Tissue resident stem cells are believed to exist in most tissues, and their identification is commonly done by a combination of immunostaining for putative stem cell markers and the label-retaining cell (LRC) strategy. In the present study we employed these approaches to identify potential stem cells in the urinary bladder.
Newborn rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU), and their bladders harvested at four different time points afterward. The bladders were processed for EdU staining and immunofluorescence staining for stem cell markers Lgr5, CD34, SSEA-1, and c-kit. EdU-positive cells were counted and co-localization with stem cell markers determined.
At day one post-EdU injection, 1804.0 ± 227.7 bladder cells were labeled in each cross section. As time increased, fewer bladders remained labeled, dropping to 236.5±53.0 cells per field. In the 1-day bladders, 27.5±4.9% of the epithelial cells were labeled as compared to 12.1±2.8% in the detrusor. The labeling rates in these two tissue compartments gradually equalized, reaching at approximately 5.5% in the 8-week samples. Distribution of LRC was random, without preferential labeling of basal cells. Lgr5 and SSEA-1 were detectable in the urothelium; CD34 and c-kit in the lamina propria and detrusor. Approximately 30 to 40% of c-kit-positive cells were EdU-positive.
Labeling of bladder cells by EdU occurred randomly, and label retaining was not associated with expression of Lgr5, CD34, or SSEA-1. The strong association between label retaining and c-kit expression appears to relate to interstitial cells of Cajal (ICCs), not stem cells.
urinary bladder; EdU labeling; label-retaining cells; stem cell markers; c-kit; interstitial cells of Cajal
We report a case of a patient who developed encrusted cystitis following transurethral resection of the prostate. This rare urologic condition is characterized by intramucosal calcifications and is commonly preceded by urologic instrumentation. Urea-splitting bacteria, most commonly Corynebacterium urealyticum, are the causative pathogen. Treatment is a combination of antibiotics, urine acidification and endoscopic removal of encrustations.
endoscopy; infectious disease; hematuria; encrusted cystitis
Introduction and Objectives
Benign prostate-specific antigen (BPSA) and [-2]pro-prostate-specific antigen ([-2]proPSA) have been shown to be predictive of prostate cancer and benign prostatic hyperplasia treatment, but little is known about longitudinal changes in these markers and how they relate to outcomes.
In 1990, a 25% subsample from a cohort of Caucasian men aged 40–79 years randomly selected from Olmsted County, MN residents completed a detailed clinical examination. BPSA and [-2]proPSA were measured from frozen sera. Subjects were evaluated biennially (median follow-up 7 years; range: 0–8.8 years). Mixed-effects regression models were used to estimate longitudinal changes in BPSA and [-2]proPSA levels overall and by outcomes. Spearman correlations were used to compare these changes with baseline levels and annualized changes in urologic measures.
Median (25th, 75th percentiles) annualized percent change for [-2]proPSA and BPSA were 3.7% (2.5%, 5.2%) and 7.3% (6.8%, 7.7%), respectively. Annualized percent change for both markers were correlated with baseline and annualized changes in PSA and prostate volume. Annualized percent change increased with increasing age decade for [-2]proPSA, but not BPSA. The median (25th, 75th percentiles) rate of increase in [-2]proPSA was significantly greater for men who developed enlarged prostates (3.5% (2.6%, 4.4%)) or prostate cancer (8.1% (6.6%, 9.8%)) compared to those who did not develop enlarged prostates (1.9% (0.9%, 3.0%)) or prostate cancer (3.5% (2.3%, 4.8%)).
BPSA and [-2]proPSA levels increase over time. The annualized percent change in [-2]proPSA increases with age and may be a useful predictor of development of prostate cancer.
To evaluate the association between dietary quality and the prevalence of lower urinary tract symptoms (LUTS).
We used urinary symptom and dietary data obtained from the 2000-2001 National Health and Nutrition Examination Survey (NHANES) for the study. Dietary quality was assessed using the 10-component United States Department of Agriculture (USDA) Healthy Eating Index (HEI). We used bivariate methods to examine rates of LUTS among men with poor versus good diets. Multivariable logistic regression was used to calculate odds ratios after applying sample weights and controlling for age, race/ethnicity, smoking status, diabetes, alcohol intake, and exercise.
