Liver Metastases in Prostate Carcinoma Represent a Relatively Aggressive Subtype Refractory to Hormonal Therapy and Short-Duration Response to Docetaxel Monotherapy.

BACKGROUND: We report a single institution's experience from a small series of patients suggesting that liver metastasis in metastatic castration-refractory prostate cancer (mCRPC) represents a relatively aggressive subtype that is refractory to hormonal manipulation treatment, including luteinizing hormone-releasing hormone agonist (LA) and abiraterone (Ab) therapy, although docetaxel is briefly effective. METHODS: Between 2007 and 2013, six patients with prostate cancer with liver metastases were analyzed. Biochemical response was defined as > 50% decrease in prostate-specific antigen (PSA) value. RESULTS: Two patients who presented with liver metastases died in less than 3 months after LA therapy. Two out of three patients (one died while receiving chemotherapy) received Ab after chemotherapy did not show any response and died while on therapy. One patient who presented with lung metastases initially received LA therapy and progressed on it with liver metastases in < 6 months. Thus, five of six patients did not respond to hormone therapy including LA and Ab. Three patients who received docetaxel after LA therapy had more than 50% objective PSA response with a mean survival of 4 months. CONCLUSIONS: No literature addresses the response to hormone treatment in hepatic metastasis in prostate carcinoma. This small series suggests that liver metastases in prostate carcinoma represent a relatively aggressive subset against which hormonal therapy, including the LA and Ab, appears to be ineffective. Although our patients responded to docetaxel chemotherapy, their responses were of short duration. A further clinical trial involving more patients will be necessary to substantiate our findings.

Transitional Cell Carcinoma of the Bladder Manifestating as Malignant Lymphoma with Generalized Lymphadenopathy.

Bladder cancer usually spreads via the lymphatic and hematogenous routes, the most common sites of metastases of urinary bladder cancers being the regional lymph nodes, liver, lung, bone, peritoneum, pleura, kidney, adrenal gland and intestines. Generalized lymph node metastasis of transitional cell cancer of the bladder is extremely rare. According to our literature search, there has been no case report of transitional cell cancer of the bladder that manifests as an extensive large lymph node metastasis involving the intraparotid, supraclavicular thoracic inlet, axillary and regional abdominal and pelvic lymph nodes without bone or visceral organs involved. Such a presentation could be mistaken as malignant lymphoma and the importance of a biopsy of the lymph nodes is emphasized. The clinical course of rapid progression of the disease and the presence of wild-type p53 with rapid response to chemotherapy and a short remission may represent a unique case, which is discussed here.

Atorvastatin protects renal function in the rat with acute unilateral ureteral obstruction.

OBJECTIVES: To examine the effects of atorvastatin on renal hemodynamics and urinary microalbumin levels in rats with acute unilateral ureteral obstruction (UUO). Previous studies have demonstrated that treatment with statins attenuated renal structural damages in rodents with chronic UUO. However, it is not known whether statins afford protection of renal function. METHODS: UUO was created by ligation of the left ureter in rats maintained on a regular diet or the same diet but supplemented with atorvastatin (50 mg/kg/d) for 2 weeks. Renal clearance experiments were performed after release of UUO at 1 hour, 6 hours, or 12 hours. RESULTS: Atorvastatin treatment lowered plasma triglyceride but not cholesterol levels. Both glomerular filtration rate and effective renal plasma flow were significantly greater in atorvastatintreated rats after release of UUO at 1 hour, 6 hours, and 12 hours. Significant reduction of urinary microalbumin to creatinine ratios occurred in the atorvastatin-treated group at 12 hours but not earlier. CONCLUSIONS: Atorvastatin treatment affords protection of renal function in acute UUO and reduces urinary microalbumin levels without lowering cholesterol levels. This pleiotropic action of atorvastatin on preservation of renal hemodynamics may be important in attenuating subsequent renal structural injury in chronic UUO.

Cutaneous BCG of the penis after intravesical therapy for bladder cancer: a case report in a 66-year-old male.

