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Objective: Dutasteride is a 5-alpha reductase inhibitor used to treat benign prostatic hyperplasia. Dutasteride lowers prostate-specific antigen (PSA) levels, which may lead to delays in the diagnosis and treatment of prostate cancer (PCa). This study investigated patients who underwent prostate biopsy (PBx) while receiving dutasteride to investigate whether this agent affects the diagnosis and treatment of PCa., Patients and Methods: PBx was performed on six patients receiving dutasteride for > 3 months at our medical institutions between January 2010 and June 2013. No patients underwent PBx before dutasteride administration. We performed PBx both for patients with high initial PSA levels and for those with elevated PSA levels with or without initial PSA decline after dutasteride administration. We also investigated clinicopathological findings., Results: Mean age at the start of administration was 69.5 ± 5.9 years (range, 59-77 years), mean duration of administration was 14.1 ± 7.4 months (range, 4.0-23.5 months), mean prostate volume at the start of administration was 70.4 ± 30.7 ml (range, 18.8-104.6 ml), and mean PSA level at the start of administration was 7.7 ± 3.3 ng/ml (range, 4.9-14.2 ng/ml). PSA density was 0.098 ± 0.045 ng/ml/cm3 (range, 0.042-0.181 ng/ml/cm3), and PSA level at PBx was 5.4 ± 2.7 ng/ml (range, 2.5-10.7 ng/ml). We detected three PCa patients, and clinical stage in each case was cT1cN0M0. Radical retropubic prostatectomy was performed in two cases, and androgen-deprivation therapy was performed in one case., Conclusion: All PCa were detected in the early clinical stage. No delays in detection or treatment of PCa were seen in any cases. Careful observation of PSA levels is simple and useful for detecting PCa in patients under dutasteride administration.

We investigated the add-on effect of dutasteride (0.5 mg once a day) on lower urinary tract symptoms (LUTS), prostate volume (PV), and serum prostate specific antigen (PSA) and testosterone level in 72 patients with benign prostatic hyperplasia (BPH) who had been treated with alpha-blocker monotherapy. Inclusion criteria were men with BPH who had PV ≧30 ml and international prostate symptom score (IPSS) ≧8 or quality of life (QOL) index ≧3 under alpha-blocker monotherapy for more than 3 months. At the baseline, 12 and 24 weeks after dutasteride add-on, we assessed IPSS, overactive bladder symptom score (OABSS), PV, serum PSA and testosterone. Among 47 patients (65%) with OAB diagnosed by OABSS, responders were defined as those with urgency score of OABSS ＜2 or total score of OABSS ＜3. At the 24th week, dutasteride significantly improved IPSS (-4.2) and OABSS (-1.9) and reduced PV (-29%) compared with the baseline. Furthermore, dutasteride significantly decreased serum PSA (-45%) and increased testosterone (36%). Among OAB patients, dutasteride significantly improved urgency and urgency incontinence but not nocturia. Responders had lower OABSS, urgency incontinence score and serum testosterone at the baseline than non-responders. In conclusion, dutasteride add-on therapy is beneficial in patients with BPH who do not show enough improvement with alpha-blocker monotherapy.

Objective: We examined the relationship between morcellation efficiency and enucleated tissue weight in holmium laser enucleation of the prostate (HoLEP) for patients with benign prostatic hyperplasia (BPH) retrospectively., Methods: From January to December 2010, 140 patients with BPH were treated by HoLEP combined with mechanical morcellation with up side down technique by a single surgeon., Results: The mean age was 70.6 years, and the mean enucleated tissue weight was 46.8 g. The mean morcellation time was 9.9 min, and the mean rate of morcellation was 6.7 g/min. No complications were reported relating to morcellation such as bladder injury. Although morcellation time and enucleated tissue weigh were proportionally related (Estimate equation: Y = - 1.186 + 0.813 * X, R^2: 0.814), larger glands with more than 80 g of tissue enucleated did not match this distribution map. Five cases with more than 100 g of enucleated tissue weight required much longer operation time (range 66-90 min) and were disproportioned to tissue weight. Morcellation efficiency tended to decrease when enucleated tissue weight exceeds 80 g and less than average in almost all cases. Morcellation efficiency significantly worsen when enucleated tissue weight exceeds more than 100 g., Conclusions: Morcellation efficency may decrease in larger gland exceeds 80 g.

Objectives: Using a portable three dimensional ultrasound scanning device (The Bladder Scan BVI6100, Diagnostic Ultrasound Corporation), we examined measured values of bladder volume, especially focusing on volume lower than 100 ml., Materials and Methods: A total of 100 patients (male: 66, female: 34) were enrolled in the study. We made a comparison study between the measured value (the average of three measurements of bladder urine volume after a trial in male and female modes) using BVI6100, and the actual measured value of the sample obtained by urethral catheterization in each patient. We examined the factors which could increase the error rate. We also introduced the effective techniques to reduce measurement errors., Results: The actual measured values in all patients correlated well with the average value of three measurements after a trial in a male mode of the BVI6100. The correlation coefficient was 0.887, the error rate was--4.6 +/- 24.5%, and the average coefficient of variation was 15.2. It was observed that the measurement result using the BVI6100 is influenced by patient side factors (extracted edges between bladder wall and urine, thickened bladder wall, irregular bladder wall, flattened rate of bladder, mistaking prostate for bladder in male, mistaking bladder for uterus in a female mode, etc.) or examiner side factors (angle between BVI and abdominal wall, compatibility between abdominal wall and ultrasound probe, controlling deflection while using probe, etc)., Conclusions: When appropriate patients are chosen and proper measurement is performed, BVI6100 provides significantly higher accuracy in determining bladder volume, compared with existing abdominal ultrasound methods. BVI6100 is a convenient and extremely effective device also for the measurement of bladder urine over 100 ml.

