Videourodynamics in patients with neurogenic bladder due to multiple sclerosis: our experience.

PURPOSE: The aims of this study were to: (a) analyse the most frequent morphofunctional features of the lower urinary tract observed during videourodynamic examination in patients with neurogenic bladder due to multiple sclerosis; (b) investigate the role of the videourodynamic examination in the clinical management of these patients; and (c) demonstrate the relationship between morphological and functional variables. MATERIALS AND METHODS: We performed videourodynamic examinations in 75 patients affected by neurogenic bladder secondary to multiple sclerosis. RESULTS: The introduction of pharmacological therapy, based on clinical and functional evaluation of the lower urinary tract, is correlated with satisfactory morphofunctional outcomes, reducing moderate-to-severe postvoid residual (PVR; p < 0.1) and compliance (p < 0.05) at the price of reduced bladder sensation. Clinical management of these patients based on morphological evaluation of the lower urinary tract decreased the occurrence of detrusor-sphincter dyssynergy (DSD) and detrusor overactivity incontinence at the following examination. CONCLUSIONS: Our study confirmed a relationship between detrusor overactivity and hypertonic bladder, bladder diverticula, vesicoureteral reflux, between detrusor underactivity and PVR and between DSD and bladder diverticula. Our data show how the videourodynamic examination may improve evaluation and urological management of these patients.

Characterization of cells from invaded lymph nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphoproliferative response.

The specific immune response against the malignant cells was investigated in patients with urinary bladder or larynx cancer. Lymphocytes from lymph nodes that drain the tumor site were tested for their proliferative and cytotoxic capacities against autologous malignant cells isolated from the primary tumor. In no occasion was a proliferative or a cytotoxic response observed. However, when the lymph node cell suspensions were depleted of cells expressing both OKM1 and Leu-7 markers by rosetting with the appropriate mAbs, a proliferative response could be observed. The lymphocytes responded to autologous tumor cells only if IL-2 was added to the cultures. IL-2 alone induced some cell proliferation, which was not, however, comparable to that observed in response to both IL-2 and tumor cells. A panel of allogeneic tumor cells consistently failed to stimulate OKM1-, Leu-7- cells in vitro. Response to autologous tumor cells was not caused by HLA-encoded molecules, as occurs in the autologous mixed lymphocyte reaction, since OKM1-, Leu-7- cells failed to be stimulated by autologous non-T cells. A proliferative response was observed only with cells from lymph nodes that had been classified as invaded by malignant cells according to histopathologic criteria. Cells from noninvaded lymph nodes consistently failed to respond. Cells stimulated with autologous tumor cells could be expanded in short-term lines by continuous addition of IL-2 and malignant cells. One of these lines, which comprised mainly T8+ cells, was stimulated to proliferate only by autologous tumor cells, and its proliferative response was inhibitable by anti-class I and not by anti-class II mAbs. This line showed lytic capacities against autologous malignant targets, while it was inefficient against all of the other allogeneic cells tested. In another set of experiments, the mechanisms whereby exogenous IL-2 had to be added to the cultures to sustain a proliferative response against neoplastic cells were investigated. When cocultured with autologous malignant cells, OKM1-, Leu-7- lymphocytes expressed IL-2 receptors, as could be assessed by anti-Tac fluorescent staining. Under these culture conditions, these cells did not produce IL-2, and no proliferation was observed. Addition of purified IL-1 to the cultures induced IL-2 production and cell proliferation. It is concluded that metastatic lymph nodes contain a T cell population that can be detected in a proliferative assay when both suppressor cells are removed and the appropriate molecular signals are supplied.

C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer?

To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of c-myc and HIF-1α was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis. We found that high c-myc level was significantly associated with HIF-1α elevated expression (p = 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (p = 0.0005) of c-myc and HIF-1α expression levels, as we found in our series. Moreover, we found high c-myc levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (p = 0.01), with high Transketolase (TKT) expression (p < 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for c-myc, and with ERG increased expression (p = 0.02). Finally, samples with low GSTP1 expression displayed higher ERG mRNA levels than samples with high GSTP1 score (p < 0.0001), as above shown for c-myc. Our study emphasizes the notion of a potential value of HIF-1α and c-myc as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer.

p53 and Ki-67 expression in renal cell carcinomas of pregnant women and their correlation with prognosis: a pilot study.

