ABSTRACT
Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.
Subject(s)
Cystitis, Interstitial/physiopathology , Epidermal Growth Factor/pharmacology , Potassium Channels/metabolism , Urinary Bladder/physiopathology , Cells, Cultured , Cystitis, Interstitial/metabolism , Cystitis, Interstitial/pathology , Dose-Response Relationship, Drug , Electric Conductivity , Epidermal Growth Factor/administration & dosage , Genistein/pharmacology , Heparin-binding EGF-like Growth Factor , Humans , Intercellular Signaling Peptides and Proteins , Large-Conductance Calcium-Activated Potassium Channels/metabolism , Potassium Channels/drug effects , Potassium Channels, Inwardly Rectifying/metabolism , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Urinary Bladder/metabolism , Urinary Bladder/pathology , Urothelium/metabolism , Urothelium/pathology , Urothelium/physiopathologyABSTRACT
OBJECTIVES: Complete urinary tract extirpation (CUTE) involves simultaneous bilateral nephroureterectomy, cystectomy or cystoprostatectomy, and the creation of a urinary diversion, if needed. Case reports of this operation have been published, but to our knowledge, this is the largest case series yet reported. We sought to evaluate the characteristics and outcomes of patients who underwent CUTE. METHODS: From 1994 to 2005, 9 patients underwent CUTE at our institution. We performed a retrospective chart review of these patients. The data reviewed included demographics, operative time, length of stay, complications, recurrences, and overall survival. RESULTS: Nine patients who underwent CUTE were identified. The mean patient age at the operation was 61 years. Five patients were men. The mean operative time was 356 minutes. Two patients required a blood transfusion. The length of stay averaged 10.8 days (range 6 to 47). Four patients had functioning renal allografts before and after surgery. Three patients needing dialysis received renal allografts postoperatively. The overall survival rate at a mean follow-up of 31 months was 86%. CONCLUSIONS: Although this report presented a small number of patients, it has illustrated that CUTE can be performed safely and allow definitive surgical treatment of patients with complex genitourinary pathologic findings.
Subject(s)
Urinary Tract/surgery , Urologic Surgical Procedures/methods , Female , Humans , Kidney Transplantation , Male , Middle Aged , Renal Dialysis , Urinary Diversion , Urologic Neoplasms/surgeryABSTRACT
PURPOSE: Variants of the bladder/cloacal exstrophy complex are rare. Different presentations and subsequent management and outcome are discussed. MATERIALS AND METHODS: We performed a retrospective review of our database of more than 815 patients with the exstrophy complex. Patients with variants of classic epispadias or bladder or cloacal exstrophy were identified. Anatomical presentation, surgical management, type of continence procedures and final outcome were evaluated. RESULTS: Of the 25 patients with variants 13 were treated primarily at our institution and 12 were referred. Time until primary bladder closure ranged from 1 day to 4 years. Followup after continence procedure ranged from 1 month to 39 years. Seven of the 25 patients are awaiting a continence procedure. Six patients are dry without a continence procedure, of whom 4 have superior vesical fistulas. A total of 11 patients underwent bladder neck reconstruction (BNR), of whom 3 are dry, 2 are dry during the day but are wet at night, 1 had a failed procedure and 5 are dry after continent diversion (CD). One additional patient underwent CD initially and is dry. Referred cases of epispadias with bladder prolapse were not recognized at birth and had delayed closure. Impaired bladder growth or failed BNR required CD in 4 patients, and 2 are awaiting a continence procedure. Skin covered and duplicate exstrophy had comparable outcomes to the classic presentations. Duplicated organs were used for reconstructive procedures. Of the 6 patients with cloacal variant 2 are continent of stool and 2 await a Pena procedure. One of these patients has an ileal stoma and 1 has a colostomy. CONCLUSIONS: The initial presentation of exstrophy variants can be confusing, often delaying initial treatment. Superior vesical fistulas permit continence without BNR due to an intact urinary sphincter. Variants such as epispadias with bladder prolapse and duplicate or skin covered exstrophy should be closed at birth with standardized techniques to promote bladder growth for later BNR. These cases are faced with the same long-term problems as the classic presentation. Cloacal variants can present with intact anal innervation, allowing a later Pena procedure.