Our study cohort consisted of 1385 men aged ≥40 years, of whom 279 (21.1%) reported LUTS. We found higher rates of LUTS among men with poor dietary intake of dairy (22.4% vs 16.4%, P = .013) and among men with poor intake of protein (24.6% vs 17.9%, P = .012) as well as among those with overall poor diet (25.8 vs 17.8%, P = .018) with little dietary variety (26.1 vs 17.6%, P = .001). On multivariate analysis, an unhealthy diet (odds ratios [OR] = 1.7; 95% confidence interval [CI] = 1.05-2.90) was associated with more LUTS, whereas alcohol intake was protective from LUTS (OR = 0.67; 95% CI = 0.48-0.93).
In an analysis of NHANES data, we found that poor diet quality was independently associated with patient-reported LUTS.
To report urethroplasty outcomes in men who developed urethral stricture after undergoing radiation therapy for prostate cancer.
Our urethroplasty database was reviewed for cases of urethral stricture after radiation therapy for prostate cancer between June 2004 and May 2010. Patient demographics, prostate cancer therapy type, stricture length and location, and type of urethroplasty were obtained. All patients received clinical evaluation, including imaging studies post procedure. Treatment success was defined as no need for repeat surgical intervention.
Twenty-nine patients underwent urethroplasty for radiation-induced stricture. Previous radiation therapy included external beam radiotherapy (EBRT), radical prostatectomy (RP)/EBRT, EBRT/brachytherapy (BT) and BT alone in 11 (38%), 7 (24%), 7 (24%), and 4 (14%) patients, respectively. Mean age was 69 (±6.9) years. Mean stricture length was 2.6 (±1.6) cm. Anastomotic urethroplasty was performed in 76% patients, buccal mucosal graft in 17%, and perineal flap repair in 7%. Stricture was localized to bulbar urethra in 12 (41%), membranous in 12 (41%), vesicourethra in 3 (10%), and pan-urethral in 2 (7%) patients. Overall success rate was 90%. Median follow-up was 40 months (range 12-83). Time to recurrence ranged from 6-16 months.
Multiple forms of urethroplasty appear to be viable options in treating radiation-induced urethral stricture. Future studies are needed to examine the durability of repairs.
Replacement of the glycosaminoglycan (GAG) layer with intravesically-administered GAGs is an effective therapy for interstitial cystitis in at least some patients. Intravesically-administered chondroitin sulfate was previously shown to bind to and restore the impermeability of surface-damaged (“leaky”) urothelium to small ions. This study investigated whether a physiologic effect of “GAG replenishment therapy” altered recruitment of inflammatory cells in an acute bladder damage model.
Rat bladders were damaged with 10mM HCl. Negative control bladders were treated with PBS. On the following day, the animal bladders were treated with 20mg/mL chondroitin sulfate in PBS, while the negative and positive controls were treated with PBS alone. Two and four days after treatment with chondroitin sulfate, animals were euthanized, and sections of their bladders were analyzed by Toluidine Blue staining for mast cells immunohistochemical labeling using antibodies against CD-45 for lymphocytes, and myeloperoxidase for neutrophils.
Chondroitin sulfate treatment statistically significantly reduced recruitment of inflammatory cells including neutrophils and mast cells to the suburothelial space but did not alter recruitment of CD-45-positive lymphocytes.
For the first time we demonstrate that intravesical GAG replenishment therapy also produces a physiological effect of decreasing recruitment of inflammatory cells in an acute model of damaged bladder. These findings support use of intravesically administered GAG for bladder disorders that result from a loss of impermeability, including interstitial, radiation and chemical cystitis, and possibly others as well.
Interstitial Cystitis; Inflammation; Glycosaminoglycans; Chondroitin Sulfate
The pancreas is vulnerable to injury at the time of shock wave lithotripsy (SWL) as evidenced by case studies; thus, concern exists for the development of diabetes mellitus following SWL. Since previous studies may have been limited by referral and detection biases, the current study was completed in a population-based cohort.
