Periurethral Zone Research Articles

Study on Estimation of Serum Prostate Specific Antigen Level and Prostate Volume with Trans-Abdominal Ultrasonography Finding in Benign Prostate Hypertrophy at Tertiary Care Hospital : A Cross Sectional Descriptive Study

Introduction: The periurethral and transition zones of the prostatic gland develop benign prostatic hyperplasia and represent an inevitable phenomenon for the ageing male population. Prostatic specific antigen, is a serine protease, level rises in the blood if the barrier between thelining epithelium and the blood stream is damaged. Benign prostatic hyperplasia, prostatic carcinoma and prostatitis are three common diseases where PSA in the serum is raised. Prostate volume also increases according to age, which can be estimated by trans-abdominal ultrasonography.
 Objective: The aim of the study is to estimate the PSA level in blood and its relationship with prostate volume in benign prostatic hyperplasia patients.
 Methodology: It is a descriptive cross-sectional study which was carried out between a periods of 1st April 2018 to 31st March 2019 at Birat Medical College Teaching Hospital. All the patients diagnosed with benign prostate hyperplasia at the department of urology were included in the study. Blood samples of patients were analyzed for Prostate specific antigen level estimation by chemiluminescence immunosorbent assay. Prostatic volume of the patients was measured by Transabdominal ultrasound technique. Data were entered and analyzed in Microsoft Excel.
 Results: A total of 68 patients were diagnosed with benign prostate hyperplasia. The mean age of the patients was 61.8±12.3 years. The maximum number 23 of patients with BPH was there in age group 51-60. The maximum no of patients 38 were having their PSA level between the range of 4.0-10.0 ng/ml. The maximum no of patients 28 was having Prostate volume in the range of 40-60 gm. The maximum number of patients 31 was having diabetes mellitus as a co-morbid association. The maximum mean PSA level and prostate volume in the patients were observed in age group >80 years,which was 20.1±8.6 ng/ml and >80 gm respectively.
 Conclusion: The prostate specific antigen level and prostate volume both increase in advance age group of patients suffering with benign prostate hyperplasia.

Apical periurethral transition zone lesions: MRI and histology findings.

Apical periurethral transition zone (TZ) cancers can pose unique problems for surgery and radiation therapy. Here, we describe the appearance of such cancers on multiparametric MRI (mpMRI) and correlate this with histopathology derived from MRI-targeted biopsy. Between May 2011 and January 2019, a total of 4381 consecutive patients underwent 3T mpMRI. Of these, 53 patients with 58 apical periurethral TZ lesions underwent TRUS/MRI fusion-guided biopsy and 12-core systematic TRUS-guided biopsy. Correlation was made with patient age, PSA, PSA density, whole prostate volume, and Gleason scores. A total 53 men (median age 68years, median PSA 7.94ng/ml) were identified as having at least one apical periurethral TZ lesion on mpMRI and 5 (9%) patients had more than one apical periurethral lesion. Thus, 58 lesions were identified in 53 patients. Of these 37/53 patients (69%) and 40/58 lesions were positive at biopsy for prostate cancer. Seven were diagnosed by 12-core systematic TRUS-guided biopsy and 34 were diagnosed by TRUS/MRI fusion-guided biopsy. Gleason score was ≥ 3 + 4 in 34/58 (58%) lesions. Identification of apical periurethral TZ prostate cancers is important to help guide surgical and radiation therapy as these tumors are adjacent to critical structures. Because of the tendency to undersample the periurethral zone during TRUS biopsy, MRI-guided biopsy is particularly helpful for detecting apical periurethral TZ prostate cancers many of which prove to be clinically significant.

Mesenchymal stem cells and the embryonic reawakening theory of BPH.

The prostate is the only organ in a man that continues to grow with age. John McNeal proposed, 40 years ago, that this BPH is characterized by an age-related reinitiation of benign neoplastic growth selectively in developmentally abortive distal ducts within the prostate transition-periurethral zone (TPZ), owing to a reawakening of inductive stroma selectively within these zones. An innovative variant of this hypothesis is that, owing to its location, the TPZ is continuously exposed to urinary components and/or autoantigens, which produces an inflammatory TPZ microenvironment that promotes recruitment of bone marrow-derived mesenchymal stem cells (MSCs) and generates a paracrine-inductive stroma that reinitiates benign neoplastic nodular growth. In support of this hypothesis, MSCs infiltrate human BPH tissue and have the ability to stimulate epithelial stem cell growth. These results provide a framework for defining both the aetiology of BPH in ageing men and insights into new therapeutic approaches.

