Age-related erectile and voiding dysfunction: the role of arterial insufficiency.
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Arteriosclerosis↗
Biomedical subjects
R J Krane
Publications and source records attributed to R J Krane.
A possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity.
PURPOSE: Digoxin use has long been recognized to affect adversely male sexual function but the underlying mechanism is poorly understood. Digoxin is a known inhibitor of sodium/potassium adenosine triphosphatase (sodium pump), a plasma membrane enzyme that has a role in the regulation of smooth muscle tone. We investigated the effects of digoxin on human corpus cavernosum smooth muscle contractility and overall erectile function. MATERIALS AND METHODS: In human corporeal smooth muscle strips the in vitro effects of digoxin were assessed on sodium pump activity as measured by digoxin inhibitable uptake of 86rubidium, basal tone and endothelium dependent, neurogenic and nitric oxide donor induced relaxation. An in vivo prospective double-blind, placebo controlled, crossover, 4-period investigation was performed in 6 healthy male volunteers. The effects of digoxin on serum hormones, erectile function questionnaire, visual sexual stimulation and nocturnal penile tumescence were recorded. RESULTS: In vitro digoxin caused concentration dependent inhibition of 86rubidium uptake (half maximum effect at 0.01 microM.) and contraction of corporeal smooth muscle (half maximum effect at 0.8 microM.). Therapeutic concentrations of digoxin (2 nM.) also inhibited relaxation induced by acetylcholine and electrical field stimulation, which release nitric oxide from corpus cavernosum endothelial cells and nonadrenergic noncholinergic nerves, respectively. In vivo digoxin diminished penile rigidity during visual sexual stimulation and nocturnal penile tumescence testing compared to placebo without influencing libido or serum testosterone, estrogen or luteinizing hormone levels. CONCLUSIONS: Digoxin associated alteration of human erectile function may be explained, in part, by inhibition of corporeal smooth muscle sodium pump activity, which promotes contraction and impedes nitric oxide induced relaxation. Such findings suggest therapeutic use of digoxin for treatment of recurrent priapism states.
Adenosine Triphosphate↗
Mechanisms of ischemia-induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction.
PURPOSE: To determine the effects of hypercholesterolemia and atherosclerosis-induced chronic cavernosal arterial insufficiency on cavernosal smooth muscle tone, nitric oxide synthase (NOS) activity and cavernosal tissue synthesis of constrictor eicosanoids. To study whether inhibition of the cyclooxygenase pathway by indomethacin and tissue treatment with nitric oxide (NO) precursor L-arginine improve hypercholesterolemia and ischemia-induced impaired endothelium-dependent and neurogenic relaxation of cavernosal tissue. MATERIALS AND METHODS: New Zealand White rabbits were divided into control (n = 10, fed a regular diet), hypercholesterolemia (Hch, n = 13, fed a diet containing 0.5% cholesterol) and chronic cavernosal ischemia (CCI, n = 14) groups. The CCI group underwent balloon deendothelialization of iliac arteries and received a diet containing 0.5% cholesterol. After 16 weeks, we examined the effects of Hch and balloon de-endothelialization induced arterial occlusive disease on iliac arterial blood flow, reactivity of cavernosal tissue, cavernosal NOS activity and cavernosal tissue synthesis of constrictor eicosanoids. RESULTS: Histology revealed significant atherosclerotic arterial occlusive disease in the CCI group. Iliac artery blood flow in the CCI group was significantly reduced compared with the control and Hch groups. In the Hch and CCI groups, endothelium-dependent relaxation of cavernosal tissue to acetylcholine was significantly reduced compared with the control group. Electrical field stimulation-induced neurogenic relaxation and cavernosal NOS activity were significantly reduced in the CCI group but not in the Hch group. The basal release of cavernosal constrictor eicosanoids, prostaglandin F2alpha (PGF2alpha) and thromboxane A2 (TXA2) was significantly increased in the CCI group. Indomethacin increased endothelium-dependent relaxation in all groups and neurogenic relaxation in the CCI group, but failed to normalize the differences in relaxation between treated and control groups. In the presence of indomethacin, L-arginine improved endothelium-dependent relaxation of cavernosal tissue in the Hch group but did not normalize endothelium-dependent or neurogenic relaxations in the CCI group. Relaxation to NO donor sodium nitroprusside and papaverine was similar in cavernosal tissue from all groups. CONCLUSIONS: Impairment of endothelium-dependent relaxation by Hch occurs secondary to disruption of the NO formation in cavernosal endothelium. Improvement of endothelium-dependent relaxation by L-arginine may suggest lack of availability of L-arginine in cavernosal tissue from the Hch animals. Impairment of endothelium-dependent and neurogenic relaxation by CCI occurs secondary to disruption of the NO formation due to an alteration in the expression or activity of NOS and increased output of constrictor eicosanoids in cavernosal tissue. These studies show that Hch and atherosclerosis-induced chronic cavernosal arterial insufficiency, beyond decreasing cavernosal perfusion pressure, also adversely affect smooth muscle relaxation mechanisms in cavernosal tissue.
