Timing and patterns of recurrences and deaths from prostate cancer following adjuvant pelvic radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate.

To determine the timing and patterns of late recurrence after radical prostatectomy (RP) alone or RP plus adjuvant radiotherapy (RT). Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have positive surgical margins, extracapsular extension and/or seminal vesicle invasion. Of these, 46 received adjuvant RT and 113 did not. The RT group generally received 45-50 Gy to the whole pelvis, then a boost to the prostate bed (total dose of 55-65 Gy). In the RP group, 62% received neoadjuvant/adjuvant androgen deprivation vs 17% in the RT group. Patients were analyzed with respect to timing and patterns of failure. Only one patient was lost to follow-up. The median follow-up for surviving patients was nearly 20 years. The median time to failure in the surgery group was 7.5 vs 14.7 years in the RT group (P=0.1). Late recurrences were less common in the surgery group than the RT group (9 and 1% at 10 and 15 years, respectively vs 17 and 9%). In contrast to recurrences, nearly half of deaths from prostate cancer occurred more than 10 years after treatment. Deaths from prostate cancer represented 55% of all deaths in these patients. Recurrences beyond 10 years after RP in this group of patients were relatively uncommon. Despite its long natural history, death from prostate cancer was the most common cause of mortality in this population with locally advanced tumors, reflecting the need for more effective therapy.

Mucinous adenocarcinoma of the prostate.

A case of mucinous adenocarcinoma of the prostate that was diagnosed with the aid of prostate-specific antigen immunoperoxidase staining is reported. Focal areas of the tumor, which were morphologically similar to the remainder of the tumor, stained with neuron-specific enolase by an immunoperoxidase technique and with the Grimelius stain. This tumor is best thought of as a variant of the classic acinotubular adenocarcinoma of the prostate with well-differentiated cells that secrete mucin, rather than as a completely different type of cancer, as proposed previously.

Furosemide-induced disturbances of renal function in patients undergoing TURP.

Furosemide remains the drug of choice for patients with the transurethral resection syndrome. Furosemide is often used intraoperatively to treat patients suspected of having excessive irrigant absorption. To examine the efficacy of such therapy, a randomized study was performed in which furosemide was administered to patients undergoing routine transurethral resection of the prostate (TURP) to determine the effect of furosemide on electrolyte and fluid volume conservation in these patients. Seven patients treated with furosemide on completion of TURP had a statistically significant delayed drop in serum sodium values after normal initial values (139 mEq/L to 134 mEq/L). Seven untreated control patients did not have a similar drop in sodium values, and the difference between groups was significant. We suggest that furosemide be used with caution in patients undergoing routine TURP, and when given it should be accompanied by the infusion of an isotonic balanced salt solution.

Management of urinary tract in children with epidermolysis bullosa.

Epidermolysis bullosa is a group of rare genetic disorders characterized by noninflammatory blistering lesions of the skin occurring after minor mechanical trauma. In association with junctional epidermolysis bullosa, a syndrome of pyloric atresia has occasionally been noted in the literature. Several infants who had this combined disorder have been reported to have severe genitourinary tract involvement. Most of these patients have died at an early age because of severe urinary tract involvement. We describe a rare survivor who was initially treated with urinary diversion. Subsequent attempts at undiversion of this patient were unsuccessful. He is presently stable following rediversion. The entities of e. bullosa and e. bullosa/pyloric atresia are reviewed with emphasis on urologic associations.

Direct vision internal urethrotomy using topical anesthesia.

A consecutive series of 18 patients underwent attempted direct vision internal urethrotomy (DVIU) under topical lidocaine anesthesia. The procedure was completed successfully in 15 of 18 (83%) patients. In these patients 12 of 15 (80%) reported either minimal or no discomfort. Direct vision internal urethrotomy using topical lidocaine anesthesia is a safe and cost effective procedure.

Anatomy of cavernous nerves distal to prostate: microdissection study in adult male cadavers.

Retrograde and antegrade dissections from the penile hilum to the prostatic area and the glans penis were performed in 4 formalin-preserved adult male cadavers. In addition to the medial branches accompanying the urethra, the lateral branches of the cavernous nerves pierced the urogenital diaphragm 4 to 7 mm from the striated muscles of the external sphincter. At the penile region, multiple communications between the cavernous and dorsal nerves were noted that suggest that either the cavernous nerves use the dorsal nerve as a carrier to the distal portion of the penis or the dorsal nerve may itself contain autonomic fibers. These findings will improve our ability to preserve erectile function during pelvic, urethral, and penile surgery.

