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Biomedical subjects

Bob Djavan

Publications and source records attributed to Bob Djavan.

At least 19 recordsLinked to original sources

11C-acetate positron emission tomography imaging and image fusion with computed tomography and magnetic resonance imaging in patients with recurrent prostate cancer.

PURPOSE: To assess the clinical value of computed tomography (CT) and magnetic resonance imaging (MRI) image fusion with 11C-acetate (AC) positron emission tomography (PET) imaging for detection and exact location of clinically occult recurrences. PATIENTS AND METHODS: Fifty prostate cancer patients with elevated/increasing serum prostate-specific antigen levels after radical therapy underwent whole-body AC PET. Uptake was initially interpreted as normal, abnormal, or equivocal. In case of abnormal or equivocal uptake, additional conventional imaging techniques, such as CT, MRI, and bone scans, were performed. To precisely define the anatomic location of abnormal uptake and to improve characterization of equivocal lesions, a software-assisted image fusion (CT-PET, MRI-PET) was performed and evaluated as site-by-site analysis of 51 abnormal (n = 37) or equivocal (n = 14) sites of all 50 patients. In 17 patients, additional histopathologic evaluation was available. RESULTS: In five (10%), 13 (26%), and 32 (64%) of the 50 patients, AC PET studies demonstrated AC uptake judged as normal, equivocal, and abnormal, respectively. Image fusion changed characterization of equivocal lesions as normal in five (10%) of 51 sites and abnormal in nine (18%) of 51 sites. It precisely defined the anatomic location of abnormal uptake in 37 (73%) of 51 sites. AC PET findings did influence patient management in 14 (28%) of 50 patients. CONCLUSION: Retrospective fusion of AC PET and CT/MRI is feasible and seems to be essential for final diagnosis. This is particularly true in patients with AC uptake in the prostate region.

Acetates↗

Sensitivity and detection rate of a 12-core trans-perineal prostate biopsy: preliminary report.

OBJECTIVES: The various prostate biopsy methods are usually compared in terms of the diagnosis rate of prostate cancer. However, the prevalence of cancer in patients with a negative prostatic biopsy is not usually known. We determined the sensitivity and detection rate of 12-core transperineal biopsies in patients not previously investigated for prostate cancer. METHODS: We performed prostate biopsy in 63 patients (median age 67 years) before radical cystoprostatectomy for high-grade bladder cancer. We then assessed the relationships between biopsy result, prostate cancer in the surgical specimen, and other variables. RESULTS: 17.2% of patients had a positive biopsy and 54% had prostate cancer on definitive histology. Biopsy sensitivity was 32.3% overall, 75% for clinically significant cancers, and 11% for non-significant cancers. Median PSA was 1.2ng/ml, PSA levels did not correlate with the presence of prostate cancer, the presence of clinically significant cancer, bioptic diagnosis, or prostate volume. Age correlated with risk of cancer. CONCLUSIONS: According to autopsy series, the prevalence of prostate cancer is greater than 50% in males older than 60, yet low PSA levels do not reliably indicate disease absence. The sensitivity of double sextant biopsy is unsatisfactory overall (32%), but acceptable (75%) for diagnosing clinically significant cancer.

Aged↗

Chemopreventive trials in urologic cancer.

Cancer prevention uses natural, synthetic, or biological chemical agents to reverse, suppress, or prevent carcinogenic progression. Chemoprevention trials are based on the hypothesis that interruption of the biological process involved in carcinogenesis will inhibit this process and, in turn, reduce cancer incidence. Bladder cancer chemoprevention trials demonstrate conflicting findings. Dietary fat, soy protein, garlic, and selenium have been reported to possess anticancer properties in the bladder, but they still remain largely unstudied in vivo. Regarding prostate cancer, vitamin D deficiency was reported to increase risk for the disease, and sunlight exposure is inversely proportional to prostate cancer mortality. The Prostate Cancer Prevention Trial reported a 24.4% prostate cancer incidence with placebo, compared with 18.4% with finasteride, and a reduction of 24.8% over 7 years. Dutasteride, a dual inhibitor of type 1 and type 2 5alpha-reductase, is the subject of the Reduction by Dutasteride of Prostate Cancer Events trial. Results are awaited from that study.

Journal Article↗

Progression delay in men with mild symptoms of bladder outlet obstruction: a comparative study of phytotherapy and watchful waiting.

