We examined serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in 32 patients with renal cell carcinoma. Serum IL-1β was elevated in only one patient (3.1%), IL-6 in 17 (53.1%) and TNF-α in 6 (18.8%). Positive rate of serum IL-6 increased with progression of the stage (stage I and II: stage III and IV=14.3%:88.9%, p<0.0001) and was higher for rapid growth type (slow and intermediate growth type: rapid growth type=36.4%:90.0%, p<0.005). However, increased serum levels of IL-1β and TNF-α were not correlated with stage, grade, or growth type.
Gene expressions of IL-1β, IL-6, IL-6 receptor and TNF-α in the tissues resected from 15 patients with renal cell carcinoma and 3 cell lines established from renal cancers were evaluated by Northern blot analysis. Gene expression of IL-1β and TNF-α were not detected in any of the tissues or cell cultures, but highly enhanced expressions of IL-6 were revealed in two tumor specimens (13.3%, 1 rapid and 1 slow growth type) and 2 of 3 cell lines. Expressions of IL-6 receptor in tissues and cells were weak.
These results suggest that IL-6 plays an important role in the progression of renal cell carcinoma, and that measurement of IL-6 in patients with renal cell carcinoma may be useful clinically.

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Clinical effects of peripheral blood stem cell autotransplantation (PBSCT) after ultra high-dose chemotherapy were evaluated in patients with chemotherapy-resistant and/or poor prognostic testicular cancer. Four patients with testicular cancer, who had high-risk malignancy, were treated with high-dose etoposide (500mg/m²×4days) in order to collect peripheral blood stem cells. After the administration of high-dose etoposide, rG-CSF (250μg/body) was administered from nadir state. Blood mononuclear cells were collected using a Fenwall CS-3000 blood cell separator. Fractions enriched for stem cells were obtained by discontinuous Percoll gradient centrifugation and were stored in liquid nitrogen using patient's sera and DMSO. The mean number of peripheral blood granulocyte-macrophage-colony-forming units (CFU-GM) collected by one apheresis was 22.3×10⁵/kg body weight. In addition, CFU-GM more than 2.0×10⁵/kg body weight could be collected in each apheresis, which was though to be sufficient dosis to perform PBSCT in safe, based upon our previous studies. All the patients were treated by a combination of cisplatin (20mg/m²×5days), etoposide (100mg/m²×5days) and bleomycin (15mg×3days). Three patients responded to BEP therapy and obtained a CR, however, remaining 1 patient failed to achieve CR, who was later treated by ultrahigh-dose chemotherapy including carboplatin (200mg/m²×4days), etoposide (250mg/m²×4days) and cyclophosphamide (50mg/kg×2days) followed by PBSCT. He responded to this therapy and obtained a CR for 10 months. The results suggested the method was promising for patients with chemotherapyresistant and/or poor prognostic testicular cancer.

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Between April 1992 and May 1993, 13 patients (age, 66-79) with localized prostate cancer underwent laparoscopic pelvic lymphadenectomy at Asahi General Hospital. Clinical stage comprised A2 for 3 patients, B1 for 1 and C for 9. Lymphadenectomy covered inner half of external iliac nodes and obturator nodes, from pubic bone to proximal end of umbilical ligament. Operating time ranged from 70 minutes to 133 minutes with median of 102 minutes. The number of total lymph nodes dissected ranged from 3 to 17 nodes with median of 7. Lymph nodal involvement was detected in one patient. Two patients needed laparotomy due to bleeding; from abdominal wall caused at insertion of trocar in one, and oozing of blood for 10 hours after procedure in the other. Other serious complications were not observed. In conclusion, laparoscopic pelvic lymphadenectomy was a good staging procedure for localized prostate cancer.