Between August 1985 and March 2004, we performed transurethral resection of the prostate (TURP) in 18 patients with benign prostatic hyperplasia (BPH) whose prostatic volume was larger than 100 ml. We divided the patients into two groups. Group A consisted of a total of 14 cases: 10 cases whose mean prostate volume was 114 ml (100 to 137 ml) and 4 cases whose prostate volume was not measured before TURP but whose mean resected prostatic tissue weight was 113 g (105 to 118 g). Group B consisted of 4 cases whose mean prostate volume was 110 ml (101 to 133 ml). Patients in group B underwent interstitial laser coagulation of the prostate (ILCP) followed by oral chlormadinone acetate (CMA) therapy (50 mg/day); TURP was performed 6 months later, once the prostate volume had shrunk to an average of 76 ml (66 to 91 ml). Mean resected weights and operation times were: group A, 93.1 g, 66.3 min; group B, 60.5 g, 55.7 min. There were 12 blood transfusion cases (85.7%; intraoperative) in group A, and 1 (25.0%; POD 1) in group B. Accordingly, this preoperative treatment was considered a safer method of TURP for BPH 100 ml or more. There were no cases of TURP syndrome or death in either group.

Purpose: There have been few reports on correlations between resection volume of benign prostatic hyperplasia, body mass index (BMI) and estrogen. This study was undertaken to evaluate the correlations., Method: In this study, we considered 50 patients who had benign prostatic hyperplasia (BPH) and underwent suprapubic prostatectomy (SPP). Men with prostate cancer or prior prostate surgery were excluded. The relationship between prostate resection volume and BMI was examined. Additionally, patients were divided into two groups according to BMI: less than 25, and more than 25. The two groups were evaluated according to stained estrogen receptors., Results: BMI was correlated positively with prostate volume (p < 0.01). However, positive rates of estrogen receptors showed no significant difference between the two groups., Conclusions: This was a study describing the relationship between BMI and prostate volume. Obesity has been hypothesized to be associated with BPH because of the endocrine changes in men that occur with age, including increased estrogen and decreased testosterone. Our findings suggest that estrogen may play a pathophysiologic role in benign prostatic hyperplasia. Further studies of large populations are needed to validate this assumption.

Purpose: With the aim of evaluating the clinical significance of systematic prostate biopsy before transurethral resection of the prostate (TUR-P), clinical data were reviewed retrospectively in patients who had underwent prostate biopsy prior to scheduled TUR-P., Patients and Methods: Between July, 1994 and June, 2000, TUR-P was scheduled in a total number of 456 patients with clinically diagnosed benign prostatic hyperplasia (BPH)., Results: In 218 (47.8%) out of 456 cases, prostatic biopsy was conducted prior to TUR-P due to abnormally elevated serum prostate specific antigen (PSA) levels of 4.0 ng/ml or more, revealing only 22 (10.1%) cases of prostatic cancer. Between these 22 cases with biopsy proven prostatic cancer and 189 cases with BPH confirmed both by biopsy and following TUR-P, statistically significant differences were noted in age (p < 0.05), prostate volume (p < 0.0001) and PSA density (p < 0.01)., Conclusion: Considering the low positive rate of preoperative prostatic biopsy, it might be suggested that a considerable number of biopsy could be avoided in patients with clinically diagnosed BPH. Based on the results obtained from this study, prostatic biopsy might be unnecessary before TUR-P for those with prostate volume greater than 60 ml or PSA density less than 0.15.

A 63-year-old male with symptomatic benign prostatic enlargement (220 ml as estimated by transrectal ultrasonography) was underwent transurethral holmium laser enucleation. Total operative time was 211 minutes and actual weight of tissue enucleated was 156 grams. There was no perioperative hyponatremia and a blood transfusion. The duration of catheterization was 3 days and the hospital stay was 5 days. Three months after treatment, the international prostate symptom score (IPSS) decreased from 19 preoperatively to 1. The quality of life (QOL) index decreased from 6 preoperatively to 1, whilst the maximum flow rate (Qmax) increased from 7 ml/sec preoperatively to 58 ml/sec.

Tissue specimens were resected from 15 patients (age 7 to 82, average 52.2 years old) with bladder diseases; i.e., 2 with neurogenic bladder, 6 recipients of kidney transplantation with defunctionalized bladder, 3 with benign prostatic hypertrophy, 3 with bladder cancer and 1 with vesicoureteral reflux. We investigated the phenotypic expression of the bladder smooth muscle cells with bladder diseases. The ratio of non-contractile to contractile phenotypes (nc/c ratio) showed a rising tendency with aging. The increase of nc/c ratio was especially notable with neurogenic bladder. Phenotypic expression was observed in human bladder smooth muscle cells as reported in vascular smooth muscle cells. Several bladder diseases cause a conversion of contractile smooth muscle cell phenotype from contractile type to non-contractile type, and this modulation of smooth muscle cell phenotype may play an important role in detrusor function.

Purpose: There had been few reports on relations between rates of prostatic tissue components, natural history and estrogen receptor. The present study was performed to evaluate these relations., Method: In this study, we examined 25 patients who had benign prostatic hyperplasia(BPH) and underwent transurethral resection of the prostate(TUR-P) or suprapublic prostatectomy(SPP). According to resection volumes of BPH, patients were divided into four groups; less than 5 g of TUR-P, more than 30 g of TUR-P, less than 70 g of SPP, more than 70 g of SPP. We also examined 13 nonhyperplastic prostates that were obtained from autopsied males. Immunoenzymatic staining and computer image analysis were used to determine the mean rate of the stromal. Additionally, resection volumes of BPH were evaluated according to estrogen receptor staining., Results: In nonhyperplastic glands, the stromal rates of age 15-40 were almost equal. We found that as resection volumes of BPH increased, the stromal rates were apt to decrease. However, positive rates of estrogen receptor showed no significant difference among the four groups., Conclusions: There was a trend of correlation between prostates with a decrease of stromal rate and increase of resection volume. Further studies of large populations are needed to validate this assumption.

