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ビカルタミド1日1回50mg群, 80mg及び100mgを12週間投与する3群比較の無作為化非盲検試験を実施した. 1)登録症例は124例で, 適格例は122例であった. 2)総合効果における奏効率は50mg群, 80mg群及び100mg群でそれぞれ50.5%, 61.0%及び53.7%であった. 3)PSAに対する奏効率は50mg群, 80mg群及び100mg群でそれぞれ84.2%, 92.7%及び97.6%であった. 4)副作用発現率は3群ほぼ6割で副作用による中止例は80mg群の1例のみで, 安全度において3群間に有意差はなかった.主な副作用は乳房腫脹, 乳房圧痛等であった, To investigate the efficacy and safety of bicalutamide (Casodex(R)) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks ; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40); 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 ing group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

We treated two children with 2, 8-dihydroxyadenine urolithiasis for over 7 years. The male prepositus was admitted to the hospital because of anuria when he was 10 months old. Bilateral urinary stones had caused the anuria. The stones were 2, 8-dihydroxyadenine and his APRT activity was low. He has been treated with about 5.0 mg/kg/day of allopurinol without purine diet restriction. His sister, 3 years old at that time, also was found to have a renal stone. She has been treated with about 3.3 mg/kg/day of allopurinol without restricting purine. The allopurinol therapy without purine-restriction resulted in normal growth of both children with neither the recurrence of stone nor renal impairment.

動脈瘤のあるドナー腎を用いた生体腎移植の1例を報告した。1)腎は十分に灌流して冷却すれば阻血によく耐え, 2時間程度であれば血流再開後の腎機能の発現に影響を与えない。2)予想阻血時間が2時間程度なら灌流液は乳酸加リンゲル液で十分である。3)ドナー腎に動脈瘤があっても体外腎手術を適用すれば移植が可能である, A case of living related renal transplantation using a kidney with renal arterial aneurysm is reported. The size of the renal arterial aneurysm was 15 mm in diameter. After ex vivo aneurysm removal, the graft was transplanted to the right iliac fossa. The total ischemic time was 79 minutes, and the urine flow started 5 minutes after declamping. In Japan, eight patients are reported to have successfully received a renal graft after removing its aneurysm extracorporeally. Renal transplantation is possible even when the donor kidney has a renal arterial aneurysm.

特発性高Ca尿症66例について検討した。1)尿中Ca排泄量はthiazide投与前に比し, 投与期間中有意に減少した。2) group formation rateはthiazide投与後有意に低下した。3)副作用として高尿酸血症, 低カリウム血症, 耐糖能異常などがあった, The prophylactic effect of hydrochlorothiazide on stone formation was studied in 66 patients with calcium urolithiasis, (49 men and 17 women between 25 and 76 years old, mean 52.2 +/- 11.7 years) due to idiopathic hypercalciuria. Urinary calcium excretion was significantly decreased during treatment when compared to the baseline value. The stone formation rate was also significantly reduced when compared with that before treatment. With regard to side effects, hyperuricemia was observed in 21 patients, hypokalemia in 9 patients, hypotension in 3 patients, and glycosuria in 4 patients. Thiazide treatment was concluded to be effective for preventing the recurrence of calcium stones in patients with idiopathic hypercalciuria. However, this therapy should be used only in conjunction with the careful monitoring of possible adverse reactions.

Between August, 1986 and August, 1992, 16 combination chemotherapies with etoposide (100 mg/body, day 1-5), ifosfamide (50 mg/kg, day 1, 3, 5), peplomycin (5 mg/body, day 1-5) were performed on 13 patients with endocrine therapy-relapsed advanced prostatic cancer. Seven trials were performed on 5 patients who received DESP (diethylstilbestrol diphosphate) (500 mg/body, day 1-5) with the chemotherapy. In 9 trials performed on 9 patients who did not receive DESP, there was no response case. In 7 trials with DESP, one trial had a partial response (PR) (14%) and 4 remained objectively stable (stable) (57%). As to adverse effects, myelosuppression was observed in all trials but there was no lethal toxicity. The one-year survival rate of these patients treated with the chemotherapy alone and combined DESP were both about 20%. Therefore we should find a more effective treatment for endocrine relapsed prostatic cancer.

