Alberto A. Antunes

Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis

OBJECTIVE MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. MATERIAL AND METHODS Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. RESULTS miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P<0.001), (55.550 vs. 8.314, P=0.010), and (33.549 vs. 2.748, P=0.001), respectively. CONCLUSION We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 β3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies.

Quality of Life and Clinical Symptom Improvement Support Prostatic Artery Embolization for Patients with Acute Urinary Retention Caused by Benign Prostatic Hyperplasia

PURPOSE To show that prostatic artery embolization (PAE) improves quality of life (QoL) and lower urinary tract symptoms in patients with acute urinary retention caused by benign prostatic hyperplasia (BPH). MATERIALS AND METHODS This was a single-center prospective study of PAE in 11 patients with BPH managed with indwelling urinary catheters. International Prostate Symptom Score (IPSS), ultrasound, magnetic resonance (MR) imaging, QoL, and urodynamic tests were used to assess outcomes. Prostate size ranged from 30 to 90 g, and embolizations were performed with 300-500-μm Embosphere microspheres. RESULTS The rate of technical success (ie, bilateral PAE) was 75%, and the rate of clinical success (ie, catheter removal and symptom improvement) was 91% (10 of 11 patients). Postembolization syndrome manifested as mild pain in the perineum, retropubic area, and/or urethra. Ten of 11 patients urinated spontaneously after Foley catheter removal 4-25 days after PAE (mean, 12.1 d). No major complications were observed. Follow-up ranged from 19 to 48 months. In an asymptomatic patient, a discrete area of hypoperfusion suggesting small ischemia of the bladder was observed on 30-day MR imaging follow-up, but the bladder was normal on 90-day MR imaging. After 1 year, mean prostate volume reduction was greater than 30%, symptoms were mild (mean IPSS, 2.8 ± 2.1; P = .04), no erectile dysfunction was observed, and QoL improved significantly (mean, 0.4 ± 0.5; P = .001) using the paired t test. CONCLUSIONS Patients with severe symptoms and acute urinary retention caused by BPH can be treated safely by PAE, which improves clinical symptoms and QoL.

miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer

BackgroundPrognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line.Materials and methodsTo determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025).ConclusionsOur results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.

Prostatic Artery Embolization for Treatment of Benign Prostatic Hyperplasia in Patients with Prostates > 90 g: A Prospective Single-Center Study

PURPOSE To describe the safety and efficacy of prostatic artery embolization (PAE) with spherical microparticles to treat lower urinary tract symptoms associated with benign prostatic hyperplasia in patients with prostate volume > 90 g. MATERIALS AND METHODS This prospective, single-center, single-arm study was conducted in 35 patients with prostate volumes ranging from 90-252 g. Mean patient age was 64.8 years (range, 53-77 y). Magnetic resonance imaging, uroflowmetry, and the International Prostate Symptom Score (IPSS) were used to assess clinical and functional outcomes. RESULTS Mean prostate size decreased significantly from 135.1 g before PAE to 91.9 g at 3 months of follow-up (P < .0001). Mean IPSS and quality-of-life index improved from 18.3 to 2.7 and 4.8 to 0.9 (P < .0001 for both), respectively. A significant negative correlation was observed between prostate-specific antigen at 24 hours after PAE and IPSS 3 months after PAE (P = .0057). CONCLUSIONS PAE is a safe and effective treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia in patients with prostate volume > 90 g. Excessively elevated prostate-specific antigen within 24 hours of PAE is associated with lower symptom burden in short-term follow-up.

The role of squamous differentiation in patients with transitional cell carcinoma of the bladder treated with radical cystectomy

OBJECTIVE We aim at determining the prognostic value of squamous differentiation in patients with transitional cell carcinoma (TCC) of the bladder that were treated with radical cystectomy. MATERIALS AND METHODS From January 1993 to January 2005, we retrospectively selected 113 patients. Correlations among squamous differentiation with other clinical and pathological features were assessed by both chi-square and Fisher tests. The Kaplan-Meier method was used to evaluate survival curves and statistical significance was determined by the log-rank test. Multivariate analysis was performed through a Cox proportional hazards regression model. RESULTS Squamous differentiation was observed in 25 (22.1%) of the 113 patients. This finding was significantly related only to the pathological stage. Mean follow-up after cystectomy was 31.7 +/- 28.5 months. Disease recurrence occurred in 16 (64%) and 30 (34%) patients with and without squamous differentiation (log-rank test, p = 0.001), and mortality occurred in 10 (40%) and 14 (16%) of the patients with and without squamous differentiation respectively. Univariate analysis revealed that pathological stage, squamous differentiation, tumor size and lymph node involvement were significant predictors of cancer-specific survival. However, only squamous differentiation and tumor size were independent prognostic variables on multivariate analysis. CONCLUSIONS Squamous differentiation was an independent prognostic factor for cancer specific survival in patients with bladder cancer treated with radical cystectomy. Further studies with a larger number of patients are necessary to confirm these results.

