly altered in patients having a Gleason grade greater than 7. Also, chromosomes 2 (P=0.020) and 3 (P=0.044) were significantly altered in patients who had early disease onset. Additionally, chromosome 10 (P=0.041) was significantly altered in patients having metastasis, and chromosomes 4 (P=0.006) and 7 (P=0.028) were significantly altered in patients having androgen-insensitive disease. In spite of the small subset of patients, chromosome 8 (p=0.003) was significantly altered in patients having small cell carcinoma of the prostate. From these results we conclude that non-random chromosomal aberrations present in PBLs of prostate cancer patients can be correlated with specific clinical parameters. These correlations can be used to identify a prostate cancer patient's risk response to therapy.

Nephrectomy and vena caval thrombectomy in patients with metastatic renal cell carcinoma.

OBJECTIVES: To report out experience with performing nephrectomy and vena caval thombectomy in patients with metastatic renal cell carcinoma. METHODS: A retrospective review was performed of 15 patients who underwent surgical excision of the primary tumor and a caval thrombus and treatment of concurrent metastases between 1989 and 1995. The sites of metastases included lungs (n = 8), bone (n = 3), bulky retroperitoneal or mediastinal lymph nodes (n = 2), liver (n = 1), and contralateral adrenal (n = 1). The level of caval involvement was suprahepatic in 3 cases, retrohepatic in 2 cases, and infrahepatic in 10 cases. Three patients had an Eastern Cooperative Oncology Group performance score of 0, 11 had a score of 1, and 1 had a score of 2. Median follow-up was 17 months. RESULTS: Median operative time was 6.5 hours and median hospitalization was 10 days. Two patients required re-exploration for postoperative hemorrhage. There were no perioperative deaths. Four patients underwent surgery for resection of solitary metastases (1 lung, 2 spine, and 1 humerus); 2 of the 4 received adjuvant radiotherapy. Two patients received biologic therapy preoperatively, 3 received it both preoperatively and postoperatively, and 6 received it only postoperatively. The median time to initiation of postoperative biologic therapy was 48 days (range 25 to 110). Eleven patients are currently alive, 7 with no evidence of disease at a median follow-up of 17 months (range 6 to 66) and 4 with stable metastases at 14 months (range 4 to 22). Ten of the 13 symptomatic patients had improved performance scores after surgery. Four patients have died from metastatic disease: 2 from rapid progression at 2 and 5 months after surgery and the other 2 at 17 and 42 months. CONCLUSIONS: Nephrectomy and vena caval thrombectomy can be safely performed in selected patients with metastatic disease. Furthermore, in patients receiving biologic therapy, nephrectomy may enable a better quality of life and prolonged survival.

Evrim Bougie: a new instrument in the management of urethral strictures.

BACKGROUND: In this study a new instrument and technique is described for the endoscopic treatment of complete posterior urethral strictures, which may result in serious complications and sometimes require troublesome treatments. METHODS: Three patients with complete posterior urethral obstruction were treated endoscopically with the guidance of a new instrument: Evrim Bougie. Evrim Bougie looks like a Guyon Bougie, has a curved end, which facilitates getting into the bladder through the cystostomy tract and with a built in channel of 1.5 mm in diameter for a sliding needle exiting at its tip. Having confirmed fluoroscopically and endoscopically that the sliding needle had passed across the strictured segment, the strictured segment was incised with internal urethrotomy, distal to the strictured segment, and urethral continuity was accomplished. At the end of the operation a Foley urethral catheter was easily placed into the bladder per urethra. Patients were instructed in self-catheterization after removal of the urethral catheter. All patients achieved normal voiding at postoperative 7th month follow-up evaluation. CONCLUSION: Internal urethrotomy could be performed under the guidance of the sliding needle of Evrim Bougie advanced from above the posterior urethral strictures, which to our knowledge was described for the first time in the English literature. We also believe that there may be other possible indications of Evrim Bougie for different procedures in urethral surgery.

Collision metastasis of bladder and prostate carcinoma to a single pelvic lymph node.

Genitourinary organs are at greater risk for multiple primary malignant neoplasms because of the high incidence of these tumours as primaries among all other organs. We present a case of prostate and bladder carcinoma metastasized to a single pelvic lymph node, called a "collision" metastasis, in a patient with four primary tumours.

Comparison of screening of vesicoureteral reflux with renal ultrasound and voiding cystourethrography.

PURPOSE: To suggest a different method for diagnosing vesicoureteral reflux (VUR) in lieu of voiding cystourethrography (VCU), in order to prevent radiation exposure. MATERIALS AND METHODS: Fifty-two ureterorenal units of 26 patients were evaluated ultrasonographically for visualizing the renal collecting systems, both before and after filling up the bladder with saline infusion. Every patient also underwent evaluation with VCU. RESULTS: All patients with Grade 2 or higher degrees of VUR on VCU can be identified by ultrasound (USG). Overall sensitivity and specificity of this technique were 66.7% and 93.48%, respectively, in our patient group. CONCLUSION: After being diagnosed with VCU initially a VUR patient can be effectively followed up by USG in order to prevent radiation exposure. Considering the clinical management of a patient with Grade 1 VUR which could not be detected with USG, it is concluded that failure to detect Grade 1 VUR will not be a handicap.

Treatment of premature ejaculation with sertralin.

To evaluate the efficacy of oral sertralin in the treatment of premature ejaculation, out of 22 patients with premature ejaculation 16 received oral sertralin, 50 mg a day for at least 2 weeks. Four patients were lost to follow-up. Two patients interrupted treatment due to side effects of sertralin. Out of 16 patients who completed at least a two-week period of treatment 14 (87.5%) responded clinically. Clinical response was achieved in the first week of treatment in 11 of 16 responders (68.75%). We conclude that low dose oral sertralin may be useful with a reasonable side effect rate in the treatment of patients suffering from premature ejaculation.

Methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy for the treatment of advanced bladder carcinoma.

Thirteen patients with advanced urothelial transitional cell carcinoma were treated with methotrexate, vinblastine, adriamycin and cisplatin combination. No complete remissions were achieved in patients with disseminated diseases; only three out of five patients (60%) with localized tumours in the bladder or perivesical space responded completely. Localized tumour recurrences in the bladder occurred in two of three complete responders at the ninth and tenth months after chemotherapy. Four patients died during or after chemotherapy: one from disease progression and the remainder from chemotherapy complications. Authors conclude that, although 23% complete and 30.8% partial remissions were achieved with the MVAC chemotherapy, strict toxicity monitoring and careful selection of patients are essential because of its non-negligible complications.

Development of urethral stricture after transurethral prostatectomy: a retrospective study.

A total of 103 patients who were diagnosed to have benign prostatic hyperplasia (BPH) without preoperative urethral stricture and underwent transurethral prostatectomy (TURP) were evaluated retrospectively from patient charts. The incidence of urethral stricture development was calculated as 11.65% (12 out of 103 patients). Among the aetiologic factors analyzed, the most important ones appeared to be postoperative infection, age of the patient, duration of postoperative catheterization and histology of the disease, in the order of significance in the development of urethral stricture after TURP.