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Intergrins are heterodimer molecule that are composed of one α subunit and one β subunit. Integrins appear to be the major receptors by which cells attach to extracellular matrices, and some integrins also mediate important cell-cell adhesion event. In recent years signaling pathway via β subunit of integrin molecule has been clarified, and 8 kinds of integrin β subunit are known to exist. And so we investigated the expression of integrin β subunit in various urological tumor cell lines by using RT-PCR method. Materials are composed of 8 renal cell carcinoma cell lines, 2 urinary bladder carcinoma cell lines, a testicular tumor cell line and a prostate tumor cell line. All 12 cell lines express integrin β1 subunit. The expression rate of β4 subunit in renal cell carcinoma lines are lower than that in other urological tumor cell lines. The expression of β6 subunit was observed in renal cell carcinoma cell lines and testicular tumor line. In testicular tumor cell line we also found the expression of β2 subunit which expression had been believed to be specific in leukocyte.

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We investigated the expression of squamous cell carcinoma-associated antigen (SCC-Ag) and proliferating cell nuclear antigen (PCNA) in bladder carcinoma cells using immunohistochemical techniques.
Tissues with 10% or more cells stained for SCC-Ag were defined as positive for the antigen. All grade 1-transitional cell carcinomas (TCCs) and 87% of grade 2-TCCs were negative for cytoplasmic SCC-Ag. However, 57.6% of grade 3-TCCs not associated with squamous metaplasia and 80% of those associated with squamous metaplasia showed strongly positive cytoplasmic SCC-Ag. Of squamous cell carcinomas, the well or moderately differentiated carcinomas showed a higher incidence (80-100%) of the antigen in the cytoplasm than the poorly differentiated ones (25%).
Nuclear SCC-Ag was found in 63.6% of grade 1-TCCs, 46.3% of grade 2-TCCs and 54.9% of grade 3-TCCs not associated with squamous metaplasia. However, grade 3-TCCs with squamous metaplasia and squamous cell carcinomas were negative for nuclear SCC-Ag.
The positive rate for PCNA increased from grade 1 to grade 2, grade 3 without squamous metaplasia and grade 3 with squamous metaplasia in the TCCs. All squamous cell carcinomas showed a high positive rate, irrespective of the differentiation.
Multiple regression analysis revealed a closer association between the expression of cytoplasmic SCC-Ag and the histological grade of TCCs.

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We performed radical nephrectomy for 166 patients with renal cell carcinoma over 25 years period between 1967 and 1991. Among them, 49 patients had stage T1-3 NOMOVO tumors less than 6cm in maximum diameter. Twenty-seven of them received radical nephrectomy by a modified translumbar approach whereas the conventional transabdominal approach was applied to the remaining 22 patients. We retrospectively studied treatment results of the 49 patients to evaluate the current translumbar approach.
There was no significant difference in the age and sex distribution of the patients, and the size, stage, grade and histological subtype of the tumor between translumbar and transabdominal groups, although the incidence of venous invasion (pVla) was significantly greater in translumbar group.
Statistical analysis revealed shortened operating time, decreased blood loss and quickened postoperative recovery (resuming oral intake or walking) in translumbar group as compared to those in transabdominal group. No major complication was observed in both groups.
There was no significant difference in actuarial survival rate or disease-free survival period between the two groups. Actuarial three-year survival rate was 96% for translumbar and 89% for transabdominal group, respectively. Sites of metastasis were lung (2 patients) or bone (1 patient) in translumbar group and bone (1 patient) or unknown (1 patient) in transabdominal group.
With the favorable prognosis comparable to that of transabdominal radical nephrectomy and the relatively small invasiveness, the current translumbar radical nephrectomy appears to be the choice for the patients with relatively confined small renal cell carcinoma.

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Hemin, which is the mitogenic oxidizing agent, has immunostinulatory properties for murine splenocytes. We studied the anti-tumor effect of hemin with IL-2 by using murine renal cell carcinoma (Renca). Treatment of cells with hemin and IL-2 resulted in a marked enhancement of mitogenicity and generation of cytotoxicity in vitro. These enhancements were achieved at low dose of IL-2. Splenocytes isolated from mice that had been treated with hemin and IL-2 incorporated increased amounts of ³H-thymidine during 20 hours incubation in vitro. Treatment with the combination of hemin and IL-2 was more effective than either hemin or IL-2 alone. The combination of hemin and IL-2 was effective in inducing cytotoxicity for Renca. Induction of cytotoxicity was optimal at the hemin concentration of 10μM, and higher concentrations were less effective. In vivo administration of hemin and IL-2 in Renca bearing mice resulted in a significant survival prolongation. IL-2 alone, at the dose used, was ineffective. The anti-tumor effect was enhanced by administration of N-acetylcysteine and by nephrectomy.
Since hemin can safely be administered to patients, it may represent a new class of biologic response modifiers that could enhance IL-2 mediated anti-tumor effects.