The Rochester Epidemiologic Project (REP) was used to identify all Olmsted County, Minnesota residents diagnosed with urolithiasis from 1985 to 2008. New onset diabetes was identified by diagnostic codes and treatment with SWL by surgical codes. Cox proportional hazards models were used to determine the risk of diabetes following SWL therapy.
There were 5,287 incident stone formers without pre-existing diabetes and with at least 3 months of follow-up. After an average follow-up of 8.7 years, 423 patients (8%) were treated with SWL and new onset diabetes developed in 743 (12%). The diagnosis of diabetes followed SWL in 77 patients. However, there was no evident association between SWL and the development of diabetes before (HR=0.98, 95% CI: 0.76 to 1.26) or after (HR 0.92, 95% CI: 0.71 to 1.18) controlling for age, gender, and obesity.
In this large, population-based cohort, the long-term risk for developing diabetes was not increased in persons who received SWL to treat their kidney stones.
lithotripsy; urolithiasis; diabetes mellitus
To describe the demographics and mechanism of genitourinary (GU) injuries related to pubic hair grooming in patients who present to U.S. emergency departments (EDs).
MATERIALS AND METHODS
The National Electronic Injury Surveillance System contains prospectively collected data from patients who present to EDs with consumer product-related injuries. The National Electronic Injury Surveillance System is a stratified probability sample, validated to provide national estimates of all patients who present to U.S. EDs with an injury. We reviewed the National Electronic Injury Surveillance System to identify incidents of GU injury related to pubic hair grooming for 2002–2010. The variables reviewed included age, race, gender, injury type, location (organ) of injury, hospital disposition, and grooming product.
From 2002 to 2010, an observed 335 actual ED visits for GU injury related to grooming products provided an estimated 11,704 incidents (95% confidence interval 8430–15,004). The number of incidents increased fivefold during that period, amounting to an estimated increase of 247 incidents annually (95% confidence interval 110–384, P = .001). Of the cohort, 56.7% were women. The mean age was 30.8 years (95% confidence interval 28.8–32.9). Shaving razors were implicated in 83% of the injuries. Laceration was the most common type of injury (36.6%). The most common site of injury was the external female genitalia (36.0%). Most injuries (97.3%) were treated within the ED, with subsequent patient discharge.
Most GU injuries that result from the use of grooming products are minor and involve the use of razors. The demographics of patients with GU injuries from grooming products largely paralleled observations about cultural grooming trends in the United States.
The objectives of this study were: 1) to determine whether there is an association between C-reactive protein (CRP) levels and lower urinary tract symptoms (LUTS) as assessed by the American Urological Association Symptom Index (AUA-SI) among both men and women, 2) to determine the association of CRP levels with individual urologic symptoms comprising the AUA-SI among both men and women.
The Boston Area Community Health (BACH) Survey used a multistage stratified design to recruit a random sample of 5,502 adults age 30–79. Blood samples were obtained on 3,752 participants. Analyses were conducted on 1,898 men and 1,854 women with complete data on C-Reactive Protein (CRP) levels. Overall LUTS was defined as an AUA-SI≥8 (moderate to severe LUTS). Urologic symptoms comprising the AUA-SI were included in the analysis as reports of fairly often to almost always vs. non/rarely/a few times.
A statistically significant association was observed between CRP levels and overall LUTS among both men and women. The pattern of associations between individual symptoms and CRP levels varied by gender. Nocturia and straining were associated with higher CRP levels among men, while incomplete emptying and weak stream were associated with higher CRP levels among women.
This study demonstrates an association between CRP levels and LUTS in both men and women. The dose-response relationship between increased CRP levels and increased odds of LUTS supports the hypothesized role of inflammatory processes in the etiology of LUTS.
C-reactive protein; lower urinary tract symptoms; epidemiology
To investigate the effects of birth trauma and estrogen on urethral elastic fibers and elastin expression
Pregnant rats were subjected to sham operation (Delivery-only), DVDO (delivery, vaginl distension and ovariectomy), or DVDO+E2 (estrogen). At 2, 4, 8, or 12 weeks, their urethras were harvested for elastic fiber staining and RT-PCR analysis. Urethral cells were treated with TGF-β1 and/or estrogen and analyzed for elastin mRNA expression. Urethral cells were also examined for the activities of Smad1 and Smad3/4 responsive elements in response to TGF-β1 and estrogen.