Objective: We have the impression that the degree of obstruction was stronger in the patients with a middle lobe of hyperplastic nodule than in those without such a lobe in patients with benign prostatic hyperplasia. In the present study, we compared the data from a pressure-flow study (PFS) and a presence of a middle lobe., Materials and Methods: A transurethral resection for benign prostatic hyperplasia was performed in 2,439 patients, 798 underwent PFS. The PFS findings and the presence of a middle lobe were compared with the following parameters, namely, the bladder detrusor function, the degree of obstruction, the post-voided residual volume, the maximum flow rate, the prostate volume and the resected volume., Results: In the pressure-flow study, the rate of the normal bladder detrusor function was higher in the patients with a middle lobe than in those without such a lobe (71.9 versus 53.3%). The degree of obstruction was also stronger in the patients with a middle lobe than in those without in the patients with a normal bladder detrusor function (89.0 versus 79.4%). Then in the patients with a middle lobe, the quantity of the post-voided residual volume was greater, however, the maximum flow rate was lower., Conclusion: Most patients with a middle lobe demonstrate an improved voiding ability after underwent a transurethral resection.

Purpose: We studied how transition zone index (TZ index) influenced the therapeutic efficacy of benign prostatic hyperplasia (BPH). In addition, we retrospectively investigated the availability of TZ index in selection of the more effective therapeutic method for BPH., Method: One hundred twenty-five patients with symptomatic BPH whose prostate volume (PV) was more than 15 ml by transrectal ultrasonography were investigated. Sixty-nine men underwent transurethral resection of the prostate (TURP) whereas 56 were treated with alpha 1-blocker. Tamsulosin hydrochloride. These patients were evaluated based on TZ index as well as ordinary parameters of BPH; international prostatic symptom score, QOL score, peak flow rate and PV., Results: The patients with TZ index > or = 0.5 showed good therapeutic results in the TURP group. On the other hand, the patients with TZ index < 0.5 showed favorable response in alpha 1-blocker group. Multivariate analysis revealed that TZ index affected the therapeutic efficacy more strongly than the other parameters., Conclusion: TZ index had strong influence on therapeutic efficacy of TURP or alpha 1-blocker and seemed to be a useful tool for the selection of BPH therapy.

Benign prostate hypertrophy weighing more than 200 g is defined as giant prostatic hypertrophy. An 81-year-old man presented with urinary retention and underwent retropubic prostatectomy. Blood loss was 1,850 ml and he received 800 ml of autologous blood. The removed specimen weighed 267 g and pathology revealed benign hyperplasia of the prostate. We collected 32 such cases from the Japanese literature.

Transurethral electrovaporization of the prostate (TVP) has been devised to eliminate prostatic tissue by electric vaporization and to create a dry coagulation layer beneath to minimize bleeding from the site of TVP. However, vaporization induces degeneration due to thermal coagulation deep in the tissue beneath the vaporized layer, and local tissue damage is thus greater than that caused by the standard transurethral resection of prostate (TURP) loop. Since this results in difficulty with histopathological examination, the percentages of tissue-diagnosable area were determined in sections resected using various vaporization electrodes (Roller Loop, Band & Wedge Loop). The percentage of tissue-diagnosable area was 92.0 +/- 3.3% with the standard TUR loop, 2.4 +/- 0.9% with the Roller Loop, 42.7 +/- 21.1% with the Band Loop, and 39.7 +/- 24.4% with the Wedge Loop. Concerning speed of resection, the best vaporization effect was obtained when the speed of operation was 1/2 or 1/3 that with the standard TUR loop. Since the region in which tissue diagnosis was smaller with the vaporization electrode than with standard TURP, more careful examination was required for diagnosis of incidental cancers. Therefore, postoperative observation by PSA measurement appeared to be important.

Objective: To study the mechanism of thermotherapy on benign prostatic hyperplasia, we examined thermal effects on alpha 1-adrenoceptors in the guinea-pig vas deferens. The histological changes in the muscle cells after thermal exposure were also examined by electron microscopy., Methods: The guinea-pig vasa deferentia were pretreated at 4 degrees C (control group), 43 degrees C, 50 degrees C, and 55 degrees C (heated group) for 1 hour and returned to 37 degrees C for 1 hour or 2 hours. Radioligand binding assay for alpha 1-adrenoceptors was performed by an incubation of [3H]prazosin with the crude membrane fraction from vasa deferentia. The dissociation constant (Kd) and the number of binding sites (NBS) of alpha 1-adrenoceptors were calculated from Scatchard analysis. The histological changes in the muscle cells were also examined at 4 degrees C, 40 degrees C, 50 degrees C, and 55 degrees C for 1 hour by electron microscopy., Results: Kd and NBS did not change at 43 degrees C, but declined significantly above 50 degrees C for 1 hour. The changes in Kd and NBS above 50 degrees C for 1 hour did not recover after returning to 37 degrees C for 1 hour or 2 hours. Electron microscopic observations revealed a loss of myofilaments and dark staining of nuclear chromatin of the smooth muscle cells after thermal exposure above 50 degrees C., Conclusion: The binding ability of [3H]prazosin to alpha 1-adrenoceptors declined after thermal exposure above 50 degrees C. Also, the muscular damages were observed histologically after thermal exposure above 50 degrees C. These results indicated that the irreversible decrease in NBS and the disruption of smooth muscle fibers were associated with the thermotherapy.

