alpha-Methylacyl-CoA racemase (AMACR) has previously been shown to be a highly sensitive marker for colorectal and clinically localized prostate cancer (PCa). However, AMACR expression was down-regulated at the transcript and protein level in hormone-refractory metastatic PCa, suggesting a hormone-dependent expression of AMACR. To further explore the hypothesis that AMACR is hormone regulated and plays a role in PCa progression AMACR protein expression was characterized in a broad range of PCa samples treated with variable amounts and lengths of exogenous anti-androgens. Analysis included standard slides and high-density tissue microarrays. AMACR protein expression was significantly increased in localized hormone-naive PCa as compared to benign (P < 0.001). Mean AMACR expression was lower in tissue samples from patients who had received neoadjuvant hormone treatment but still higher compared to hormone-refractory metastases. The hormone-sensitive tumor cell line, LNCaP, demonstrated stronger AMACR expression by Western blot analysis than the poorly differentiated cell lines DU-145 and PC-3. AMACR protein expression in cells after exposure to anti-androgen treatment was unchanged, whereas prostate-specific antigen, known to be androgen-regulated, demonstrated decreased protein expression. Surprisingly, this data suggests that AMACR expression is not regulated by androgens. Examination of colorectal cancer, which is not hormone regulated, demonstrated high levels of AMACR expression in well to moderately differentiated tumors and weak expression in anaplastic colorectal cancers. Taken together, these data suggest that AMACR expression is not hormone-dependent but may in fact be a marker of tumor differentiation.
Objectives: To determine the outcome of patients with a serum prostate-specific antigen (PSA) level 420 ng/ml that underwent radical prostatectomy (RP). Methods: We retrospectively reviewed the medical records of 147 patients who underwent RP for clinically localized prostate cancer with a pre-treatment PSA (PSApt) 420 ng/ml. Fifty-two patients had positive pelvic lymph nodes and were excluded from analysis. Of 95 patients remaining, 15 were lost to follow-up. Therefore, the study group included 80 patients. The end points for this analysis were biochemical relapse-free survival (bRFS), surgical and post-operative complications and urinary continence. PSApt, pathological grade, surgical margin status, age, clinical stage and immediate androgen ablation were evaluated in a multivariate analysis regarding bRFS. Results: Forty-nine resected specimens (61.2%) were pathologically classified as pT3 or pT4. After a mean follow-up of 64 months, the estimated 5-year bRFS rate was 58% for the overall group. Immediate androgen ablation was the only independent prognostic factor for biochemical relapse (P ¼ 0.001). Concerning the 21 patients who received an immediate androgen ablation after RP, the estimated 5-year bRFS rate was 92%. Complete urinary continence was achieved in 76.5% of patients. Early complications occurred in 13 patients (16.2%). Conclusions: Clinically localized prostate cancer with a PSApt 420 ng/ml is considered as having a poor prognosis. However, RP performed in these patients led to an acceptable morbidity and good functional results. Immediate adjuvant hormonal therapy seems mandatory in this setting to improve bRFS.
Introduction: Treatment options for lymph node positive prostate cancer are limited. We retrospectively compared patients who underwent external radiotherapy (ERT) to patients treated by radical prostatectomy (RPX). Materials and Methods: A total of 102 lymph node positive patients from the RPX series at Ulm University were evaluated. In all, 76 patients received adjuvant androgen withdrawal as part of their primary treatment. In the ERT group, 44 patients were treated at the University of Michigan using a fractionated regimen. Of these, 21 patients received early adjuvant hormonal therapy. Patients with neoadjuvant therapy before RPX or ERT were excluded. Results: In the RPX group, PSA nadir (nadirp0.2 vs 40.2 ng/ml) showed a strong association with outcome. In the ERT group, pretreatment PSA was an independent predictor of outcome (P ¼ 0.04) and patients with adjuvant hormonal therapy had a significant longer recurrence-free interval compared to patients without adjuvant therapy (P ¼ 0.004). Comparing only patients with adjuvant hormonal treatment after cancer-specific therapy, the ERT-treated patients had a borderline longer PSA recurrence-free survival time compared to the RPX-treated patients (P ¼ 0.05). Conclusions: In case of positive lymph nodes, RPX and ERT might be considered and need to be explained to the patient. For future treatment decisions, the presented findings and a potential survival benefit need to be evaluated in a larger prospective setting.
Endo-ultrasound with surface rendering proved to be highly effective for evaluating ESWL success in cases of prevesical ureteral stones. This technique is independent from bowel gas or other factors that impede radiological imaging. It is safe, easy to learn, well tolerated by patients and does not expose them to radiation.
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