OBJECTIVE: Transitional cell carcinoma of the bladder is commonly treated with intravesical BCG. We report a cutaneous complication of BCG after therapy in 66-year-old male 4 years after initiating treatment. MATERIALS AND METHODS: A case review including pathological slides, laboratory data, and radiographic findings. RESULTS: Biopsy findings showed an ill defined granulomatous process with chronic inflammation and necrosis. CONCLUSION: The patient was managed on antituberculous therapy for a period of 6 months with resolution of symptoms.

Atorvastatin ameliorates tubulointerstitial fibrosis and protects renal function in chronic partial ureteral obstruction cases.

PURPOSE: Tubulointerstitial fibrosis, the histological feature of chronic obstructive nephropathy, is delineated in complete unilateral ureteral obstruction models. Histological changes during chronic partial ureteral obstruction are not well studied. We describe changes in a rat model of partial ureteral obstruction. We examined the effects of atorvastatin on histological alterations, fibrosis and function in this model. MATERIALS AND METHODS: All rats underwent right nephrectomy. To create partial ureteral obstruction the left ureter was incorporated into the psoas muscle, which was split and reapproximated. Excretory urogram, histology, Western blot of alpha-smooth muscle actin and renal clearance were examined in rats with sham, 14-day or 30-day partial ureteral obstruction. Obstructed rats received a regular or a diet supplemented with 50 mg/kg body weight atorvastatin per day. RESULTS: At 14 days of partial ureteral obstruction pyelogram showed hydronephrosis, which was more pronounced on obstruction day 30. Histological studies on obstruction days 14 and 30 revealed tubulointerstitial fibrosis in the medulla and cortex. Atorvastatin significantly decreased tubulointerstitial fibrosis seen in alpha-smooth muscle actin expression. On obstruction day 14 or 30 the glomerular filtration rate in rats on a regular diet was significantly lower than in sham PUO rats or rats on atorvastatin. CONCLUSIONS: This model of partial ureteral obstruction enables chronic studies of morphological and histological changes of the obstructed kidney. It showed progressive fibrosis and decreased filtration function. Atorvastatin ameliorated fibrosis and helped preserve kidney filtration function.

Diagnosis and treatment of urethral prolapse in children: experience with 34 cases.

OBJECTIVES: To retrospectively review 34 cases of urethral prolapse at an inner-city institution with an emphasis on diagnosis and treatment in the pediatric population. METHODS: We performed a retrospective chart review of 34 patients of all age groups with urethral prolapse treated at our institution and reviewed the relevant published data. RESULTS: A total of 34 patients with urethral prolapse were treated at our institution during a 23-year period. The diagnosis was made mainly by physical examination. The findings from the history, physical examination, and pertinent laboratory investigations were reviewed. Most patients were treated successfully with excision of the prolapsed mucosa circumferentially over a Foley catheter and discharged home within 24 hours of the operation. No major complications occurred. CONCLUSIONS: Urethral prolapse primarily affects premenarchal black girls and should be treated promptly with excision of the prolapsed mucosa and early hospital discharge.

Penile fracture: preoperative evaluation and surgical technique for optimal patient outcome.

OBJECTIVE: To review the preoperative diagnostic evaluation and surgical treatment of penile fracture, as the condition is a urological emergency that requires immediate surgical exploration and repair. PATIENTS AND METHODS: Between January 2003 and October 2007 eight patients presented to the emergency department with penile fracture after sexual intercourse. The clinical presentation, preoperative evaluation and imaging, surgical technique, and postoperative care were assessed to determine the optimal patient outcome. RESULTS: Seven of the eight patients were treated surgically and one refused surgical intervention. Four cases involved unilateral corporal injury, two involved unilateral corporal injury with an associated urethral injury, and one involved bilateral corporal injury with an associated urethral injury. Although retrograde urethrogram were taken of all three urethral injuries, none of them revealed the injury. Diagnostic cavernosography or magnetic resonance imaging were not used in any of the patients. No complications occurred in the patients treated surgically. CONCLUSIONS: Preoperative imaging should not delay surgical repair. If an associated urethral injury is suspected, flexible cystoscopy is recommended in the operating room, as opposed to a retrograde urethrogram. A subcoronal circumcising incision is recommended to deglove the entire penile shaft and have complete access to all three corporal bodies, as well as the neurovascular bundle. Saline mixed with indigo carmine can be injected both into the corpora cavernosum or corpus spongiosum via the glans penis, after a tourniquet is placed at the base of the penis, to evaluate the surgical repair and to determine if there are any missed injuries.

