Cell Cycle Markers in the Evaluation of Bladder Cancer.

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

Immunohistochemistry Biomarkers in Nonmuscle Invasive Bladder Cancer.

Bladder cancer (BCa) is the most frequent urinary tract neoplasm. BCa results in significant mortality when the disease presents as muscle invasive. Around 75% to 80% of patients present with nonmuscle invasive bladder cancer (NMIBC), but recurrence and progression are significant issues, compelling current guidelines to recommend long-term surveillance. There is therefore an urgent and unmet need to identify and validate accurate biomarkers for the detection of disease recurrence to improve quality of life for the patients and reduce costs for health care providers, while maintaining or improving current outcomes. In this review, 38 publications on immunohistochemistry prognostic biomarkers, that were studied may be related in nonmuscle invasive bladder cancer, have been analyzed. The studies were organized according to the evaluated marker and their findings. It was demonstrated that the combination of independent complementary biomarkers could allow a more accurate prognosis than an isolated marker. Biomarkers, including p53, Ki-67, and CK20, with classic and prognostic factors with recurrence and novel markers such as EN2 may provide a more accurate prediction of outcome compared with any single marker, improving risk stratification and clinical management of patients with BCa.

Magnetic spheres as foreign body into the bladder.

INTRODUCTION: A great variety of foreign bodies in the lower urinary tract have been described; many of them are self-inflicted by the patient with masturbatory purposes. Depending on the nature of the foreign body the diagnostic and management might be challenging. AIMS: We report a case of an unusual magnetic self-inserted foreign body into the bladder for autoerotism and briefly discuss the diagnostic and therapeutic implications in this challenging situation. METHODS: We describe all the steps we have used to adequately diagnose the problem, describe the foreign body and treatments for the patient. Related articles were found by utilizing the PubMed database and are summarized in this study. RESULTS: The management approach must be planned according to the nature of the foreign body and should minimize bladder and urethral trauma. However, most of cases can be managed endoscopically. CONCLUSION: Removal of magnetic foreign body may be quite challenging, requiring high-level surgical skills and minimally invasive techniques resulting in fast recovery and low complication rate.

Long-term follow-up of penile curvature correction utilizing autologous albugineal crural graft.

PURPOSE: Peyronie 's disease is an acquired connective tissue disorder of the penile tunica albuginea with fibrosis and inflammation. The disease produces palpable plaques, penile curvature and pain during erections. Usually it results in impairment of the quality of life. Our objective is to review the long-term results of the albugineal grafting harvested from the penile crura for the treatment of severe penile curvature. MATERIALS AND METHODS: Thirty-three patients with Peyronie 's disease were submitted to a grafting with tunica albuginea from the penile crura for the correction of penile curvature. The results were evaluated after 6 months of the procedure. Variables studied were overall satisfaction with the procedure, correction of the penile curvature, erectile capacity, penile shortening and the presence of surgical complications. RESULTS: Mean follow-up after surgery was 41 months. Complete correction of the curvature was achieved in 30 patients (90%). The mean preoperative curvature was 91.8 degrees and median plaque length was 2 cm (ranged from 1 to 5 cm). Three patients (9%) experienced recurrence of the penile curvature and required a new procedure. In 30 men (90%) the procedure fulfilled their expectations and in 31 patients (93.9%) their opinions were that sexual partners were satisfied with the penile correction. Penile shortening or augmentation was referred in 6 (18.1%) and 1 (3%) patient, respectively. CONCLUSION: Our series demonstrated that grafting the albugineal defect after incision of the tunica albuginea with tunica from the crus for the correction of penile curvature is safe and results in satisfactory straight erections during along-term follow-up.

