The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5mg/kg, i. p.) or carboplatin (CBDCA, 40mg/kg, i. p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (<10mm³, n=8) were suppressed more than that of larger tumors (10-35mm³, n=11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2±146.6 (mean±S. D.) in the control (n=20), 116.3±98.9 in HESW alone (n=11), 75.5±110.7 in THP alone (n=8), 90.7±61.6 in CBDCA alone (n=6), 75.8±72.2 in THP+HESW (n=9), 3.2±4.5 in CBDCA+HESW (n=8) and 0.8±1.3 in CBDCA+HESW 2 cycles (n=9). Evident suppression on tumor growth was more often seen in CBDCA+HESW and CBDCA+HESW 2 cycles therapies than in the other therapies (p<0.01). The cumulative survival rates were higher in CBDCA+HESW and CBDCA+HESW 2 cycles therapies than in the other therapies (p<0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA+HESW and 1/5 in CBDCA+HESW 2 cycles therapy, respectively.

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We studied the nocturnal penile tumescence (NPT) value obtained by simple method and the vascular and neurological findings closely related to the ability to achieve/maintain an erection in order to investigate the causative factors of organic erectile dysfunction seen in diabetes. Studies were carried out on 62 male diabetics (32-78 y. o.). The results were as follows.
1. There were no cases of a decrease in the nocturnal penile tumescence (NPT) value among eight subjects who showed no erectile dysfunction. However, a decrease in the NPT value was recorded in 28 (85%) of 34 subjects who showed complete failure to achieve/maintain an erection. It was, therefore, surmised that there is a large organic contribution to the erectile dysfunction seen in diabetes.
2. We determined the penile blood pressure index (PBPI), the reactions of papaverine tests, conduction velocity of the dorsal nerve of the penis and the latency of the bulbocavernosus reflex. 42 (67.7%) of the 62 subjects had penile vascular disorders and the cases with severe vascular disorders were skewed to the high age brackets. There were also many cases with neuropathy involved in the ability to achieve/maintain an erection: 38 (61.2%) of the 62 subjects. Moreover, many of the subjects were found to have damage to both the blood vessels and the nerves relating to an erection, and these forms of damage were surmised to be deeply involved in the decrease in the NPT value.
3. Multivariate analysis indicated that the most important factor involved in the decrease in the NPT value was vascular damage (contribution rate: 30.8%), followed by neuropathy (6.9%). These two factors represented the most important explanatory factors of the organic erectile dysfunction seen in diabetes.
4. The contribution rate of vascular damage to the decrease in the NPT value was 18.8% for diabetic subjects under the age of 60 years, but 45.1% for subjects aged 60 years or more. The contribution rate was thus higher in the elderly subject group. On the other hand, the contribution rate of neuropathy to the decrease in the NPT value was 7.7% for diabetic subjects under the age of 60 years, but the rate decreased to 4.7% for subjects aged 60 years or more.

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To introduce the proper voiding modality to patients with myelodysplasty, urethral opening pressure (UOP), an intravesical pressure just at the beginning urine flows out beyond the external urethral sphincter, was measured in 63 myelodysplastic patients.
Among 45 renal units with any morphological or functional changes at the first UOP measurement, 37 units (82.2%) were included in the high UOP group (≥35cmH₂O). And among 41 ureters with VUR of more than grade 2, 32 (78.0%) were in the high UOP group. In addition, deformity of the urinary bladder was observed in 36 patients, and 26 (72.2%) of these bladders showed high UOP values. Therefore, all the patients could be divided into two groups: high UOP group (≥35cmH₂O, 28 cases) and low UOP group (<35cmH₂O, 35 cases). Twenty-three patients (82.1%) with high UOP values had been mainly treated with clean intermittent catheterization (CC). In contrast, 24 patients (68.6%) with low UOP values had been allowed to urinate by Credè' or Valsalva's method. In the followup study for 40 to 44 months, patients in the CIC group obtained good prognosis as for morphological or functional changes of the urinary tract. On the other hand, patients in the Credè' or Valsalva's method group showed a significantly higher deterioration rate in the high UOP group (80.0%) than that in the low UOP group (9.1%) (p<0.005).
From these results, hopely that in myelodysplastic patients with the underactive detrusor, CIC may be introduced for low pressure voiding to those who show high UOP values as early as possible. On the other hand, those who show low UOP values may be managed with Credè' or Valsalva's method as well as CIC. Thus, UOP is considered a possible prognostic factor for the morphological and functional changes of the urinary tract, which may be a useful parameter in decision of voiding modalities in myelodysplastic patients.