Animals↗
Sexual dysfunction associated with the management of prostate cancer.
Improvements in the management of prostate cancer have increased the need to consider patients' quality of life, in particular in relation to sexual function. The causes of sexual dysfunction are varied and derive from both the condition and its management. Health professionals must choose their treatment strategies with great care. Patient expectations must be understood, and patients should be offered counselling, as an understanding of what can reasonably be expected contributes to patients' perception of their quality of life. There are few studies on sexual dysfunction in patients with prostate cancer. A first step would be to develop reliable questionnaires for the assessment of the problem. This article describes and discusses the findings of one such recently developed questionnaire. When baseline measures of sexual function have been established and the extent of sexual dysfunction in patients with prostate cancer is reliably quantified, large multicentre trials can be performed to evaluate the impact of different therapies on sexual function and quality of life. Sexual dysfunction is an area which will be of increasing importance to urologists who manage prostate cancer and one that should not be underestimated.
Aged↗
Intracavernosal forskolin: role in management of vasculogenic impotence resistant to standard 3-agent pharmacotherapy.
PURPOSE: We investigated forskolin, a direct adenylate cyclase activator, as an intracavernosal vasoactive agent in management of vasculogenic impotence. MATERIALS AND METHODS: Concentration responses for forskolin and prostaglandin E1 induced relaxation of phenylephrine precontracted strips of human corpus cavernosum smooth muscle were constructed in vitro. Cyclic adenosine monophosphate (cAMP) synthesis was determined with papaverine, phentolamine, prostaglandin E1 and forskolin in human corpus cavernosum smooth muscle cell cultures. Dose-dependent hemodynamic responses to intracavernosal forskolin (5 to 20 micrograms) were evaluated in a New Zealand White rabbit model. Safety and efficacy outcome data were obtained in vasculogenically impotent patients who signed informed consent and met strict inclusion and exclusion criteria that included having had standard self-injection therapies fail. RESULTS: In vitro forskolin and prostaglandin E1 alone caused concentration dependent relaxation with an EC50 of approximately 200 nm. and 16 nm., respectively. When the 2 agents were combined, the concentration response curve for relaxation shifted to the left. cAMP production was highest in cells treated with prostaglandin E1 and forskolin and was unaffected by papaverine or phentolamine. In 3 animals, equilibrium intracavernosal pressure and duration of erection had a dose dependent increase. Clinical investigation in 31 patients showed no adverse events with a mean of 14 +/- 4, range 11 to 18 months of followup. Overall 61% reported improvement in rigidity and/or erection duration using intracavernosal forskolin (98 micrograms./ml.), papaverine (29 mg./ml.), phentolamine (0.98 mg./ml.) and prostaglandin E1 (9.8 micrograms./ml.). CONCLUSIONS: Forskolin is a United States Food and Drug Administration nonapproved vasoactive agent that acts in synergism with prostaglandin E1 to induce smooth muscle relaxation. In combination with other vasoactive agents, forskolin has demonstrated preliminary safety and efficacy in patients with vasculogenic impotence resistant to standard 3-agent pharmacotherapy.
Alprostadil↗
Schistosomal myelopathy as a cause of neurogenic bladder dysfunction.
Schistosoma hematobium most commonly affects the bladder and S. mansoni has a predilection for the liver, spleen, and the mesenteric territories. Schistosomal spinal cord involvement is an extremely unusual primary presentation of schistosomiasis, especially in the United States. We report 2 patients with documented schistosomiasis who presented with urinary incontinence as their chief urologic complaint. One patient had no sensorimotor deficit and presented with isolated incontinence as the harbinger of spinal involvement. The other patient presented 5 years after initial exposure, emphasizing the possibility of a long latent period between exposure and onset of symptoms.
Adult↗
Vasculogenic female sexual dysfunction: the hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency.
