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Biomedical subjects

A J Wein

Publications and source records attributed to A J Wein.

At least 19 recordsLinked to original sources
PubMed2006

Radiofrequency ablation of small renal cell carcinomas using multitined expandable electrodes: preliminary experience.

PURPOSE: Radiofrequency ablation is a minimally invasive, nephron-sparing option for renal cell carcinoma (RCC) in poor surgical candidates. We report our contemporary experience with RCC radiofrequency ablation using multitined expandable electrodes along with an aggressive treatment strategy to displace adjacent viscera away from probe tines. Involution of the treatment zone was assessed over time. MATERIALS AND METHODS: Over a 36-month period, a quality-assurance database identified 22 patients with 26 sporadic RCC who underwent 43 ablations during 27 radiofrequency ablation sessions. The mean age of the cohort was 71 years (range, 47-89 y). Mean RCC diameter was 2.2 cm (range, 1-4 cm). Twenty-six of radiofrequency ablation sessions were performed using multitined expandable electrodes. All ablations used CT guidance with moderate sedation. Adjunctive techniques used during ablation were recorded, as were instances in which ablation mandated penetration of tines beyond the kidney margin. Post-treatment ablation zones were measured from CT/MR images to evaluate serial involution and treatment response. RESULTS: Technical success in targeting and ablation was 100%. Follow-up periods ranged from 1 to 31 months (mean, 11.2). During this period, one patient presented with marginal local recurrence and underwent repeat radiofrequency ablation. Adjunctive techniques in four patients included water injection for displacement of the tail of the pancreas (n = 1) or descending colon (n = 3). Deliberate penetration of tines beyond the margins of the kidney was performed in 41% of cases; no hemorrhage occurred in these cases. No major complications occurred. Minor complications occurred in 17% of patients, including asymptomatic pneumothorax, perirenal hematomas, subcutaneous hematoma, and subcutaneous abscess. After 6 months, mean involution of the ablation zone was 15% from baseline volume per year. CONCLUSION: Multitined expandable radiofrequency electrodes produce a high rate of local control for small RCCs with a low complication rate, even when tine penetration of the kidney is required for an adequate tumor treatment margin. Adjacent organs can be protected with adjunctive percutaneous maneuvers.

Aged↗
PubMed2006

Transitional cell carcinoma of the fossa navicularis in a man with preexisting adenocarcinoma of the prostate.

In this report we present a patient with a history of prostatic adenocarcinoma who was found to have a low-grade/low-stage transitional cell carcinoma of the fossa navicularis. The patient underwent transurethral resection and at approximately 2 years of follow-up he has no evidence of tumor recurrence. Very limited follow-up data exist on which to base management decisions, and this report lends support to the use of transurethral resection alone as a means to treat low-grade/low-stage lesions.

Adenocarcinoma↗
PubMed2005

Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors.

Genetic factors may be used not only to assess risk of prostate cancer development but also to evaluate prostate cancer outcomes including clinical prognosis, treatment methods, and treatment response. To assess the role of family history on prostate cancer outcomes, we evaluated tumor characteristics, diagnostic precursors and biochemical (prostate specific antigen) relapse-free survival in men with and without a family history of prostate cancer. A total of 684 prostate cancer cases unselected for family history were identified from an ongoing hospital based prostate cancer case-control study between 1995 and 2002. Self-reported family history was grouped within the following categories: none, any, moderate (one affected first or second degree relative) and high (2 or more affected first or second degree relatives). We further considered groups defined by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor stage was not significantly associated with any (odds ratio [OR] = 1.43 95% confidence interval [CI] = 1.00-2.05) or moderate (OR = 1.48, 95% CI = 1.0-2.19) family histories. Men diagnosed before age 60, however, had higher tumor stages if they had any (OR = 2.19, 95% CI = 1.28-3.75) or moderate (OR = 2.15, 95% CI = 1.2-3.9) family histories. Men diagnosed after age 60 with any family history were significantly more likely to experience biochemical (PSA) failure (Hazard ratio [HR] = 2.60, 95%CI = 1.08-6.25). Men with any and moderate family histories were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI = 1.25-4.95 and HR = 2.46, 95% CI = 1.17-5.16, respectively). Moderate family history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI = 1.06-4.34). Our results suggest that a family history of prostate cancer may be associated with predictors of clinical outcome in prostate cancer cases unselected for a family history of prostate cancer.

Adenocarcinoma↗
PubMed2005

Renal angiomyolipoma: long-term results after arterial embolization.

