[Cost-effectiveness analysis of prostatic cancer screening].

BACKGROUND: To evaluate how much mass screening for prostatic cancer (PC) would benefit the nation economically, cost-effectiveness of PC screening was analyzed. METHODS: The cost per life-year saved (cost-effectiveness ratio; CER) was compared between PC screening and other 5 already established cancer screenings in Japan by an analytical simulation model to estimate cost and effectiveness of various screening programs, which was proposed recently by Hisamichi and Kamae. RESULTS: Although CER in PC screening amounted 204 x 10(3) yen for males aged from 55 to 59 years of age, among males more than 60 years of age. CER became negative, which meant a positive balance might be obtained economically by the adoption of screening. CER of PC screening was similar to that of colorectal cancer screening, while was 2 to 14 times lower than that of the remaining 4 established cancer screenings. According to the sensitivity analysis, the rate of the prevalence of PC, as well as the rate of the examinees for the secondary study influenced remarkedly the cost-effectiveness of PC screening. CONCLUSION: The morbidity and mortality of PC has seriously increased in the past years in Japan and the number of PC patients in 2015 is anticipated to show a 5.19-fold increase of that in 1990. According to such considerable increase of PC patients in the near future, PC screening is thought to be an economically well-balanced public activity.

[Mass screening for prostatic cancer].

Two mass screening programs for prostatic cancer (PC) have been conducted at our institution. The first program, based on transrectal ultrasonography (TRUS), was performed between 1975 and 1995 in a total of 16,313 men over 55 years of age. Those showing abnormal findings on TRUS were referred to the secondary urological examination including needle biopsy of the prostate. PC was detected in 93 men (0.6%) and 43 of them were in the early stage. In 1995, a new mass screening program for PC was performed in an urban area of Kyoto. Of 3,749 men over 55 years of age who took the annual health checkup organized by the government, 2,387 wished to receive this screening. The primary examination consisted of Delfia prostate specific antigen (PSA) assay of dried blood samples on a filter paper. Men with PSA levels > 4.0 and < or = 10.0 ng/ml showing abnormal findings on TRUS and/or digital rectal examination, or PSA density > 0.15, underwent 6 sextant biopsies under transrectal ultrasonography, as well as men with PSA levels > 10.0 ng/ml. PSA levels were < or = 4.0 in 2,217 men, > 4.0 and < or = 10.0 in 107, and > 10.0 in 43. Prostatic biopsy was performed in 102 men. PC was detected in 28 men (1.2%) and 17 of them were in the early stage. These findings suggest that the PSA-based mass screening program for PC combined with the annual health checkup is suitable for future "national-level" screening.

Comparison of the inhibitory action of natural rotenone and its stereoisomers with various NADH-ubiquinone reductases.

Two stereoisomers of natural rotenone (5'alpha-epirotenone and 5'beta-epirotenone) were synthesized to identify the stereochemical factor of rotenone required for the inhibition and also to probe the structure of the rotenone binding site. The inhibitory action of the stereoisomers was compared with that of rotenone using NADH-ubiquinone reductases from bovine heart submitochondrial particles (SMP), potato tubers (Solanum tuberosum L.) SMP and Escherichia coli (GR19N) membranes. With respect to bovine heart SMP, it was found that the bent form of rotenone is essential for the activity. The modification of the E-ring moiety also affected both the inhibitory potency and the pattern of inhibition. These results indicated that the rotenone-binding site recognizes the whole molecular structure (or shape) of rotenone in a strict sense. Rotenone and 5'beta-epirotenone inhibited the NADH-ubiquinone reductase of bovine heart SMP in a noncompetitive manner against exogenous quinones. In contrast, the inhibition pattern of 5'alpha-epirotenone varied from noncompetitive to competitive as the concentration of quinone increased. These results suggest that rotenone binds close to, but not at a site identical to, the location for ubiquinone in the ubiquinone-catalytic reaction site, whereas the 5'alpha-epirotenone-binding site overlaps that for ubiquinone due to a structural modification of E-ring moiety. Furthermore, the complex inhibition pattern of 5'alpha-epirotenone suggests that there are two quinone-binding sites in NADH-ubiquinone reductase. In contrast, the order of the inhibitory potencies of the three inhibitors with proton-pumping NADH-ubiquinone reductase of potato SMP was the same as that observed for the bovine enzyme. This suggests that the structure of rotenone-binding sites (or ubiquinone-binding sites) of these enzymes are similar. It was further demonstrated that 5'alpha-epirotenone inhibits quinone binding to both proton-pumping and non-proton-pumping NADH-ubiquinone reductases of potato SMP in a competitive manner. With respect to the proton-pumping NADH-ubiquinone reductase of the E. coli membrane, the sensitivity of the enzyme to the inhibitor was remarkably decreased and the difference in the inhibitory potencies of the three inhibitors became ambiguous. In addition, the inhibition pattern of the three inhibitors was competitive against quinone. These results indicated that, contrary to the mammalian enzyme, only part of the rotenone molecule is recognized by the quinone-binding site of this enzyme.