33症例の上部尿路結石患者にアメリカ製Biolithos MARK 3を用いてESWLの臨床治験を行った。治療後1ヵ月目の効果判定では, 有効率は72.7%でありほぼ満足のいく結果がえられた。特に問題となるような副作用・合併症もなく外来通院・無麻酔・鎮痛剤の投与なしでもESWL施行が可能であった, The results of clinical use of an extracorporeal shock wave lithotripter (Biolithos MARK III) are presented. From May 1991 through February 1992, a total of 50 sessions were carried out on 33 patients with upper urinary tract stones. Treatments were performed on an outpatient basis, and none of the patients needed anesthesia or analgesia. One month after the last session, 18 patients (54.5%) were free from stone fragments and 6 (18.2%) had stone fragments equal to or smaller than 4 mm. The over-all successful rate obtained by these categories was 72.7%. After treatment no serious complications were observed. Although gross hematuria appeared in almost all patients, pain was noted in only 5 patients. Laboratory data after treatments showed slight and transient changes. It is concluded that Biolithos MARK III is useful and safe in the management of upper urinary tract stones on an outpatient basis.

全国多施設の共同研究により, 腎細胞癌に対するn-TNFとn-IFN-αの併用療法による有効性と安全性を検討した.1)腎細胞癌31例においてPRが4例認められ奏効率は12.9%であった.IFN-αが前治療に使用された症例にも有効例が認められたことより, 本併用療法の有用性が示唆された.2)副作用は(35例/36例)に認められ, おもな自他覚的副作用は発熱72.2%, 悪寒・戦慄69.4%, 食欲不振22.2%, 全身倦怠感16.7%であり, おもな臨床検査値異常は白血球減少47.2%, 血小板減少22.2%, GOT上昇16.7%, GPT上昇13.9%であった.ほとんどの症例が解熱剤等の処置あるいは無処置で投与継続可能であった.本併用療法による副作用の増強はほとんどなかった, The combination therapy with natural type human tumor necrosis factor (n-TNF; MHR-24) and human lymphoblastoid interferon-alpha (n-IFN-alpha; MOR-22) was investigated for antitumor effect against renal cell carcinoma in a multiclinic cooperative study throughout Japan. The "Response criteria of Japan Society for Cancer Therapy" were followed for the handling of subjects and the evaluation of antitumor effect. MHR-24 was administered at a daily dosage of 5, 000-10, 000 JRU by intravenous drip and MOR-22 at a dosage of 5, 000, 000 IU daily was administered intramuscularly at the same time. Both drugs were administered for 4 weeks or longer. A total of 36 patients were enrolled as subjects in the study. None of them were classified as ineligible. Five patients, were classified as imperfectly evaluable, and 31, as evaluable for the results of treatment. The responses in the evaluable patients were partial response (PR) in 4 patients, minor response (MR) in 3 patients, no change (NC) in 14 patients and progressive disease (PD) in 10 patients, with a response rate of 12.9%. Adverse reactions to the therapy were investigated in all 36 patients. The frequent subjective and objective reactions that occurred were fever, rigors and shivering, anorexia, and generalized malaise, and the frequent abnormal laboratory findings were leukopenia, thrombocytopenia, elevation of GOT, and elevation of GPT.

実験には体重約100 gのWistar系成熟雄ラットを使用した.実験群は, Cs投与群(Cs群)と対照群の2群とし, 動物数は各群7匹とした.Cs群の各ラットには, 1日体重1 kg当り50 mgのCsを10日間連日腹腔内投与した.対照群の各ラットには, 溶媒として用いた生理食塩水(生食)だけを10日間連日腹腔内投与した.Cs投与により, 腎皮質の組織血流量は減少した.この原因として, 小葉間動脈より末梢の細い血管系に変化が起き, 末梢血管抵抗が上昇した可能性が考えられた.Cs投与でRAA系が活性化されることから, 障害が生ずるのは糸球体の輸入細動脈である可能性が大きい, To elucidate the relationship between cyclosporine (Cs) nephrotoxicity and renal blood flow (RBF), we carried our experiments using rats. Adult male Wistar strain rats each weighing about 100 g were used. Rats were divided into 2 groups; the Cs group (Cs 50 mg/kg/day was intraperitoneally given for 10 consecutive days) and the control group (normal saline solution for 10 consecutive days). The renal cortical blood flow was measured in each group by electrolytic hydrogen gas clearance method. We also carried out renal angiography with barium sulfate (BaSO4). Then we measured blood vessel area/renal sagittal section area ratio and the diameter of interlobar arteries. The Cs group showed a significant decrease of renal cortical blood flow compared with the control group. On the other hand there was no significant change in renal angiogram. In conclusion, Cs decreased renal cortical blood flow. We suppose that vascular resistance increased following afferent arteriolopathy caused by Cs administration.