PURPOSE: Selective arterial embolization of renal angiomyolipomas (AMLs) was performed to prevent hemorrhage in patients with AMLs larger than 4 cm. This study was conducted to evaluate the long-term efficacy of AML embolization. MATERIALS AND METHODS: Nineteen patients underwent embolization for 30 renal AMLs between July 1991 and June 2002. Of these, 10 patients had tuberous sclerosis (TS) with multiple AMLs and nine patients had a solitary sporadic AML. Embolization was performed with use of ethanol mixed with iodized oil (Ethiodol) in 29 tumors; coils were used in addition to the ethanol/Ethiodol mixture in one case. All tumors were completely embolized according to angiographic criteria including vascular stasis and absence of arterial feeders. The efficacy of embolization was determined over a mean follow-up period of 51.5 months (range, 6-132 months). Recurrence was defined as an increase in tumor size of greater than 2 cm on follow-up imaging and/or recurrent symptoms that required repeat embolization. An institutional review board exemption was obtained to perform this retrospective study. RESULTS: Embolization of the renal AMLs was technically successful in all 19 patients and for all 30 lesions. AML recurrence was noted in 31.6% of patients (n = 19) and for 30% of lesions overall (n = 9). Six of 10 patients in the TS group had AML recurrences. No recurrences occurred in the patients with sporadic AML. In the TS group of 10 patients, there was a total of 21 AMLs and the overall tumor recurrence rate was 42.9% (nine of 21). Six lesions in four patients had to be reembolized because of recurrent symptoms, including one hemorrhage, and three lesions in two patients required repeat embolization because of a greater than 2 cm increase in size. The median time interval from embolization to recurrence was 78.7 months (range, 13-132 months). Statistical testing with use of the Fisher exact test demonstrated that patients with TS were significantly more likely to develop recurrence than those without TS (P = .01). CONCLUSIONS: Transarterial embolization is effective in preventing hemorrhage in patients with renal AMLs. However, long-term follow-up revealed a high AML recurrence rate in patients with TS. Lifelong surveillance for recurrence after AML embolization is essential in patients with TS.

Adult↗
PubMed2004

Pharmacologic management of urinary incontinence in the female.

Pharmacotherapy combined with behavioral therapy is often used for the initial therapy of urinary incontinence (UI) in the female. Although there are multiple central and peripheral sites and mechanisms that can potentially influence bladder and urethral function, the pharmacological manipulation of only a select few are clinically useful. The problems are: 1) how to affect bladder function without interfering with the function of other organ systems (uroselectivity); and, 2) how to eliminate UI without disturbing normal micturition. Multiple categories of drug therapies are potentially useful to treat UI. It is clear that the ideal agent for this indication has not yet been identified. Although significant improvement can be seen with several different agents for the treatment of various types of incontinence, complete cure is rarely seen with pharmacological therapy of UI. However, several new pharmacologic treatments including some with novel approaches to drug delivery and/or mechanisms of action have emerged in clinical development over the last few years. In initial studies, some of the agents appear to compare favorably to existing therapies. Whether these promising results will hold up when subjected to large scale, well controlled clinical trials is unclear.

Adrenergic alpha-Agonists↗
PubMed2003

Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta.

Corpus cavernosum smooth muscle (CCSM) from rabbits made diabetic for 6 months as a result of alloxan injection exhibited increased sensitivity (3vs 9 nM EC(50)) and generated 20-50% greater force to endothelin-1 (ET-1) compared to CCSM from normal rabbits. In contrast, the force produced by the CCSM in response to KCl and phenylephrine was not significantly altered in diabetic CCSM. The increased ET-1 sensitivity is associated with a two to three-fold upregulation of ET receptor A at both mRNA and protein levels in diabetic CCSM. ET-1-induced CCSM contraction is largely dependent upon Rho-kinase (ROK), since it is almost completely blocked by Y-27632 (a highly selective ROK inhibitor). Furthermore, expression of ROKbeta isoform is selectively upregulated in CCSM from diabetic rabbits. Thus, an increased CCSM tone, modulated by sensitization of the endothelin-mediated contractile pathway via ROK, may be a key component of the molecular mechanism of diabetes-induced erectile dysfunction.

Animals↗
PubMed2003

Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.