To determine the effect of phytotherapy (Serona repens) on the clinical progression in men with mild symptoms of bladder outlet obstruction (BOO). A total of 189 patients with mild symptoms of BOO, recruited from four different European clinics, were included in the analysis. Age, prostate specific antigen (PSA), international prostate symptom score (IPSS), quality of life (QOL), maximum urinary flow rate (Qmax) and total prostate and transitional zone volume were recorded. Clinical progression was defined as change from the mild-IPSS group into the moderate or severe group or the occurrence of urinary retention and need of surgery. Cumulative progression rate was 1, 7, 9 and 16% at 6, 12, 18 and 24 month, respectively, for the active group (Serona repens) as compared to 6, 13, 15 and 24% for the watchful waiting group. (P=0.03) significant improvements in the Qmax, IPSS and QOL were seen in the group receiving Serona repens. Serona repens significantly reduced the clinical progression rates in men with mild symptoms of BOO. It also led to improvements in urinary symptoms, QOL scores and urinary flow rates.

Androgen Antagonists↗

Are repeat biopsies required in men with PSA levels < or =4 ng/ml? A Multiinstitutional Prospective European Study.

OBJECTIVES: Pathological and biochemical features of prostate cancers detected on repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were evaluated and compared to those cancers detected on first biopsy. METHODS: 315 men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound guided sextant biopsy and two additional transition zone biopsies (Octant Biopsy). All subjects whose biopsy samples were negative for prostate cancer underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers were offered surgery or radiation therapy. Pathological and clinical features of patients diagnosed with prostate cancer on initial and repeat biopsy were compared. RESULTS: Cancer detection rates on first and second biopsy were 24% (75/315) and 13% (29/224), respectively. Overall, of patients with clinically localized disease (83% of cancers detected), 87% underwent radical prostatectomy, 11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found in the first biopsy group were more multifocal (p = 0.01) while cancers found on second biopsy were more located in the apical-dorsal region (p = 0.003). No significant differences were noted with respect to extracapsular extension, seminal vesical invasion, positive margins, final pathological stage, Gleason score, percentage Gleason grade 4/5, serum PSA and patient age between first and second biopsy. CONCLUSIONS: With an octant biopsy regime, biochemical and pathological features of cancers detected on initial and repeat biopsy in the PSA range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer volume suggesting identical cancer characteristics, thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy.

Aged↗

Natural history and clinical predictors of clinical progression in benign prostatic hyperplasia.

PURPOSE OF REVIEW: Prevalence of benign prostatic hyperplasia (BPH) is increasing with the aging population worldwide. Knowledge of the natural history of BPH is crucial for primary, secondary and tertiary prevention of its progression. This review examines the evidence of the natural history of BPH, highlighting the group of patients with mild symptoms and the risk factors for progression. RECENT FINDINGS: Several community and clinical studies have demonstrated the progressive nature of BPH. Different surrogate endpoints, which include symptom score, peak urinary flow rate, prostate volume, and the occurrence of acute urinary retention and need for surgery, have been described. Prostatic specific antigen and prostate volume are the two most common predictors of clinical progression and are helpful to the clinician for identifying high-risk patients. SUMMARY: With further understanding of the natural history and the predictors of progression of BPH, management can be better tailored according to risk stratification and the results of clinical trials of effectiveness can be better interpreted.

Disease Progression↗

Role of phytotherapy in men with lower urinary tract symptoms.

PURPOSE OF REVIEW: Serenoa repens extract is a popular phytotherapeutic agent in men with lower urinary tract symptoms. Although the exact mechanism of action is unknown, the agent is generally well accepted for its easy availability and good tolerability. This paper reviews the evidence of its efficacy in comparison with placebo, 5-alpha reductase inhibitor and alpha-1 adrenoreceptor antagonist. RECENT FINDINGS: Serenoa repens extract is comparable with 5-alpha reductase (finasteride) and alpha-1 antagonist in the treatment of benign prostatic hyperplasia in terms of symptom score and peak urinary flow rate improvement, but has a lower incidence of associated sexual dysfunction. Furthermore, long-term usage (36 months) of Serenoa repens decreases the progression rate of the condition as compared with watchful waiting. In addition, the efficacies of Serenoa repens are proven in several placebo-controlled trials. SUMMARY: Serenoa repens has proven its role in the management of benign prostatic hyperplasia and will remain as a viable first-line treatment option.

5-alpha Reductase Inhibitors↗

The Vienna nomogram: validation of a novel biopsy strategy defining the optimal number of cores based on patient age and total prostate volume.