A 44-year-old man suspected of having transitional cell carcinoma (TCC) of the prostate was referred to our hospital. He had a painful semi-erect penis at his first visit. Then needle biopsy of the corpus cavernosum histologically revealed metastatic TCC. CT of the pelvis showed bilateral ureteral obstruction caused by the advanced tumor but no lymph node swelling was found. Under the diagnosis of prostatic TCC with penile metastasis, bilateral percutaneous nephrostomy followed by two courses of combination chemotherapy (IFEP regimen) was carried out, which resulted in the disappearance of priapism. Radical cystectomy with total penectomy was performed. The final pathological diagnosis was corrected to TCC of the urinary bladder with invasion to the prostate and metastasis of the corpus cavernosum and the right obturator lymph node. Enlargement of the prostate proved to be caused by glandular hyperplasia with atypical hyperplasia of the prostate gland. Three courses of adjvent IFEP chemotherapy was given post-operatively and he has been alive with no evidence of the disease for 10 months.

Alpha adrenergic blocker has become the first choice in the medical treatment of benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has been suggested to be related to the prostatic tissue components, and to be ineffective in treating the clinical symptoms caused by BPH in some cases. The efficacy and prostate reduction of an anti-androgenic agent, chlormadinone acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were evaluated using 40-BPH patients insufficiently treated with tamsulosin hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin hydrochloride were administered orally once a day for 16 weeks to patients with a prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin hydrochloride alone for more than four weeks. Total I-PSS decreased significantly after four weeks. The total irritative symptom score did not change for 16 weeks, but the total obstructive symptom score decreased significantly, as did the total I-PSS. In objective data, the estimated volume of both total prostate and the transition zone on transrectal ultrasonogram decreased significantly at the end of the treatment, and the peak flow rate decreased significantly after 12 weeks. These findings suggest that the addition of chlormadinone acetate may be a reasonable alternative in the treatment of BPH patients responding insufficiently to tamsulosin hydrochloride alone, and that combination therapy using chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients with serious obstructive symptoms.

Background: Surgical therapy for Benign Prostatic Hypertrophy (B.P.H.) has mainly depended upon Transurethral Resection of the Prostate (TUR-P) using a cutting loop electrode. Recently, a new technique TVP was reported using the VaporTrode apparatus. We assessed the safety and efficacy of the VaporTrode in a preliminary study., Methods: Histological changes of the muscle and liver of pigs were examined after vaporization using the VaporTrode and a cutting loop electrode. First, histological changes were investigated following vaporization after one stroke at a slow hand speed. Next, histological changes were assessed following vaporization at fixed stroke speed in an experimental model., Results: At an electrical output of less than 275 W, the depth of the vaporized layer increased as the stroke speed became slower (4.0 cm/s-2.5 cm/s). When the electrical output was 300 W, the depth of vaporized layer increased even at a faster stroke speed (2.5 cm/s-3.0 cm/s.) The depth of the desiccated layer increased as the stroke speed became slower at any electrical output. However, when the stroke speed was 4.0 cm/s, the depth of this layer was less than 2.0 mm. With the cutting loop electrode, the depth of the desiccated layer increased at a higher electrical power, but the change was very small., Conclusion: To achieve deep enough vaporized and desiccated layers safely, the VaporTrode should be used at a stroke speed slower than 3.0 cm/s and a high electrical power of about 275 W.

A case of inverted papilloma of the posterior urethra is reported. A 59-year-old male was admitted with the chief complaint of difficulty in urination. Cystourethroscopy revealed a polypoid tumor with a smooth surface on the stalk arising from the prostatic urethra, concomitant with prostatic hypertrophy. Transurethral resection of the tumor and the prostate was performed. No evidence of recurrence has been noted in the 9 months after surgery. This is the 26 th case of inverted papilloma of the posterior urethra reported in Japan.

Background: Conventional transurethral Nd:YAG laser ablation of the prostate does not significantly reduce the volume of prostate and patients frequently experience post-operative urinary retention. Thus in the present study, prostatic tissue was extensively vaporized with laser fiber to produce a definite cavity during the operation., Methods: Between August 1993 and April 1995, laser prostatectomy utilizing Ultraline was carried out on 91 patients with BPH, 38 of these patients had histories of urinary retention. The size and form of the prostate were examined by transurethral ultrasonography (TUUS) prior to surgery and ablation was conducted based on the findings. The results were checked by TUUS a second time., Results: Operating time was 84.1 minutes on the average including the time for systematic needle biopsy and cystostomy for irrigation. Total irradiation dose was 132,035J on the average. The catheter was removed at an average 5.8 days postoperatively. I-PSS was noted to improve from 15.3 to 5.6, maximum flow rate, 9.3 to 15.8 ml/s, average flow rate, 4.6 to 9.2 ml/s and residual urine, 76.0 to 15.9 ml. The volume of the prostate was reduced by 31.5% (39.3 to 26.6 ml) and the patients could urinate for more than a year without discomfort. No serious complications were encountered though epididymitis was noted in 5 and urethral stricture in 10 patients., Conclusion: The present laser prostatectomy is less invasive than TUR-P and the results might be equal to it.

Background: There have been few reports on the relationship between the prostatic tissue components and the effect of alpha adrenergic blocker on urination. The present study was undertaken to correlate the rates of the prostatic tissue components and the clinical response to alpha adrenergic blocker in benign prostatic hyperplasia., Methods: 40 patients with symptomatic benign prostatic hyperplasia were treated with 0.2 mg/day tamsulosin, a alpha adrenergic blocker, for 4-8 weeks followed by transurethral resection of the prostate. The mean weight of resected prostatic tissues was 25.2 g (range 5-96 g). Specimens were stained with antibodies to muscle-specific actin and to prostate-specific antigen for the detection of the smooth muscle and the glandular epithelium, respectively. Double-immunoenzymatic stained tissue sections were divided into four groups: smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The rates of the areas of respective prostatic tissue components were evaluated with computer-assisted quantitative color image analysis., Results: The mean rate of the area of smooth muscle, connective tissue, glandular epithelium, and glandular lumen was 32.7%, 46.9%, 10.8%, and 9.6%, respectively. International prostatic symptom score, maximum flow rate and residual urine volume before the treatment were not related to the rates of respective prostatic tissue components. International prostatic symptom score and residual urine volume were reduced and maximum flow rate was increased after the treatment with tamsulosin. A significant relationship was proved between the rate of smooth muscle and the change in maximum flow rate. The large hyperplastic adenoma contained less smooth muscle and showed a lower sensitivity to alpha adrenergic blocker than the small one., Conclusion: The clinical response to alpha adrenergic blocker was related to the rate of smooth muscle in benign prostatic hyperplasia.