복분자 미숙과 추출물이 전립선암 세포주와 전립선비대 백서모델에 미치는 영향

본 연구는 전립선암세포주인 LNCaP 세포주와 테스토스테론으로 유도된 전립선비대 백서모델에서 복분자 추출물의 전립선비대 억제 효과를 조사하였다. 첫째, 전립선암 세포주(LNCaP)에서 복분자 미숙과 추출물의 안드로겐 관련 전립선비대 유전자 억제 효과를 조사한 결과 미숙과 50% 에탄올 추출물은 안드로겐 수용체(AR)뿐만 아니라 전립선특이항원(PSA)과 5-알파 환원 효소 type 2(5AR2)의 발현을 가장 높게 억제하였다. 또한 LNCaP 세포에 DHT로 안드로겐 관련 유전자를 유도한 후 복분자 미숙과 50% 에탄올 추출물을 처리한 결과 AR과 PSA mRNA의 발현이 억제됨을 확인하였다. 둘째, 테스토스테론을 이용하여 전립선비대를 유도한 동물모델에서 복분자 미숙과 50% 에탄올 추출물을 6주간 투여한 후 전립선비대 개선 효과를 조사한 결과, 전립선비대 유발군에 복분자 미숙과 추출물을 투여한 군에서 전립선 무게, 전립선 소포의 상피세포 두께 및 면적이 감소함을 확인할 수 있었고, 전립선비대 유발 호르몬인 DHT level이 감소함을 확인할 수 있었다.

Evaluation of ultrasound elastography in the diagnosis of prostate cancer

Objective To evaluate the application of transrectal ultrasound elastography (TRE) in the detection of prostate cancer(PCa).Methods One hundred and eighteen patients with suspected PCa were enrolled in this study.Each patient underwent transrectal ultrasound (TRUS), TRE and sonography guided prostatic biopsy on the same day.The accuracy rate of PCa detection using TRE were compared with the pathology results.Results Patients with PCa were detected in 62 of the 118 patients,including 48 cases by TRE and 38 cases by TRUS.The sensitivity for TRE (73.6％) was significantly higher than that of TRUS (52.8％) in periurethral zone(P ＜0.05).The sensitivity and specificity for strain ratio(SR) in predicting PCa were 85.7％ and 67.7％ respectively(cut off value：3.6,area under the curve 0.8, P ＜0.01,95％CI [0.68 - 0.92]).Conclusions TRE can detect PCa in the periurethral zone with good accuracy and has potential to increase ultrasound-based PCa detection rate. Key words: Endosonography; Prostatic neoplasms; Elastography ; Strain ratio

Making anatomic terminology of the prostate and contiguous structures clinically useful: Historical review and suggestions for revision in the 21st Century

Herein we review nomenclature of the prostate and contiguous structures in each of the 10 official publications from the 1895 [Basel] Nomina Anatomica to the 1998 Terminologia Anatomica. We then compare existing clinical terminology with official terminology endorsed by anatomists over the years with a goal to modernize official terminology. Problematic terms, namely, lobes and lobuli, fascia versus capsule, Denonvilliers' fascia, and transition versus periurethral zone, are addressed. The idea of recognizing prostate arteries, veins, nerves, and neurovascular bundles is introduced. Prostatic and membranous urethras and the closely related external urethral sphincter are covered. We believe urogenital hiatus should also be called anterior levator hiatus. Trapezoid zone should be discarded in future editions of nomenclature. Our recommended changes are supported by a series of pertinent photographs of gross and whole mount histologic specimens and magnetic resonance images. Finally, we provide a new table of terms for the prostate with recommended amendments and deletions to existing official nomenclature as contained in the 1998 Terminologia Anatomica.

UP-3.044: Benign Prostatic Hyperplasia: Histologic Confirmation of an Ever-Progressing Disease

BPH morphogenesis starts from initial mesenquimal nodules and myxoid primitive structures usually localized in the periurethral zone (transition zone). It has been supposed that the younger is an individual the more of these structures would be identified in the samples coming from TURP or open adenomectomy. We challenged this hypothesis when looking for the role of mononuclear cells infiltration on these primitive structures.