PURPOSE: We conducted a trial in patients with prostate specific antigen (PSA) levels from 2 to 10 ng/ml to validate a newly developed nomogram that defines the optimal number of biopsy cores required for prostate cancer (PCa) detection based on patient age and total prostate volume (Vienna nomogram). MATERIALS AND METHODS: A total of 502 patients underwent transrectal ultrasound guided prostate biopsy using the Vienna nomogram. These results were compared with those of a previous group of 1,051 patients who had standard octant biopsies followed by systematic repeat biopsies after 6 to 8 weeks if the initial biopsy result was negative for PCa. RESULTS: The overall PCa detection rate using the Vienna nomogram was 36.7% compared with 22% on first and 10% on repeat biopsy in the control group. The PCa detection rate using the Vienna nomogram was superior (p=0.002) to the octant biopsy technique, and comparable to a combination of first and repeat biopsy in the control group. Multivariate analysis of the Vienna nomogram showed that only PSA and the number of cores were independent predictors of PCa detection (chi-square = 49, p <0.001). Total prostate volume, transition zone volume and age were not independent predictors of PCa detection. CONCLUSIONS: The Vienna nomogram offers an easy tool to select the optimal number of prostate biopsy cores based on patient age and total prostate volume in PSA range 2 to 10 ng/ml. Cancer detection is significantly improved (66.4%) compared to the control group. The bias factor of larger prostate volume is eliminated by using the Vienna nomogram. Moreover, the Vienna nomogram is advantageous not only in terms of the improved PCa detection rate but also economically makes systematic repeat biopsies unnecessary.

Adult↗

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia: latest update on alpha-adrenoceptor antagonists.

An update of a systematic review of alpha1-adrenoceptor (AR) antagonists in the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) showed that these agents have comparable efficacy. The total symptom score is improved by 30-45% and maximum urinary flow rate by 15-30% vs baseline. alpha1-AR antagonists that can be started at their therapeutic dose have a more rapid onset of action than alpha1-AR antagonists that have to be titrated. alpha1-AR antagonists can be differentiated according to their tolerability. Alfuzosin (especially the 10 mg once daily dose) and tamsulosin (especially the 0.4 mg once daily dose) are better tolerated than doxazosin and terazosin. However, alfuzosin might induce more cardiovascular adverse events (AEs) in the elderly and/or patients with cardiovascular comorbidity and/or comedication. Tamsulosin tends to interfere less with blood pressure regulation and induce less vasodilatory AEs than alfuzosin, especially in the elderly, and is well tolerated in patients with cardiovascular comorbidity and/or comedication. Cardiovascular AEs might lead to potentially serious complications such as falls, fractures and institutionalization. Abnormal ejaculation has mainly been reported in placebo-controlled trials with tamsulosin but in direct comparative trials its rate with tamsulosin 0.4 mg was similar to, or only slightly higher than, the rate with alfuzosin. In addition, abnormal ejaculation is not reported as bothersome by the patient or associated with serious complications. It can be concluded that an alpha1-AR antagonist with a low potential to interfere with blood pressure regulation and to induce cardiovascular AEs, also in patients with cardiovascular comorbidity and/or comedication, can be considered a first-choice treatment option in LUTS/BPH.

Adrenergic alpha-Antagonists↗

Dutasteride: a novel dual inhibitor of 5alpha-reductase for benign prostatic hyperplasia.

Dutasteride is a new dual 5alpha-reductase inhibitor for the treatment of benign prostatic hyperplasia. It differs from finasteride as it inhibits both isoenzymes of 5alpha-reductase and results in near-complete suppression of serum dihydro-testosterone. Similar to finasteride, it reduces serum prostatic specific antigen by approximately 50% at 6months and total prostate volume by 25% in 2years. Randomised, placebo-controlled trials conducted over 2years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and the need for surgery. The main side effects are erectile dysfunction, decreased libido, gynaecomastia and ejaculation disorders. However, long-term usage for > 4years did not reveal increased new onset of sexual side effects. In addition, the combination of dutasteride and tamsulosin is well-tolerated and has the added advantage of rapid symptomatic relief. Finally, dutasteride has been shown to possess tumour regression properties invitro and its role in chemoprevention of prostate cancer will be confirmed in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Prostate biopsy: who, how and when. An update.