Transrectal ultrasound and biopsy in diagnosis of malakoplakia of prostate.

We report our experience with the use of transrectal ultrasound and ultrasound-guided needle biopsy in the diagnosis of 4 cases of malakoplakia of the prostate. Prostatic malakoplakia is rare with a total of 25 cases reported in the literature. It may simulate carcinoma on digital rectal examination and transrectal ultrasound. Herein are 4 additional cases in which transrectal ultrasound of the prostate was compatible with carcinoma. Subsequent needle biopsy of the suspicious regions revealed the classic pathologic features of malakoplakia. Malakoplakia is a difficult pathologic diagnosis, and the prevalence of this disease may be underestimated. As the use of transrectal ultrasound becomes more common in diagnosing carcinoma of the prostate, and due to the difficulty in diagnosing malakoplakia pathologically, we recommend maintaining a high index of suspicion for malakoplakia to avoid possible unnecessary radical surgery.

Randomized clinical trial comparing balloon dilatation to transurethral resection of prostate for benign prostatic hyperplasia.

To evaluate the effectiveness and clinical outcome of patients treated by balloon dilatation of the prostate (BDP) compared with transurethral resection of the prostate (TURP) we performed a prospective, randomized clinical trial. Fifty-one men were randomized to either BDP or TURP. Both groups demonstrated a significant decrease in symptom score from preoperative levels (TURP 13.6 to 6.0 [p < 0.05]; BDP 14.1 to 8.1 [p < 0.01] at 1 year). The TURP group improved peak urinary flows; while, after initial improvement, the balloon group returned to pre-procedure levels. At twelve months 14 of 19 BDP patients (74%) and 14 of 18 TURP patients (78%) considered themselves improved. BDP results in symptomatic improvement; however, the effect may not persist. Objective improvement after BDP does not always occur. The morbidity of BDP is low and compares favourably to that of TURP. Thus BDP does not appear to be as effective as TURP and may offer only temporary relief of symptoms.

Effects of androgen deprivation on prostate alpha 1-adrenergic receptors.

OBJECTIVES: Benign prostatic hyperplasia (BPH), the most common benign tumor in men, consists of two components-static (enlargement regulated by androgens) and dynamic (smooth muscle contraction through alpha 1-adrenergic receptors [alpha 1-ARs]). Because medical therapy of BPH involves tissue androgen deprivation, we studied the influence of androgen deprivation and replacement on regulation of rat ventral prostate alpha 1-ARs. METHODS: Prostate weight, alpha 1-AR density, autoradiographic images, histologic features, and cell-specific protein were examined before and after castration and androgen replacement. RESULTS: Castration decreases ventral prostate wet weight, a process reversed by testosterone administration. In contrast, there is an apparent increase in alpha 1-AR density (29 +/- 4 versus 65 +/- 6 fmol/mg total protein, mean +/- SEM) after castration, returning to baseline with testosterone replacement; alpha 1-AR density remains constant in control liver membranes. Alpha 1-ARs predominate in stroma throughout androgen deprivation therapy. Epithelially derived cells decrease (83% to 67%) after castration, resulting in a relative doubling in stroma (17% to 33%); the protein content of epithelial and stromal cells remains identical. Therefore, prostate-specific increases in alpha 1-ARs appear to result from relative increases in the ratio of smooth muscle to epithelium after castration rather than from direct upregulation of alpha 1-AR protein. CONCLUSIONS: Because alpha 1-AR density does not decrease with androgen deprivation, these studies suggest that alpha 1-AR antagonists remain an important component in BPH therapy, even when 5-alpha-reductase inhibitors are utilized.

Bacterial biofilms and implantable prosthetic devices.

Erectile dysfunction afflicts millions of men. A group of patients with advanced degeneration of their erectile tissue do not respond to pharmacological therapy, and surgical prosthetic reconstruction represents an attractive and highly satisfying alternative. Yet many men are unwilling to take this step due to fear of infection. Implanted prosthetic devices are at risk for infection because they provide a platform for the development of a bacterial biofilm, an organized bacterial colony that grows on the surface of the implanted material. The biofilm is resistant to all efforts to eradicate it short of removal of the foreign material. Bacteria may attach to the surface of the foreign material by surface charge attraction, hydrophilic/hydrophobic interactions, and by specific attachment by fimbrae. Growth, colonization, and maturation follow bacterial attachment. A mature biofilm is composed of three layers: a linking film binding the biofilm to the surface; a base film made up of a compact layer of bacteria; and a surface film from which free-floating bacteria can arise and spread. The majority of the surface layer is made up of exopolysaccharide matrix. Bacteria deep within the biofilm matrix live in a protected environment; diffusion of antibiotics is difficult, low oxygen tension leads to a lower bacterial metabolic rate rendering the bacteria functionally resistant to high levels of antibiotics. Effective strategies to reduce prosthetic infection levels must rely on the prevention of biofilm formation through surface modification. Possible mechanisms include the addition of antimicrobials to the surface of the device, or chemical modifications, which reduces bacterial attachment.

