Mitra Fakhari

PROSPECTIVE EVALUATION OF PROSTATE CANCER DETECTED ON BIOPSIES 1, 2, 3 AND 4: WHEN SHOULD WE STOP?

PURPOSE We evaluated biochemical parameters and pathological features, as well as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml. These features were compared to those detected on prostate biopsy 1. MATERIALS AND METHODS In this prospective European Prostate Cancer Detection study 1,051 men with total PSA between 4 and 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy and 2 additional transition zone biopsies. All patients in whom biopsy samples were negative for prostate cancer underwent biopsy 2 after 6 weeks. If also negative, biopsies 3 and even 4 were performed at 8-week intervals. Those patients with clinically localized cancer underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS Cancer detection rates on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of 737) and 4% (4 of 94), respectively. Overall, of the patients with clinically localized disease, which was 67% of cancers detected, 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies 1, 2, 3 and 4, respectively. Despite statistically significant differences in regard to multifocality (p = 0.009) and cancer location (p = 0.001), including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location, there were no differences in regard to stage (p = 0.2), Gleason score (p = 0.3), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between biopsies 1 and 2. However, cancer detected on biopsies 3 and 4 had a significantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5 (p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001), respectively. CONCLUSIONS Despite differences in location and multifocality, pathological and biochemical features of cancer detected on biopsies 1 and 2 were similar, suggesting comparable biological behaviors. Cancer detected on biopsies 3 and 4 had a lower grade, stage and volume compared with that on biopsies 1 and 2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 and 4 had a slightly higher complication rate. Therefore, biopsy 2 in all cases of a negative finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and/or poor prognostic factors on biopsy 1 or 2.

Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma

Recent studies show that vascular endothelial growth factor (VEGF) and its receptors Flt‐1 and KDR, and a series of other angiogenic molecules, are upregulated in advanced but not low stage human neuroblastoma. Neuropilin‐1 and 2 (NRP) are novel specific receptors of VEGF165, whose role is unknown in human neuroblastoma.

A NOVEL INTRAURETHRAL PROSTATIC BRIDGE CATHETER FOR PREVENTION OF TEMPORARY PROSTATIC OBSTRUCTION FOLLOWING HIGH ENERGY TRANSURETHRAL MICROWAVE THERMOTHERAPY IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

PURPOSE We evaluate the efficacy and safety of a novel intraurethral prostatic bridge catheter in preventing temporary prostatic obstruction following targeted high energy transurethral microwave thermotherapy in patients with benign prostatic hyperplasia. MATERIALS AND METHODS A total of 54 patients with benign prostatic hyperplasia underwent high energy transurethral microwave therapy under topical urethral anesthesia followed by placement of a prostatic bridge catheter, which remained indwelling as long as 1 month (prostatic bridge catheter group). Patient evaluation included determination of peak urinary flow rate, International Prostate Symptom Score (I-PSS) and quality of life score at baseline, immediately following transurethral microwave therapy and prostatic bridge catheter placement, and periodically thereafter for 1 month. Results were retrospectively compared with those of 51 patients who underwent transurethral microwave therapy followed by standard temporary urinary catheterization, typically for 24 hours (standard catheterization group). RESULTS Immediately following transurethral microwave therapy and prostatic bridge catheter placement significant improvements (p <0.0005) were observed in mean peak flow rate, I-PSS and quality of life score of 59.3, 33.5 and 23.6%, respectively, compared with baseline values. Further improvements were noted up to 1 month, at which time mean peak flow rate, I-PSS and quality of life score had improved 79.0, 54.9 and 56.5%, respectively, versus baseline (p <0.0005). In a retrospective comparison at baseline and 14 days between the prostatic bridge catheter group and standard catheterization group mean baseline peak flow rate, I-PSS and quality of life score were similar. However, at the 14-day followup evaluation in the prostatic bridge catheter group mean peak flow rate was 101.8% higher, and I-PSS and quality of life score were 47.9 and 51.1% lower, respectively, than the corresponding values in the standard catheterization group (p <0.0005). The prostatic bridge catheter was well tolerated and remained indwelling throughout the entire 1-month followup in 48 of 54 patients (88.9%). Early prostatic bridge catheter removal was required in 3 patients (5.6%) due to urinary retention and in 3 (5.6%) due to catheter migration. CONCLUSIONS Prostatic bridge catheter placement provides an effective and well tolerated option for preventing prostatic obstruction in the acute period after transurethral microwave therapy. This approach avoids the inconvenience and infection risk of standard indwelling catheters or intermittent self-catheterization. Prostatic bridge catheter insertion and removal are rapid, facile, nontraumatic procedures. Prostatic bridge catheter may potentially be used in an array of minimally invasive procedures involving thermal treatment of the prostate gland.

Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia : A randomized, prospective clinical trial

OBJECTIVES Improved long-term results with respect to symptoms, voiding function, and quality of life (QOL) in patients with lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high-energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker treatment alone. However, maximal improvement after TUMT is not attained until 3 to 6 months after treatment. Measures to provide earlier symptom relief and improved voiding function and QOL would add to the clinical utility of TUMT. The objective of the present study was to determine whether neoadjuvant and adjuvant alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of patients with BPH. METHODS In this randomized, prospective study of 81 patients with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before treatment and at periodic intervals thereafter up to 12 weeks after TUMT. RESULTS Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95% confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were 15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to 17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005). However, by the final evaluation at 12 weeks, no significant difference between the groups in mean IPSS was evident. A similar temporal pattern of difference between the two study groups was also observed in QOL score. No significant between-group difference in mean Qmax was evident after TUMT. Urinary retention 1 week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater early symptom reduction and QOL score improvement after TUMT, adding to the clinical utility of this minimally invasive treatment modality. In addition, post-TUMT complications such as urinary retention may be reduced.

Targeted transurethral microwave thermotherapy versus alpha-blockade in benign prostatic hyperplasia: outcomes at 18 months.

OBJECTIVES To compare directly the efficacy, safety, and durability of targeted transurethral microwave thermotherapy with that of alpha-blocker treatment for lower urinary tract symptoms of benign prostatic hyperplasia. METHODS In a randomized, controlled clinical trial, 52 patients with lower urinary tract symptoms due to benign prostatic hyperplasia received terazosin treatment and 51 underwent microwave treatment under topical anesthesia. The patient evaluation included the International Prostate Symptom Score, peak flow rate, and quality-of-life score before microwave treatment or initiation of terazosin treatment and at periodic intervals thereafter up to 18 months. RESULTS The mean International Prostate Symptom Score, peak flow rate, and quality-of-life score all improved significantly in both groups by 6 months. However, the magnitude of improvement was significantly greater in the microwave group than in the terazosin group. The significant between-group differences observed at 6 months in the mean International Prostate Symptom Score, peak flow rate, and quality-of-life score were fully maintained at 18 months, at which time the improvements in these three outcome measures were significantly greater (P <0.0005), by 35%, 22%, and 43%, respectively, in the microwave group than in the terazosin group. The actuarial rate of treatment failure at 18 months was significantly greater by sevenfold in the terazosin group. Adverse events were generally infrequent and readily manageable in both groups. CONCLUSIONS Although the initial onset of terazosin action was more rapid, the longer term clinical outcomes of targeted microwave treatment were markedly superior. The more favorable results in patients who underwent microwave treatment were maintained for at least 18 months.