[Clinical evaluation of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for advanced urothelial cancer].

M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy was performed on 27 patients with advanced urothelial cancer. The patients included 20 with bladder cancer, 4 with upper urinary tract cancer and 3 with both lesions. Complete response (CR) was observed in 2 (7.4 +/- 9.9%) patients and partial response (PR) in 10 (37.0 +/- 18.2%) patients after the treatment, i.e., the overall objective response rate was 44.4 +/- 18.7%. The rate of relapse or recurrence in the patients with CR and PR was 100% and 90.0%, respectively. The mean duration of the response was 18.5 +/- 13.4 months and 10.7 +/- 10.9 months for CR and PR, respectively. The overall survival rate after one year was 30.2%. Bone marrow suppression was the most serious side effect. The white blood cell count became below 1,000/microliters in 10 patients (36.7%). Among them, 4 patients suffered from sepsis. In conclusion, M-VAC chemotherapy was effective for induction therapy against advanced urothelial cancer, although the effective duration was short. Further maintenance therapy should be established.

[Clinical evaluation on renal pelvic and ureteral tumors].

We report 82 patients with renal pelvic and ureteral tumors admitted to Kyoto Prefectural University of Medicine, Kyoto Second Red Cross Hospital and Shakai-Hoken Kyoto Hospital between January, 1981 and December, 1991. Sixty two were males and 24 were females, and they were between 47 and 93 years old (average: 68.2 years). The tumor occurred on the right side in 34 patients, on the left side in 51 patients and on both sides in one patient. There were 43 renal pelvic tumors, 37 ureteral tumors and 6 renal pelvic with ureteral tumors. The most frequent symptom was macrohematuria, which was seen in 54 patients (62.8%). Urinary cytology was performed in 76 patients and a positive result was obtained in 44 patients (57.9%). We performed surgical treatment on 71 patients. The most frequently adopted method was total nephroureterectomy with partial cystectomy which was performed on 51 patients (71.8%). Of the 73 specimens diagnosed histopathologically, 71 specimens were transitional cell carcinoma (TCC), one was a squamous cell carcinoma (SCC) and one was a mixed type of TCC and adenocarcinoma. As to grading, 6 specimens were G1, 28 G2, 38 G3 and one GX. As to staging, 8 specimens were pTa, 17 pT1, 21 pT2, 18 pT3, 8 pT4 and one pTX. The overall survival rate (by Kaplan-Meier's method) at 3 and 5 years was 47.0% and 39.5%, respectively. The patients with high grade tumors and those who had ureter preservation, the survival rate was lower than in the other patients.

[A clinical study of 17 cases of penile cancer].

A clinical evaluation of 17 patients with penile cancer treated in our hospital from 1965 to 1991 were surveyed. They were between 34 and 74 years old with a mean age of 63.8 years. The average interval between the onset and the first visit was 22.8 months. Fourteen patients (83%) complained of the manifestation of a tumor and 14 patients (83%) were phimotic. The stage classified according to Jackson was Stage I for 6, Stage II for 6, Stage III for 4 and Stage IV for 1 patient. At the first visit, the inguinal lymph nodes were palpated in 8 patients and metastasis was confirmed in 5 (63%) of them. Surgical treatment was given to 15 patients (88%) (radical or partial penectomy was performed in most cases). Chemotherapy was given to 9 patients (60%) (main chemotherapeutic agent was bleomycin) and irradiation to 5 patients (30%). The overall 3-year survival rate was 71%, and 5-year survival rate was 56%. The 5-year survival rate in the low stage group (Stage I, II) was 75%, while that in the high stage group (Stage III, IV) was 0%, showing a significant difference.

[A workshop on the high risk group and the preventive oncology of renal cell carcinoma].