OBJECTIVE: Organic female sexual dysfunction may be related in part to vasculogenic impairment of the hypogastric-vaginal/clitoral arterial bed. The aim was to develop an animal model of vaginal engorgement insufficiency and clitoral erectile insufficiency. METHODS: Pelvic nerve stimulated vaginal engorgement and clitoral erection were achieved in control (normal diet, n = 8) and atherosclerotic (balloon injury of aorto-iliac arteries and 0.5% cholesterol diet, n = 7) New Zealand White female rabbits. After 16 weeks, novel hemodynamic variables including vaginal wall and clitoral blood flow, vaginal wall and clitoral intracavernosal pressure, vaginal length, vaginal luminal pressure, blood levels of cholesterol and triglycerides, aorto-iliac angiography and vaginal wall and clitoral erectile tissue histology were recorded in the two groups. RESULTS: Concerning pelvic nerve stimulated vaginal hemodynamic changes, there was significantly less increase in blood flow (ml/min/100 gm tissue), wall pressure (mmHg) and length changes (mm) in atherosclerotic (9.3 +/- 3.7, 4.8 +/- 3.8, 67.3 +/- 8.3) compared to control (13.9 +/- 4.5, 5.5 +/- 2.6, 74.1 +/- 10.0) animals respectively. Histologic examination of clitoral erectile tissue demonstrated cavernosal artery atherosclerotic changes and diffuse vaginal and clitoral fibrosis. Aorto-iliac angiography in atherosclerotic animals revealed diffuse moderate to severe atherosclerotic occlusion. CONCLUSIONS: Vaginal engorgement and clitoral erection depend on increased blood inflow. Atherosclerosis is associated with vaginal engorgement insufficiency and clitoral erectile insufficiency.
Adrenergic alpha-Antagonists↗
Safety and efficacy outcome of mentor alpha-1 inflatable penile prosthesis implantation for impotence treatment.
PURPOSE: We investigated safety and efficacy outcome pertaining to the Mentor Alpha-1, 3-piece inflatable penile prosthesis for impotence treatment. MATERIALS AND METHODS: A 2-phase, multi-institutional, large scale retrospective study, with independently analyzed medical record (phase I) and questionnaire (phase II) data from consecutive eligible patients of 7 physician investigators was performed from March to October 1993. RESULTS: In phase I there were no morbidities of any type in 394 of the 434 patients (90.8%) (mean age 61 years, range 24 to 88) who underwent Alpha-1 implantation (mean followup 22.2 months, range 0.67 to 44.5). The risk of prosthesis malfunction (fluid leak and auto-inflation) was 2.5%. No cylinder aneurysms were reported. A total of 93.1% of Alpha-1 devices was free from explantation (4.4%) or revision surgery (2.5%) for approximately 2 years from the original implant date. Kaplan-Meier actuarial analyses revealed that cumulative survival of the Alpha-1 prostheses at 12, 24 and 36 months was 98 +/- 1%, 93 +/- 2% and 85 +/- 7% until device malfunction, and 91 +/- 2% 83 +/- 4% and 75 +/- 7% until surgical intervention (revision or explantation). In phase II 89% of the men claimed fulfilled expectations with the Alpha-1 prosthesis as impotence treatment. Satisfaction responses 80% or greater were noted with regard to intercourse ability and confidence, and device rigidity and function. Implantation did not result in greater than 80% satisfaction in partner relationships or feelings (as judged by the patient), social or work confidence, or intercourse frequency. Factors adversely affecting satisfaction included partner feelings of dissatisfaction (as judged by the patient), specific physician investigators and need for explantation/revision surgery. CONCLUSIONS: In 1 of the largest multi-institutional implant outcome studies thus far performed, safety and efficacy data concerning the Alpha-1 contemporary inflatable device were found markedly improved over earlier inflatable prostheses and now compare favorably with historical data from noninflatable rod type devices.
Actuarial Analysis↗
Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure.