Microvascular tumour invasion in renal cell carcinoma: the most important prognostic factor.

To evaluate the role of microvascular invasion (MVI) in the primary lesion for predicting tumour behaviour in patients with renal cell carcinoma (RCC), as reliable clinical prognostic factors would be very valuable.

Transient Ischemic Rectitis as a Potential Complication after Prostatic Artery Embolization: Case Report and Review of the Literature

Prostatic artery embolization (PAE) is an alternative treatment for benign prostatic hyperplasia. Complications are primarily related to non-target embolization. We report a case of ischemic rectitis in a 76-year-old man with significant lower urinary tract symptoms due to benign prostatic hyperplasia, probably related to nontarget embolization. Magnetic resonance imaging revealed an 85.5-g prostate and urodynamic studies confirmed Inferior vesical obstruction. PAE was performed bilaterally. During the first 3 days of follow-up, a small amount of blood mixed in the stool was observed. Colonoscopy identified rectal ulcers at day 4, which had then disappeared by day 16 post PAE without treatment. PAE is a safe, effective procedure with a low complication rate, but interventionalists should be aware of the risk of rectal nontarget embolization.

Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It

Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality of life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.

Upgrading the Gleason Score in Extended Prostate Biopsy: Implications for Treatment Choice

PURPOSE To determine the incidence of overestimation of Gleason score (GS) in extended prostate biopsy, and consequently circumventing unnecessary aggressive treatment. METHODS AND MATERIALS This is a retrospective study of 464 patients who underwent prostate biopsy and radical prostatectomy between January 2001 and November 2007. The GS from biopsy and radical prostatectomy were compared. The incidence of overestimation of GS in biopsies and tumor volume were studied. Multivariate analysis was applied to find parameters that predict upgrading the GS in prostate biopsy. RESULTS The exact agreement of GS between prostate biopsy and radical prostatectomy occurred in 56.9% of cases. In 29.1% cases it was underestimated, and it was overestimated in 14%. One hundred and six (22.8%) patients received a diagnosis of high GS (8, 9, or 10) in a prostate biopsy. In 29.2% of cases, the definitive Gleason Score was 7 or lower. In cases in which GS was overestimated in the biopsy, tumors were significantly smaller. In multivariate analysis, the total percentage of tumor was the only independent factor in overestimation of GS. Tumors occupying less than 33% of cores had a 5.6-fold greater chance of being overestimated. CONCLUSION In the extended biopsy era and after the International Society of Urological Pathology consensus on GS, almost one third of tumors considered to have high GS at the biopsy may be intermediate-risk cancers. In that condition, tumors are smaller in biopsy. This should be remembered by professionals involved with prostate cancer to avoid overtreatment and undesirable side effects.

The “PErFecTED Technique”: Proximal Embolization First, Then Embolize Distal for Benign Prostatic Hyperplasia

AbstractProstatic artery embolization requires a refined technique to achieve good imaging and clinical success. The PErFecTED (Proximal Embolization First, Then Embolize Distal) technique has produced greater prostate ischemia and infarction than previously described methods with clinical improvement of lower urinary symptoms and lower recurrence rates. The microcatheter should cross any collateral branch to the bladder, rectum, corpus cavernosum, gonad, or penis and be placed distally into the prostatic artery before its branching to the central gland and peripheral zone. This technique allows better distribution of embolic material in the intraprostatic arteries and reduces risk of spasm or thrombus. Because benign prostatic hyperplasia develops primarily in the periurethral region of the prostate, the urethral group of arteries should be embolized first. Subsequent distal investigation and embolization completes occlusion and stasis of blood flow to the prostatic parenchyma. Since we added the second step to the PErFecTED technique, we have observed infarcts in all patients submitted to prostatic artery embolization.