RESUMEN
Olaparib is (ADP-ribose) polymerase inhibitor (PARPi), which stops the repair of single-stranded DNA breaks. This leads to the death of cancer cells with BRCA1/BRCA2 mutations or homologous recombination deficiency. Since being approved by the FDA in 2023 for treating castrate-resistant prostate cancer (CRPC), there have been some reports of myelodysplastic syndrome (MDS) and acute leukemia linked to PARP inhibitor use for ovarian, breast, pancreatic and breast cancers, there have been no reports of aplastic anemia after receiving PARPi therapy. This case report describes a 75-year-old man with BRCA2-positive metastatic castrate-resistant prostate cancer who developed aplastic anemia after taking olaparib.
RESUMEN
Synchronous or sequential development of multiple myeloma and prostate carcinoma is rare. It is not sure whether these two occur independently or if one influences the development of the other. We reviewed the cases published in the English literature; eight cases of myeloma developing after diagnosis and treatment for prostate carcinoma, five cases of simultaneous occurrence of myeloma and prostate carcinoma, and five cases where the patient with multiple myeloma later developed prostate carcinoma were found. This short review attempts to analyze the occurrence of these two diseases in the same patient and dissect whether there is a close association or it is just a mere coincidence.
Asunto(s)
Carcinoma , Mieloma Múltiple , Neoplasias de la Próstata , Masculino , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Carcinoma/patologíaRESUMEN
We report the rare case of a primary malignant melanoma of the urethra. An 89-year-old African American woman who was referred to our urology clinic for intermittent gross hematuria and a palpable vaginal mass of two months duration. Cystoscopy revealed a 3 cm mass in the distal urethra and urethral meatus that was surgically resected by wide local excision. The histopathologic diagnosis was primary malignant melanoma of the urethra. The patient was subsequently treated with adjuvant EBRT and immunotherapy with nivolumab and ipilimumab. Post-treatment PET-CT showed good response to treatment and patient remained in remission at eight month follow up.
RESUMEN
Neuroendocrine prostate cancer (NEPC) is a rare entity. De novo NEPC is extremely rare; other cases are usually adenocarcinoma previously treated with hormonal therapies transforming to NEPC. Most of the cases are metastatic at diagnosis and regardless of the histology types, the prognosis is poor. In this report, we reviewed the checkpoint inhibitor (CPI) immunotherapies used for neuroendocrine tumors of the prostate. Very limited data with only a few cases were published which showed a limited activity by immunotherapy; therefore, we present our experience of 2 cases: (1) adenocarcinoma with foci of NEPC and (2) adenocarcinoma transforming to NEPC after treatment with androgen deprivation therapy (ADT); both of which were initially managed with ADT, chemotherapy followed by immunotherapy with durvalumab, a programmed death ligand 1 inhibitor. In these 2 cases, CPI therapy showed limited efficacy, suggesting that neuroendocrine histology is not very responsive to CPI treatment, regardless if onset is early or late. Other therapies need to be explored for the treatment of NEPC.
Asunto(s)
Adenocarcinoma , Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Neoplasias de la Próstata , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Antagonistas de Andrógenos/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Humanos , Factores Inmunológicos/uso terapéutico , Inmunoterapia , Masculino , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/patología , Próstata , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Pirroles/uso terapéutico , Obstrucción Ureteral/prevención & control , Obstrucción Ureteral/fisiopatología , Animales , Atorvastatina , Enfermedad Crónica , Fibrosis , Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Masculino , Pirroles/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
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.
Asunto(s)
Pene/lesiones , Uretra/lesiones , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Adulto , Coito , Humanos , Masculino , Persona de Mediana Edad , Erección Peniana , Pene/cirugía , Cuidados Preoperatorios/métodos , Rotura/diagnóstico , Rotura/cirugía , Resultado del Tratamiento , Uretra/cirugíaRESUMEN
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.
Asunto(s)
Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Riñón/efectos de los fármacos , Riñón/fisiopatología , Pirroles/uso terapéutico , Obstrucción Ureteral/tratamiento farmacológico , Enfermedad Aguda , Albuminuria/prevención & control , Animales , Atorvastatina , Hemodinámica/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Obstrucción Ureteral/fisiopatologíaRESUMEN
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.
Asunto(s)
Prolapso , Enfermedades Uretrales/diagnóstico , Enfermedades Uretrales/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Índice de Masa Corporal , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , Sobrepeso/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Resultado del Tratamiento , Enfermedades Uretrales/epidemiología , Cateterismo UrinarioRESUMEN
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.
Asunto(s)
Bacteriemia/etiología , Bacteriemia/microbiología , Biopsia con Aguja , Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli/etiología , Salud de la Familia , Personal de Hospital , Próstata/patología , Ultrasonografía Intervencional , Biopsia con Aguja/efectos adversos , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/microbiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
Asunto(s)
Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pirroles/uso terapéutico , Obstrucción Ureteral/tratamiento farmacológico , Animales , Atorvastatina , Enfermedad Crónica , Pruebas de Función Renal , Masculino , Ratas , Ratas Sprague-Dawley , Obstrucción Ureteral/fisiopatologíaRESUMEN
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.
Asunto(s)
Factor Natriurético Atrial/fisiología , Riñón/fisiopatología , Neprilisina/antagonistas & inhibidores , Obstrucción Ureteral/fisiopatología , Animales , Riñón/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
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.
Asunto(s)
Hemodinámica/fisiología , Riñón/irrigación sanguínea , Receptor de Endotelina A/fisiología , Obstrucción Ureteral/fisiopatología , Animales , Arginina/farmacología , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Perros , Antagonistas de los Receptores de la Endotelina A , Endotelinas/fisiología , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Oligopéptidos/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiología , Equilibrio Hidroelectrolítico/efectos de los fármacos , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
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.