Distribution of immunoreactive inhibin like material in different regions of human prostate.

Distribution of immunoreactive inhibin material (IR-ILM) in different regions of human prostate was studied by using specific radio-immunoassay. Mean IR-ILM concentrations in the central, peripheral and periurethral zones were 27.3 +/- 9.3, 2.4 +/- 0.7 and 3.0 +/- 1.5 micrograms/mg protein respectively (P central vs periurethral and peripheral less than 0.05).

Effect of Short-term Dutasteride Therapy on Prostate Vascularity in Patients With Benign Prostatic Hyperplasia: A Pilot Study

In this study we assessed the possible influence of dutasteride (types 1 and 2 isoenzymes of 5-alpha-reductase inhibitors) on prostate tissue vascularity. We also attempted to evaluate whether preoperative treatment with dutasteride could help to avoid excessive bleeding in patients undergoing transurethral resection of prostate (TUR-P). This pilot study has 3 phases. All patients enrolled in the study had a prostate-specific antigen < 4 ng/mL and normal digital rectal examination. In the first phase we included 10 patients with benign prostatic hyperplasia treated with alpha-blockers. The end point of this phase was to choose the preset that could exclude noise signals and be reproducible. In the second phase, we included 32 patients in whom color Doppler sonography (CDS) was performed before and 6 weeks after treatment with 0.5 mg dutasteride per day. We counted every discrete color Doppler signal (CD-spot). To compare the CDS data, we used the Student t test, and P < .05 was considered significant. Afterward, 46 patients joined the third phase. Patients were assigned to the control and study groups according to sequentially numbered sealed envelopes. Patients in the study group received 0.5 mg dutasteride 6 weeks before TUR-P. In the first phase: color Doppler preset with pulse repetition frequency of 0.3 kHz was chosen as the most sensible. In the second phase, a significant decline in CD-spots count was detected in 23 (72%) patients (P < .05) and was more distinctive in the periurethral zone. In the third phase, only 43 of the patients continued with TUR-P (in 3 patients, voiding symptoms improved). Operating time and volume of irrigation fluid were significantly different (50.55 minutes/42.65 minutes, P = .014; 8.03/13.10 L, P = .047). Six weeks of dutasteride treatment may reduce prostate tissue vascularity in the periurethral area proximal to the verumontanum. The third phase of our study confirmed that preoperative treatment with dutasteride could improve operative performance and avoid TUR syndrome.

CAN PATIENTS WITH LUTS AND BPH DISCERN CHANGES IN PEAK URINARY FLOW RATE AND DO SUCH CHANGES CONTRIBUTE TO OVERALL SATISFACTION WITH TREATMENT?

The development of finasteride (PROSCAR, Merck & Co., Whitehouse Station, NJ) for the treatment of benign prostatic hyperplasia (BPH) has had variable results. Numerous short-term and long-term studies comparing finasteride with placebo have been reported. The results suggest that, physiologically, treatment with finasteride significantly decreases levels of both serum and intraprostatic dihydrotestosterone about 70% to 80% from baseline. In addition, total gland size decreases significantly—about 15% to 25% from baseline—particularly in the area of the periurethral zone of the prostate after finasteride treatment. Baseline prostate size has been found to have a relation to efficacy of finasteride treatment. The larger the prostate at baseline, the greater the urinary flow rate increase and symptom score decrease compared with placebo. Health-related quality-of-life parameters improved in those taking finasteride. In studies evaluating combination therapy, no significant differences were noted between those treated with an α blocker, such as terazosin or doxazosin in combination with finasteride, and those receiving an α blocker alone. Long-term finasteride versus placebo studies, such as the PROSCAR Long-Term Efficacy and Safety Study (PLESS), suggest that long-term medical therapy with finasteride affects the natural history of the disease as manifested by the decrease in rates of acute urinary retention and surgery. In patients who are “therapeutic responders,” the degree of symptomatic improvement in those treated with finasteride appears to be equal to that seen in patients receiving α blockers. Prostate cancer detection rates did not differ between those treated with finasteride and those receiving a placebo. The results of these studies suggest that physicians must evaluate what role finasteride plays in the spectrum of available options for the treatment of BPH and lower urinary tract symptoms. Baseline parameters, such as prostate volume, prostate-specific antigen values, and whether to administer finasteride in combination with α blockers, are among the factors that will determine the appropriateness of such therapy.