Erectile dysfunction in men under 40: etiology and treatment choice.

We undertook a retrospective review of 100 impotent men under age 40 to determine the underlying etiologic factors in the group and to evaluate the role of surgery in their care. Although patients ranged in age from 18 to 40 (mean--32.2 years), the number of patients increased steadily with advancing years. The majority of patients (72) had vasculogenic impotence (arteriogenic--15, venogenic--46, mixed--11), followed by psychogenic (13), neurogenic (12) and other causes (4). The differential diagnosis did not correlate with age. Contributing factors were present in 76%, trauma and substance abuse being most common. Essentially equal numbers of patients were treated surgically (40) and with intracavernous injection of vasoactive agents (39). Considerably fewer had a vacuum constriction device (5), oral medication (5), psychotherapy (4), other therapy (4), and none (3). The majority of patients referred to our tertiary urologic practice for treatment of vasculogenic impotence were sent by other urologists. Although the referral source did not appear to influence the choice of treatment, it probably has accounted for the preponderance of vasculogenic impotence in this series.

Intracavernosal injections of vascular endothelial growth factor protects endothelial dependent corpora cavernosal smooth muscle relaxation in the hypercholesterolemic rabbit: a preliminary study.

Atherosclerosis is a major risk factor for erectile dysfunction, and loss of endothelium-dependent vasodilation appears early in the development of this disorder. Nitric oxide (NO) appears to be the principle mediator of erectile function and is generated in part by the sinusoidal endothelium. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and an endothelial cell-specific mitogen and the actions of VEGF are coupled to NO. In this preliminary study, we investigated whether VEGF could be used to protect endothelial dependent cavernosal relaxation from the atherosclerotic injury induced by a hypercholesterolemic diet.Two groups of New Zealand white adult male rabbits received a 1% cholesterol diet for four weeks, and two groups consumed normal rabbit chow. Half of the rabbits consuming the 1% cholesterol diet received weekly penile injections of 0.3 mg VEGF (n=8), and half injections of normal saline (n=8). Rabbits fed normal chow followed a similar protocol, half received weekly penile injections of 0.3 mg VEGF (n=6) and half were given weekly penile injections of normal saline (n=6). Isometric tension studies (with norepinephrine, acetylcholine, sodium nitroprusside and histamine) were performed on isolated strips of corpora cavernosa. The degree of corporal smooth muscle relaxation in response to ACH and SNP administration was recorded and compared. Significant elevation in serum total cholesterol levels occurred in rabbits receiving 4 weeks of the 1% cholesterol diet (727+/-75.6 mg/dl vs 38.7+/-5.53 mg/dl) P<0.01. There were no significant differences in cavernosal contraction in any group, while cavernosal smooth muscle from rabbits on normal chow retained the ability to relax in response to ACH and SNP in tissue bath. The hypercholesterolemic rabbits receiving VEGF had a significantly higher maximal per-cent relaxation to ACH (111+/-28.9) compared to the hypercholesterolemic rabbits that received NS (77+/-23.1, P<0.001). This difference in percent maximal relaxation to SNP was also present for hypercholesterolemic/VEGF rabbits (129.4+/-24) versus the hypercholesterolemic/NS rabbits (115.0+/-18, P=0.033). In conclusion, intracavernosal injections of VEGF appear to protect corporal endothelium from hypercholesterolemia induced injury, thus preserving endothelial dependent corporal smooth muscle relaxation in hypercholesterolemic rabbit.

The effect of intracavernous injection of potassium channel openers in monkeys and dogs.