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We studied on subjective and objective findings of 69 patients with lumbar spinal canal stenosis. Of the patients 51 (73.9%) had not only orthopedical symptoms but also urological complaints of mostly emptying disorders such as protracted and retardated dysuria and urinary retention, 14 (20.3%) no urological symptom and four (5.8%) urological complaint alone. Cystometrographic findings investigated from all of the patients revealed normoactive detrusor in 34 (49.3%) of them, underative or acontractile detrusor in 28 (40.6%) and oveactive detrusor 7 (10.1%). Eighteen of the patients underwent a surgical treatment for the lumbar spinal canal stenosis. All of seven patients with normoactive detrusor had a good micturition and four of nine with underactive or acontractile detrusor and one of two with overactive detrusor required clean intermittent catheterization (CIC) even after the surgeries. Pre and post surgical urodynamic studies demonstrated that the seven patients resulted in normoactive in four and overactive in three, the nine underactive in six and overactive in three and the two overactive and underactive in one, respectively. It was suggested from the results that the bladder of a patient with limbar spinal canal stenosis could become more irritable state after the surgery than before the therapy.

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A clinical survey was performed on 95 cases who were treated by total cystectomy with urinary diversion at our hospital between August 1971 and March 1992. Urinary diversions were classified by ureterocutaneostomy (Group I) in 27 patients, ileal or colon conduit (Group II) in 45 and continent urinary reservoir (Group III) in 23. The patients ranged in age from 29 to 76 with an average age of 60.6 year and the male to female ratio was 68 to 27.
Histopathological typing of bladder cancers showed 82 cases of trnasitional cell carcinoma, 8 cases of squamous cell carcinoma, 4 cases of adenocarcinoma, and 1 mixed carcinoma with transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma.
At present, patients alive of Group I, II and III were 14, 27 and 16, respectively, totally 57 (60.0%) patients were alive. Five-year actuarial survival rates of Group I, II and III were 45.2%, 54.1%, and 56.8%, respectively.
A questionnaire survey was carried out to assess the quality of life (QOL) of 57 alive patients. The analysis of replied questionnaire showed that even all patients of each groups adapted to the basic life activities after urinary diversion, though a step forward quality of life with hobby, travel and job were decreased postoperatively in 3 groups. We obtained results that the patients of Group III were more satisfactory with daily (bath) and social life (job) than the patients of Group I, II and preoperatively.
We have a new comprehension of importance of enough informed consent and mental support to the urinary diversion patients preoperatively, and of a new operative procedure not to impair the QOL.

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We presented 15 patients with advanced testicular cancer treated with to 7 courses (mean: 3.2 courses) of COMPE chemotherapy. The low dose COMPE, given 14 patients, consisted of the chemotherapeutic agents as follows: cisplatin, 5mg/m² by intravenous push infusion and thereafter 25mg/m² by continuous 24-hour-infusion on day 3 and 30mg/m² by continuous 24-hour-infusion on day 4; vincristine, 0.6mg/m² by drip intravenous infusion (div) on days 1 and 2; methotrexate, 10 mg/m² by div on day 1; peplomycin, 10mg/m²/day, divided to three times by intramuscular injection on days 1 to 3; etoposide, 100mg/m², by div on days 3 to 5. The regular dose COMPE (given one patient) had CDDP dosage up to 50mg/m²/day on days 3 and 4. the regimens were given every 3 or 4 weeks in admission. Patients were adequately hydrated but no diuretics were used.
The patients were diagnosed as 5 seminomas with 4IIA and one IIB and as 10 non-seminomas with 2IIA, one IIB, one IIIB 1, 4 IIIB2, and 2 IIIC stagings, respectively.
Of the 15 patients, 12 patients are alive with no evidence of disease at 13-86 months (mean: 39.5 months) of follow-up duration. Six patients achieved complete remission. Of 8 patients achieved partial remission with chemotherapy alone, 6 patients achieved complete remission by following resection of residual masses or irradiation but another 2 patients (IIB2: 1, IIIC: 1) failed to achieve complete remission had relapse and died after 19 and 25 months, respectively. One patient (IIIC) showed no change had progression and died after 5 months.
The toxicities were not severe, but anorexia, nausea, vomiting, hair loss, leukopenia and thrombocytopenia were noticed.
COMPE chemotherapy was effective and useful for advanced testicular cancer but dose intensity of CDDP is necessary for far-advanced testicular cancer.