Background: To develop a new procedure for laser prostatectomy through a biopsy needle, we evaluated the efficacy of interstitial laser irradiation with a pulsed Ho:YAG laser (lambda: 2.1 microns) in the normal canine prostate., Methods: Pathological studies were performed up to 6 months after interstitial laser irradiation in 26 mongrel dogs (15.4 +/- 2.6 kg). Two dogs underwent the identical procedures without irradiation as controls (control group). Prostate glands of the other 24 dogs were irradiated interstitially with a Ho:YAG laser through a silica glass fiber (400 microns phi). In one prostate, each lobe was irradiated with 500 J/cm2 or 150 J/cm2 in energy density (fluence). Four prostates were irradiated with 150-175 J/cm2 in fluence (low-fluence group). Nineteen prostates were irradiated with 500-600 J/cm2 in fluence (high-fluence group). Prostates glands were excised immediately, 1 month, 2 months, 3 months, or 6 months after irradiation and examined histologically. To investigate the influence of interstitial irradiation with a Ho:YAG laser on smooth muscle and/or on the adrenergic activity of the prostate, we also measured changes in intraluminal pressure of the prostatic urethra upon administration of epinephrine (10 micrograms/kg) in six dogs before and after irradiation. We developed a novel three-membrane balloon catheter with an open end for measuring this pressure change., Results: Specimens harvested immediately in control and low-fluence groups showed slight hemorrhage in areas surrounding the punctured or irradiated site, but the surrounding smooth muscles or small vessels were not destroyed. In the high-fluence group, smooth muscles and small vessels approximately 1 mm thick that surrounded the ablated hole were destroyed, but the thickness of the thermal coagulation layer was only approximately 0.2 mm. These findings suggested that damage to the small vessels and smooth muscle may have been caused by laser-induced stress waves rather than by a thermal effect. In the control and low-fluence groups, prostatic volume remained unchanged 1 month after puncture or low-fluence irradiation. In the high-fluence group, huge cavities were created in the laser-irradiated prostate gland 1 or 2 months after irradiation and prostatic volume was reduced maximally by 60%. In the high-fluence group, the cavities collapsed and prostatic volume was reduced by up to 50% at 6 months post-procedure. The prostatic urethra expanded following the reduction in volume. The maximal intraluminal change in pressure of the prostatic urethra decreased significantly after laser irradiation (p < 0.05)., Conclusion: Results indicate that interstitial irradiation of the prostate with a Ho:YAG laser with high-fluence may relieve the anatomical and functional obstruction of the prostatic urethra in benign prostatic hyperplasia.

Background: We evaluate the usefulness of 1H endorectal resonance spectroscopy to characterize prostate pathology., Methods: With an endorectal surface coil we have studied 20 individuals with normal (1), benign hyperplastic (9) and malignant (10) prostates., Results: The major findings of our studies were that the patients with cancer have a significantly lower citrate-to-choline ratio (cit/cho) and creatin-to-choline ratio (cre/cho) than the patients with BPH (p < 0.05). There is well correlation between cit/cho and gland-to-stroma ratio of the BPH tissue as well as histological grade of the cancer tissue. 1H spectroscopy offers the advantages of differential diagnosis between benign and malignant prostates. We, however, failed to demonstrate cancer in 2 cases; the lesion was too small in one case, and out of the region of interest in the other. It is necessary that the foci in the prostate is at least 1.5 X 1.5 X 1.5 cm3 of the volume in order to obtain genuine spectrogram of carcinoma., Conclusion: Endorectal 1H magnetic resonance spectroscopy can characterize metabolic differences between the normal and malignant prostate.

Background: To study reasons why serum PSA value (Markit-F) elevates in benign prostatic hyperplasia (BPH)., Methods: The relationship between total prostatic weight and the outer gland weight in 48 cases of BPH undergoing subcapsular prostatectomy was studied by ultrasound measurement. PSA was compared with prostatic weight, inner gland weight, outer gland weight, growth speed of the inner gland and age in the 48 cases., Results: 1) The weight of the outer gland increased slightly in proportion to the development of BPH. However, the increase was not significant statistically. 2) PSA correlated with the inner gland weight and growing speed of the inner gland well. 3) PSA did not correlate with the outer gland weight and age., Conclusions: It is well known that PSA elevates not only in the cases of prostatic cancer but also in the cases of BPH and that PSA correlates with the whole prostatic weight. This study revealed that the elevation of PSA in the cases of BPH was caused by enlargement of the inner gland.