In the present study, we reported two cases of renal cell carcinoma (RCC) diagnosed in pregnant women (Pt) that were submitted to radical nephrectomy, in both cases within the fourth month. The patients, after 13 and 3 years, respectively, did not show evidence of recurrent disease. We performed an immunohistochemical study on RCC specimens in comparison to seven age-matched controls (Cl). The panel of antibodies included Ki-67, p53, bcl-2, ER, PgR, PCNA, and IGF-1. We describe a difference in the expression of p53 and Ki-67. Specifically, p53 was highly expressed in RCC of both Pt but scarcely present or absent in Cl; by contrast, Ki-67 was hardly expressed or negative in RCC of both Pt, being commonly positive in Cl. These results may correlate with a good outcome of the disease in Pt. Although the limited number of cases did not permit any statistical evaluation, we postulate that these differences have not to be underestimated since they may disclose a correlation between pregnancy and biological behavior of tumoral disease. Further study may (dis)prove this hypothesis.

Testicular metastasis as isolated recurrence after radical prostatectomy. A first case.

Prostate cancer synchronously or metachronously metastasizing to the testis is a rare finding. We herein report on the first case of a solitary testicular metastasis from an organ-confined prostate cancer, diagnosed 6 months after a radical prostatectomy, without evidence of previous or concomitant biochemical and local recurrence.

Prulifloxacin versus levofloxacin in the treatment of chronic bacterial prostatitis: a prospective, randomized, double-blind trial.

Ninety-six patients with chronic bacterial prostatitis (CBP) and evidence of infection were randomized to receive a 4-week oral course of either prulifloxacin (a new fluoroquinolone) 600 mg or levofloxacin 500 mg once daily. They were evaluated with the Meares-Stamey test and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at baseline and one week after therapy completion. Patients with microbiological eradication were evaluated again with the Meares-Stamey test 6 months after therapy completion. The microbiological eradication rate was 72.73% for prulifloxacin and 71.11% for levofloxacin (p=0.86) and the reduction in the NIH-CPSI was 10.75 and 10.73, respectively (p=0.98). Safety was comparable, with 18.18% adverse events for prulifloxacin and 22.22% for levofloxacin (p=0.79). Thus, a 4-week course of prulifloxacin 600 mg once daily is at least as effective and safe as levofloxacin 500 mg once daily in the treatment of CBP.

Epistaxis after PDE-5 inhibitors misuse.

A 32-year-old male presented to our department for recurrent epistaxis during sexual intercourses. The patient controlled the bleeding each time with sponge packs and gauzes. During the consultation, he volunteered that the trigger for the epistaxis appeared to have been misuse of phosphodiesterase (PDE)-5 inhibitors, Viagra and Cialis. This first report of epistaxis after PDE-5 inhibitors in a young patient underline the possibility that in the next years the number of similar cases might increase due to the diffusion of PDE-5 inhibitor misuse in recreational settings.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Presence of activated T-cells with a T8+ M1+ Leu 7+ surface phenotype in invaded lymph nodes from patients with solid tumors.

The lymphocyte surface phenotype of lymph nodes from patients with larynx or urinary bladder carcinoma was investigated by using a panel of monoclonal antibodies. The phenotype pattern of lymphocytes from lymph nodes invaded by malignant cells (as assessed by histopathology) was different from that of the cells from noninvaded or normal control nodes. Although the proportion of natural killer cells or macrophages was similar in the 3 groups of lymph nodes, invaded lymph nodes contained a higher proportion of T-cells and a lower B-cell percentage. Furthermore, cells from invaded nodes comprised 15-20% of T3+ T8+ cells that coexpressed the M1 marker and, to some extent, also the Leu 7 marker. A large proportion of cells with multiple markers were activated, as shown by the expression of Tac and HLA-DR antigens. In 2 patients activated T8+ cells expressing also M1 and Leu 7 markers infiltrated the tumor site. The presence of these activated cells both in involved nodes and tumor mass may indicate that they originate in response to cancer.

Alterations of store-operated calcium entry and cyclopiazonic acid-induced endothelium-derived relaxations in aging rat thoracic aorta.