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The TOSOH II PA (AIA-PACK PA in the U. S. A.) monoclonal immunoenzyme assay was used and the clinical usefulness of prostate specific antigen (PSA) was evaluated in 39 men with prostatic cancer and 32 men with benign prostatic hyperplasia (BPH) confirmed pathologically. We evaluated the lower limit of detection in this assay by the mean PSA level plue 3 standard deviations in 5 separate experiments with a zero control sera as well as the mean PSA level minus 3 standard deviations in 5 separate experiments with serial dilutions of a known concentration of PSA. PSA concentrations of 0 to 0.25ng/ml could not be distinguished from the zero control. Therefore, we set the lower limit of detection for the assay as 0.25ng/ml. At our laboratory, the normal standard value was determined by the mean PSA level plus 3 standard deviations in 79 healthy men as 2.3ng/ml. Of patients that underwent radical cystoprostatectomy for bladder cancer, all had PSA levels less than 0.25ng/ml, while only 6% had PAP levels less than 0.11ng/ml, the lower limit of detection in the TOSOH II PAP assay. We compared TOSOH II PA with Markit PA, a commonly used assay in Japan. Although there was a close linear correlation (r=0.90) between the TOSOH II PA and Markit PA, the difference of slope in the linear regression lines was great, it was thought due to anti-PSA antibodies in each assay recognizing different epitopes of PSA in the blood. In all of 39 patients with prostatic cancer, serum PSA levels were more than 2.3ng/ml, the normal upper limit in TOSOH II PA. However, only 25% of 32 patients with BPH had PSA values below 2.3ng/ml. The mean serum PSA values in patients at each stage of prostatic cancer were higher than those in patients with BPH (p<0.01). In all of 5 patients with localized prostatic cancer, the serum PSA levels were more than 2.3ng/ml, while in one patient the serum PAP was higher than 1.6ng/ml, the normal upper limit in TOSOH II PAP.
We conclude that serum PSA values in TOSOH II PA are more sensitive in detecting localized prostatic cancer than serum PAP values and its sensitivity, specificity and efficacy to differentiate prostatic cancer from BPH are satisfactory. Further clinical studies with a larger series will be required to clarify the role of PSA in TOSOH II PA as a tumor marker in prostatic cancer.

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Nocturnal penile tumescence (NPT) occurs in all healthy males as a physiological phenomenon. Male sexual function can be evaluated by NPT. However, the age dependent changes and the significance of NPT have still remained unknown. Thus, we measured NPT throughout the night in healthy 189 subjects, ranging from 3 to 84 years old, and studied the relationship between this phenomenon and age.
The parameters obtained by NPT appeared to be greater in men over about 10 years old. This increase of the parameters was related to the maturation of the hypothalamo-pituitarytesticular axis, which starts rapidly at puberty. A significant decrease in the total tumescence time in men over 30 years of age was related to a decrease of androgen. In men over 55 years of age, the maximum penile circumference change and the maximum increase rate in penile circumference were significantly lower than those of men in their twenties. These results suggest that the decrease in the parameters of NPT in men over 55 years of age had a relationship with the decrease of androgen, and organic changes in the corpus cavernosum and penile vascular system that occurred with aging.
In conclusion, NPT may be related to the sexual maturation and decline in men. We also provide standard reference parameters for NPT in Japanese, which could be useful in the diagnosis and treatment of male sexual dysfunction.