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In 23 male patients, the electrical activity of external urethral sphincter muscle was sampled before examination of cystometry (Rest), at first desire to void (FDV), maximum desire to void (MDV) and during urination (Void) by means of electromyography (EMG). Sampling time of each event was 2400 msec. The electrical activity was amplified with a lower limiting frequency of 20Hz and an upper limiting frequency of 10000Hz, and recorded on magneto-optical desk. Spectra were obtained using a Hamming window. The action potential of the muscle was quantitatively analyzed and power spectrum of the needle EMGs were analyzed from the magneto-optical disk by a spectrum analyzer using fast Fourier transformation (FFT, Sande-Tukey method). From each power spectrum, mean power frequency (MPF) was obtained from a calculator connected to the spectrum analyzer.
Twenty three patients were divided into three groups as follows: 8 patients without any neurological abnormality (normal group), 7 patients with neurogenic bladder showing detrusorsphincter-dyssynergia (DSD+group) and 8 patients with neurogenic bladder without detrusorsphincter-dyssynergia (DSD-group).
The results obtained were as follows:
1) The motor unit potentials at Rest had the mean amplitude of 210±59.4μV, 329.3±157.1μV and 177.6±132.8μV in normal group, DSD+group and DSD-group, respectively. The mean duration were 4.3±0.2 msec., 5.9±1.9 msec, and 7.3±4.5 msec., respectively. The mean phases were 2.8±0.6, 2.8±0.5 and 2.5±0.3, respectively. Statistically there was no difference in amplitude, duration and phase among three groups.
2) In normal group, the power over than -20dB was distributed from 150 to 220Hz windows at Rest and FDV. The needle EMGs at MDV showed interference pattern and the power increased over -20dB in all windows. The power of high frequency area relatively increased. The action potential of the muscle disappeared during urination and the power also disappeared. The average MPF was 103Hz, 102Hz, 150Hz and 98Hz at Rest, FDV, MDV and Void, respectively.
3) In DSD+group, the needle EMGs showed interference pattern in MDV and Void, and the power increased only in low frequency area. The average MPF was 104Hz, 105Hz, 114Hz and 120Hz at Rest, FDV, MDV and Void, respectively.
4) Because of damage to nerves, the action potential of the muscle was difficult to obtain from 3 patients of DSD-group, and the power was not demonstrated.
5) The distribution of frequency of interference pattern of the needle EMG is shifted toward higher frequencies in normal patients and toward lower frequencies in patients with neurogenic disorders (DSD+and DSD-groups). The MPF is decreased in neurogenic muscle compared with normal muscle.
From the results described above, power spectrum analysis of sphincter EMG using FFT was thought to be useful to evaluate the abnormal activity of the urethral sphincter in neurogenic bladder