At 8 weeks post-treatment, the urethras of DVDO rats had fewer and shorter elastic fibers when compared to Delivery-only rats, and those of DVDO+E2 rats had fewer and shorter elastic fibers when compared to DVDO rats. Elastin mRNA was expressed at low levels in Delivery-only rats and at increasingly higher levels in DVDO rats at 2, 4, and 8 weeks but at sharply lower levels in DVDO+E2 rats when compared to DVDO rats at 8 weeks. Urethral cells expressed increasingly higher levels of elastin mRNA in response to increasing concentrations of TGF-β1 up to 1 ng/ml. At this TGF-β1 concentration, urethral cells expressed significantly lower levels of elastin mRNA when treated with estrogen prior to or after TGF-β1 treatment. Both Smad1 and Smad3/4 responsive elements were activated by TGF-β1 and such activation was suppressed by estrogen.
Birth trauma appears to activate urethral elastin expression via TGF-β1 signaling. Estrogen interferes with this signaling, resulting in improper assembly of elastic fibers.
Urethra; Urinary incontinence; Birth trauma; Elastic fibers; Estrogen; TGF-β
To investigate the effects of estrogen, raloxifene, and levormeloxifene on the expression of Rho-kinase signaling molecules in urethral smooth muscle cells (USMCs).
USMCs were isolated from female rats. Expression of calponin and estrogen receptors α (ERα was detected by immunofluorescence staining. Cells were treated with estrogen, raloxifene, or levormeloxifene at 0, 1, 10, and 100 nM for 48 h and then processed for western blotting with antibodies against RhoA, Rho kinase I and II (Rock-I and Rock-II), myosin light chain (MLC), phosphorylated MLC (p-MLC), and β-actin. Protein expression was quantitated by densitometry, followed by statistical analysis with β-actin as control.
USMCs expressed calponin and ERα. Treatment of USMCs with estrogen, raloxifene or levormeloxifene resulted in decreased expression of RhoA, Rock-I, Rock-II, and p-MLC in a dosage-dependent manner.
Estrogen, raloxifene, and levormeloxifene may affect urinary continence by inhibiting the expression of Rho-kinase signaling molecules.
urethral smooth muscle cells; estrogen; raloxifene; levormeloxifene; SERMs; Rho-kinase signaling
prostate cancer; patient-specific mold; multiparametric MRI; registration; correlation
Diabetes has been associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) in aging men. We conducted a study to determine if diabetes treatment was associated with BPH/LUTS and progression in black and white men.
Using the Olmsted County Study of Urinary Symptoms and Health Status among Men (OCS) and the Flint Men’s Health Study (FMHS), we examined how use of medical therapy (e.g., insulin regimens, oral hypoglycemics, etc.) related to changes in LUTS severity, maximum urinary flow rate measured by uroflowmetry, prostate volume determined by transrectal ultrasound, and serum PSA concentrations.
Of the 2,226 men participating in the OCS and the FMHS, 186 men reported a history of diabetes, 76.9% of which were treated with medical therapy. Overall, men with diabetes had significantly greater odds of moderate/severe LUTS (age- and race-adjusted OR=1.37, 95% CI=1.00, 1.87) compared to non-diabetics. However, among diabetic men, those not taking medications had higher odds of moderate/LUTS than those taking medications. This association among men not taking medications was seen for five of the seven individual symptoms. Prostate volume and PSA were not significantly associated with diabetes treatment. No significant differences were observed for annual change in BPH characteristics by diabetes treatment status.
These findings suggest that the presence of diabetes and subsequent poor glycemic control may be less related to prostate growth and more to the dynamic components of lower urinary tract function. Further evaluations of the associations between glycemic control and BPH progression are warranted.
diabetes; BPH; LUTS; diabetes; men; aging
This multicenter cooperative group single arm trial assessed the efficacy of a multiagent taxane-based chemotherapy in combination with hormonal therapy in men with metastatic androgen-dependent prostate cancer.