Biochemical parameters and pathological features as well as biopsy related morbidity of prostate cancer detected on second, third and fourth repeat prostate biopsy in men with a serum total PSA level between 4 ng/mL and 10 ng/mL were evaluated and compared to those cancers detected on initial prostate biopsy. In a prospective European Prostate Cancer Detection study, 1051 men with a total PSA level between 4 ng/mL and 10 ng/mL underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a first repeat biopsy after 6 weeks. If also negative a third and even a fourth biopsy was performed at 8 weeks intervals. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. Cancer detection rates on first, second, third and fourth biopsy were 22% (231/1051), 10% (83/820), 5% (36/737) and 4% (4/94), respectively. Percent free PSA and PSA-TZ were the most powerful parameters to predict cancer on repeat biopsy. Overall, of patients with clinically localized disease (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% had organ confined disease on first, repeat, third and fourth biopsy, respectively. Despite statistical significant differences with respect to multifocality (p=0.009) and cancer location (p=0.001) (cancers on second biopsy showing a lower rate of multifocality and a more apico-dorsal location), there were no differences with respect to stage (p=0.2), Gleason score (p=0.3), percentage Gleason grade 4/5 (p=0.2), serum PSA and patient age between first and second biopsy. However, cancers detected on third and fourth biopsy had a significantly lower Gleason score (p=0.001 and 0.001), lower rate of grade 4/5 cancer (p=0.02), lower cancer volume (p= 0.001 and 0.001) and lower stage (p= 0.001). Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Interestingly, patients under 60 years of age reported a higher pain apprehension as quantified with the visual analog pain scale (VAS). Further, the use of the Vienna tables allowed an accurate calculation of the number of biopsy cores required based on prostate volume and age. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and second biopsy were similar, suggesting similar biological behavior. Cancers detected on third and fourth biopsy had a lower grade, stage and cancer volume as compared to cancers on first and repeat biopsy. Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Hence, a second prostate biopsy in all cases of a negative finding on initial biopsy appears justified. Third and fourth repeat biopsies however, should only be obtained in very selected patients with high suspicion of cancer and/or poor prognostic factors on the first or second biopsy. Power Doppler TRUS will further enhance prostate cancer detection as will artificial neural networks as patient selecting tools.

Adult↗

Dutasteride: a review of current data on a novel dual inhibitor of 5alpha reductase.

Dutasteride is used in the treatment of benign prostatic hyperplasia. Like finasteride, it reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% in 2 years. It differs from finasteride in that it inhibits both isoenzymes of 5alpha reductase and results in near-complete suppression of serum dihydrotestosterone. Randomized placebo-controlled trials over 2 years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and need for surgery. Side effects occurring in therapy with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia. However, when dutasteride treatment is compared with placebo, these sexual adverse events are only modestly elevated. Long-term use over 4 years did not increase side effects. An efficient treatment of side effects is the combination of dutasteride and tamsulosin, especially for patients with large prostate volumes. Finally, the anticancer properties of dutasteride have been shown in placebo-controlled trials and are being investigated in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Duplicate Publication↗

Is seminal vesicle ablation mandatory for all patients undergoing radical prostatectomy? A multivariate analysis on 1283 patients.

OBJECTIVE: With a shift in prostate cancer stage and a majority of patients operated nowadays with PSA levels <10 ng/ml, rates of seminal vesicle (SV) invasion found on radical prostatectomy specimens have decreased as compared to historical data. Since SV-sparing surgery may possibly have an influence on post-operative erectile dysfunction and urinary recovery, we tried to determine which patients could be safely spared SV excision during radical prostatectomy. MATERIAL AND METHODS: We used preoperative data from 1283 patients operated by radical retropubic prostatectomy--777 with serum PSA <10.0 ng/ml--to predict SV invasion on final pathological examination. Variables analyzed included age, digital rectal examination, serum PSA, biopsy Gleason score and percentage of biopsy cores invaded by prostate cancer. Statistical analysis included univariate, multivariate logistic regression analysis and receiver operating characteristic (ROC) curves. RESULTS: Out of 1283 patients, 137 (10.6%) had SV involvement, 41/777 (5.2%) with PSA <10.0 ng/ml, 16.1% in the 10-20 ng/ml range and 26.2% when PSA was >20 ng/ml. Percentage of biopsies affected by prostate cancer and biopsy Gleason score were significant predictors of SV invasion in multivariate analysis, both in the entire population and in the subset of patients with PSA <10.0 ng/ml (p < 0.0001). Probability graphs created for patients with PSA <10 ng/ml indicate a risk of seminal invasion <5% when Gleason score on biopsy is <7 or when the percentage of biopsies affected by cancer is <50%. CONCLUSIONS: Resection of SV might not be "oncologically" necessary in all patients undergoing RP when PSA levels are below 10 ng/ml except when biopsy Gleason score is > or =7 or when more than 50% of prostate biopsy cores show cancer involvement. SV-sparing surgery could be prospectively compared to standard retropubic prostatectomy in selected individuals analyzing potential benefits on erectile function and urinary continence.

Aged↗