Three-dimensional Proton MR Spectroscopy of Human Prostate at 3 T without Endorectal Coil: Feasibility

To evaluate sensitivity and specificity of proton magnetic resonance (MR) spectroscopy of the prostate with external surface coil elements at 3 T for differentiation of cancer from healthy tissue within an acceptable measurement time, by using histopathologic findings as the reference standard. The study was approved by the institutional review board; informed consent was obtained. Forty-five men (age range, 51-70 years) underwent 3-T MR imaging with external radiofrequency surface coils for signal reception. MR spectroscopy was performed with acquisition-weighted three-dimensional water- and lipid-suppressed point-resolved spectroscopy pulse sequence. Voxels were classified into healthy peripheral zone, central gland, and periurethral zone and cancer tissue. Cancer voxels were classified according to cancer size and certainty in matching histopathologic findings with MR images. After visual inspection of automated fitting of classified voxels, the choline plus creatine-to-citrate (Cho + Cr/Cit) ratio was calculated for all tissues. Area under the receiver operating characteristic curves (A(z)) values were used to assess accuracy of discrimination of cancer from healthy tissues. P < .05 indicated a significant difference. After exclusion of four patients with no voxels that passed visual inspection of the automated fit, a median of 82% of the classified voxels per patient was used in the analysis. Mean Cho + Cr/Cit ratios for healthy tissues were 0.22 +/- 0.12 (standard deviation) for peripheral zone, 0.34 +/- 0.14 for central gland, and 0.36 +/- 0.20 for periurethral area; all were significantly different from that of cancer (P < .001). A(z) for discrimination of probable and definite cancer tissue from healthy tissue for the peripheral zone (0.84) was significantly higher than that for the central gland (0.69) (P < .05). Three-dimensional proton MR spectroscopy of the prostate, with a combination of only external radiofrequency surface coils at 3 T, can be used to discriminate cancer from healthy tissue.

Correlation Between Ultrasound Alterations of the Preprostatic Sphincter and Symptoms in Patients With Chronic Prostatitis-Chronic Pelvic Pain Syndrome

We investigated ultrasound alterations of the preprostatic sphincter in patients with chronic prostatitis-chronic pelvic pain syndrome. We evaluated the frequency of these alterations, standardized their ultrasound measurement and correlated them with symptoms in patients with chronic prostatitis-chronic pelvic pain syndrome. In 37 patients with chronic prostatitis-chronic pelvic pain syndrome and 23 healthy volunteers certain parameters were measured by transrectal ultrasound, including prostate volume, hypoechoic periurethral zone volume, posterior prostate lip thickness, bladder neck thickness, detrusor thickness and the degree of echogenicity of the anterior fibromuscular stroma. All patients were evaluated with the International Prostate Symptom Score and National Institutes of Health Chronic Prostatitis Symptom Index. Urinary flow rate and post-void residual urine volume were also considered in each patient. All assessments were done independently and consecutively by 3 operators. A hypoechoic periurethral zone volume was found in 36 of 37 patients with chronic prostatitis-chronic pelvic pain syndrome. No significant intra-observer and interobserver differences were found in ultrasound parameter measurements. In the chronic prostatitis-chronic pelvic pain syndrome group ultrasound findings showed greater post-void residual urine volume, detrusor thickness and hypoechoic periurethral zone volume, increased posterior prostate lip thickness and bladder neck thickness, and greater anterior fibromuscular stroma hyperechogenicity. On multivariate analysis hypoechoic periurethral zone volume was an independent predictive factor for worse National Institutes of Health Chronic Prostatitis Symptom Index pain, urinary and total scores. Posterior prostate lip thickness was the only factor predictive of a worse International Prostate Symptom Score in patients with chronic prostatitis-chronic pelvic pain syndrome. A hypoechoic periurethral zone volume, posterior prostate lip thickness and bladder neck thickness with calculated threshold values revealed fair to excellent accuracy for identifying a patient with chronic prostatitis-chronic pelvic pain syndrome. Ultrasound evaluation of the bladder neck-posterior urethra in patients with chronic prostatitis-chronic pelvic pain syndrome led us to identify a set of lesions that cannot be found in healthy subjects. The measurement of hypoechoic periurethral zone volume, posterior prostate lip thickness and bladder neck thickness could be useful for following patients with chronic prostatitis-chronic pelvic pain syndrome and maybe for better understanding the complicated pathophysiological mechanisms of chronic nonbacterial prostatitis.

