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1.
BJU Int ; 111(6): 934-40, 2013 May.
Article in English | MEDLINE | ID: mdl-23350937

ABSTRACT

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Little is known as to the potential for over-treatment of young men diagnosed with prostate cancer. We show that for men aged ≤55 years with PSA screen-detected disease, 45% of the tumours are classified as very low risk and 85% of these have favourable pathology, yet most are actively treated. These findings raise the spectre of over-treatment for a group of men likely to be affected by treatment side-effects. OBJECTIVE: To identify a population of young men (aged <55 years at diagnosis) with very-low-risk prostate cancer (stage cT1c, with prostate-specific antigen [PSA] density of <0.15 ng/mL/g, Gleason score ≤6, and ≤2 positive biopsy cores with <50% tumour involvement) that may be candidates for active surveillance (AS). PATIENTS AND METHODS: We queried a Department of Defense tumour registry and hard-copy records for servicemen diagnosed with prostate cancer from 1987 to 2010. Statistical analyses were undertaken using Fisher's exact and chi-square testing. RESULTS: From 1987-1991 and 2007-2010, PSA screen-detected tumours diagnosed in men aged ≤55 years rose >30-fold. Data for a subset of men (174) with PSA screen-detected cancer were evaluable for disease risk assessment. Of the 174 men with screen-detected disease, 81 (47%) had very-low-risk disease. Of that group, 96% (78/81) selected treatment and, of 57 men undergoing radical prostatectomy (RP), the tumours of 49 (86%) carried favourable pathology (organ confined, <10% gland involvement, Gleason ≤6). CONCLUSIONS: Nearly half of young men with PSA screen-detected prostate cancer are AS candidates but the overwhelming majority seek treatment. Considering that many tumours show favourable pathology at RP, there is a possibility that these patients may benefit from AS management.


Subject(s)
Biomarkers, Tumor/blood , Early Detection of Cancer/methods , Population Surveillance , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/immunology , Adult , Age Distribution , Humans , Male , Middle Aged , Military Personnel , Neoplasm Grading , Patient Selection , Predictive Value of Tests , Prostatic Neoplasms/epidemiology , Risk Assessment , United States/epidemiology
2.
J Renin Angiotensin Aldosterone Syst ; 11(4): 234-42, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20807796

ABSTRACT

INTRODUCTION: Angiotensin II (AngII) regulates blood pressure and water and electrolyte metabolism through the stimulation of NAD(P)H oxidase and production of reactive oxygen species (ROS) such as O2⁻, which is metabolised by superoxide dismutase, catalase and glutathione peroxidase. We assessed the role of AT1 and AT2 receptors, NAD(P)H oxidase and protein kinase C (PKC) in Ang II-induced sodium and water excretion and their capacity to stimulate antioxidant enzymes in the rat hypothalamus, a brain structure known to express a high density of AngII receptors. MATERIALS AND METHODS: Male Sprague-Dawley rats were intracerebroventricularly (ICV) injected with AngII and urinary sodium and water excretion was assessed. Urine sodium concentration was determined using flame photometry. After decapitation the hypothalamus was microdissected under stereomicroscopic control. Superoxide dismutase, catalase and glutathione peroxidase activity were determined spectrophotometrically and extracellular signal-regulated kinase (ERK1/2) activation was analysed by Western blot. RESULTS: AngII-ICV resulted in antidiuresis and natriuresis. ICV administration of losartan, PD123319, apocynin and chelerythrine blunted natriuresis. In hypothalamus, AngII increased catalase, superoxide dismutase and glutation peroxidase activity and ERK1/2 phosphorylation. These actions were prevented by losartan, apocynin and chelerythrine, and increased by PD123319. CONCLUSIONS: AT1 and AT2 receptors, NAD(P)H oxidase and PKC pathway are involved in the regulation of hydromineral metabolism and antioxidant enzyme activity induced by AngII.