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The East Japan Testicular Tumor Study group has studied advanced testicular tumors. Treatment and prognosis of the patients who did not achieved complete response on the primary chemotherapy were discussed in this paper.
Also 8 patients who had once reached complete response by primary treatments and relapsed later have been clinically analyzed.
1. Concerning the patients non-achieving complete response on the primary chemotherapy: Two cases who had resection of the residual tumors and 4 cases who had radiationtherapy had reached NED in 7 cases of seminoma stage II. Nine of 10 cases in non-seminoma stage II reached NED on resection of the residuals. Moreover, 10 out of 17 cases in stage III showed NED on excision of the residuals. On the other hand, recuperating was very difficult in the cases who could not have excision of residual tumor.
The histological findings of the residual tumors after chemotherapy were necrosis and fibrosis in 13 cases, viable cells in 4 cases, teratoma in 6 cases and other 2 cases were not clear. Five out of 15 who had teratoma in the primary lesion had teratoma in the resected residuals on metastatic lesion.
On the other hand 5 patients who did not have teratoma originally had no any teratoma elements in the residuals.
2. Concerning the relapse cases by primary treatments: Although relapses were possible in any stages, they were more common with stage IIIB and IIIC cases. Those who achieved complete response after chemotherapy alone fewer relapse than those who had partial response after chemotherapy and there after had excision of residual tumor. Of those who achieved complete response having had excision of residual tumor after chemotherapy, 2 out of 4 who had viable cells suffered relapses, while only 2 out of 12 who did not have viable cells had relapses. Moreover, among those who did not have viable cells, 2 out 6 who did not have prophylatic chemotherapy after operation suffer relapses. But 6 who received chemotherapy did not suffer relapses.
Our results in treatment of relapse cases were good and NED was achieved in 75% of the cases.
From the above it can be understood that even when there is only partial response after chemotherapy, the prognosis is good if we succeed in excising the residual tumor completely. If there is teratoma elements in the primary lesion, the possibility of resudual teratoma in metastatic lesion is very high and excision is need. In far-advanced cases and the cases had residual tumors with viable cells after chemotherapy, the possibility of relapse is very high and the need for treatment to prevent relapse will be suggested.

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The monoclonal antibody Ki-67 recognizes a human nuclear antigen that is present in proliferating cells (G1, S, G2 and M cycling stages of cell division) exclusively, but is absent in GO cycling stage. We performed immunohistochemical analysis of renal cell carcinomas using Ki-67 antibody, and investigated the relationship between the proportion of Ki-67 positive cells and pathological findings of renal cell carcinomas.
The tissues were obtained from 36 patients with renal cell carcinoma who underwent radical nephrectomy. Cryostatfrozen sections were cut at 5μm and stained with avidin-biotin-peroxidase complex method. The percentage of Ki-67 positive cancer cells to the total amount of cancer cells was expressed as growth fraction (GF). We obtained the following results with regard to the relationship between GF and pathological findings of renal cell carcinomas.
1) GFs in pathological grades were 6.58±4.57% (mean±SD) for grade 2 (n=13) and 1.20±0.70% for grade 1 (n=21). GF in grade 2 was significantly higher than that in grade 1(p<0.01). GF for Grade 3 (n=2) were 9.2% and 27.8% respectively.
2) GFs in the pathological stages were 8.12±7.64% for pT3 (n=13) and 1.84±1.30% for pT2 (n=23). GF in pT3 was significantly higher than that in pT2 (p<0.01).
3) GFs in the cancers with and without lymph node involvement were 13.84±8.48% (n=5) and 2.80±2.74% (n=27), respectively. GF in the cancers with lymph node involvement was significantly higher than that without lymph node involvement (p<0.01).
GF, which was determined by immunohistochemical analysis using Ki-67 antibody, apparently correlated with pathological grade, stage, and lymph node involvement. These findings suggest that GF in the renal cell carcinoma indicates a growth potential of each cancer and is useful for estimating malignancy of the renal cell carcinoma.