Forty-one patients with newly diagnosed metastatic prostate cancer involving both the axial and appendicular skeletons or viscera were enrolled. Thirty-five were treated with combined androgen blockade and up to 4 cycles of oral estramustine (280 mg orally 3 times per day) and etoposide (50 mg/m2 daily) for 14 days of each 21 day cycle, with paclitaxel (135 mg/m2 IV over 1 hour) on day 2 of each cycle. Chemotherapy was started within 30 days of initiation of hormonal therapy. Patients were followed to determine progression-free survival.
The median progression-free survival for the evaluable population was 13 months (95% CI 10–16 mo) with a median overall survival of 38 months (95% CI 28–49 mo). The main toxicities were myelosuppression with 9 patients with ≥ grade 3 neutropenia, and 1 with grade 4 thrombocytopenia. One patient died with neutropenic infection. Four episodes of thrombosis embolism occurred (3 grade 4, 1 grade 3) with one episode of grade 4 cardiac ischemia.
Administration of chemotherapy to this population is feasible with moderate toxicity. This is a high-risk population with poor prognosis and this study serves as a basis for ongoing phase III trials assessing this approach in metastatic prostate cancer.
Lumagel™, a non-toxic polymer may be administered intra-arterially under fluoroscopy to obtain a bloodless operative field during partial nephrectomy while maintaining normal circulation to uninvolved renal tissue. We extend previous robotic assisted techniques developed in the swine model to studies of laparoscopic and open partial nephrectomy conducted in pigs and calves, designed to encompass vessel diameters similar to those encountered in humans.
Materials and Methods
10 Animals (7 pigs, 3 calves) underwent flow interruption to the kidney, 2 with cross-clamping of the main renal artery, the remaining with Lumagel. Other than the first pig and calf, all animals then underwent partial nephrectomy.
Results and Conclusions
Using Lumagel, targeted blood flow interruption was achieved while circulation to uninvolved renal tissue was maintained. Hemostasis lasted for 30 minutes or more. Surgical resection averaged 11 minutes (range 10–13) and 23.3 (range 9–40) in the open and laparoscopic groups, respectively. Estimated blood loss was negligible with the exception of two cases, one in which an error in angiographic assessment lead to an unoccluded vessel near the resection site and a second case where a guide wire was inadvertently passed through a vessel. Time to complete flow return as determined by direct visualization of the kidney and its corresponding angiogram averaged 7 and 2.5 minutes for Lumagel and arterial clamping, respectively. Lumagel provides reliable and reproducible intraluminal blood flow interruption and flow restoration in both main and segmental renal arteries. By providing blood free resection, techniques described may facilitate partial nephrectomy without global renal ischemia.
Partial Nephrectomy; Minimally Invasive; Warm Ischemia; Laparoscopy
The aim of this study is to identify urodynamic changes that correlate with successful outcomes after stress urinary incontinence (SUI) surgery.
655 women were randomized to Burch colposuspension or autologous fascial sling as part of the multi-center Stress Incontinence Surgical Treatment Efficacy Trial. Preoperatively and 24 months after surgery, participants underwent standardized urodynamic testing which included non-invasive uroflowmetry, cystometrogram and pressure flow studies. Changes in urodynamic parameters were correlated to a successful outcome, defined a priori as: 1) negative pad test, 2) no urinary incontinence on 3-day diary, 3) negative cough and valsalva stress test, 4) no self-reported SUI symptoms on the Medical, Epidemiological and Social Aspects of Aging Questionnaire and 5) no retreatment for SUI.
Subjects who met criteria for surgical success showed a greater relative increase in mean Pdet@Qmax (baseline vs 24 months) than women who were considered surgical failures (p = 0.008). While a trend suggested an association between greater increases in bladder outlet obstruction index and outcome success, this was not statistically significant. Other urodynamic variables such as maximum uroflow, bladder compliance, and the presence of preoperative or de novo detrusor overactivity did not differ with respect to outcome status.
Successful outcomes in both surgical groups (Burch and sling) were associated with higher voiding pressures relative to preoperative baseline values. However, concomitant changes in other urodynamic voiding parameters were not significantly associated with outcome.