A workshop on the high risk group and the preventive oncology of renal cell carcinoma was held in Kyoto on September 7, 1990. The following subjects were presented: 1. Cohort study of renal cell carcinoma (Dr. Hirayama). 2. Pathoepidemiological study on the background of occurrence of renal cell carcinoma (Dr. Aoki). 3. Case-control study on renal cell carcinoma (Dr. Watanabe). 4. Geographic distribution of renal cell carcinoma in Japan (Dr. Minowa). 5. Pathological findings of small renal cell carcinoma (Prof. Yatani). 6. Pathoepidemiological study on occurrence of renal cell carcinoma (Dr. Tsuchihashi). 7. Clinical evaluation of small renal cell carcinoma (Dr. Masuda). 8. Clinical (biological) characteristics of renal cell carcinoma (Dr. Satomi). 9. Mass screening program for renal cell carcinoma on private urological clinic (Dr. Mishina). 10. Early stage detection of renal cell carcinoma (Dr. Ohe). 11. A review on the literature of epidemiology for renal cell carcinoma (Dr. Nakagawa). Possible risk factors reported for renal cell carcinoma were as follows: 1) Work in petroleum-related and dry-cleaning industries were positive risk. A predominant lifetime occupation as a professional was negative risk. 2) Milk or coffee consumption and use of artificial sweeteners were positive. Drinking of alcohol was negative. 3) Obesity was positive. 4) Personal history of cancer was positive. 5) Cigarette smoking was positive. 6) Exposure to radiation or hydrocarbon was positive. 7) Use of estrogen, diuretic and pain relievers was positive. 8) History of myocardial infarction, hypertension and diabetes mellitus was positive.

[Clinical evaluation of nonseminomatous testicular germ cell tumors].

We treated 26 patients with nonseminomatous germ cell tumors (NSGCT) between January 1976 and March 1989. Histologically, 7 were embryonal carcinoma (27%), 4 were teratoma (15%), 2 were yolk sac tumor (8%), 10 were teratocarcinoma (38%) and 3 were other mixed tumors. As regards staging, 18 belonged to stage I (69%), 1 to stage II A (4%), 1 to stage IIB (4%), 1 to stage IIIA, 2 to stage III B1 (8%) and 3 to stage III B2 (12%). Patients in stage I were treated by orchidectomy with lymphadenectomy and occasionally chemotherapy before 1984, resulting in a 100% 5-year survival. However, after 1985, 5 cases in stage I were treated by orchidectomy alone according to a watch-and-see policy. Two cases among them relapsed within two years and both of them contained immature teratoma elements. Six patients with metastatic tumor were treated with PVB therapy of which response rate was 66.7%. The total 5-year survival rate of patients in stage I, II and III was 100%, 50%, 50%, respectively and that in overall cases was 84.6%.

[PVB therapy for advanced testicular cancer].

Twelve cases of advanced testicular cancer, including 5 cases of seminoma, 3 cases of teratocarcinoma, 1 case of yolk sac tumor, 1 case of embryonal carcinoma and 2 cases of mixed cell type, were treated with cisplatin-vinblastine-bleomycin (PVB) therapy. Among them, 10 cases had measurable metastatic lesions and the objective response rate was 80%. Three cases showed complete response. Ten cases showed nonexistent disease after PVB therapy and salvage operation. Though PVB therapy was useful for the treatment of advanced testicular cancer, a few cases having poor prognostic factors showed no response to the therapy.

[Prognosis of bladder tumor patients treated by TUR].

One hundred and eleven cases of bladder tumors were treated with transurethral resection (TUR) and transurethral electrocoagulation as the initial treatment from 1974 and 1983. Eighty nine cases were male and 22 cases were female. The average age was 60.1 years old. Of the 111 patients, 57, 33, 2, 1 and 15 patients had a tumor of Ta, T1, T2, T3a and Tx respectively. The number of grades G0, G1, G2, G3, GX cases was 1, 38, 40, 17, 12, respectively. Other than these, 2 cases of squamous cell carcinoma and 1 of adenocarcinoma were included. The actual survival rates for 5 years in Ta and T1 were 84.4 and 88.9% respectively, and the relative survival rates were 99.5 and 109.1%. TUR was recommended for superficial bladder tumor because of good prognosis. The 5-year recurrence rates for single tumors with and without prophylactic bladder instillation were 21.4 and 27.5% respectively, and those for multiple bladder tumors were 58.6 and 51.8%. There was no significant difference between the group with and without bladder instillation.

[Clinico-statistical study on bladder tumor].

A survey was performed on 277 cases of bladder tumor including 221 males and 56 females (3.9:1), treated in the Department of Urology, Kyoto Prefectural University of Medicine. The result was as follows. The age distribution was from 24 to 86 years old with the average of 65.7. Histologically, 2 cases were diagnosed as transitional cell papilloma, 53 cases as transitional cell carcinoma G1, 111 cases as G2, 88 cases as G3, 16 cases as GX, 5 cases as squamous cell carcinoma and 2 cases as adenocarcinoma. As to the relationship between the grade and the stage, all cases of papilloma or G1 were superficial, while 7.2% of G2 and 45.5% of G3 were invasive, showing a close correlation. As to the relationship of cystoscopic findings and the stage, invasive tumors occupied 1.7% of tumors less than 1 cm in diameter, 16.7% of those 1 to 3 cm, 48.0% of 3 to 5 cm and 41.7% of more than 5 cm in diameter. Also 7.1% of papillary pedunculated tumors, 57.1% of non-papillary pedunculated, 21.7% of papillary sessile and 53.5% of non-papillary sessile were invasive. Thus cystoscopic findings of tumors correlated with the stage. The 5 year survival rates were 61.7% in all cases, 81.4% in pTa, 70.5% in pT1, 58.7% in pT2, 50.0% in pT3a, 32.6% in pT3b and 25.0% in pT4. The stage of tumors reflected the prognosis well. Careful cystoscopy and accurate grading were thought to be helpful for correct staging and for choosing a suitable treatment.