Cavernous smooth muscle relaxation is effected through a complex biochemical pathway; therefore, a defect in any step of this pathway may result in erectile dysfunction. Administration of pharmacologic agents which cause relaxation of the cavernous smooth muscle through a different mechanism may serve as an effective therapeutic alternative for impotent patients. To test this hypothesis two potassium channel openers, pinacidil and cromakalim, were used to initiate and maintain cavernous smooth muscle relaxation. The drugs were given as intracavernous injections in two animal models. In 10 dogs pinacidil and cromakalim produced full erection. With pinacidil (10(-2) M), the mean intracavernous pressure increased from a baseline pressure of 32.6 +/- 3.43 cm H2O to a peak intracavernous pressure of 131.8 +/- 12.01 cm H2O, and remained elevated for a period of 17.8 +/- 9.4 min. With cromakalim (10(-2) M) intracavernous pressure rose from a baseline pressure of 32 +/- 2.55 cm H2O to a peak intracavernous pressure of 140 +/- 3.39 cm H2O, for a period of 19.4 +/- 0.89 min. Additionally, in 5 primates injected with cromakalim (10(-2) M) intracavernous pressure rose from 24 +/- 3.81 to 131.2 +/- 7.56 cm H2O, for 27.0 +/- 4.79 min. It is concluded that both pinacidil and cromakalim can initiate and maintain erection in dogs and that cromakalim produces a similar erectile response in monkeys. Further study of the local and systemic effects of chronic injection is needed to determine whether this class of pharmacologic agents can provide therapy for impotent patients.

Sodium nitroprusside: physiologic effects as a nitric oxide donor in three species.

Recent in vitro and in vivo studies have suggested that nitric oxide may be the neurotransmitter responsible for cavernous smooth muscle relaxation and penile erection. Sodium nitroprusside, after combining with different kinds of thiols in the cellular cytoplasm, can effect nitric oxide release. We undertook this study to determine the physiologic response to sodium nitroprusside injection when used to induce and maintain penile erection in three species. Sodium nitroprusside was injected in increasing concentrations into the cavernous tissue of rats, dogs and monkeys. Dosages injected were 10(-4) M, 10(-3) M and 10(-2) M in 10 rats; 10(-4) and 10(-3) M in five dogs and five monkeys. The volume of drug injected was 0.05 ml for the rats and 0.5 ml for dogs and monkeys. The results show a dose-dependent erectile response to sodium nitroprusside injection (mean intracavernous pressure increase of 102.4 cm H2O in dogs, and 98.4 cm H2O in monkeys after injection of 10(-3) M nitroprusside). However, only a slight increase in intracavernous pressure (mean increase 28.4 cm H2O after injection of 10(-2) M of sodium nitroprusside) was noted in rats. The drop in blood pressure was > 15 mmHg in dogs and monkeys, while in rats it varied according to the dose studied. Sodium nitroprusside induced excellent erections in dogs and monkeys with minimal alteration in blood pressure. However, administration in rats resulted in hypotension. Nitroprusside may not be an acceptable nitric oxide donor for the treatment of male erectile dysfunction.

Vasculogenic impotence. Arterial and venous surgery.

Arterial revascularization and venous ligation procedures have been introduced within the past 2 decades. Each procedure has in common with the other the fact that initial applications of the operations were widespread among the population of men with vasculogenic erectile dysfunction. In each case, disappointing long-term results led to more limited use of surgery targeting specific groups that clearly would benefit from the procedures. The wider application of these procedures in vasculogenic erectile dysfunction is not supported by the available results. The Clinical Guidelines Panel of the American Urological Association supported this view in 1996 after a meta-analysis of literature reports and declared that venous and arterial surgery was not justified in routine use, especially in patients with arteriosclerosis. Further studies are likely to refine patient selection but are unlikely to expand the therapeutic use of these procedures.

Sexual bother and function after radical prostatectomy: predictors of sexual bother recovery in men despite persistent post-operative sexual dysfunction.

Changes in sexual bother (SB) following radical prostatectomy (RP) negatively affect health-related quality of life (HRQoL) of prostate cancer survivors. However, post-operative SB tends to be neglected whereas sexual function (SF) is thoroughly assessed in clinical practice and few studies have focused on and evaluated patients' SB. We retrospectively reviewed 2 345 consecutive patients who underwent RP between 2001 and 2009 at a single institution. SF and SB were assessed using Expanded Prostate Cancer Index Composite (EPIC) questionnaires. We stratified our cohort by SB recovery and post-operative SF status, including a subset of men who recovered SB despite persistent post-RP sexual dysfunction. Multivariable logistic regression analyses were conducted to identify factors for men who have SB recovery. Of 319 eligible patients, 133 (41.7%) recovered their SB at a mean of 20 months after RP. Among the 133 men who demonstrated SB recovery, 109 had post-operative sexual dysfunction. Patients with SB recovery despite post-RP sexual dysfunction were more likely to be old (p = 0.004), to have higher clinical T stage (p < 0.001), to have more non-nerve-sparing RP (p < 0.001), to have lower pre-operative EPIC-SF/SB scores (p < 0.001), to have more extracapsular extension (p = 0.031) and to be PDE5i non-users after surgery (p < 0.001). In multivariable analysis, predictors for this subset were lower comorbidity (OR 0.62, p = 0.043), higher clinical cancer stage (OR 2.35, p = 0.026), worse pre-operative SF (OR 0.98, p = 0.010), SB (OR 0.98, p < 0.010) and no PDE5i use (OR 0.37, p = 0.002); age was not related (OR 0.99, p = 0.555). As SB can influence patients' overall HRQoL, expectations of SB recovery should be provided to patients in the same way that SF recovery is presented. This study may help clinicians to discuss SB with patients and assess their potential for SB recovery following RP.