Isometric contractile force of rabbit prostatic tissue in response to electric field stimulation (EFS), KCl, and phenylephrine were measured at incubation temperature of 37 degrees C, before and after thermal exposure to 42 degrees C, 45 degrees C, 48 degrees C and 50 degrees C for 30 minutes. The contractile force in response to EFS decreased after thermal exposure above 45 degrees C, and the contractile force in response to KCL or phenylephrine decreased after thermal exposure above 48 degrees C. All the contractile response abolished after thermal exposure to 50 degrees C. The results indicate that the nerve is more hear-sensitive than the smooth muscle in the prostate. Histological examination revealed shrinkage of cell body and dark staining of nuclear chromatin of the smooth muscle cells after thermal exposure above 48 degrees C. The same histological change of the smooth muscle as well as degenerative change of the nerve cells was observed on the prostate 3-7 months after clinical thermotherapy. From these results, it is suggested that clinical effect of thermotherapy is brought about from both neural and muscular damage of the prostate. Since the least temperature to cause an irreversible tissue damage ranges from 48 degrees C through 50 degrees C, we believe it is ideal to heat the prostate around 50 degrees C to obtain a good clinical effect of thermotherapy on benign prostatic hyperplasia as a minimum invasive treatment.

Stromal-epithelial cell interaction is very important for the development of human benign prostatic hyperplasia (BPH). Growth factors and their receptors in the prostate are thought to mediate the cell communication and play some roles in the development of BPH. Among many growth factors, fibroblast growth factor (FGF) family members have received the most intensive study, and mRNAs for acidic FGF (aFGF), basic FGF (bFGF) and keratinocyte growth factor (KGF) have been identified in rat or human prostate. However, synthesis sites and roles of them in stromal-epithelial cell interaction remain to be undefined. In the present study, to define the mechanisms for the regulation of prostatic cell growth by stromal cells in human BPH, we established the method for isolation and culture of epithelial cells as well as stromal cells from human BPH tissue. Using these primary cultured prostatic cells, we evaluated the effects of stromal cell conditioned medium (SCM) and stromal cell extract (SCE) on the growth of stromal cells and epithelial cells by [3H]-thymidine incorporation assay. We also examined the expression of mRNAs for aFGF, bFGF, KGF, FGF receptor 1 (FGFR1) and FGFR2 in epithelial and stromal cells using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) analysis. As the results, both SCM and SCE stimulated the growth of stromal cells, and the growth promoting effects of them to stromal cells were completely suppressed by anti-bFGF neutralizing antibody, but not by anti-aFGF neutralizing antibody at all. SCM also stimulated the growth of epithelial cells. The growth promoting effect of it to epithelial cells was not completely suppressed by anti-bFGF neutralizing antibody, and not by anti-aFGF neutralizing antibody at all. Furthermore, RT-PCR analysis demonstrated the expression of mRNAs for bFGF, KGF and FGFR1 in stromal cells and that of FGFR2 in epithelial cells. These findings suggest that bFGF produced by stromal cells acts on stromal cells through FGFR1 by an autocrine mechanism, KGF produced by stromal cells acts on epithelial cells through FGFR2 by a paracrine manner in human BPH. These mechanisms for the regulation of cell growth by stromal cells were thought to contribute to the development of human BPH.

Primary epithelial and fibroblast cells from benign hypertrophic prostate tissue were established. The prostate tissues were obtained by transurethral resection of the prostate or retropubic prostatectomy in patients with benign prostatic hypertrophy. Growth factors for cultured epithelial cells and fibroblasts were studied. The epithelial cells grew well in the WAJC-404 culture medium with insulin, epidermal growth factor and dexamethasone. Fibroblasts grew well in culture medium containing 10% fetal calf serum. The prostate tissue was stored at 4 degrees C for 7 days and no degenerative change in the stromal cells was seen during this period. Although epithelial cells did degenerate with the passage of time, epithelial cells cultured after storage for 4 days at 4 degrees C behaved similarly to those cultured immediately after being isolated. These primary cultures of epithelial cells and fibroblasts from hypertrophic prostate may be useful for various studies.

Fifty patients with benign prostatic hypertrophy were treated with chlormadinone acetate (CMA) at the dose of 50 mg/day for 12 months. Subjective symptoms and objective findings were evaluated before, and after 4 and 12 months of treatment. Better improvement was observed in all of the subjective symptoms and in almost all the parameters of objective findings, in proportion to the period of CMA treatment. Generally speaking, 12 months of treatment was more effective than 4 months of treatment. Two patients had impotence (4.0%). Both of them complained of side effects within 4 months after treatment, but they were not severe. In conclusion, long-term treatment of benign prostatic hypertrophy with CMA was useful.

The prostatic weight was evaluated in 264 patients with benign prostatic hyperplasia before transurethral resection of the prostate (TUR-P) by transrectal ultrasonotomography. In the first group of 121 among 132 patients, the weight of both the total prostate (EPWt) and the internal prostatic gland (EPWi) was estimated and compared to the actual weight of resected specimens (RPW). In the remaining 11 patients, EPWt was obtained but not EPWi because their prostatic gland echograms were obscure. The correlations between RPW and EPWi, and between RPW and EPWt in 121 patients were proved to be RPW = 0.999 EPWi-0.586 (r = 0.851), RPW = 0.537 EPWt-1.914 (r = 0.766), respectively. In the second group of 132 patients, the weight of the prostatic adenoma to be resected was estimated preoperatively by the measurement of EPWt and the application of the latter formula (CRPW). The correlation between RPW and CRPW was proved to be RPW = 0.930 CRPW-1.570 (r = 0.824). It is presumed from this study that preoperative estimation of EPWi or EPWt may be useful not only for selection of the treatment modality for BPH, namely TUR-P or open surgery, but also for prediction of an operation time in TUR-P.

Of 160 newly diagnosed cases of prostate cancer during last 11 years, six (3.75%) had a prior subcapsular prostatectomy. Digital rectal examination in these six cases revealed a significant prostatic abnormality and multiple bone metastases were showed. Histological examination by step-section technique was done retrospectively using surgical materials from subcapsular prostatectomy. Two cases of incidental carcinoma were detected histologically. One showed stage A1 and another stage A2. Continuous observation should be performed after prostatectomy, even if the surgical specimens revealed no carcinoma.