Subject(s)
Angiotensin II/pharmacology , Antioxidants/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Hypothalamus/drug effects , Hypothalamus/enzymology , NADPH Oxidases/metabolism , Receptor, Angiotensin, Type 1/metabolism , Acetophenones/administration & dosage , Acetophenones/pharmacology , Animals , Benzophenanthridines/administration & dosage , Benzophenanthridines/pharmacology , Catalase/metabolism , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Glutathione Peroxidase/metabolism , Imidazoles/administration & dosage , Imidazoles/pharmacology , Injections, Intraventricular , Losartan/administration & dosage , Losartan/pharmacology , Male , Pyridines/administration & dosage , Pyridines/pharmacology , Rats , Rats, Sprague-Dawley , Sodium/urine , Superoxide Dismutase/metabolism , Water
3.
Article in English | MEDLINE | ID: mdl-19286753

ABSTRACT

INTRODUCTION: Central administration of angiotensin II (Ang II) is known to reduce urinary volume and to increase sodium and potassium excretion. Recently, a novel signalling mechanism for Ang II in the periphery has been shown to involve reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase-derived reactive oxygen species (ROS).Although ROS are now known to be involved in numerous Ang II-regulated processes in peripheral tissues, and are increasingly implicated in CNS neurodegenerative diseases, the role of ROS in central regulation of Ang II-induced hydromineral metabolism remains unexplored.The hypothesis that ROS are involved in central Ang II signalling and in Ang II-dependent antidiuresis, natriuresis and kaliuresis was tested by the use of selective antagonists of the NAD(P)H oxidase cascade. MATERIALS AND METHODS: In intracerebroventricular (ICV)-cannulated rats,Ang II was injected ICV and urinary sodium and potassium excretion was assessed at 1-, 3-, and 6-hour periods of urine collection. Urine sample was analysed for sodium and potassium concentration using a flame photometer. The role of NAD(P)H oxidase-dependent signalling cascade was evaluated using the selective NAD(P)H oxidase inhibitor, apocynin; the superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol); and the protein kinase C inhibitor, chelerythrine. RESULTS: ICV administration of Ang II to conscious hydrated rats resulted in a significant decrease in urinary volume in the first hour, and an increased sodium and potassium excretion during the 6-hour period of urine collection, which was most effective during the 3 and 6 h. Interference with the NAD(P)H oxidase signalling by central administration of apocynin, tempol or chelerythrine, blunted the natriuretic and kaliuretic effect induced by central administration of Ang II, without affecting its antidiuretic action. CONCLUSION: This study demonstrates that increases of urinary sodium and potassium excretion elicited by central administration of Ang II are mediated by NAD(P)H oxidase- dependent production of superoxide and protein kinase C activation in conscious hydrated rats.


Subject(s)
Angiotensin II/administration & dosage , Angiotensin II/pharmacology , Natriuresis/drug effects , Oxidative Stress/drug effects , Acetophenones/administration & dosage , Acetophenones/pharmacology , Animals , Benzophenanthridines/administration & dosage , Benzophenanthridines/pharmacology , Cyclic N-Oxides/administration & dosage , Cyclic N-Oxides/pharmacology , Injections, Intraventricular , Male , NADPH Oxidases/antagonists & inhibitors , Potassium/urine , Protein Kinase C/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Sodium/urine , Spin Labels , Superoxide Dismutase/metabolism , Time Factors , Water
4.
Urology ; 71(1): 32-5, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18242360

ABSTRACT

OBJECTIVES: To investigate the holding strength and slippage of Lapra-Ty clips on various suture types and sizes. METHODS: Using an automated materials testing system with the Lapra-Ty in a fixed position, Lapra-Ty holding strength and displacement were determined with 0, 2-0, 3-0, and 4-0 Vicryl, Monocryl, and polydioxanone suture (PDS). To simulate clinical application, Lapra-Tys were also tested by applying a load to these sutures after being passed through a full-thickness layer of tautly suspended fresh porcine bladder tissue. Three trials were performed with each suture type and size. RESULTS: The Lapra-Ty holding strength with Vicryl suture was significantly higher than with Monocryl or PDS of the same suture size in bladder tissue trials. Monocryl suture had a significantly higher displacement than Vicryl or PDS of the same suture size in bladder tissue trials (except for 4-0 Monocryl and PDS having insignificantly different displacements). Lapra-Tys slipped off Vicryl, Monocryl, and PDS in 25%, 67%, and 67% of their respective trials. Lapra-Tys did not slip during any of the trials with 2-0 suture of any type or 3-0 Vicryl. Lapra-Tys with holding strengths on suture less than approximately 8 Newtons (N) slipped and greater than 8 N pulled through the bladder tissue without slipping. CONCLUSIONS: The optimal suture type and size to maximize Lapra-Ty holding strength and minimize slippage was determined to be 2-0 and 3-0 Vicryl, 2-0 Monocryl, and 2-0 PDS. Monocryl suture stretches more than Vicryl and PDS at higher loads.