On-demand use of erectile aids in men with preoperative erectile dysfunction treated by whole gland prostate cryoablation.

Prostate cryoablation is an established minimally invasive treatment for localized prostate cancer (PCa). However, the impairment of erectile function (EF) is considered a serious complication of the procedure. To investigate the efficacy of erectile aids following cryotherapy, 93 patients who underwent whole gland prostate cryoablation with required complete medical records were analyzed. The changes in postoperative EF were evaluated using the International Index of Erectile Function (IIEF-5) questionnaire. Additionally, independent factors that could have a correlation to the postoperative IIEF-5 score or postoperative Expanded Prostate Cancer Index Composite (EPIC) score were assessed. In the entire cohort, the mean preoperative IIEF-5 score was 7.0 ± 6.2. A total of 72 (77.4%) patients had moderate-to-severe preoperative erectile dysfunction. In longitudinal investigation, the patients using erectile aids showed the ability to recover to baseline after 24 months from cryoablation compared with the patients not using erectile aids. There were significant differences of IIEF-5 scores between these groups at 24 months (7.5 vs 3.0; P = 0.025) and 36 months (8.5 vs 3.5; P = 0.010). In multivariate analysis, the use of erectile aids correlated with restoration of IIEF-5 scores (odds ratio, 5.11; confidence interval (CI), 1.87-13.96; P < 0.001) and lower EPIC sexual bother (coef, 19.61; CI, 0.32-38.89; P = 0.046). Our data indicate that on-demand use of erectile aids could help restore EF and reduce sexual bother after whole gland prostate cryoablation. Although, erectile aids could not play a role as an adequate treatment for ED after whole gland prostate cryoablation, these results may aid in the decision-making process for PCa patients with preoperative and postoperative ED who have concern about sexual health-related quality of life.

Concordance in the perception of couples recovering from primary surgical treatment of prostate cancer.

Although prostate cancer affects men, research shows effects on both members of the couple. We analyzed concordance in couples recovering from primary surgical treatment of prostate cancer when surveyed on psychological domains including emotional status, relationship, self-image, partnership quality and support. Retrospective Sexual Surveys were utilized to survey physiological changes as well as psychological effects. In total, 28 heterosexual couples (56 people) were enrolled. Patients were treated between February 2002 and March 2007 with a median follow-up of 26 (range: 4-59) months. When polled on psychological aspects that may have been affected by treatment, overall concordance was 75.0%. Partnership had the highest concordance (92.2%) with treatment satisfaction questions following in second (90.7%). Subcategories focused on self-image (77.5%), relationship (67.3%), support (66.4%) and emotional status (55.6%), were less concordant. Although couples report relationships as strong and team-like, misconception between partners is widespread. Further research with regards to the effect of such disparities in couples might provide additional insight into improving recovery.

Alternative methods for management of prostatic outflow obstruction.

During the past year no new therapies for prostatic outflow obstruction were introduced. Instead, research focused on refinement of treatments previously available. Further reports on the efficacy and safety of alpha 1-adrenergic receptor subtype selective agents have appeared. The long-term effects of finasteride on the natural history bladder outflow obstruction have become clearer. The clinical efficacy of device therapy has evolved, and information regarding intermediate-term outcomes is now available.

Correction of penile deformity assisted by intracavernous injection of papaverine.

Sexual dysfunction resulting from penile deformity is amenable to surgical correction. We describe a simplified technique in which surgical plication with nonabsorbable sutures is assisted by intraoperative erection induced by intracavernous papaverine. This procedure can be performed in an ambulatory surgery center with the patient under local anesthesia with minimal postoperative morbidity. To date we have treated 6 patients and followup ranges from 12 to 24 months. All patients have straight erections and retain normal erectile function.