Detection of occult lymph node metastases in locally advanced node-negative prostate cancer.

PURPOSE: The purpose of this study was to determine the incidence and clinical significance of occult metastases in the lymph nodes of patients with prostate cancer originally considered node negative by routine histologic evaluation. METHODS: Two hundred seventy four patients with pT3 prostate carcinoma treated by radical prostatectomy and bilateral lymph node dissection were included in this study. One hundred eighty patients were staged node negative (N0), while 94 patients were lymph node positive (N+), based on routine histologic evaluation. All lymph nodes from the 180 N0 patients were evaluated for occult metastases by immunohistochemistry using antibodies to cytokeratins and, if positive, prostate-specific antigen. Recurrence and overall survival were compared among patients with occult tumor cells (OLN+), with patients whose lymph nodes remained negative (OLN-), and with the 94 N+ patients. RESULTS: A total of 3,914 lymph nodes were evaluated from 180 N0 patients (average, 21.7 lymph nodes per patient). Occult tumor cells were found in 24 of 180 patients (13.3%). The presence of OLN+ was significantly associated with increased recurrence and decreased survival compared with OLN- patients (P < .001 and P = .019, respectively; relative risk of recurrence, 2.27; relative risk of death 2.07, respectively). The presence of occult lymph node metastases was an independent predictor of recurrence and death in a multivariable analysis. The outcome for patients with OLN+ disease was similar to that for patients with N+ disease. CONCLUSION: The detection of occult lymph node metastases in patients with pT3N0 prostate cancer identifies those with significantly increased risk of prostate cancer recurrence and death.

Role of coordinated molecular alterations in the development of androgen-independent prostate cancer: an in vitro model that corroborates clinical observations.

OBJECTIVE: To investigate the role of potential downstream targets of HER-2/neu, including the cell-cycle regulator p27, proliferation-associated protein Ki-67, apoptosis inhibitor Bcl-2, and signal-transduction molecule Akt (which is associated with cell survival), as the development of androgen-independent prostate cancer (AIPC) in patients who are initially responsive to androgen-ablation therapy (AAT) is a significant clinical problem. PATIENTS AND METHODS: Earlier studies showed that high levels of HER-2/neu tyrosine kinase receptor expression as assessed by immunohistochemistry were significantly associated with the development of AIPC, and we hypothesised that HER-2/neu overexpression provides an alternative proliferative stimulus upon androgen depletion. We established a unique clinical model system, comprising patients who received no AAT, or who had preoperative AAT, or those with advanced tumours resistant to AAT. To test our hypothesis in vitro, we stably transfected full-length HER-2/neu cDNA in androgen-responsive LNCaP cells and examined the effects of HER-2/neu overexpression on cell proliferation, apoptosis, androgen-receptor activation, and Akt phosphorylation upon androgen deprivation by using immunohistochemistry and Western blot technique. RESULTS: p27 expression was initially induced on exposure to AAT, and significantly decreased in AIPC (P < 0.001). There was also a significant increase in the Ki-67 index in AIPC (P = 0.001). Elevated Bcl-2 expression was closely associated with AAT (P = 0.002), suggesting that Bcl-2 expression is induced on initial exposure to AAT. Further, Bcl-2 expression was highest in hormone-resistant cancers (P < 0.001). Using the HER-2/neu transfected cell-line model, we confirmed the mechanistic basis of the clinical observations which elucidate the pathway leading to HER-2/neu-mediated androgen independence. On androgen deprivation, the HER-2/neu transfected cells had higher proliferation rates, lower G1 arrest, inhibited p27 up-regulation, a lower apoptotic index, and higher Bcl-2, prostate-specific antigen and phosphorylated Akt expression than the mock-transfected LNCaP cells. CONCLUSION: This study suggests that prostate cancer cells undergo a series of coordinated changes after exposure to AAT, which eventually result in the development of androgen independence. Further, in support of previous results, it appears that a major factor in this process is the induction of HER-2/neu overexpression, which occurs after initial exposure to AAT. HER-2/neu may contribute to the development of androgen independence through: (i) maintaining cell proliferation; (ii) inhibiting apoptosis; and/or (iii) inducing AR activation in a ligand-independent fashion. These effects may be mediated, at least in part, through activation of the PI3K/Akt pathway.

Voiding dysfunction in children: role of urodynamic studies.

INTRODUCTION: Urodynamic examination is said to be the most reliable, but also a rather invasive tool for the diagnosis of dysfunctional voiding in children. We compared the usefulness of baseline diagnostics to urodynamics. MATERIALS AND METHODS: 60 children, mean age 9 years, admitted for further evaluation of voiding dysfunctions (monosymptomatic nocturnal enuresis, 17; recurrent urinary tract infection, 12; reflux, 2; urgency, incontinence or residual urine, 29) underwent clinical examination, ultrasound, uroflowmetry, endoscopy and urodynamics. RESULTS: Urodynamic evaluation revealed pathologic findings in 37 patients. Detrusor instability was found in 26 children, 11 children (18%) demonstrated signs of pelvic floor overactivity. Treatment decision was based on baseline diagnostics exclusively in 14 children, mainly on baseline diagnostics in 56 patients, and on urodynamics exclusively in 4 children (7%). CONCLUSION: In children with idiopathic dysfunction, urodynamics did not have a significant additional value compared to baseline diagnostics. Therefore, noninvasive methods should be the first-line diagnostic tools. Only in patients with unsuccessful initial treatment should a urodynamic examination be performed to rule out severe bladder dysfunction.