Subject(s)
Sutures , Anastomosis, Surgical , Animals , Materials Testing , Polydioxanone , Polyglactin 910 , Swine , Tensile Strength , Urinary Bladder/surgery , Urologic Surgical Procedures
5.
Nat Clin Pract Urol ; 4(2): 111-4, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17287872

ABSTRACT

BACKGROUND: A 67-year-old male, with a history of stable lower urinary tract symptoms, diabetes mellitus, benign prostatic hyperplasia, gonococcal urethritis, and excessive alcohol consumption, presented to the emergency room with sepsis and acute bacterial prostatitis. He had recently returned from a visit to Indonesia, where he had been a first-hand witness to the 2004 tsunami. INVESTIGATIONS: Complete blood cell count, urine analysis, blood, urine, and prostatic abscess cultures, chest X-ray, contrasted CT of the abdomen and pelvis, and (18)F-fluorodeoxyglucose PET. DIAGNOSIS: Melioidosis. MANAGEMENT: Broad-spectrum empiric antibiotics were administered initially; therapy was then changed to intravenous imipenem plus cilastatin with slow initial clinical improvement. (18)F-fluorodeoxyglucose PET localized the prostate as the only nidus of infection. Ultrasound-guided fine needle aspiration of a small fluid collection of the prostate also grew Burkholderia pseudomallei. The patient improved clinically and was discharged to complete a 2-week course of intravenous imipenem plus cilastatin followed by a 3-month course of oral trimethoprim plus sulfamethoxazole. This medication was switched to co-amoxiclav and doxycycline to complete the 3-month course. The patient was well at his last follow-up, 3 months following hospital discharge.


Subject(s)
Burkholderia pseudomallei , Melioidosis/diagnostic imaging , Prostatitis/diagnostic imaging , Prostatitis/microbiology , Aged , Burkholderia pseudomallei/isolation & purification , Humans , Male , Melioidosis/microbiology , Radiography
6.
Urology ; 68(5): 1121.e13-6, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17095056

ABSTRACT

We report the clinical, sonographic, and pathologic findings of an incidentally discovered testicular granulosa cell tumor of the adult type in a 32-year-old man. Serum tumor markers were within normal limits. The sonographic findings revealed a well-circumscribed, hypoechoic mass. Gross inspection confirmed a unilobular, well-circumscribed mass without necrosis. Microscopically, the mass was demarcated by a thin capsule, with tumor cells arranged in nests with low mitotic activity. These cells were diffusely immunoreactive for vimentin and focally for inhibin. The entrapped rete epithelium stained positive for pancytokeratin (Lu-5). We present our management of this rare malignancy.


Subject(s)
Granulosa Cell Tumor/diagnosis , Testicular Neoplasms/diagnosis , Adult , Humans , Male
7.
Urology ; 68(5): 983-7, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17095059

ABSTRACT

OBJECTIVES: To evaluate the use of computed tomography-guided, resistance-based, percutaneous radiofrequency ablation of renal malignancies using conscious sedation. METHODS: Twenty-three patients with a mean age of 74 years underwent 27 PRFA treatments, using only conscious sedation, for enhancing renal masses, with a mean renal mass of 2.69 cm. All patients had multiple medical comorbidities that precluded standard operative management. Patients were followed up postoperatively at 3-month intervals with renal function studies and enhanced imaging. Successful ablation was defined as a lack of enhancement or resolution of the renal mass. RESULTS: Of the 23 patients, 16 (80%) had successful ablation with a single treatment, 4 had initial failure, and 3 were lost to follow-up. Of the 4 patients with initial failure, 2 underwent reablation successfully, 1 patient elected watchful waiting, and 1 patient died of metastatic renal cell carcinoma. The overall cancer-free survival rate was 90% (18 of 20 patients) at a mean follow-up of 24 months. The exclusion of 2 patients who underwent four sessions for renal masses greater than 4 cm improved the survival rate to 94% (17 of 18). No statistically significant difference was found between the preoperative and postoperative serum creatinine levels (P = 0.46), even in the patients with a preoperative creatinine level greater than 1.5 (P = 0.51). Our only complication was a single perinephric hematoma that resolved spontaneously. CONCLUSIONS: We have demonstrated promising oncologic results for computed tomography-guided percutaneous radiofrequency ablation of tumors in select patients with small renal masses. The procedure was well tolerated under conscious sedation. None of the patients demonstrated significant changes in renal function.


Subject(s)
Catheter Ablation/methods , Conscious Sedation , Kidney Neoplasms/surgery , Nephrectomy/methods , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Follow-Up Studies , Humans , Middle Aged , Retrospective Studies , Time Factors
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