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We studied the correlation of nocturnal penile tumescence (NPT) and serum free testosterone, which were evaluated in 123 healthy males and in 6 cases of primary hypogonadotropic hypogonadism before and after treatment with human chorionic gonadotropin (hCG).
In healthy subjects 3 to 84 years old, the serum free testosterone levels had a relationship with 4 parameters revealed by NPT: total tumescence time, mean tumescence time, maximum penile circumference change and maximum increase rate in penile circumference.
In men who showed the peak value for each NPT parameter and those who were younger, the serum free testosterone levels were correlated with all 6 parameters revealed by NPT: total tumescence time, NPT frequency, mean tumescence time, circumference in flaccid penis, maximum penile circumference change and maximum increase rate in penile circumference. In 6 cases of the primary hypogonadotropic hypogonadism, total tumescence time, mean tumescence time, maximum penile circumference change, and maximum increase rate in penile circumference significantly increased after hCG treatment. This indicated that an increase of the serum free testosterone level was responsible for the increase of the parameters of NPT.
In men who were older than the subjects showing the peak value for each NPT parameter, the serum free testosterone levels were correlated with 4 parameters revealed by NPT: total tumescence time, mean tumescence time, maximum penile circumference change and maximum increase rate in penile circumference. These results suggest that the free testosterone level may be involved in the decrease of maximum penile circumference change as well as in age-related changes of the penile vascular system that were the major factor responsible for the decrease.
This is the first report that studied the relationship between NPT and androgen in any group. NPT as a parameter for the erectile function was related to androgen levels.

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The collagen crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), were recently identified as potential markers of the rate of bone resorption. To determine whether urinary concentrations of Pyr and D-Pyr might provide an early warning of bone metastases in patients being monitored for cancer of the prostate, we compared these two newer parameters with the conventional indicators, that is, the serum concentrations of Bone Gla protein (BGP: osteocalcin) and alkaline phosphatase (ALP), in patients with prostate cancer with and without bone metastases vs. those of age-matched patients with benign prostatic hyperplasia (BPH). Urinary excretion of these compounds, expressed as a ratio to urinary creatinine (mg/dl), was determined by high performance liquid chromatography (HPLC) in 23 patients with prostate cancer (16 with bone metastases and 7 without bone metastases) and in 23 patients with BPH. The mean values of urinary Pyr and D-Pyr; 65.02±38.16pmol/μmol of creatinine and 8.87±7.01pmol/μmol of creatinine and 8.87±7.01pmol/μmol of creatinine, respectively, for patients with bone metastases of prostate cancer were significantly higher than those for patients without bone metastases of prostate cancer (27.43±10.29pmol/μmol of creatinine and 4.24±1.88pmol/μmol of creatinine) or for patients with BPH (25.58±7.54pmol/μmol of creatinine and 3.52±1.07pmol/μmol of creatinine). Among these three groups of patients, there were statistically significant (Pyr: P=0.0001, D-Pyr: P=0.001). The mean value of serum ALP for patients with bone metastases of prostate cancer (266.50±147.46IU/L) was significantly higher than that for patients without bone metastases of prostate cancer (135.14±20.32IU/L) and for patients with BPH (144.52±30.95IU/L) (P=0.0001). Urinary levels of both Pyr and D-Pyr were significantly correlated with serum ALP activity in patients with prostate cancer with bone metastases. Contrary to above results, differences in serum BGP levels of three groups of patients were not statistically significant.
Measurement of urinary Pyr and D-Pyr may provide a useful marker of metastatic spread to bone in patients with prostate cancer.

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We studied a relationship between in vitro sensitivity of the tumors to anti-cancerous drugs and histopathological effectiveness of an intra-arterial infusion chemotherapy in 15 patients with bladder cancers. The in vitro sensitivity test was performed by measuring intra-cellular ATP contents (ATP assay). The intra-arterial chemotherapy were performed by injecting methotrexate (MTX), adriamycin (ADM) and eisplatin (CDDP) from the internal iliac artery. When the intra-cellular ATP contents of the tumor cells treated with an anti-cancerous drug decreased to less than 50% of the untreated tumor cells, the tumor was evaluated as sensitive to the drug. The effectiveness of the chemotherapy were histipathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. When the histopathological responses of higher than grade 2 were observed in the tumor, the chemotherapy was evaluated as effective. In 8 of 9 tumors sensitive to ADM, chemotherapy were effective histopathologically and in all 6 tumors resistant to ADM, histopathological response of the chemotherapies were poor. The overall coincidence ratio between sensitivity to ADM and the histopathological effectiveness of the chemotherapy was 93%, showing statistically significant correlation. In 7 of 12 tumors sensitive to CDDP, the chemotherapies were effective and in 2 of 3 tumors resistant to CDDP, the chemotherapies were ineffective. Although the overall coincidence ratio between the sensitivities to CDDP and chemotherapeutic effectiveness was 60%, there was no significant correlation between them. In 7 of 8 tumors sensitive to both of ADM and CDDP, the chemotherapies were effective and in 6 of 7 tumors resistant to at least one of them, the chemotherapies were ineffective. The chemotherapies were significantly more effective on the tumors sensitie to ADM and CDDP than on those resistant to at least one of them. Therefore, the ATP assay to assess the in vitro chemosensitivity of the tumor would be a potential tool to predict the chemotherapeutic effectiveness in bladder cancers.