[Detection of precancerous lesions of the bladder by contact-micro-cystoscopy].

Contact-micro-cystoscopy is a new method to examine the bladder epithelium by micro-endoscope after staining. According to this method, normal epithelium was stained slightly and showed smooth surface and small, sparse nuclei. Neoplastic lesions were stained deeply and showed irregular surface and large, dense nuclei. One hundred and sixty nine biopsy specimens of cystoscopically normal bladder mucosa were analyzed. The diagnostic accuracy of neoplastic lesions by this method was 75.9%. In vivo mapping of the bladder epithelium was also possible using this method in association with random biopsy. Contact-micro-cystoscopy was thought to be useful to detect precancerous lesions or flat carcinoma of the bladder which was difficult to be detected by conventional cystoscopy.

[Treatment of hormonal refractory adenocarcinoma of the prostate with ifosfamide (IFM) and the combination of vincristine ifosfamide and peplomycin (VIP)].

Nineteen patients with hormonal refractory adenocarcinoma of the prostate were treated with ifosfamide (IFM) and the combination of vincristine, ifosfamide and peplomycin (VIP). Nine of them were treated with IFM, and nine with VIP, and one with IFM and also VIP. In the case of the IFM therapy, the over-all response rate was 0% by the Karnofsky's category of response, 20% by the response criteria of Shida et al., 50% by the National Prostatic Cancer Project (NPCP) criteria, and 0% by the response criteria of Koyama and Saito. In the case of the VIP therapy, the over-all response rate was 30% by the Karnofsky's category, 30% by the response criteria of Shida et al., 70% by the NPCP criteria and 20% by the response criteria of Koyama and Saitoh. The one-year survival rates of these patients treated with IFM and VIP were both about 20%. Only one patient treated with VIP therapy showed a partial response. Therefore, a more effective regimen for hormonal refractory adenocarcinoma of the prostate must be developed.

[Complete remission of brain metastasis of bladder cancer treated by M-VAC therapy].

A case of brain metastasis from transitional cell carcinoma of the bladder that attained complete remission by methotrexate-vinblastine-adriamycin-cisplatin (M-VAC) therapy was reported. The patient was a 53-year-old male, already treated with total cystectomy and CAP therapy against pulmonary metastasis, which disappeared completely. At 8 months after complete remission of pulmonary metastasis, brain metastasis was found. One course of M-VAC therapy brought a complete remission persisting for 7 months. He is alive with no relapse.

[The primary mucinous adenocarcinoma of renal pelvis: a case report].

A case of primary mucinous adenocarcinoma of the renal pelvis is reported. A 55-year-old man visited our clinic with lumbar pain. He had a history of left renal stone and had left partial nephrectomy four years previously. Physical examination revealed a hard, child-head-sized, unmovable and uneven tumor in the left side of the abdomen. Intravenous pyelography revealed the non-functioning left kidney with calcification, in which hydronephrosis was detected by computed tomography. In transabdominal sonography a huge mass with mixed echo pattern was observed. Aspiration biopsy under interventional ultrasound was performed, aspirating yellow-white semi-transparent mucinous substance, which was highly suspicious of malignancy by cytology. He died 74 days after the first admission. Autopsy revealed primary mucinous adenocarcinoma of the renal pelvis. This was thought to be the 14th case of primary mucinous adenocarcinoma of the renal pelvis reported in the Japanese literature.

[Combination chemotherapy of cyclophosphamide, adriamycin and cisplatin in advanced urothelial cancer].

Sixteen patients with advanced evaluable urothelial cancer were treated with a chemotherapy regimen of cyclophosphamide, adriamycin and cisplatin (CAP). Cisplatin 50 mg/m2 and adriamycin 30 mg/m2 were given on the first day and cyclophosphamide 200 mg/m2 was given from the second to the fifth day. This course was repeated every 3 weeks. The objective response rate was 25% (4 of 16 patients), with 1 patient achieving complete remission. The survival time of responders was longer than that of nonresponders, although the difference was not significant (generalized Wilcoxon method). As side effects, nausea with vomiting (43.8%), renal dysfunction (6.3%), anemia (12.5%), leucopenia (12.5%), thrombocytopenia (25.0%), alopecia (68.8%), heart failure (6.3%) and peripheral neuropathy (6.3%) were noticed. One patient died of sepsis due to agranulocytosis and another died suddenly of heart failure.