The purpose of our study was to investigate whether endothelium-derived relaxations induced by store depletion are altered in aging rat thoracic aorta. Vascular responses were measured in aortic segments isolated from young (2-4 month) and old (20-24 month) male Sprague-Dawley rats. In phenylephrine-contracted intact tissues, receptor-mediated and receptor-independent endothelium-derived relaxations were induced by acetylcholine (ACh) and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) blocker cyclopiazonic acid (CPA), respectively. In addition, CPA-induced changes in intracellular calcium levels were monitored in fura-2-loaded endothelium-denuded tissues. Real-time quantitative reverse transcription polymerase chain reaction and western blot analysis were performed to determine the transient receptor potential canonical (TRPC) 4 mRNA and protein levels. Endothelial TRPC4 mRNA levels were apparently decreased in aging rats. Immunoblot analysis showed that TRPC4 protein levels significantly decreased in intact aorta from 20- to 24-month-old rats compared to that from 2- to 4-month-old rats. ACh- and CPA-induced endothelium-dependent relaxations decreased in old rat aorta without any change in direct vasodilation induced by sodium nitroprusside. Store-operated Ca2+ entry (SOCE) induced by CPA was significantly decreased, whereas sarcoplasmic reticulum Ca2+ release was unaffected in endothelium-denuded aging rat aorta. In conclusion, TRPC4 downregulation could be associated with decreased endothelium-dependent vasorelaxations. As endothelial nitric oxide synthase is activated by SOCE-induced caveolar internalization, tracking the expression levels of SERCA, ion channels, and/or associated proteins involved in SOCE would lead to the development of novel therapeutics for age-related vasospastic disorders with dysfunctional endothelium.

Comparison of telomerase activity in bladder carcinoma and exfoliated cells collected in urine and bladder washings, using a quantitative assay.

Telomerase activity was measured with a quantitative assay, based on a modification of telomeric repeat amplification protocol method, in bladder cancers and apparently normal mucosa in 33 patients. In the same patients, the enzyme was also measured in exfoliated cells collected both with voided urine and bladder washings. Results obtained in urine were compared with those from 20 healthy subjects. Telomerase activity was present in 31 (94%) bladder cancer tissues and in 23 (72%) apparently normal mucosa samples. However, the levels of enzyme activity were significantly higher in cancer tissues in comparison with normal mucosa (mean +/- SD, 47.3 +/- 23.2 and 14.9 +/- 6.1 ng DNA/microg protein, respectively; P < 0.0001). Telomerase activity in bladder cancer tissues was not related to tumor stage and grade. Enzyme activity was present in 27 urine samples and in 27 (82%) bladder washings collected from cancer patients. We did not find correlation between the activity in urine and washings, and their mean levels were not different (22.2 +/- 10.1 and 20.7 +/- 8.0, respectively). Telomerase activity in bladder cancer tissues was correlated to its activity in urine (r = 0.650, P < 0.001) and in bladder washings (r = 0.410, P < 0.05). Only 2 of 20 urine samples from control subjects were found to express telomerase activity at a very low level. This was the first attempt to correlate telomerase activity in exfoliated cells from urine and bladder washings with the activity in corresponding bladder cancers. According to these results we postulate that telomerase activity in urine sediment reflects the activity in bladder cancers better than bladder washings and, for its easy collection, is to be preferred as diagnostic marker in this tumor.

Role of pharmacologic rehabilitation in the recovery of sexual function following radical prostatectomy.

AIM: The aim of the present study is to evaluate the role of pharmacological postoperative sexual rehabilitation in the recovery of erectile function following radical retropubic prostatectomy. METHODS: Following radical retropubic prostatectomy 113 patients were divided into 2 groups: 77 (group 1) underwent pharmacologic rehabilitation with intracavernous PGE1 starting with 5 mg once or twice weekly beginning 1 month after surgery, followed by oral sildenafil 50-100 mg twice a week after recovery of spontaneous erections, while 36 (group 2) acted as controls. The 2 groups were homogeneous for age and preoperative IIEF5 score, while nerve-sparing techniques were used more frequently in group 1. RESULTS: With 1 year follow-up 42% of group 1 patients have recovered sexual function, versus 8% of group 2 (P < 0.001). The mean recovery time was 7 months, and 56% of rehabilitated patients with bilateral preservation of the neurovascular bundles recovered sexual function, compared to 37.5% of those with unilateral preservation and 28.5% of those operated with non nerve-sparing technique. Intracavernous PGE1 caused pain in 27% of cases. CONCLUSIONS: Pharmacologic rehabilitation significantly impacts on the recovery of sexual function following radical prostatectomy, and the optimal treatment schedule is still to be defined.

Dopamine D2 receptor gene expression and binding sites in adrenal medulla and pheochromocytoma.