OBJECTIVES: To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder. PATIENTS AND METHODS: In a multicentre, single-blind study at 51 Scandinavian centres, 505 patients aged >or= 18 years with symptoms of urinary frequency (>or= 8 micturitions/24 h) and urgency, with or without urge incontinence, were randomized to oral treatment with either tolterodine 2 mg twice daily plus simplified BT or tolterodine alone. Changes in voiding diary variables were evaluated after 2, 12 and 24 weeks of treatment. The patients' perceptions of their bladder symptoms and tolerability (adverse events) were also determined. RESULTS: In all, 501 patients (75% women) were evaluable on an intention-to-treat basis (244 on tolterodine + BT and 257 on tolterodine alone). Tolterodine significantly reduced the voiding frequency and increased the volume voided per void at all sample times; these effects were significantly increased by adding BT. At the end of the study the median percentage reduction in voiding frequency was greater with tolterodine + BT than with tolterodine alone (33% vs 25%, P < 0.001), while the median percentage increase in volume voided per void was 31% with tolterodine + BT and 20% with tolterodine alone (P < 0.001). There was a median of 81% fewer incontinence episodes than at baseline with tolterodine alone, which was not significantly different from that with tolterodine + BT (- 87%). The two groups had comparable median percentage reductions in urgency episodes. Some 76% of patients on tolterodine + BT reported an improvement in their bladder symptoms relative to baseline, compared with 71% on tolterodine alone. Tolterodine was well tolerated; the most common adverse event was mild dry mouth. CONCLUSION: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.

Administration, Oral↗
PubMed2003

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Adult↗
PubMed2002

Prevalence and burden of overactive bladder in the United States.

CONTEXT: the National Overactive BLadder Evaluation (NOBLE) Program was initiated to better understand the prevalence and burden of overactive bladder in a broad spectrum of the United States population. OBJECTIVE: to estimate the prevalence of overactive bladder with and without urge incontinence in the US, assess variation in prevalence by sex and other factors, and measure individual burden. DESIGN: US national telephone survey using a clinically validated interview and a follow-up nested study comparing overactive bladder cases to sex- and age-matched controls. SETTING: noninstitutionalized US adult population. PARTICIPANTS: a sample of 5,204 adults >/=18 years of age and representative of the US population by sex, age, and geographical region. MAIN OUTCOME MEASURES: prevalence of overactive bladder with and without urge incontinence and risk factors for overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and MOS sleep scores were used to assess impact. RESULTS: the overall prevalence of overactive bladder was similar between men (16.0%) and women (16.9%), but sex-specific prevalence differed substantially by severity of symptoms. In women, prevalence of urge incontinence increased with age from 2.0% to 19% with a marked increase after 44 years of age, and in men, increased with age from 0.3% to 8.9% with a marked increase after 64 years of age. Across all age groups, overactive bladder without urge incontinence was more common in men than in women. Overactive bladder with and without urge incontinence was associated with clinically and significantly lower SF-36 quality-of-life scores, higher CES-D depression scores, and poorer quality of sleep than matched controls. CONCLUSIONS: the NOBLE studies do not support the commonly held notion that women are considerably more likely than men to have urgency-related bladder control problems. The overall prevalence of overactive bladder does not differ by sex; however, the severity and nature of symptom expression does differ. Sex-specific anatomic differences may increase the probability that overactive bladder is expressed as urge incontinence among women compared with men. Nonetheless, overactive bladder, with and without incontinence, has a clinically significant impact on quality-of-life, quality-of-sleep, and mental health, in both men and women.

Adolescent↗
PubMed2002

Osteopontin gene expression and immunolocalization in the rabbit urinary tract.

PURPOSE: Osteopontin is a highly phosphorylated, calcium binding sialoprotein characterized by a conserved arginine-glycine-aspartate sequence. Vitronectin receptor (alphavbeta3 integrin) and hyaluronan receptor (CD44) are documented as receptors for osteopontin and their expression has been established in the bladder. Based on that finding and the fact that osteopontin protein is present in urine we hypothesized that osteopontin is expressed in the lower urinary tract. MATERIALS AND METHODS: Osteopontin messenger (m)RNA and protein were analyzed in 5 adult urinary tracts and 5 neonatal bladders of New Zealand White rabbits using reverse transcriptase-polymerase chain reaction and immunohistochemical testing. Analysis of mRNA expression and localization of osteopontin receptors, alphavbeta3 integrin and CD44 were also performed in adult bladders and primary cultures of detrusor myocytes. RESULTS: Adult renal pelvis, ureter, bladder and urethra, and neonatal bladders contained significant levels of osteopontin mRNA. Immunohistochemical staining revealed osteopontin expression in all layers of the transitional epithelium of the bladder, co-localizing with alphavbeta3 integrin mainly in the superficial layers and with CD44 mainly in the basal layers. Osteopontin was detected within the cytoplasm of smooth muscle cells, while alphavbeta3 integrin was located closer to the plasmalemma. Furthermore, primary cultured detrusor myocytes expressed osteopontin mRNA in stable fashion for up to 4 passages. Treating bladder myocyte cultures with insulin-like growth factor-1 and 17beta-estradiol resulted in up-regulation and down-regulation of osteopontin mRNA, respectively. CONCLUSIONS: Adult and neonatal rabbit detrusors are a prominent source of osteopontin in vivo and in vitro. Epithelial osteopontin may be a source of osteopontin in urine. The co-localization of osteopontin in the bladder epithelium with alphavbeta3 integrin and CD44 suggests a role in maintaining the integrity of the transitional epithelium by providing the sealing and adhesiveness needed for the impermeable state of the bladder.