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We studied the difference in the proportion of fast and slow myosin subunits in axially subdivided external urethral sphincter of male rabbit using myosin light chain and heavy chain analyses. The whole urethras from 6 adult male Japanese White rabbits were sagittally bisected and one halves from all animals were processed for myosin light chain analysis and another halves from all animals for myosin heavy chain analysis. Each half urethra containing the external urethral sphincter was subdivided into 4 parts, namely prostatic (P), prostatic apical (PA), infraprostatic (IP) and bullbourethral glandular (BUG) portions, from cranial to caudal direction. The electrophoretic samples from 4 different parts were separately processed. The external urethral sphincter muscle in each part from all animals were processed together for a sample because of the minute amount of the muscle. Two-dimensional electrophoresis according to the procedure of O'Farrell for myosin light chains and SDS-polyacrylamide gel electrophoresis containing 40% glycerol for myosin heavy chains were carried out. Molar ratio of myosin subunits were estimated by the dye elution procedure. The relative proportions of slow myosin molecules in respective parts were 33.4% (P), 26.3% (PA), 18.5% (IP) and 11.0% (BUG) from myosin light chain analysis and 20.3% (P), 16.1% (PA), 7.2% (IP) and 5.0% (BUG) from myosin heavy chain analysis. The urethral striated musculature in male rabbit was predominantly composed of fast myosin subunits as a whole. But the proportion of slow myosin subunits occupied a relatively high percentage in the proximal region and tended to decrease toward the distal end. From these study we infer that slow twitch fibers in the proximal region are likely responsible for continence at rest and that fast twitch fibers of the whole of external urethral sphincter are recruited in stress conditions, for example, during coughing or sneezing.

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Diagnostic utility of serum markers and their relative values to prostatic volume were evaluated using Receiver Operator Characteristics Analysis (ROC analysis) in 173 patients who underwent ultrasound guided biopsy of the prostate gland. Seventy cases (40.5%) of prostate cancer were detected. As a whole, prostate specific antigen density (PSAD) and prostate specific antigen (PSA) were more useful than gammaseminoprotein density (GSMD), gammaseminoprotein (GSM) and prostatic acid phosphatase in diagnosing cancer judged by the area under the ROC curve denoting a test's diagnostic accuracy (p<0.05). No significant difference was noted, however, between PSAD and PSA (p>0.05). Prostate specific antigen density was more predictive for prostate cancer than PSA in a subgroup of patients with PSA levels of 2.0-10.0ng/ml (p<0.05). No advantage of PSAD was obtained in patients with intermediate PSA levels of 2.0-5.0ng/ml or benign-feeling glands (p>0.05).
Higher sensitivity could be achieved by using Eiken PSA 2.0ng/ml as a cutoff rather than the recommended value of 3.0ng/ml. This helped to diagnose 5 more cases of prostate cancer who otherwise might have been missed if PSA cutoff of 3.0ng/ml had been used. A PSAD cutoff of 0.15 has a sensitivity of 81.4%, a specificity of 87.4% and an accuracy of 85.0%. However, use of this cutoff for biopsy could result in unacceptable numbers of undiagnosed cases, including many potentially curable cancers. Though PSAD may enhance sensitivity and specificity in a certain group of patients, this gain is not sufficient to reliably define the group at highest risk of prostate cancer. Indication of biopsy should still be determined based upon PSA concentration rather than PSAD value.

