John T. Stoffel

Novel expression of N-cadherin elicits in vitro bladder cell invasion via the Akt signaling pathway

Novel N-cadherin expression has been linked to the invasive phenotype in bladder tumors yet a primary role for N-cadherin in invasion has not been defined in this model. To address this, N-cadherin was stably transfected into E-cadherin expressing bladder carcinoma cells. This resulted in an enhanced invasive capacity in in vitro assays that was blocked by incubation with an N-cadherin function-blocking antibody in a dose-dependent manner. Analysis of the signaling pathway(s) implicated in N-cadherin-mediated invasion in bladder carcinoma cell lines revealed no correlation between MAPK signaling and invasion, in the presence or absence of fibroblast growth factor 2. Also, while MAPK and p38 kinase inhibitors did not alter the invasive behavior of these cells, an increase in the phosphorylation of Akt at serine-473 was detected in N-cadherin transfectants, suggestive of N-cadherin-mediated Akt activation in bladder cell invasion. Incubation of N-cadherin transfectants with either PI3 kinase or Akt inhibitors resulted in a significant decrease in the invasive capacity of these cells. Exposure of cells to PP2, a src family kinase inhibitor, also decreased the invasive potential of N-cadherin transfectants and resulted in reduced phosphorylation of Akt. The involvement of Akt signaling in bladder cell invasion was also supported by the inhibition of bladder cell invasion by cells constitutively expressing an activated Akt kinase, using the PI3 kinase and Akt inhibitors and PP2. These results suggest that activation of PI3/AKT kinase following N-cadherin expression contributes to the increased invasive potential of bladder carcinoma cells.

Molecular analysis of PTEN and MXI1 in primary bladder carcinoma.

Loss of heterozygosity (LOH) on 10q is associated with late‐stage events in urothelial neoplastic progression. The tumor suppressor gene PTEN, which is mutated or homozygously deleted in numerous cancers, maps to a region of 10q within the reported region of minimal loss in bladder tumors. In two recent studies alterations in the PTEN gene occur at a low frequency in bladder tumors displaying 10q LOH. We have screened 35 late‐stage bladder tumors for mutations in PTEN and MXI1, both genes mapping to chromosome 10q. Using single‐strand conformation polymorphism analysis, we identified 6 tumors harboring mutations in PTEN and 2 additional tumors displaying homozygous deletion at this locus. No MXI1 mutations were identified within the same tumor panel. Of 16 bladder tumor cell lines analyzed, 2 showed homozygous deletion of PTEN and 3 harbored point mutations resulting in an amino acid change. Two cell lines harbored missense mutations in MXI1. We report a significantly higher frequency of PTEN alterations in bladder carcinoma (23%) than was previously recorded, with no accompanying mutations in the MXI1 gene. Int. J. Cancer 88:620–625, 2000.

Male Urethral Stricture: American Urological Association Guideline

Purpose: The purpose of this Guideline is to provide a clinical framework for the diagnosis and treatment of male urethral stricture. Materials and Methods: A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates 1/1/1990 to 12/1/2015) was conducted to identify peer‐reviewed publications relevant to the diagnosis and treatment of urethral stricture. The review yielded an evidence base of 250 articles after application of inclusion/exclusion criteria. These publications were used to create the Guideline statements. Evidence‐based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional guidance is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. Results: The Panel identified the most common scenarios seen in clinical practice related to the treatment of urethral strictures. Guideline statements were developed to aid the clinician in optimal evaluation, treatment, and follow‐up of patients presenting with urethral strictures. Conclusions: Successful treatment of male urethral stricture requires selection of the appropriate endoscopic or surgical procedure based on anatomic location, length of stricture, and prior interventions. Routine use of imaging to assess stricture characteristics will be required to apply evidence based recommendations, which must be applied with consideration of patient preferences and personal goals. As scientific knowledge relevant to urethral stricture evolves and improves, the strategies presented here will be amended to remain consistent with the highest standards of clinical care.

Analysis of peripheral blood for prostate cells after autologous transfusion given during radical prostatectomy

To determine if cells expressing prostate‐specific antigen (PSA) can be detected in blood collected by a cell‐saver during radical prostatectomy (RP) or in the peripheral blood after intraoperative autotransfusion (IAT).

Management Goals for the Spina Bifida Neurogenic Bladder: A Review from Infancy to Adulthood

Patients with spina bifida require longitudinal urological care as they transition from childhood to adolescence and then to adulthood. Issues important to urological health, such as protection of the upper tracts and prevention of incontinence, need vigilant follow-up throughout the patients life. As the child ages, additional issues such as sexual functioning also become increasingly important for social integration. Despite this need for regular assessment, many adult patients with spina bifida lose coordinated urological care after leaving specialized pediatric spina bifida clinics. Consequently, urologists frequently encounter an adult patient with spina bifida in practice and they need to understand the basic urological treatment goals and potential complications for this population.

Patient reported outcomes measures in neurogenic bladder and bowel: A systematic review of the current literature

To describe existing bladder and bowel specific quality of life (QoL) measurement tools, QoL in patients with multiple sclerosis (MS), spinal cord injury (SCI), Parkinsons Disease (PD), stroke, or spina bifida (SB) affected by bladder or bowel dysfunction, and the impact of specific bladder and bowel management on QoL.

Contemporary management of the neurogenic bladder for multiple sclerosis patients

Urinary symptoms related to multiple sclerosis (MS) present a complex challenge for the treating physician. However, several treatment options are available for the symptomatic patient once the physician understands basic MS disease epidemiology and pathophysiology. Depending of disease status and symptoms, MS urinary symptoms may respond to directed behavioral, pharmacologic, intravesical, neuromodulation, or surgical therapies.

The src-family kinase inhibitor PP2 suppresses the in vitro invasive phenotype of bladder carcinoma cells via modulation of Akt†

To evaluate PP2 as a modulator of the cadherin/catenin complex in late‐stage bladder carcinoma cells, and to assess its potential invasion‐suppressor activity in this model.

The artificial genitourinary sphincter.

Since its introduction by Scott in 1973, the artificial genitourinary sphincter (AUS) has proven to be an effective treatment for refractory urinary incontinence [1]. Over the years, the original AUS 721 model had many revisions to the cuff, pump and reservoir components. The most current development, the narrow back-cuff AMS 800 (American Medical Systems, Minnetonka, MN, USA), has reported continence rates of 61–96% and with low morbidity [2,3]. In this article describing the implantation of the AMS 800 AUS, our goal is to outline proper patient selection, define current surgical technique, and identify troublesome postoperative care issues.

Are persistent or recurrent symptoms of urinary incontinence after surgery associated with adverse effects on sexual activity or function

We sought to determine if postoperative urinary incontinence (UI) symptoms are associated with (1) sexual activity status and (2) sexual function using validated health-related quality of life instruments. In this mailed cross-sectional survey of 687 women who underwent stress incontinence surgery, 437 (63.6%) completed a questionnaire protocol. Clinical and sociodemographic factors independently associated with sexual activity status were identified with logistic regression. Sexually active respondents completed the Pelvic Organ Prolapse and Urinary Incontinence Sexual Function Questionnaire (PISQ-12) as a measure of sexual function. Factors independently associated with sexual function were identified with linear regression. Sexual activity was reported by 57.6% (252/437). The likelihood that a respondent was sexually active was moderated by an interaction between age and UI symptom severity (p = 0.059). Among the sexually active women, increasing UI symptom severity was associated with poorer sexual function (r = −0.42, p < 0.001). The severity of postoperative recurrent or persistent UI is associated with a lower probability of being sexually active and an adverse effect on sexual function.