Androgens and Benign Prostatic Hyperplasia

Background A close interaction between androgens, in particular dihydrotestosterone (DHT), and prostate tissue is universally recognised. The continuous biologic effects of this hormone are fundamental during the normal development and maintenance of the gland, as well as in the case of hyperplasic growth of the organ. Methods This article reviews the association between androgens and benign prostatic hyperplasia. Results The bioavailability of DHT within prostate tissue depends on the correct functioning of a complex hormonal signalling axis that mainly includes the synthesis of testosterone in testes and adrenal glands, the peripheral conversion of this precursor to DHT operated by 5-α-reductase, and finally the transport to target sites. The real function of DHT consists in promoting the expression of specific genes through a fine molecular mechanism, leading to synthesis of growth-stimulating or growth-inhibiting factors that modulate cell proliferation and function. The complete pattern of molecular factors involved in this mechanism is not yet completely defined. However, it is generally accepted that DHT, which controls the expression of specific molecular mediators, maintains a constant balance between proliferative and apoptotic processes in the prostate tissue during the normal development and growth of the gland. With advancing age, and for processes not entirely understood, this homeostatic equilibrium between proliferative and apoptotic processes is disrupted, all of which leads to progressive growth and enlargement of the prostate, mainly based on expansion of the epithelial compartment. A complex series of tissue modifications is then activated, especially in the periurethral zone of the gland where a higher sensitivity to androgens is registered, thereby explaining how BPH leads to bladder outlet obstruction. Conclusion DHT is instrumental in the development of BPH. Under normal conditions, and in the presence of normal circulating and intraprostatic levels of androgens and estrogens, an homeostatic equilibrium between proliferative and apoptotic processes is present.

Effect of Dutasteride Therapy on Doppler US Evaluation of Prostate: Preliminary Results

To prospectively determine the effect of short-term therapy with dutasteride on the suppression of Doppler ultrasonographic (US) signal in benign prostate tissue and thus on improvement in the depiction of prostate cancer with Doppler US-guided core-needle biopsy. After institutional review board approval and informed consent were obtained as part of this HIPAA-compliant study, 11 men (age range, 59-77 years) were evaluated with gray-scale, color, and power Doppler US at baseline and weekly for up to 3 weeks while taking 0.5 mg of dutasteride per day. Flow intensity in the periurethral, transition, and peripheral zones was subjectively scored by using a four-point scale. The Wilcoxon matched-pairs signed-ranks test was used to compare pre- and posttherapy scores. After flow was reduced to "diminished" or "none" with at least a 1-score difference on the four-point scale, up to four targeted cores were obtained from areas of persistent flow within the peripheral zone, followed by laterally directed sextant biopsy. Doppler US flow suppression occurred in 11 of 11 patients after 1 week of dutasteride therapy (P < .01). Further suppression was noted after 2 weeks in eight of 10 patients (P = .04) and after 3 weeks in two of two patients. Biopsy was performed after 1 (n = 1), 2 (n = 8), or 3 (n = 2) weeks of therapy. Flow suppression was greatest in the peripheral zones (mean decrease: 0.64 and 0.76 after weeks 1 and 2, respectively) and least in the periurethral zones (mean decrease: 0.30 after 1 week). Cancer was detected in eight (20%) of 40 targeted cores and in five (8%) of 66 sextant cores. Four patients had cancer at targeted biopsy, and three of these four patients had cancer at sextant biopsy. In the four men with cancer, targeted cores were 5.9 times more likely to be positive (P = .027). Selective suppression of flow in benign tissue was observed in two of the four men with cancer. Short-term dutasteride therapy reduces Doppler US flow in the prostate and may improve depiction of hypervascular cancer.