Five cases of prostatic cancer developed after transurethral resection of prostate for benign hypertrophy are reported. Duration of transurethral resection of prostate (TUR-P) to diagnosis of prostatic cancer ranged from one year and seven months to seven years and two months, on average four years and seven months and frequency of prostatic cancer after TUR-P was estimated at 1.2%. Four of five patients complained of macroscopic hematuria. The cystourethrogram showed the mass protruded in the dilated prostatic urethra or bladder-neck in four patients (80%), a remarkable finding, and four cases were at stage D. Risk of development of prostatic cancer is not decreased even after prostatectomy and prostatic carcinoma diagnosed after TUR-P often advances in stage. Therefore, periodical examinations of the patients who had a prior prostatectomy are very important.

In this study the multicenter, fixed-flexible dose regimen was taken to evaluate the effective dose range of Terazosin for the treatment of micturition disturbance in benign prostatic hypertrophy (BPH) and to clarify the characteristics of patients who are more responsive to Terazosin therapy. After a 1-week washout (placebo) the first two weeks 1 mg/day of Terazosin was administered, then depending on efficacy of subjective symptoms, Terazosin doses were increased up to 2 mg/day and 4 mg/day at intervals of two weeks. After six weeks the final efficacy and safety were assessed. The subjective symptom improvement rate was 18.5% by 1 mg/day, 55.6% by 2 mg/day and 65.4% by 4 mg/day cumulatively. The objective symptom improvement rate were 13.2% by 1 mg/day, 42.1% by 2 mg/day and 50.0% by 4 mg/day cumulatively. The global improvement rate was 14.5% by 1 mg/day, 50.0% by 2 mg/day and 61.8% by 4 mg/day cumulatively. The patients who had a higher subjective symptom score in the lead-in period were more improved rather than those who had a lower score. In objective symptoms, voided volume, maximum flow rate (MFR), MFR nomogram score and average flow rate improved and the ratio of residual urine volume decreased. There was no relationship between clinical improvement on either subjective or objective symptoms and prostatic weight. Adverse reactions, such as dizziness, vertigo, tinnitus, nausea and blurred vision; were seen in 10 cases. In conclusion Terazosin was effective and well tolerated for the treatment of patients who had micturition disturbance with BPH in the dose range of 2 to 4 mg/day.

To determine the influence of endocrine factors on benign prostatic hyperplasia (BHP), the levels of three sex steroid hormones i.e., total testosterone (Total-T), free testosterone (Free-T) and estradiol (E2), were measured in serum of healthy 154 men. Their ages ranged from 18 to 91 years old. In 59 men, prostatic size was estimated by digital examination and was subdivided into three groups: smaller than or equal to walnut size, small hen's egg size and equal to or larger than hen's egg size. Firstly, relationships of sex hormone levels with age were studied. There was a slight decrease in Total-T over 60 years old, a significant decrease in Free-T, and no change in E2 with age. Thus, E2/Total-T and E2/Free-T ratio increased significantly after middle-age. Secondly, relationships of hormone levels with prostatic size were studied. In the larger prostate group, a significantly lower level of Total-T and significantly higher level of E2 were detected. But there was no difference in Free-T. Thus, the prostatic size was correlated positively with E2 level, E2/Total-T and E2/Free-T ratio. These suggest that the endocrine environment tended to be estrogens-dominant with age, in particular, after middle-age, and that patients with large prostates have more estrogens-dominant environments. We conclude that estrogens are key hormones for the induction and the development of BPH.

An assessment has been made of the histopathological characteristics of latent prostatic carcinoma and the tumor volume in 500 male Japanese patients who underwent dissection at The Jikei University since 1983. A microscopic observation was made of the prostatic glands extirpated totally at the necropsy, fixed with formalin and prepared as a step-section in a thickness of 3 mm. In the cases of latent carcinoma, after photographing the lesion in the same magnification and measuring the area of the carcinoma lesion with a digitizer, the volume was calculated by multiplying the thickness of 3 mm, and carcinoma volume was determined by integrating the value of each slice and adjusted by a conversion formula. The incidence of latent carcinoma was 104 cases out of 500 (22%). The incidence increased as the age layer becomes higher, and latent carcinoma was observed in 44% of the patients aged 80 and above. Complication of latent carcinoma with prostatic hyperplasia was presumed to be an independent phenomenon in so far as it is seen from the statistical aspect. The patients were classified histopathologically into well-differentiated type (64%), mixed type (27%) and poorly-differentiated type (9%), showing high incidence in the low-aged layer of well-differentiated lesions and in the high-aged layer of mixed type lesions and in the high-aged layer of mixed type lesions. The average tumor volume of latent carcinoma was so small as 231 mm3, but many of the lesions in the cases of well-differentiated type were small, being on average 103.9 mm3, but many of the lesions in the cases of poorly-differentiated type were large, being on average 642.2 mm3. Statistically, with a tumor size of 200 mm3 as the boundary, a difference was observed in the distribution of histological constitution between the group with smaller lesions and the group with larger lesions. As an application of this result to the clinical carcinoma of stage A, the value of volume of 200 mm3 was considered to be important as a diagnostic criterion in deciding the necessity of treatment.