Animals↗
PubMed2001

Effects of Bowman-Birk inhibitor concentrate (BBIC) in patients with benign prostatic hyperplasia.

BACKGROUND: The Bowman-Birk inhibitor is a soybean-derived protease inhibitor that has anti-inflammatory and anticarcinogenic activities. METHODS: A Phase I trial of Bowman-Birk inhibitor concentrate (BBIC) in 19 male subjects with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) has been performed. RESULTS: The results of the trial indicated that there was no dose-limiting toxicity of BBIC. There was a statistically significant decrease in serum PSA levels in all BBIC-treated patients. Some BBIC-treated patients exhibited a relatively large reduction in serum PSA levels, ranging up to a 43% reduction. There was also a statistically significant decrease in serum triglyceride levels and a decrease in prostate volume in the treated patients. The scores recorded in response to a urinary symptom questionnaire indicated improved urinary activities in the BBIC-treated patients; however, the control subjects exhibited similar improvements in urinary activities during the course of the trial. CONCLUSIONS: The data obtained in this trial, particularly the data suggesting that BBIC treatment may lead to reduced serum PSA levels and reduced prostate volumes, suggest that a Phase II clinical trial of BBIC for the therapy of BPH is warranted.

Aged↗
PubMed2001

Simultaneous upper and lower urinary tract obstruction associated with severe genital prolapse: diagnosis and evaluation with magnetic resonance imaging.

Genital prolapse causing both urethral and ureteral obstruction is an infrequent occurrence, especially in the absence of uterine prolapse. We report on a patient with massive genital prolapse causing both urethral and ureteral obstruction in whom magnetic resonance imaging demonstrated the level of obstructive uropathy and, after surgical repair of the prolapse, confirmed restoration of the normal pelvic and upper urinary tract anatomy.

Aged↗
PubMed2001

ROC optimization may improve risk stratification of prostate cancer patients.

OBJECTIVES: Rational treatment decision requires accurate projection of the clinical course of a patient. Current methods in clinical outcome analysis mostly focus on population data. We investigated the applicability and optimization of the widely used actuarial method to project individual clinical outcomes. METHODS: We designed and implemented a Clinical Outcome Prediction Expert (COPE) that performs, assesses, and optimizes actuarial prediction on individual cases. We analyzed a post-prostatectomy database, consisting of 1043 patients. Sixty percent of the database was used for training and 40% for validation. Stratified actuarial curves are used to project individual outcomes. The prostate-specific antigen (PSA) level, the Gleason score, and the clinical American Joint Commission on Cancer Staging T-stage before treatment were used as predictors. The area under the receiver operator characteristic (ROC) curve was used to measure predictive performance. RESULTS: We obtained simple optimized stratification of pretreatment PSA level of 10 ng/mL or less, or more than 10 ng/mL; Gleason score of 6 or lower, or higher than 6; and clinical AJCC T-stage of T2a or lower, or higher. The optimized univariate risk scores were used to generate a multivariate score. After optimization, we found the higher risk group consisted of patients with PSA more than 10 ng/mL, or with PSA of 10 ng/mL or less and Gleason score higher than 6 and clinical AJCC T-stage higher than T2a. The optimized multivariate risk score has the highest ROC area of 0.77 among all predictors. CONCLUSIONS: The best conditions to perform actuarial prediction on individual cases are not known a priori and require optimization. This study shows that ROC optimization simplifies risk stratification and may improve the accuracy of clinical outcome prediction.

Data Interpretation, Statistical↗
PubMed2001

Significance of hematuria in patients with interstitial cystitis: review of radiographic and endoscopic findings.