Multi-drug-resistant bacteremia after transrectal ultrasound guided prostate biopsies in hospital employees and their relatives.

OBJECTIVES: To evaluate the incidence of multi-drug-resistant (MDR) organisms causing bacteremia in hospital employees and their relatives after transrectal ultrasound (TRUS) guided prostate biopsies. METHODS: We retrospectively reviewed all TRUS-guided prostate biopsies between November 2006 and November 2007. Of the 378 patients, we identified 4 cases of post-procedure bacteremia requiring hospital admission. All 4 of these patients had MDR organisms causing bacteremia. These patients were then contacted to determine whether they or their relatives were hospital employees. RESULTS: We identified 4 patients among a total of 378 who developed MDR bacteremia after TRUS prostate biopsy (1.06%). Three of these patients or their relatives were hospital employees (75%). All 3 of these patients had bacteremia caused by Escherichia coli that was resistant to ciprofloxacin and levofloxacin, the perioperative antibiotic given. CONCLUSIONS: In addition to the standard TRUS biopsy preoperative questions it is beneficial to ask patients whether they are hospital employees or live in the same household as hospital employees. This way, if patients return postoperatively with fever and chills, there is a higher index of suspicion that bacteremia may be caused by MDR organisms and empiric broad spectrum parenteral antibiotics can be started immediately.

Atorvastatin preserves renal function in chronic complete unilateral ureteral obstruction.

PURPOSE: The pleiotropic effects of hMG-CoA (3-hydroxy-3-metylglutaryl coenzyme A) reductase inhibitors may provide renal protection in chronic kidney disease. We examined whether atorvastatin administration preserved renal function in rats with chronic unilateral ureteral obstruction. MATERIALS AND METHODS: Renal clearance experiments were performed in sham operated rats and rats subjected to 3 or 12-day unilateral ureteral obstruction. Hemodynamics parameters and urinary microalbumin levels from the obstructed kidney were also measured. The rats were maintained on a regular diet or the same diet but supplemented with atorvastatin (50 mg/kg daily). RESULTS: Atorvastatin administration did not alter plasma total cholesterol but it significantly decreased triglyceride levels. In sham operated and 3-day unilateral ureteral obstruction rats atorvastatin treatment did not have effects on the glomerular filtration rate or effective renal plasma flow and it also did not affect urinary microalbumin levels. In rats with 12-day unilateral ureteral obstruction the glomerular filtration rate but not effective renal plasma flow was significantly higher and urinary microalbumin was significantly lower in atorvastatin treated rats than in those without atorvastatin treatment. CONCLUSIONS: Atorvastatin treatment decreased microalbuminuria and helped preserve filtration function in chronic unilateral ureteral obstruction without altering plasma cholesterol levels, suggesting that pleiotropic renal protection is offered by this statin.

Renal responses to atrial natriuretic peptide are preserved in bilateral ureteral obstruction and augmented by neutral endopeptidase inhibition.

PURPOSE: Atrial natriuretic peptide (ANP) contributes to post-obstructive diuresis in bilateral ureteral obstruction (BUO). In this study we examined the activity of neutral endopeptidase (NEP), an enzyme responsible for degradation of ANP, in the kidney in rats subjected to BUO for 24 hours. MATERIALS AND METHODS: Renal function was examined by the clearance method in sham operated rats and BUO rats after obstruction release. Renal responses to an intravenous bolus injection of ANP (5 microg/kg) were studied in sham operated and BUO rats with or without pretreatment with intravenous phosphoramidon (100 microg/kg per minute), a NEP inhibitor. RESULTS: In BUO rats natriuresis and diuresis occurred despite a marked decrease in the glomerular filtration rate (GFR). ANP administration increased GFR and induced marked natriuresis and diuresis in sham operated and BUO rats. Inhibition of ANP degradation by phosphoramidon induced natriuresis and diuresis, and accentuated these renal responses to ANP. CONCLUSIONS: Renal responses to ANP and renal NEP activity were preserved in 24-hour BUO. NEP inhibition to attenuate ANP degradation augmented responses to ANP in increasing GFR, natriuresis and diuresis. These findings provide the theoretical potential for facilitating the recovery of GFR after BUO release by inhibiting ANP degradation by pharmacological means.