Epithelioid cells that had grown in short-term cultures derived from 10 cases of adenocarcinoma (PCa) and 10 cases of hyperplasia (BPH) of the prostate were karyotyped by the G-banding method for the pathogenesis of these disease. PCa specimens included 4 well, 2 moderately, and 4 poorly differentiated types, and were obtained by perineal needle biopsy from 4 patients in stage B and 6 patients in stage D2. Cells liberated from metastatic lymph node lesions of 2 patients with poorly differentiated PCa were also analyzed directly without cultivation in vitro. All BPH specimens were obtained by prostatectomy, and cells that had grown in epithelioid pattern in short-term cultures were analyzed. In PCa, hyperploidy was seen in all but 2 cases. Structure analysis disclosed abnormality of chromosome 16 in 4 PCa, deletion of Y in 3 PCa, abnormality of chromosomes 7, 14, 15, 18, and 19 in 2 PCa, and abnormality of chromosomes 3, 4, 17, and 21 in 1 PCa. Multiple markers were observed in 1 patient, and hyperploidy in another patient with metastatic lymph nodes. All but 2 cases of BPH were diploid. Normal male karyotypes were seen in 6 BPH. Trisomy of chromosomes 7 and 16 were observed in 2 BPH. Of 4 patients with stage B PCa, 3 who have been alive for 3 years to date had multiple abnormalities, whereas 1 patient who died 2 years after diagnosis had few abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

A total of 20 patients with benign prostatic hyperplasia underwent transrectal local hyperthermia. For heating of the prostate gland, the PROSTATHERMER (Biodan-Medical System, Israel) was used. Patients were treated twice weekly, for 1 hour, with 6 sessions on an outpatient basis. Four of the 20 patients who had acute toxicity such as urethral irritability due to urethral thermoprobe could not tolerate the treatment. In the majority of the patients who were completely treated, a significant decrease in frequency of nocturia, decrease in post-void residual urine capacity and increase in urine flow rate were observed. No significant change in prostate volume was noted. With a mean follow-up of 6 months, only 1 patient required subsequent prostatic resection. These findings indicate that local hyperthermia applied by this method is effective in the treatment of benign prostatic hyperplasia and that improvement of the thermometry system is needed.

We evaluated the effect of anti-androgen therapy for benign prostatic hypertrophy. Patients showed a significant reduction in the prostatic weight measured by means of transrectal ultrasonography after 3 to 4 months of treatment. However, there were no patients who showed any symptomatic improvement despite a reduction in the prostatic weight. They had prostatic stones more frequently than the group who showed symptomatic improvement properly. We summarized some problems of anti-androgen therapy for benign prostatic hypertrophy.

To determine the value of prostatic markers for prostate cancer, serum prostatic acid phosphatase (PAP), prostate specific antigen (PSA) and gamma-Seminoprotein (gamma-Sm) were measured in 81 patients with benign prostatic hypertrophy and in 12 patients with incidental prostatic cancer. gamma-Sm was the most sensitive but the least specific of the three markers. Large prostate glands, especially hyper-glandular type tended to be associated with high gamma-Sm levels in our study. Patients with acute urinary retention, acute prostatitis and necrosis also showed positive markers. Out of 12 patients with incidental cancer, 5 patients had more than 2 elevated markers. Four patients with poorly differentiated adenocarcinoma failed to show increased markers.

The correlation between the resected weight of prostate and the estimated weight of prostate by transrectal longitudinal ultrasound was evaluated for 53 patients with benign prostatic hypertrophy. Sonography was done with a real time linear scanner and 5.0 MHz transducer. Maximal prostatic dimensions were measured along the two major axes, namely the maximal length and the maximal thickness of total prostate and adenoma. By regarding benign prostatic hypertrophy as an ellipsoid, we calculated the weight of prostate according to the ellipsoid formula. The correlation coefficient was calculated as; r = 0.929, Y = 0.942Xt - 2.642 (Xt: total estimated weight), r = 0.962, Y = 0.965Xa + 0.028 (Xa: estimated weight of adenoma). The estimated weight of the prostate correlated with the resected weight of the prostate. These results suggested that rough estimation of the weight of benign prostatic hypertrophy was found to be possible by using this calculation technique.

We reviewed 157 patients retrospectively with incidental carcinoma of the prostate who had been treated at our collaborating hospitals during the past ten years. Of 5212 patients with benign prostatic hyperplasia who received subcapsular prostatectomy or transurethral resection of the prostate (TUR-P), 157 (3.0%) were diagnosed as having an incidental carcinoma of the prostate, which was somewhat lower than that in previously published reports. Of these, 30 and 127 patients were in stage A1 and A2, respectively. Well, moderately and poorly differentiated carcinomas were found in 44.6%, 36.7% and 18.5% of the patients, respectively. The incidence of poorly differentiated carcinoma in the study seemed to be higher than that in the previous reports. A positive correlation was identified in TUR-P specimens between the carcinoma differentiation and its extension which was evaluated by cancer-positive chip ratio. Atypical adenomatous hyperplasia and intraductal dysplasia were identified in 36.9% and 85.3% of the patients with incidental carcinoma, respectively. These incidences tended to become lower as the carcinoma became less differentiated or more extended. Further studies will be necessary to define the significance of these pathological findings as a direct biological precursor of prostatic carcinoma. Six out of the 157 patients with incidental carcinoma showed a progression during the follow-up period. All of these patients were in stage A2 and all but one showed a histology of moderately or poorly differentiated carcinoma at the time of diagnosis. Radical prostatectomy or radiation therapy as well as endocrine therapy should be considered as treatment modalities for stage A2 patients, when staging lymphadenectomy shows no pelvic lymph node metastasis.

To investigate the relationship between some clinico-pathological features of incidental prostatic carcinoma and its prognosis, totally 96 consecutive cases with simple prostatectomy from 1968 to 1973 under the diagnosis of prostatic hypertrophy were examined by the 3 mm step-section technique. Twenty-one cases (21.9%) of incidental carcinoma were detected histologically. The age of the patients with or without prostatic carcinoma ranged from 59 to 81 years old, 72.0 years old on the average, and from 54 to 87 years old, 69.9 years old on the average, respectively. The weight of the specimen varied from 7 to 84 grams, 32.4 g on the average, for the patients with carcinoma, and 10 to 64 grams, 29.7 g on the average, for the patients without carcinoma. Fifteen of 21 cases showed well differentiated carcinoma. None of the Japanese histological differentiation, Gleason's classification and volume of carcinoma presumably affected the survival of the patients.