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The inhibitory effect of Lactobacillus casei (L. casei) in superficial bladder tumors was investigated in an experimental study using N-butyl-N (4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer as an experimental system. The study consisted of two experiments; in a short-term experiment, the inhibitory effect of 6-week treatment with L. casei was assessed in vitro in terms of the capacity for agglutination by concanavalin A (Con A) of bladder epithelial cells in their incipient stage of malignant transformation induced by 1-week exposure to BBN. As a result, the number of bladder epithelial cell aggregates caused by Con A was significantly smaller in the L. casei-treated group than in the non-L. casei-treated group (p<0.001). In a long-term experiment, treatment with L. casei of varying duration was investigated for effectiveness against bladder tumors induced by 7-weeks exposure to BBN that arose 22 weeks. The results indicate that both bladder weight and tumor volume per organ were significantly lower in the L. casei-treated than non-L. casei-treated group (p<0.05). The inhibitory effect on these parameters was more pronounced with treatment with L. caesi of longer duration. While there was no significant difference among the treatment groups in the degree of extension of induced malignancy, tumors with a high degree of extension (T1b, T2) developed only in the non-L. casei-treated group. The degree of malignancy of induced tumors was significantly lower in those groups receiving L. casei while BBN was being administered as compared to the non-L. casei-treated group (P<0.05). These results clearly indicate a bladder carcinogenesis-suppressant effect of orally administered L. casei, suggesting clinical usefulness of this probiotic preparation.

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A peritoneal dialysis patient was reported who had ultrafiltration loss due to a marked increase in lymphatic absorption and peritoneal membrane permeability. A 33-year-old male was transferred from hemodialysis to peritoneal dialysis because of acute subdural hematoma. His complicated history included left testicular tumor with retroperitoneal lymph node metastasis in 1982. He was treated with CDDP, Etoposide, Bleomycin, Vinblastine sulfate and Vincristine and received operation of retroperitoneal lymph node dissection in 1982. He had been on hemodialysis since 1983 due to cisplatinum nephropaty. Ultrafiltration failure was found immediately following the insertion of Tenckhoff catheter without malfunction of peritoneal catheter. Peritoneal equilibrate test and lymphatic absorption measurement showed a high permeability peritoneum with a marked increase in lymphatic absorption rate (3.7ml/min). These two factors were thought to result in ultrafiltration loss. CAPD with 4-6 times exchange daily did not maintain ultrafiltration, because it gave approximately 2000ml negative water balance every day. He was well maintained on a short time exchange intermittent peritoneal dialysis (IPD) with cycler using 18 L for 8 hours.
We concluded that increased lymphatic absorption is one of the important factors for ultrafiltration fafilure and IPD with frequent exchange by cycler is suitable for the patient with ultrafiltration loss.

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We report 2 cases of primary malignant lymphoma arising in the urinary bladder. The first case was a 64-year-old woman complaining of gross hematuia during the follow-up period of transitional cell carcinoma (grade 2, stage pTa) of the bladder that was treated with TUR in 1989. Her bladder tumor of this time was broad based, not papillary, and situated on the right side wall with bleeding. The pathological diagnosis of transurethral biopsy specimens was non-Hodgkin lymphoma, diffuse large, B cell type. Four courses of CAP chemotherapy was so effective that she has been free of the disease up to now. The second was a 51-year-old woman presenting with painless gross hematuia. A solid, round and intramural tumor, which was recognized on the left side wall by cystoscopy, was resected endoscopically as much as possible. Three courses of VEPA chemotherapy was done because pathologically it was non-Hodgkin lymphoma, diffuse medium, B cell type, although no evidence of other tumors in any organs was fortunately detected with further examinations. She has been doing well without recurrence for 9 months after discharge from the hospital.
Primary malignant lymphoma of the bladder is unusual. About 70 cases have been reported in foreign countries, but only 23 cases in Japan. When malignant lymphoma is confined to the bladder, radiation and chemotherapy can be curative, and yet preserve the function of the bladder.

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A rare case of urogenital sinus cyst in a child is reported.
A 10-month-old boy was referred to our hospital under the diagnosis of acute epididymitis. IVP showed left hydronephrosis and round filling defect in the bladder. Ultrasonography and CT scan demonstrated a retrovesical cystic lesion. Right vesiculography under general anesthesia revealed a midline cystic lesion. Fenestration between the prostatic urethra and cystic lesion was performed by TUR-velmontanum. However, that cystic lesion did not disappeared.
Our case seems to be the youngest case of urogenital sinus cyst reported in the Japanese literature.

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