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To evaluate the prognostic value of mean nuclear area (MNA) and mean nuclear volume (MNV) in bladder cancer, a retrospective study was performed comprising 67 bladder cancer patients who could be followed up for more than 3 years.
Cosmozone 1SA, a Nikon image analyzing system was used for the morphometric study. The specimen of initially biopsied tumor tissue was set in an Olympus microscope at 400-fold magnification, and the image was superimposed on the monitor picture through a video camera attached to the microscope, MNA and MNV were measured by tracing the contour of the nucleus which were selected by the point-sampled intercept methods. The time required for measurement of the area and volume was about 15 minutes per case.
MNA in cases with histological grade 1, 2 and 3 were 35±3μm² (mean±SD), 42±10μm² and 62±12μm² respectively. MNV with grade 1, 2 and 3 were 282±46μm³, 371±148μm³ and 644±182μm³ respectively. The morphometric results were significantly related to histological grade. In cases with a value of MNA of 40μm² or more and/or a value of MNV of 370μm³ or more, the proportion of cases who underwent cystectomy or died of cancer was significantly high and demonstrated poor survival. In contrast, those who showed MNA and MNV less than the above value had better prognosis.
These results suggest that the measurements of MNV seems to be useful for objectively evaluating the malignant potential of bladder cancer.

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In order to clarify the ultrastructural consequence of the VX2 cancer cell exposed to underwater shock waves. The VX2 cancer implanted to the urinary bladder of rabbit was received the shock waves (1000 shots, 100MPa, 5/sec.) generated by the piezo-ceramics. Damage to the cancer cell were manifested by the three kind of findings: the one was the cell junction failure which caused the isolated cells; the second was the destruction of organelle which seemed to form the vacuole in cytoplasm; and the last finding was the emergence of moth eaten appearance in the exposed cell. We conclude that underwater shock wave exposure induces lethal injury in VX2 implanted cancer.

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Lipoma of the adrenal gland is extremely rare. This condition was first described in 1988 and only seven cases have been reported to date. We have experienced a case of adrenal lipoma which was thought to be adrenal myeloiopoma on computed tomography (CT). A 56-year-old man was admitted to our department with a complaint of left abdominal pain. Sonography revealed a hyperechoic mass above the left kidney, and a CT scan revealed the mass to be comprised sharply marginated and an inhomogenous structure. The tumor was comprised of areas of different density including a fatty tissue portion. These findings were strongly suggestive of adrenal myelolipoma or liposarcoma, and a left adrenalectomy was performed.
Macroscopically, the tumor was consisted of yellow fatty mass and necrotic areas, which were surrounded by thin fibrous capsule. The adrenal gland was compressed at the bottom of the tumor. The weight of tumor was 290g.
Microscopically, the tumor consisted of large fat cells in direct contact with adrenal cortical cells, and it was then diagnosed adrenal lipoma.
Postoperatively, the patient no longer experienced left abdominal pain and there has been no recurrence in the 31 months since the operation.

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A rare case of bilateral spermatocele developed 17 years after vasectomy was presented.
A forty-seven year old man visited to our hospital with a chief complaint of swelling of bilateral intrascrotal contents. Sonographic findings demonstrated multilocular lesions of the bilateral intrascrotal contents. Operative procedure revealed bilateral cysts originating from the caput of the epididymis. Bilateral epididymectomy were performed. It was diagnosed as spermatocele because of demonstration of spermatozoa in the cystic fluid.
We concluded that bilateral spermatocele has been induced by prolonged increased pressure of the intraepididymal duct following vasectomy 17 years ago.

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Stripping and ligation of the renal lymphatics has been a standard operation for patients with chyluria in Japan. However, recently, inguinal lymph node-saphenous vein anastomosis and lymphangiovenous anastomosis in the spermatic cord or the lower limb are introduced as a microsurgical treatment of chyluria with good result from China. We present a case of 50-year-old female with chyluria, which was cured by the lymphatic-venous anastomosis at the groin. The patient had lived in Okinawa, an area of endemic filariasis, till 23 years of age. She noted chyluria for the first time at 28 years of age, when it was treated by irrigation of the renal pelvis with silver nitrate solution. The symptom recurred at 48 years of age, and fatigue developed two months before admission. The conservative treatments including rest, low fat diet and repeated irrigation of the renal pelvis were carried out, but these were ineffective. Therefore, bilateral inguinal lymph node-saphenous vein anastomosis and lymphangiovenous anastomosis in the same wound on the right were performed. The chyluria disappeared five months after the operation. The lymphaticvenous anastomosis at the superficial part of the body may be the surgical procedure of choice, because they are effective, simple, less invasive and less traumatic.

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