Alterations of renal hemodynamics in unilateral ureteral obstruction mediated by activation of endothelin receptor subtypes.

PURPOSE: Unilateral ureteral obstruction (UUO) for 21 hours causes severe renal vasoconstriction. We examined the role of endothelin (ET)-A receptor in renal hemodynamic alterations induced by UUO. MATERIALS AND METHODS: Hemodynamic and clearance experiments were performed in 3 groups of anesthetized dogs. In group 1, 6 sham operated dogs received intrarenal infusion of the specific ET-A receptor antagonist BQ-610 (Peninsula Laboratories, Inc., Belmont, California), followed by infusion of the nitric oxide synthase substrate L-arginine. In the 7 group 2 dogs release of 21-hour UUO was followed by intrarenal infusion of BQ-610 and L-arginine. In the 5 group 3 dogs release of 21-hour UUO was followed by L-arginine infusion. RESULTS: UUO caused marked decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) in groups 2 and 3 compared with group 1. In group 1 BQ-610 and L-arginine infusion did not alter RBF or GFR. In contrast, BQ-610 infusion in group 2 after UUO release led to a significant increase in RBF and GFR as well as additional increases after L-arginine infusion. After UUO release in group 3 L-arginine infusion alone did not change RBF or GFR. CONCLUSIONS: After UUO release blockade of the ET-A receptor ameliorates renal vasoconstriction. The addition of L-arginine, which is a substrate for nitric oxide synthase, superimposed on ET-A receptor blockade confers a further decrease in renal vascular resistance, suggesting that the ET and L-arginine-nitric oxide systems are involved in renal hemodynamic alterations caused by UUO.

Pharmacological characterization of isolated human prostate.

PURPOSE: Human prostate contains alpha-1 adrenergic, cholinergic and nonadrenergic noncholinergic neuroreceptors. Using agonistic and antagonistic agents at these neuroreceptors we studied the resultant contractile responses in isolated human prostate. MATERIALS AND METHODS: Human prostate tissue was obtained at prostatectomy for benign prostatic hyperplasia in 37 adult male patients. Tissues were suspended in tissue bath chambers connected to force displacement transducers. Specimens were subjected to agonist induced contractions, the first always being norepinephrine (NE). Specimens were pretreated with antagonist (adrenergic, cholinergic, nonadrenergic noncholinergic or none if control), followed by contraction with a second agonist (NE or other). Contractile tensions were recorded on a polygraph and then statistically analyzed. RESULTS: The order of highest to lowest agonist induced tensile forces was NE, dopamine, acetylcholine, bethanechol, histamine and serotonin. Excitatory concentration EC(50) values were determined for each agonist tested. Significant differences were found between specific alpha-1 adrenergic receptor blockers (terazosin, prazosin and the experimental drug LY253352). In addition, many other agents antagonized the alpha-1 adrenergic receptor. Inhibitory concentration IC(50) values were obtained and the order of alpha-1 adrenergic antagonistic strengths from strongest to weakest was LY253352, prazosin, terazosin, ketanserin, SCH23390, diphenhydramine, DO710, dopamine, serotonin and histamine. CONCLUSIONS: Human prostate neuroreceptors were determined to be alpha-1 adrenergic, dopaminergic, muscarinic cholinergic, 2A serotonergic and H1 histaminergic. Dopamine, serotonin, histamine and their antagonists blocked the adrenergic response, indicating possible receptor-receptor interaction. Further study of the pharmacology of human prostate would likely identify new drugs for treating patients with bladder outlet obstruction due to benign prostatic hyperplasia.