Urodynamics; Stress Urinary Incontinence; Burch Colposuspension; Pubovaginal Sling; Obstruction
To characterize urodynamic changes in subjects 24 months after Burch urethropexy and autologous fascial sling surgeries for stress urinary incontinence.
Materials and Methods
In the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr)l, 655 women underwent standardized urodynamics prior to and 2 years after Burch or sling surgery. Paired t- tests were used to compare pre- and post surgery urodynamic measures by treatment group. ANOVA models were fit predicting change in UDS measures controlling for treatment group.
Noninstrumented maximum flow rate decreased 3.6 ml/sec (Burch) and 4.7 ml/sec (sling), p=0.42. Average flow rates decreased [2.4 ml.sec (Burch) vs. 3.8 ml/sec (sling), p=.039]. There was no difference in increases in first sensation (23.3 and 29.3 ml, respectively, p=0.61). There were no differences in reductions in pressure flow study maximum flow rates [(2.3 (Burch) and 4.4 ml/sec (sling), p=0.11]. Increased detrusor pressure at maximum flow (Pdet@Qmax), (11.4 cm H20, p<0.001) was seen only after the sling procedure. Increases in bladder outlet obstruction index (BOOI) occurred after both procedures with greater increases seen after sling (change, Burch +6.27 versus sling +20.12, p=0.001).
The Burch colposuspension and autologous fascial sling procedures were associated with similar decreases in noninstrumented flow rates and the sling was associated with greater increases in Pdet@Qmax and BOOI. These changes suggest that both procedures are effective, in part, because of increased outlet resistance; the sling procedure may be more obstructive.
stress urinary incontinence; urodynamics; Burch Coloposuspenion; Pubovaginal sling
To examine changes in the association between pain and patient quality of life (QoL), depressive symptoms, and disability in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) at varying levels of spouse responses to pain.
One-hundred and eighty-eight men with CP/CPPS completed a questionnaire including demographic information. The outcome variables were mental QoL (SF-12 MCS), physical QoL (SF-12 PCS), depressive symptoms (Center for Epidemiological Studies Depression Scale), and disability (Pain Disability Index). Patients also reported on the types of responses they experienced from their spouses (Multidimensional Pain Inventory), and pain (Short-Form McGill Pain Questionnaire).
The association between pain and disability was stronger at higher levels of solicitous responses (e.g., “does some of my chores) (β = 0.66, p<.05) than it was at moderate (β = 0.44, p<.05) and lower (β = 0.23, ns) levels. In contrast, the association between pain and disability was stronger at lower levels (β = 0.64, p<.05) of distracting responses (e.g., “tries to get me involved in some activity”) than it was at moderate (β = 0.44, p<.05) and higher (β = 0.25, p<.05) levels.
Solicitous responses to pain increased the negative impact of pain on disability, while distracting responses to pain decreased the negative impact of pain on disability in men with CP/CPPS. Solicitous responses may be a reaction to patient pain and associated disability, or may help create or maintain the patient’s pain and disability. In either case, distracting rather than solicitous responses to patient pain are to be encouraged in symptom management.
chronic prostatitis/chronic pelvic pain syndrome; spousal responses to pain behavior; disability
The treatment of localized renal cell carcinoma remains overly subjective. The R.E.N.A.L.- Nephrometry Score (NS) quantifies the salient characteristics of renal mass anatomy in an objective and reproducible manner. We evaluated treatment patterns of solid renal masses based on quantifiable anatomic features using Nephrometry.
Nephrometry scores were available in 615 patients in our prospective kidney tumor database (2000-2010). The NS sum and its individual component scores were analyzed to determine their relationship to treatment approach.
Median age, age-adjusted Charlson Co-Morbidity Index (CCI), and estimated GFR were 60 years (25-89), 2 (0-10), and 80.5 ml/min (5.1-120.0), respectively. Increasing tumor complexity as measured by a higher overall Nephrometry Score was associated with both radical nephrectomy (RN) and open partial nephrectomy (PN) (p<0.0001). Compared to patients who underwent PN, patients treated with RN had significantly higher size (R), central proximity (N), and location (L) component scores (p<0.001). Furthermore, tumors treated with a RN were more often hilar (p<0.001). Similarly, compared to minimally-invasive PN (laparoscopic or robotic), open PN was associated with an increasing individual component score for size, endophycity and central proximity to the collecting system (p<0.001) and non-polar location (p=0.016).