PURPOSE: We investigated the pathophysiology of structurally based corporeal veno-occlusive dysfunction. MATERIALS AND METHODS: We prospectively evaluated 24 impotent patients (mean age plus or minus standard error 46 +/- 3 years) who had exposure to vascular risk factors and/or disorders inducing diffuse trabecular structure alterations and who underwent penile prosthesis insertion. Preoperative indexes of veno-occlusive function (flow to maintain, venous outflow resistance and pressure decay measurements using repeat dosing pharmacocavernosometry) were correlated with postoperative erectile tissue computer assisted color histomorphometry (percent trabecular smooth muscle to total erectile tissue area). To develop further study findings and correlate histomorphometric findings with molecular biological properties molecular biological studies (ribonuclease protection analysis, reverse transcription-polymerase chain reaction assay for expression of transforming growth factor-beta 1 messenger [m] ribonucleic acid [RNA] and protein affinity labeling techniques for specific transforming growth factor-beta receptors) were performed in representative patients with high (39 to 43%), intermediate (30 to 37%) and low (13 to 29%) trabecular smooth muscle content (normal 42 to 50%). RESULTS: Flow to maintain, venous outflow resistance and pressure decay values significantly correlated with trabecular smooth muscle cell content (r = -0.89, 0.82 and -0.85, respectively). In the high, intermediate and low smooth muscle content subgroups flow to maintain, venous outflow resistance and pressure decay values were 1 to 5, 9 to 30 and 50 to 120 ml. per minute, 17 to 84, 3 to 9 and 1 to 2 mm. Hg/ml. per minute, and 40 to 60, 48 to 80 and 110 to 120 mm. Hg decrease in 30 seconds from 150 mm. Hg, respectively. There were no significant differences in patient age or prevalence of risk factors among the 3 subgroups. Patients representative of all 3 subgroups had transforming growth factor-beta 1 mRNA, auto-induction of transforming growth factor-beta 1 mRNA and induction and/or increased availability of all 3 types of transforming growth factor-beta receptors. CONCLUSIONS: The pathophysiology of structurally based corporeal veno-occlusive dysfunction is related to elevated corporeal connective tissue content. Based on our data and those in the literature corporeal fibrosis is hypothesized to develop secondary to abnormalities in the regulation of normal collagen synthesis and degradation, most likely associated with adverse influences of chronic ischemia.
Adult↗
Implications of prostate micrometastases in pelvic lymph nodes: an archival tissue study.
OBJECTIVES: In the United States, radical retropubic prostatectomy for adenocarcinoma usually includes a staging pelvic lymphadenectomy. If frozen section analysis of the lymph nodes fails to reveal any evidence of metastases, the prostate is removed. We have previously noted that as many as 56% of patients undergoing radical prostatectomy demonstrate rising serum prostate-specific antigen (PSA) levels by 4 years postoperatively. This report was designed to determine whether micrometastases undetectable by conventional pathologic methods: could have accounted for these biochemical failures. METHODS: A retrospective analysis of formalin-fixed paraffin-embedded pelvic lymph node material was undertaken using a reverse transcription-polymerase chain reaction (RT-PCR)-based assay designed to amplify messenger RNA from PSA. All specimens were obtained from a group of 57 patients with prostate cancer who had undergone staging pelvic lymphadenectomy at the time of radical prostatectomy, and whose long-term follow-up was known. RESULTS: Although all of these nodes appeared to be free of tumor by conventional pathologic methods, a RT-PCR assay was used to identify evidence of prostate metastases in 44% of evaluable samples. Of these, 14 of 16 went on to manifest rising serum PSA values by 5 years postoperatively. CONCLUSIONS: These results suggest that molecular staging of pelvic lymph nodes prior to planned therapy for clinically organ-confined prostate cancer may better distinguish between patients with local disease and those for whom local therapy alone will not be curative. To our knowledge, this is the first large-scale retrospective gene expression study published.
Adenocarcinoma↗
Altered contractility of urinary bladder in diabetic rabbits: relationship to reduced Na+ pump activity.
We studied the effect of alloxan-induced diabetes on Na+ pump activity in isolated rabbit bladder strips. In addition, the effects of diabetes and the Na+ pump inhibitor ouabain on contractions induced by carbachol (CCh) and KCl were studied. In bladder strips from diabetic rabbits, ouabain-sensitive 86Rb+ uptake (a measure of Na+ pump activity) was approximately 50% less compared with strips from normal bladder. Diabetes also reduced the maximum contractions induced by CCh and KCl. Treatment of bladder strips with ouabain alone caused an acute concentration-dependent increase in tone. In contrast, longer incubation with ouabain inhibited CCh- and KCl-induced contractions in normal and diabetic bladders. Furthermore, differences in agonist-mediated contractions observed between normal and diabetic bladders were abolished in the presence of the maximally effective concentration of ouabain (10 microM). The ability of CCh to cause contraction in normal and diabetic rabbit bladders was also significantly inhibited by the Na+ ionophore monensin but not by the Ca2+ ionophore A-23187 or by depolarization with KCl. Monensin also inhibited KCl-induced contractions in normal bladder strips. These results indicate that 1) Na+ pump activity is an important modulator of bladder smooth muscle tone, 2) diabetes diminishes Na+ pump activity and inhibits agonist-induced contractions in bladder, and 3) an increase in intracellular Na+ concentration, secondary to inhibition of bladder smooth muscle Na+ pump activity, is associated with reduced responsiveness to contractile agonists. Diminished Na+ pump activity in diabetes may, in part, contribute to the development of bladder cystopathy.