To determine whether dopamine D2 receptors are present in normal and neoplastic chromaffin tissues, 10 pheochromocytomas and 5 human adrenal glands were studied. Dopamine D2 receptor messenger ribonucleic acid corresponding to a single band of approximately 2.5 kilobases was detected in both pheochromocytoma and human adrenal gland by Northern blot analysis. D2 receptor messenger ribonucleic acid levels determined by dot blot analysis were 3.1-fold lower in human adrenal medullas than in pheochromocytomas (P < 0.001). Simultaneous Scatchard analysis of [3H]spiperone binding experiments demonstrated the presence of two different binding sites in membrane preparations from bovine adrenal medullas [R1: Kd = 0.14 nmol/L; binding capacity (Bmax) = 6.2 fmol/mg protein: R2: Kd = 16 nmol/L; Bmax = 223 fmol/mg protein]. Similarly, two binding sites were present in membrane preparations from pheochromocytomas (R1: Kd = 0.39 nmol/L; R2: Kd = 61 nmol/L]. Binding capacities were greatly variable among pheochromocytomas (R1: Bmax = 12.0-372.5 fmol/mg protein; R2: Bmax = 1,000-11,586 fmol/mg protein). The relative potencies of different compounds to displace [3H]spiperone were spiperone > domperidone > (+)-butaclamol > quinpirole > SCH 23390 in bovine adrenal medulla, and spiperone >> domperidone > quinpirole > (+)-butaclamol > SCH 23390 in pheochromocytoma. We conclude that dopamine D2 receptors are synthesized in human adrenal medulla and pheochromocytoma tissues.

Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP-4 in human prostatic hyperplastic tissue: gene expression and its cellular localization.

It has been previously reported that 1) type I insulin-like growth factor (IGF) receptors are present in the human prostatic tissue; 2) IGF-I receptors are mainly localized in the epithelial cells; 3) IGF-I is a mitogen for prostatic epithelial cells in culture; and 4) IGF-binding proteins (IGFBPs) are released by these cells in the conditioned medium. To add information on the mechanism of IGF-I action in the human prostate, we studied the expression and cellular localization of mRNA encoding IGF-I and IGFBP-4 in human prostatic hyperplastic (BPH) tissue. Northern analysis of total RNA extracted from BPH tissues with cDNA probes containing the entire coding regions for IGF-I and IGFBP-4 documented the presence of multiple IGF-I mRNA transcripts with lengths of 7.5, 1.7, 1.3, and 1.1 kilobases and a single 2.1-kilobase transcript of IGFBP-4 mRNA. In situ hybridization with the cDNA probes used for Northern analysis and with cRNA probes synthesized from the respective cDNA demonstrated that IGF-I mRNA was only localized in the stromal cells, whereas IGFBP-4 mRNA was predominantly expressed by epithelial cells. In addition, immunoreactive IGF-I was measured in BPH tissue extracts after acidification and reverse phase chromatography. The mean (+/- SD) IGF-I content of six BPH tissues was 28.1 +/- 4.0 ng/g tissue. Our results suggest that in the human prostate, the locally secreted IGF-I exerts its principal biological effects with a paracrine mode of action and demonstrate that IGFBP-4 is mainly expressed by IGF-I target cells.

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Surgical treatment of retroperitoneal fibrosis with omentoplasty.

The main goal of surgery for retroperitoneal fibrosis is to free the ureters from sclerotic tissue and pressure them from further extension of the disease; the omentum may be used as an efficient barrier against recurrence of fibrosis. We present 11 patients with idiopathic retroperitoneal fibrosis treated with ureterolysis and omentoplasty - in four patients the procedure was performed bilaterally, in seven the omentum was used to protect only one ureter, but in six there was a surgical or functional solitary kidney. Out of 15 ureters, residual dilatation was observed only in two, with marked clinical improvement in all patients. Mean follow-up was 51 months.

Bladder carcinoma arising from regenerated urothelium over lyophilized dura patch.

Lyophilized human dura was used for augmentation cystoplasty in a woman who had a scarred bladder because of multiple resections and fulgurations of superficial bladder tumors. Thirty months later, two sessile tumors developed from the urothelium regenerated over the dura patch, together with infiltrating recurrences elsewhere in the bladder, and a radical cystectomy was performed. This case supports the concept that implantation of tumor cells is a factor in the recurrence of superficial bladder carcinoma.

Recurrent reflux caused by vesicoureteral fistula.

We present an unusual case of recurrent reflux on the right side after bilateral vesicoureteroplasty with modified Hutch I technique.

Retrovesical echinococcal cyst causing acute urinary retention.

A case report of a fifty-six-year-old man with acute urinary retention due to a retrovesical echinococcal cyst is presented. He had a history of surgery for hepatic hydatidosis; diagnosis was made preoperatively with the help of conventional x-ray studies, pelvic sonography, and CT scanning. Treatment consisted of removal of the cyst.

Late intrascrotal metastases from renal cell carcinoma.

A case of bilateral epididymal metastases appearing sixteen years after nephrectomy for renal cell carcinoma is reported. A literature review of intrascrotal metastases from renal cancer reveals that they are uncommon. The possible mechanisms of spread are discussed.