The R.E.N.A.L. – Nephrometry score standardizes reporting of solid renal masses and appears to effectively stratify by treatment type. Although only one part of the treatment decision-making process, Nephrometry aids in objectifying previously subjective measures.
kidney cancer; Nephrometry; small renal mass (SRM)
To develop a robust sterile, fully demucosalized and vascularized seromuscular patch for use as an adjunct to novel bioengineering techniques aimed at augmenting, reconstructing, or replacing the bladder because of endstage disease. To eliminate deep colonic epithelial crypts to prevent the possibility of colonocyte regrowth. To maintain sterility by excluding the possibility of contamination from the bowel contents.
Pilot studies were performed on euthanized pigs to optimize the technique, with tissue samples examined by immunohistochemistry. In vivo, vascularized seromuscular colonic flaps were created from the bowel exterior in 7 large white hybrid pigs. The dissection was facilitated by placing an inflated Foley catheter within the colonic lumen. The seromuscular ends were approximated with 5/0 Vicryl sutures and excess mucosa intussuscepted within the lumen. Demucosalized flaps were used to augment the bladder by composite cystoplasty and were examined immunohistochemically at 3 months.
Pilot studies showed that the technique was successful in creating seromuscular segments with no epithelial remnants. When applied surgically, the seromuscular flaps survived and showed no evidence of colonocyte regrowth at 3 months.
Extraluminal dissection creates robust seromuscular flaps and prevents both regrowth by colonic epithelial cells and contamination of the tissue by exposure to the bowel contents. This technique should find application in a range of bladder reconstruction techniques, including composite cystoplasty and autoaugmentation.
To analyze the practice patterns of recently fellowship-trained reconstructive urologists to help guide fellowship program curriculum development and to evaluate the impact that formal reconstructive urology training has on academic urology programs.
We evaluated the case logs of 7 recently fellowship-trained reconstructive urologists affiliated with US academic institutions from August 2009 to August 2011 (median years in practice = 2, range 1-6 years). We categorized cases into endoscopic, oncological, female, general (nononcological), and reconstructive. Our primary outcome was the volume of reconstructive procedures as a percentage of all procedures. Our secondary outcome was the correlation between years in practice and reconstructive volume and case complexity.
A total of 3561 cases were analyzed, representing 12 surgeon-years. Endoscopic surgery was most common (42.7%), followed by reconstructive (36.1%), general urologic (10.5%), and oncological (3.7%). The most common type of reconstructive procedure performed was anterior urethroplasty (mean 42.8 per year) followed by bladder reconstruction (mean 17.7 per year). The percentage of yearly cases considered reconstructive was positively associated with total years in practice (r = .688, P = .013) as was the complexity of artificial urinary sphincter cases (r = .857, P = .0004), but not urethral reconstructive complexity (r = .40, P = .197).
The demand for services delivered by fellowship-trained reconstructive urologists is high, as evidence by the large percentage of reconstructive procedures in this cohort even early in practice. With additional years in practice comes further specialization.
Hydronephrosis is the most common abnormality found on prenatal ultrasound. The utility of prophylactic antibiotics in the postnatal management of this condition is controversial. No study has assessed practice patterns of general pediatricians in the management of prenatally-detected hydronephrosis.
An 18 question survey was sent to a random cross-sectional national sample of pediatricians from the American Medical Association Masterfile. Participants answered questions regarding practice location and type, practice experience, frequency of cases seen, familiarity with the literature, use of antibiotics, work-up of hydronephrosis, and specialist referral. Multivariate logistic regression identified factors associated with prescribing antibiotics.
244 of 461 (53%) subjects responded. 56% routinely prescribe antibiotics for prenatally-detected hydronephrosis. 57% perform postnatal work-up themselves. Of these, 98% routinely order ultrasounds while ~40% routinely order voiding cystourethrograms. 94% have specialists readily available, but only 41% always refer to a specialist. On multivariate logistic regression, those who believe prophylactic antibiotics to be beneficial are significantly more likely to prescribe antibiotics compared with those who have not read the literature (OR 6.1, 95%CI 2–15). Those without specialist consultation readily available have an increased odds of starting prophylactic antibiotics compared with those who have consultation available (OR 7.2, 95%CI 1.3–39).