OBJECTIVES: Hematuria may be found in up to 30% of patients with interstitial cystitis (IC). However, few studies have described its etiology based on the findings of a complete evaluation. We reviewed the clinical significance of hematuria in the setting of IC. METHODS: We retrospectively reviewed the records of 148 patients fulfilling the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases inclusion criteria for IC. Patients with gross or microscopic hematuria were identified. Evaluation consisted of urine culture and cytology, cystoscopy, and intravenous urography (or retrograde pyelography plus renal ultrasound). Patients with urinary tract infections were excluded. RESULTS: Of 148 patients, 60 (41%) were found to have had at least one episode of hematuria during a mean follow-up of 18 months. Of 56 patients who agreed to be evaluated, 8 (14%) had positive urologic findings. Of these, none were highly significant; five were simple renal cysts (8.9%), one was a renal stone (1.8%), one was reflux nephropathy (1.8%), and one was medullary sponge kidney (1.8%). Cystoscopy, cytology, and bladder biopsy did not demonstrate malignancy in any patient. No statistically significant differences were found in age (49.9 versus 46.7 years), sex (90% versus 91% female), bladder capacity (792 versus 808 mL), and the presence of Hunner's ulcers (5% versus 2.4%), glomerulations (60% versus 59.9%), or detrusor mastocytosis (55% versus 47.6%) between patients with hematuria and those without (P >0.05). CONCLUSIONS: The incidence of hematuria in patients with IC may be higher than previously reported. Nevertheless, although many of these patients present with pelvic pain and irritative voiding symptoms, the hematuria evaluation is unlikely to reveal a life-threatening urologic condition.

Adult↗
PubMed2001

Endoluminal magnetic resonance imaging in the evaluation of urethral diverticula in women.

OBJECTIVES: Accurate determination of the size and extent of urethral diverticula can be important in planning operative reconstruction and repair. Voiding cystourethrography (VCUG) is currently the most commonly used study in the preoperative evaluation of urethral diverticula. We reviewed our experience with the use of endoluminal (endorectal or endovaginal) magnetic resonance imaging (eMRI) in these patients as an adjunctive study to VCUG to evaluate whether the MRI provided anatomically important information that was not apparent on VCUG. METHODS: A retrospective analysis of all patients with a clinical diagnosis of urethral diverticula undergoing MRI at a single institution was performed. Patients were evaluated with history, physical examination, cystoscopy, VCUG, and eMRI. Endoluminal MRI was retrospectively compared to VCUG with respect to size, extent, and location found at operative exploration. RESULTS: Twenty-seven consecutive patients underwent endorectal or endovaginal coil MRI in the evaluation of suspected urethral diverticula. Twenty patients subsequently had attempted transvaginal operative repair of the diverticulum. In 2 patients, eMRI demonstrated a urethral diverticulum, whereas VCUG did not. Operative exploration in these patients revealed a urethral diverticulum. In 14 of 27 patients, the VCUG underestimated the size and complexity of the urethral diverticulum as compared to eMRI and operative exploration. In 13 of 27 patients, the size, location, and extent of the urethral diverticulum on VCUG correlated well with the eMRI and/or operative findings. CONCLUSIONS: We have found endorectal and endovaginal coil MRI to be extremely accurate in determining the size and extent of urethral diverticula as compared to VCUG. This information can be critical when planning the approach, dissection, and reconstruction of these sometimes complex cases.

Adult↗
PubMed2001

Using the receiver operating characteristic curve to select pretreatment and pathologic predictors for early and late postprostatectomy PSA failure.

OBJECTIVES: Pretreatment prostate-specific antigen (PSA), prostatectomy Gleason score, margin status, and pathologic T stage are known explanatory variables for the postprostatectomy PSA outcome. We used the receiver operating characteristic (ROC) curve to select those factors that were optimal for predicting early and late postoperative PSA failure. METHODS: We designed and implemented a clinical outcome prediction expert that performs, assesses, and optimizes the actuarial prediction on individual cases. A postprostatectomy database of 1022 patients was divided into 60% for training and 40% for validation. The ROC areas of the predictors were calculated over a range of cutoff time from 24 to 60 months. RESULTS: Multivariate pathologic T stage/prostatectomy Gleason score/margin status had the highest ROC area of 0.900. Patients with Stage T disease less than T3, negative surgical margins, and Gleason score of 6 or less had a 90% probability to be PSA failure free at 4 years versus 36% otherwise. The pathologic T stage/margin status accurately predicted PSA failure at 24 months or less after prostatectomy with an ROC area of 0.800. Lower risk patients (less than Stage T3, negative surgical margins) had a 94% probability to be PSA failure free at 2 years versus 46% otherwise. CONCLUSIONS: A combination of actuarial analysis and ROC optimization accurately identified the individual patients at high risk of early and late postprostatectomy PSA failure.

Actuarial Analysis↗