Animals↗
Direct measurement of blood flow in the human bladder.
PURPOSE: We evaluated blood flow in the human bladder. MATERIALS AND METHODS: In 8 surgical cases a laser Doppler flow probe was placed in the bladder dome and anterior wall. In 10 endoscopic cases the flow probe was placed in the bladder trigone and lateral wall. RESULTS: Bladder filling resulted in reduced mean blood flow in the dome and anterior wall. After prostatectomy blood flow decreased in the dome but not the anterior wall. During endoscopy bladder filling resulted in diminished blood flow. CONCLUSIONS: Laser Doppler flowmetry can measure blood flow changes in the human bladder.
Aged↗
The treatment of loss of penile rigidity associated with Peyronie's disease.
Patients with Peyronie's Disease on occasion present with loss of rigid erections. A full evaluation is required to determine the presence or absence of arterial insufficiency or corporal veno-occlusive dysfunction. Treatment for these patients include intracavernosal pharmacotherapy, a vacuum/constrictor device, venous ligation surgery or a penile prosthesis. Whatever the therapeutic approach, the angulation produced by the Peyronie's plaque must be taken into account. Patients with Peyronie's Disease will present to their physicians with a variety of clinical scenarios. They may merely be concerned with the presence of an asymptomatic penile plaque and will simply require reassurance. More typically, however, penile curvature, pain, and/or difficulty with sexual relations will prompt the desire for medical advice. Treatment of penile pain which usually abates with time and attempts at non surgically treating the Peyronies plaque will not be discussed in this paper. Patients with penile plaque and curvature present in three distinct ways: a. penile rigidity preserved and the ability to continue sexual relations; b, penile rigidity preserved and the inability to continue with sexual relations because of significant angulation; c. the inability to have rigid erections. The patient who is able to continue sexual relations with preserved penile rigidity and the lack of significant penile angulation requires no treatment. However, the patient who has lost his ability to have sexual relations because of significant angulation is a candidate for penile straightening surgery (e.g. graft) (1, 11). It is the last group of patients. Namely those who are not able to maintain penile rigidity because of their Peyronie's Disease that will be addressed in this paper. Patients who present with impotence (i.e. loss of penile rigidity) and Peyronie's disease should be evaluated in a similar manner as patients who present with erectile dysfunction and do not have Peyronie's Disease. The standard approach would therefore include a detailed medical and sexual history, a measurement of penile arterial pressure or flow to determine adequate arterial inflow (5,8), a measurement of penile sensation (10) to determine if an underlying neurological problem is present and lastly an evaluation of the veno-occlusive mechanism (12,17). In addition, the presence of penile curvature and plaque may cause significant and disturbing psychological manifestations and it is advisable that these patients undergo a psychological interview to determine the presence or absence of psychiatric influences. Obviously, many older patients with Peyronie's Disease may suffer concomitant arterial insufficiency leading to loss of rigidity and impotence. An evaluation of arterial input into the penis by penile Doppler studies, duplex ultrasound, or cavernosal occlusion pressures is required to determine the presence of arterial insufficiency. Patients who are found to have significant decreases in arterial flow and/or pressure would therefore become candidates for either self-injection with vasoactive agents or a vacuum constrictor device. It is our feeling in general that these nonsurgical therapies should be tried prior to considering the implantation of a penile prosthesis in any patient who presents with erectile dysfunction. It should be noted, however, that many patients with Peyronie's Disease who present with loss of penile rigidity will have an underlying veno-occlusive dysfunction secondary to the plaque itself. Normally, venules draining the corpora are passively compressed between the expanding corporal tissue and the tunica albugince (6). When a Peyronie's plaque is present compliance of the underlying corporal smooth musculature may be decreased thus preventing venous compression. In a recent evaluation of 92 patients who presented in this manner 87% were noted to have veno-occlusive dysfunction as determined by dynamic cavernosometry and cavernosography (3)...