Long-term follow-up of penile curvature correction utilizing autologous albugineal crural graft

PURPOSE: Peyronie's disease is an acquired connective tissue disorder of the penile tunica albuginea with fibrosis and inflammation. The disease produces palpable plaques, penile curvature and pain during erections. Usually it results in impairment of the quality of life. Our objective is to review the long-term results of the albugineal grafting harvested from the penile crura for the treatment of severe penile curvature. MATERIALS AND METHODS: Thirty-three patients with Peyronie's disease were submitted to a grafting with tunica albuginea from the penile crura for the correction of penile curvature. The results were evaluated after 6 months of the procedure. Variables studied were overall satisfaction with the procedure, correction of the penile curvature, erectile capacity, penile shortening and the presence of surgical complications. RESULTS: Mean follow-up after surgery was 41 months. Complete correction of the curvature was achieved in 30 patients (90%). The mean preoperative curvature was 91.8 degrees and median plaque length was 2 cm (ranged from 1 to 5 cm). Three patients (9%) experienced recurrence of the penile curvature and required a new procedure. In 30 men (90%) the procedure fulfilled their expectations and in 31 patients (93.9%) their opinions were that sexual partners were satisfied with the penile correction. Penile shortening or augmentation was referred in 6 (18.1%) and 1 (3%) patient, respectively. CONCLUSION: Our series demonstrated that grafting the albugineal defect after incision of the tunica albuginea with tunica from the crus for the correction of penile curvature is safe and results in satisfactory straight erections duringa long-term follow-up.

Rastreamento e diagnóstico de câncer de próstata / Screening and diagnosis of prostate cancer

Não existem até o momento provas contundentes que a população coberta pelo plano de saúde UNIMED-POA deva ser submetida ao rastreamento sistemático do câncer de próstata com o intuito de reduzir a mortalidade decorrente deste tipo de câncer, uma vez que não existem estudos desenhados no Estado do Rio Grande do Sul que contemplem este aspecto. Recentemente, dois grandes estudos randomizados que visavam a esclarecer se o rastreamento populacional poderia reduzir a mortalidade por câncer de próstata concluíram: em estudo realizado nos Estados Unidos (prostate, lung, colorectal and ovary trial), não houve diferença na mortalidade da população rastreada ou não; no estudo europeu (European randomized of screening for prostate cancer), houve uma redução de 20 por cento da mortalidade da população rastreada em relação à não rastreada. Cabe ressaltar que ambos os estudos apresentaram, entre outros problemas, viés de seleção dos pacientes, onde mais de 50 por cento do grupo teoricamente não rastreado efetivamente realizou exames antes ou durante o estudo. Sendo assim, permanece recomendada realização de rastreamento nas diretrizes da Associação Americana de Urologia, Associação Europeia de Urologia e Sociedade Brasileira de Urologia.

So far, there is no compelling evidence that the local population covered by the health plan UNIMED-POA should be submitted to systematic screening for prostate cancer in order to reduce mortality resulting from this type of cancer, as no studies in Rio Grande do Sul have been performed to address this particular issue. In other countries, two large randomized studies aimed at clarifying whether such screening could reduce mortality from prostate cancer were conducted recently: the prostate, lung, colorectal and ovary trial in the United States, and the European randomized screening for prostate cancer. In the former, there was no difference in mortality between screened and non-screened groups; in the latter there was a 20 percent reduction in mortality in the screened as compared to the non-screened group. It should be highlighted that both studies had many design problems including biased selection of patients, as more than 50 percent of the supposedly non-screened group was in fact submitted to medical tests either before or during the trial. Therefore, screening still should be performed according to the guidelines of the American Association of Urology, European Association of Urology and the Brazilian Society of Urology.

Overactive bladder: prevalence and implications in Brazil.

OBJECTIVES: To assess overactive bladder (OAB) prevalence, associated factors and implications in a young population. METHODS: An independent population-based study was carried out. A self-applicative questionnaire covering urinary symptoms, coping strategies, quality of life and treatment seeking behavior was developed. RESULTS: A total of 848 subjects between 15 and 55 years completed the questionnaire. The overall prevalence of OAB was 18.9%. Women were significantly more affected than men (p = 0.001). All age groups were equally affected (p = 0.152). Subjects with OAB reported significant impairment on household chores (p = 0.009), physical activities (p = 0.016), sleep (p < 0.001), work (p < 0.001), social life (p < 0.001) and sexual life (p < 0.001). In addition, OAB individuals present higher prevalence of depression (p = 0.036), anxiety (p < 0.001), shame (p < 0.001) and tiredness (p < 0.001) OAB was independently associated to sexual life impairment (OR = 3.36, 95% CI=1.20-9.39). Only 27.5% of OAB subjects sought for medical counseling. CONCLUSIONS: OAB is a highly prevalent condition, even in such a young population. It affects both genders, yet it is more frequently observed in women. OAB is an important health condition, with serious impact on quality of life and sexual function. A large percentual of individuals remain unrecognized, under treated and consequently suffer for long periods of time.