Expression of different genes in transitional zone and peripheral zone of human normal prostate

To detect the expression of different genes in the transitional zone and peripheral zone of human normal prostate. Seventeen specimens of normal prostate gland were obtained from dead kidney donors and patients undergoing total cystectomy. The transitional zone and peripheral zone were isolated. Twenty specimens of benign prostate hypertrophy (BPH) were obtained from patients undergoing prostatic enucleation. The periurethral significantly hypertrophic nodules were isolated. BioDoor Chip-40S containing 6700 clones of targeting gene cDNA was used to detect the gene expression. The peripheral zone RNA samples were labeled with cy3, and the transitional zone RNA samples labeled with Cy5. The genes with the ratio average (RA) < 0.5 or > 2 were identified as differentially expressed genes, and those with a RA < 0.2 or > 4 were identified as the most significantly differentially expressed genes. RT-PCR was used to investigate semi-quantitatively the expression of epidermal growth factor (EGF) mRNA in the 17 specimens of transitional zone and peripheral zone from the 17 normal prostate glands and the 20 specimens of periurethral zone from BPH. A total of 640 genes differentially expressed in transitional zone and peripheral zone were screened out (comprising 269 unknown genes and 371 known genes), of which 294 genes were expressed in the transitional zone and 346 in the peripheral zone. Fourteen genes were identified as markedly differentially expressed, among which the EGF gene was highly expressed in the central zone, and the OSF-1 (osteoblast stimulating factor-1) gene was highly expressed in the peripheral zone. RT-PCR proved that in comparison with the expression of the internal marker beta-actin gene, the expression levels of EGF in the normal transitional zone and in the periurethral zone from BPH were markedly higher than that in the peripheral zone. There are differently expressed genes between the peripheral zone and central zone of normal human prostate, which may be the background of different biological behavior between these zones. EGF may markedly contribute to the growth of central zone of normal prostate.

Transrectal ultrasonography and ultrasound-guided biopsies of the prostate gland: How, when, and where

Transrectal ultrasound (TRUS) has revolutionized prostate biopsy technique and plays a central part in diagnosis of prostate cancer. Nevertheless TRUS is an inherently operator-dependent modality and its performance varies significantly due to equipment quality. Thus it is of great importance to the detailed knowledge of the complex 3D prostate anatomy, the integrated scanning procedure, the evaluation of every zone for chronic or suspicious change, and the performance of ultrasound-guided biopsies. 1 Anatomy The prostate is an exocrine gland lying just below the bladder neck and surrounding the urethra. Superolaterally to it lay the seminal vesicles and the vas deferens. The lateral venous plexus intermixed with arteries and nerves comprise the neurovascular bundles that pass from above to below along the posterolateral aspects of the prostate, piercing the capsule. Vessels, connective tissue, and fat surround the prostate. Histologically the prostate is composed of four zones: anterior fibromuscular stroma, periurethral transition zone (TZ), posterior peripheral zone (PZ), and posterosuperior central zone (CZ). Since the majority of patients referred for TRUS examination are middle aged or older, almost all of them have a hyperplastic transition zone. Peripheral and central zones are usually thin and compressed in a posterolateral position. This process is described as benign prostatic hyperplasia (BPH). 2 The previously described middle lobe consists of part of the transition zone that protrudes in the urinary bladder base. Anteriorly lying fibromuscular stroma is nonglandular tissue. Virtually all BPH arise in the transitional zone. Seventy percent of adenocarcinomas arise in the peripheral zone, 20% arise in the transitional zone, and 10% arise within the central zone. 2

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI.

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4 +/- 0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k(ep) and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k(ep) decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.

Benign Prostatic Hyperplasia: Correlations between Receptor Density and Binding Affinity of α1-Adrenoceptors and Several Clinical Parameters

The aim of the study was to determine whether relations do exist between the concentration and activity of α₁-adrenoceptors, both inside the prostatic adenoma and the periurethral zone corresponding to the bladder neck, and clinical and biological parameters such as symptoms, evaluated by the American Urological Association (AUA) score, age, weight of the prostate, PSA, and the flow rate. Twenty patients with symptomatic benign prostatic hyperplasia were selected for an open prostatectomy. One gram of tissue was dissected from inside the adenoma and 1 g from the periurethral zone corresponding to the bladder neck. The α₁-adrenoceptors were evaluated for the apparent dissociation constant (K_d) and the maximal number of binding sites (B_max). A correlation seems to exist between receptor density inside the adenoma and the bladder neck and an inverse correlation between receptor density and the AUA total symptoms score. Finally, a highly significant difference was found in patients with an AUA score of <15 or >15. No relationship was found between receptor binding affinity and the considered clinical parameters.