Erectile Dysfunction↗
A rapid and simple method for the detection of prostate-specific antigen mRNA in archival tissue specimens using a reverse transcription-polymerase chain reaction assay.
OBJECTIVES: Polymerase chain reaction (PCR) amplification of DNA from archival, fixed tissue sources is now performed routinely. In this report, we describe a reproducible technique for mRNA amplification from archival tissues. METHODS: Archival, fixed tissue was treated with a modification of a rapid, acid guanidinium technique. The RNA yielded was reverse transcribed and subjected to 40 cycles of two-step PCR, using a panel of primers designed to encompass relatively short (less than 250 bp) cDNA fragments. PCR products were analyzed by agarose gel electrophoresis followed by ethidium bromide staining. RESULTS: Using fixed, paraffin-embedded specimens of human prostate, we have demonstrated a reproducible pattern of reverse transcription (RT)-PCR products using several different primer sets. Our data suggest that RNA degradation proceeds to fragments approximately 250 bp or shorter in length but that many of these fragments survive intact over extended periods of time and are of suitable quality to serve as a template for RT and subsequent PCR amplification. CONCLUSIONS: We describe a technique that will allow the retrospective analysis of archival tissues for gene expression. These methods are generally applicable to a wide variety of systems. Such a method will make it possible to perform retrospective studies of gene expression in the archival tissues of patients whose eventual clinical course is already known, greatly shortening the time needed for genetic outcome studies in slowly growing tumors, such as prostate cancer.
Base Sequence↗
Prostate cancer screening in a large corporation population.
The Polaroid Medical Department conducted a prostate cancer screening program of all male employees over the age of 49 years. The screening consisted of a World Health Organization (WHO) questionnaire, a digital rectal examination (DRE) by an occupational medicine doctor, and a serum prostate-specific antigen (PSA) study. There were 2241 eligible employees (males between 50 and 65 years of age). 1219 (54%) took part in the screening. Thirty-seven PSAs above the 3.9 level were found (3%) and were further evaluated with ultrasound and/or biopsy. Twelve previously unknown cancers of the prostate (1%) were discovered. The cost of the entire program to the Polaroid Medical Department, including ultrasound and biopsy studies, was $72,130 ($6,012 per cancer detected). Of the 12 cancers, two were discovered by abnormal DRE alone, eight by an elevated PSA alone, and two by both an abnormal DRE and elevated PSA. There appeared to be no correlation between the WHO symptom score and the detection of prostate cancer. Our final conclusion was that a corporate medical department screening for cancer of the prostate is both effective and cost efficient.
Aged↗
Radical prostatectomy for adenocarcinoma of the prostate: the influence of preoperative and pathologic findings on biochemical disease-free outcome.
OBJECTIVE: This retrospective study evaluated the outcome for a cohort of men undergoing radical retropubic prostatectomy alone as primary treatment for clinical T1-2 prostate adenocarcinoma. METHODS: Sixty-two patients treated at Boston University Medical Center between 1987 and 1992 underwent radical prostatectomy alone without adjuvant or neoadjuvant endocrine therapy. Actuarial and multivariate analyses were made of disease-free outcome according to preoperative tumor T stage, prostate-specific antigen (PSA), and biopsy grade, and according to the pathologic findings at surgery. Recurrence was defined as the persistence or recurrence of detectable serum PSA four or more weeks following surgery. RESULTS: Of all patients judged clinically to have localized disease (T1-2), 52 percent proved to have pathologic T3 tumors. Of these, 81 percent had positive surgical margins. The strongest preoperative predictors of pT3 disease were the biopsy Gleason grade and the initial serum PSA value. Actuarial analysis showed the overall likelihood of remaining free from detectable PSA at four years to be 43 percent (75% for those with organ-confined disease and 27% for those who were pT3). The poorest prognosis was seen in those with seminal vesicle involvement. Biopsy Gleason grade and initial PSA were independent preoperative predictors of biochemical failure in a Cox regression analysis but clinical T stage was not. CONCLUSIONS: The biopsy Gleason grade and initial PSA were identified as strong preoperative predictors of disease-free outcome. We confirmed the favorable prognosis of men with organ-confined disease, but emphasize the high likelihood of relapse in those with positive surgical margins or seminal vesicle invasion.
Adenocarcinoma↗
Adoptive cellular therapy of urological neoplastic disease.
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Carcinoma, Renal Cell↗