Laparoscopic prostatectomy for benign prostatic hyperplasia--a six-year experience.

PURPOSE: The Authors present their results using laparoscopic prostatectomy in the treatment of large benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Between March 1999 and March 2005, 60 patients were submitted to laparoscopic prostatectomy with vascular control for large BPH. The demographic, operative period and outcome data were recorded. RESULTS: The average prostate weight was 144.50+/-41.74 gm. Mean operative time was 138.48+/-23.38 minutes and estimated blood loss of 330.98+/-149.52 ml. No patient required transfusions or conversion to open surgery. Post operative complications included one case of septicemia and three cases of prolonged ileum. The most frequent long-term complication was retrograde ejaculation, presented in all patients after 6 months of follow-up. The erectile function was preserved in all those patients who were potent before surgery. No urinary incontinence was reported by patients. CONCLUSIONS: The results demonstrate that resection of large prostatic adenomas can be performed with a laparoscopic approach. The patients had a shorter hospital stay and early return to normal activity.

Low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy: hypogonadism represents bad prognosis in prostate cancer.

PURPOSE: It has been reported that more aggressive prostate cancer (PC) can be associated with low serum testosterone levels. The relationship between serum androgens and PC is still not completely understood. In this study we examined the association of prognostic factors in men who underwent radical retropubic (RRP) prostatectomy with low or normal total testosterone. MATERIALS AND METHODS: We retrospectively evaluated 64 consecutive patients with localized PC treated with RRP between July 2002 and November 2003. PC was diagnosed by transrectal ultrasonography guided biopsy performed for either a suspicious digital rectal examination or serum prostate specific antigen greater than 4.0 ng/ml. Gleason score was determined in prostatic biopsies. Pathological TNM staging (1997), capsular perforation, seminal vesicle involvement and surgical margin status were determined in all surgical specimens. The threshold for serum total testosterone was 270 ng/dl. In all analyses p <0.05 was considered statistically significant. RESULTS: There were no statistically significant differences among prostate specific antigen, Gleason score (biopsy or specimen), pathological stage, capsular perforation and seminal vesicle involvement. However, patients with low total testosterone had increased positive surgical margins (p = 0.026). CONCLUSIONS: Patients with low total testosterone more frequently present with positive surgical margins in RRP specimens. The true association between low testosterone and poor clinical outcome in the long term needs validation in large prospective studies.

Long-term effect of ovariectomy and simulated birth trauma on the lower urinary tract of female rats.

PURPOSE: Using an animal model we studied the long-term effects of ovariectomy and simulated birth trauma in the development of apoptosis as well as the urodynamic, histological and ultrastructural findings 9 months after such procedures. MATERIALS AND METHODS: A total of 24 pregnant Sprague-Dawley female rats were used. Immediately after delivery 14 animals underwent vaginal ballooning and ovariectomy, while the remaining 10 served as controls. At 9 months the animals underwent urodynamic evaluation, which included the urethral pressure profile. The rats were then sacrificed and urogenital tissue was obtained for immunostaining using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling, histomorphometry evaluation and electron microscopy. RESULTS: Immunostaining demonstrated a significant increase in the apoptotic index in the urethra of castrated/ballooning rats with a predominance in the submucosa layer. Maximum urethral closure pressure was significantly lower in that group, although there was no correlation of apoptosis with maximum urethral closure pressure measurement. Urodynamic evaluation revealed only discrete alterations in cystometric parameters. Morphometric evaluation showed increased connective tissue in the vagina. Electron microscopy of urethral smooth muscle demonstrated altered cellular shape, increased intercellular space with collagen deposition and some degeneration of the mitochondria. CONCLUSIONS: Apoptosis in the urethra occurs 9 months after castration and simulated birth trauma. However, this finding was not seen in the muscle layers or in other urogenital tissues. Some ultrastructural changes also occurred that may explain some symptoms that women have after vaginal childbirth and menopause.