Most pediatricians initiate postnatal management of prenatally-detected hydronephrosis, therefore pediatricians truly are gatekeepers to children with this condition. Knowledge of practice patterns is crucial for the dissemination of evidence-based information to the appropriate providers and enables us to learn more about the utility of antibiotic prophylaxis in future studies.
kidney disease; antibiotic prophylaxis; practice variation; survey; prenatal diagnosis
Prostate cancer (CaP) has been associated with other common malignancies. Recently, numerous single nucleotide polymorphisms (SNPs) have been associated with CaP susceptibility; however, it is unknown whether these risk alleles are responsible for the relationship between CaP and other malignancies.
We have genotyped 1121 CaP patients for 36 risk alleles known to be significantly associated with CaP susceptibility and determined their relationships to other malignancies in CaP probands and in their first-degree relatives.
The most common other malignancies in CaP probands were non-melanoma skin cancer (13.6%), leukemia (7.3%), melanoma (3.9%), non-Hodgkin’s lymphoma (0.7%), colorectal cancer (0.6%), and multiple myeloma (0.3%). Among probands, there was a significantly increased frequency of leukemia in carriers of SNP rs2736098 (5p15, P=0.03) and melanoma in carriers of either SNP rs1512268 (8p21, P=0.006) or SNP rs5759167 (22q13, P=0.02). Multiple myeloma was more common in carriers of SNP rs9364554 (6q25, P=0.02). Probands who were carriers of SNP rs16901979 (8q24) were significantly more likely to report a family history of melanoma (P=0.03), while probands with family histories of multiple myeloma and non-Hodgkin’s disease were significantly more likely to be carriers of SNPs rs12621278 (2q31, P=0.04) and rs6465657 (7q21, P=0.02), respectively.
Certain alleles associated with CaP susceptibility may be associated with increased or decreased risk of other malignancies in CaP probands and their first-degree relatives. Further studies are warranted to examine the underlying mechanisms of these SNPs in CaP and other malignancies.
Single nucleotide polymorphism (SNP); prostate cancer; genetic predisposition; other malignancy; family history
Kidney cancer; Nephron-sparing surgery; Renal cell carcinoma; Learning curve; Robot-assisted partial nephrectomy
To investigate whether fluorochrome-conjugated phalloidin can delineate cavernous smooth muscle (CSM) cells and whether it can be combined with immunofluorescence (IF) staining to quantify erectile dysfunction (ED)-associated changes.
ED was induced by cavernous nerve crush in rats. Penile tissues of control and ED rats were stained with Alexa-488-conjugated phalloidin and/or with antibodies against rat endothelial cell antigen (RECA), CD31, neuronal nitric oxide synthase (nNOS), and collagen-IV (Col-IV).
Phalloidin was able to delineate CSM as composed of a circular and a longitudinal compartment. When combined with IF stain for CD31 or RECA, it helped the identification of the helicine arteries as covered by endothelial cells on both sides of the smooth muscle layer. When combined with IF stain for nNOS, it helped the identification that nNOS-positive nerves were primarily localized within the dorsal nerves and in the adventitia of dorsal arteries. When combined with IF stain for Col-IV, it helped identify that Col-IV was localized around smooth muscles and beneath the endothelium. Phalloidin also facilitated the quantitative analysis of ED-related changes in the penis. In rats with cavernous nerve injury, RECA or Col-IV expression did not change significantly, but CSM and nNOS nerve contents decreased significantly.
Phalloidin stain improved penile histology, enabling the visualization of the circular and longitudinal compartments in the CSM. It also worked synergistically with IF stain, permitting the visualization of the dual endothelial covering in helicine arteries, and facilitating the quantification of ED-related histological changes.
phalloidin; cavernous smooth muscle; cavernous endothelium; nNOS-positive nerves; collagen-IV; cavernous nerve injury; erectile dysfunction