5 α-reductase inhibitors: what role should they play?

The development of finasteride (PROSCAR, Merck & Co., Whitehouse Station, NJ) for the treatment of benign prostatic hyperplasia (BPH) has had variable results. Numerous short-term and long-term studies comparing finasteride with placebo have been reported. The results suggest that, physiologically, treatment with finasteride significantly decreases levels of both serum and intraprostatic dihydrotestosterone about 70% to 80% from baseline. In addition, total gland size decreases significantly—about 15% to 25% from baseline—particularly in the area of the periurethral zone of the prostate after finasteride treatment. Baseline prostate size has been found to have a relation to efficacy of finasteride treatment. The larger the prostate at baseline, the greater the urinary flow rate increase and symptom score decrease compared with placebo. Health-related quality-of-life parameters improved in those taking finasteride. In studies evaluating combination therapy, no significant differences were noted between those treated with an α blocker, such as terazosin or doxazosin in combination with finasteride, and those receiving an α blocker alone. Long-term finasteride versus placebo studies, such as the PROSCAR Long-Term Efficacy and Safety Study (PLESS), suggest that long-term medical therapy with finasteride affects the natural history of the disease as manifested by the decrease in rates of acute urinary retention and surgery. In patients who are “therapeutic responders,” the degree of symptomatic improvement in those treated with finasteride appears to be equal to that seen in patients receiving α blockers. Prostate cancer detection rates did not differ between those treated with finasteride and those receiving a placebo. The results of these studies suggest that physicians must evaluate what role finasteride plays in the spectrum of available options for the treatment of BPH and lower urinary tract symptoms. Baseline parameters, such as prostate volume, prostate-specific antigen values, and whether to administer finasteride in combination with α blockers, are among the factors that will determine the appropriateness of such therapy.

CAN THE INTRAPROSTATIC CONCENTRATION OF EPIDERMAL GROWTH FACTOR INFLUENCE THE VARIANCE OF SERUM PROSTATE SPECIFIC ANTIGEN LEVELS IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA?

Except for prostate volume, little is known about the factors influencing serum prostate specific antigen (PSA) levels. Considering that dihydrotestosterone and epidermal growth factor are regulators of the proliferation and differentiation in the epithelial component of human prostate tissue and that PSA is produced only by the epithelial cells of the gland, studies were performed on patients with a histological diagnosis of benign prostatic hyperplasia (BPH) to establish whether a significant association exists between the intraprostatic concentration of dihydrotestosterone or epidermal growth factor and serum PSA levels.A total of 20 patients with BPH who had not been previously treated were part of a larger study on the correlation among PSA, prostate volume and age, and were evaluated according to the algorithm in the guidelines of the international consultation on BPH. All men underwent open suprapubic prostatectomy to enucleate the entire adenoma and in each case sections were made in the periurethral, subcapsular and intermediate zones of the BPH tissue. Dihydrotestosterone and epidermal growth factor concentrations were evaluated by radioimmunoassay in the periurethral zone and in total BPH tissue.In these 20 patients with BPH serum PSA levels were significantly associated with epidermal growth factor but not with dihydrotestosterone concentrations in total BPH tissue (r = 0.7762, p = 0.00002836 and r = 0.3923, p = 0.0956307, respectively). A stronger association was found between PSA levels and the periurethral concentration of epidermal growth factor and dihydrotestosterone (r = 0.8117, p = 0.000005 and r = 0.5656, p = 0.0098326, respectively). On the contrary, epidermal growth factor and dihydrotestosterone were not significantly associated with prostate volume (p = 0.957415 and p = 0.531439, respectively).To our knowledge this study is the first report in the literature to demonstrate an association between serum PSA, and dihydrotestosterone and epidermal growth factor levels, particularly in the periurethral zone of human BPH tissue. These data suggest the importance of epidermal growth factor and dihydrotestosterone in influencing serum PSA levels.