Long-term survival of autotransplanted major pelvic ganglion in the corpus cavernosum of adult rats.

PURPOSE: Neurogenic impotence is a common complication after radical pelvic surgery, irradiation or perineal trauma. Neuronal transplantation is a new frontier for treating neurological disorders. We investigated whether the major pelvic ganglion can survive and become functional after being implanted into the corpus cavernosum in adult rats. MATERIALS AND METHODS: Adult male rats (13) were divided into 3 groups and sacrificed at 3 time points, namely 30 (4), 60 (5) and 90 (4) days. All rats underwent excision of the right major pelvic ganglion and left cavernous nerve. The right ganglion was implanted into the right crus of the penis. Electrostimulation was applied to the left major pelvic ganglion and cavernous nerve (1.5 mA.) and right crus (10 mA.) at sacrifice. The crural region and left ganglion were then excised for immunostaining of neuronal nitric oxide synthase (nNOS), protein gene product 9.5 and growth associated protein 43. Image analysis was used to calculate the area stained in pixels. Electron microscopy of the implanted area was performed to assess neuronal survival. RESULTS: Although the degree varied, all neuronal implants survived after transplantation. The response to electrostimulation was insufficient to produce erection. No difference was noted among the areas of nNOS staining when specimens from the 3 time points were compared. The area of expression of nNOS, protein gene product 9.5 and growth associated protein 43 was larger in the implanted area than in the surrounding cavernous tissue. Under electron microscopy most surviving implants showed normal ultrastructure, although areas of fibrotic replacement were seen in several implants. CONCLUSIONS: Our results show that the autotransplanted major pelvic ganglion expresses nNOS, protein gene product 9.5 and growth associated protein 43, and survived up to 90 days after implantation into the corpus cavernosum. Further studies with fetal neuronal tissue seem warranted.

The effect of vascular endothelial growth factor on a rat model of traumatic arteriogenic erectile dysfunction.

PURPOSE: We tested the hypothesis that intracavernous injection of vascular endothelial growth factor (VEGF) can restore erectile function in a rat model of traumatic arteriogenic erectile dysfunction. MATERIALS AND METHODS: Exploration of bilateral internal iliac arteries was performed in 50, 3-month-old male rats. A total of 44 rats underwent bilateral ligation of the internal iliac arteries and 6 that underwent exploration only served as the sham operated group. Minutes later intracavernous injection of phosphate buffered saline (PBS) plus bovine serum albumin in 16 rats, 2 microg. VEGF plus PBS plus BSA in 12 and 4 microg. VEGF plus PBS plus BSA in 16 was performed. At weeks 1, 2 and 6 about a third of the rats in each group underwent electrostimulation of the cavernous nerves to assess erectile function and were then sacrificed. Penile tissues were collected for histochemical and electron microscopy examinations. RESULTS: No impairment of erectile function was noted in sham operated rats. Immediately after arterial ligation all rats showed little or no erectile response to neurostimulation. In PBS treated rats modest recovery of erectile function was noted at week 6. Significant recovery of erectile function was noted in VEGF treated rats at weeks 1 and 2 in the 4 microg. group only and at week 6 in the 2 and 4 microg. groups. Neuronal nitric oxide synthase staining showed a reduction in neuronal nitric oxide synthase positive nerve fibers in the dorsal or intracavernous nerves at week 1. Moderate recovery of neuronal nitric oxide synthase positive nerve fibers was noted in the 2 and 4microg. VEGF treated groups but not in the PBS treated group. Electron microscopy revealed no pathological change in sham operated rats. In dorsal nerves the atrophy of myelinated and nonmyelinated nerve fibers was noted in ligated plus PBS treated rats. Partial recovery was observed in VEGF treated rats. Scattered atrophic smooth muscle cells were seen in PBS and occasionally in VEGF treated rats but not in the sham operated group. The most dramatic findings in VEGF treated rats were hypertrophy and hyperplasia of the endothelial cells, especially those lining the small capillaries. CONCLUSIONS: Ligation of bilateral internal iliac arteries produced a reliable animal model of traumatic arteriogenic erectile dysfunction. Intracavernous injection of VEGF minutes after arterial ligation facilitated the recovery of erectile function.