TAP-144-SRの前立腺癌に対する比較対照試験をリン酸ジエチルスチルベストロールを対照薬として行った.有効性では, 前立腺癌の判定基準の適格例で, TAP群54.5%(36/66), 対照群47.1%(32/68)のPR例が得られ, 両群間に有意差はみられなかった.病巣別効果や自他覚症状に対する効果でも両群間に差はみられなかった.PAPなど腫瘍マーカーに対して対照群の方が有意に優れる効果を示した.内分泌効果では両群とも全例で血清testosteroneがcastration levelに低下した.安全性については, 副作用発現率はTAP群64.1%(41/64)に対し, 対照群は95.4%(62/65)と有意に高く, 対照群で4例が副作用のため試験が中止された.主治医判定による全般安全度では"問題あり"と判定された症例はTAP群6.3%(4/64), 対照群36.9%(24/65)であった.主治医判定による有用度では"有用"以上でみると, TAP群65.6%(42/64), 対照群52.3%(34/65)であった, A randomized controlled phase III clinical trial comparing TAP-144-SR (TAP) and diethylstilbestrol diphosphate was conducted for patients with prostatic cancer. Patients with Stage B, C, or D disease, who were previously untreated, were enrolled. TAP-144-SR 3.75 mg was administered subcutaneously at 4-week intervals for 12 weeks (a total of 3 injections) in the TAP-144-SR group, while 100 mg of diethylstilbestrol diphosphate was administered orally three times a day (before meals) for 12 weeks in the control group. A total of 141 patients were enrolled using a centralized telephone registration system. Four of these patients were ineligible, and there were 3 drop-outs who never received drugs because they withdrew their consents to participate in the trial. These 7 were excluded from the evaluation, and as a result, 134 patients (66 in the TAP group and 68 in the control group) were evaluable in safety and efficacy. Between the two groups, there were no significant differences in patient characteristics, except the age distribution. Clinical response rates (CR+PR) in evaluable patients according to the criteria of Japanese Prostatic Cancer Study Group were 54.5% in the TAP group and 47.1% in the control group. In addition, the rates according to the criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria were 7.6% in the TAP group and 8.8% in the control group and 18.2% in the TAP group and 20.6% in the control group, respectively. Using any of the three criteria, there were no significant differences in response rate between the two groups. The incidence of side effects was 64.1% in the TAP group and 95.4% in the control group; the incidence being significantly higher in the control group (p less than 0.001; chi 2-test). Therefore, the overall safety was significantly greater in the TAP group than in the control group (p less than 0.001; chi 2-test). On the basis of the efficacy and safety the clinical usefulness rate of TAP-144-SR was significantly higher than that of diethylstilbestrol diphosphate (p = 0.038; U-test). In conclusion, TAP-144-SR was confirmed to be more useful than diethylstilbestrol diphosphate as a standard drug for hormonal therapy of prostatic cancer.

Endoscopic photography, double contrast cystography, transurethral echography, X-ray CT scan, and MRI (magnetic resonance imaging) were utilized for the staging diagnosis of the four patients with carcinoma of the bladder. In the first case, a 70-year-old man, since all of the five imaging procedures suggested a superficial and pedunculated tumor, his bladder cancer was considered T1. The classification of stage T3 carcinoma was made for the second 86-year-old male. Because all of his imaging examinations showed a tumor infiltrating deep muscle and penetrating the bladder wall. The third case was a 36-year-old male. His clinical stage was diagnosed as T2 or T3a by cystophotography, double contrast cystogram, ultrasonography, and X-ray CT scan. However, MRI showed only thickened bladder wall and the infiltrating tumor could not be distinguished from the hypertrophic wall. The last patient, a 85-year-old female, had a smaller Ta cancer. Her double contrast cystography revealed the small tumor at the lateral bladder wall. But, the tumor could not be detected by transaxial, sagittal and coronal scans. Multiple imaging procedures combining MRI and staging diagnosis of the bladder carcinoma were discussed.

1981年1月1日から5年間に当院を訪れた前立腺癌の新来患者74例の集計を行った.1)初診時年齢の平均は72.2±7.7歳であり, 65歳から85歳までが87.9%を占めた.2)主訴は, 排尿困難(75.7%), 頻尿(52.7%)が多かった.3)進行癌(病期C, D)が70%を占めた.4)初回治療法としては, 内分泌療法が88.9%(64/72例)であり, エストロゲン療法とLH-RHアナログ単独療法の割合は1.7:1であった.5)初回内分泌療法施行例の21.9%(14/64例)は再燃・増悪で治療を中断した.6)病理組織学的には, 低分化型が約半数をしめた.7) 5年間の経過観察中, 確認できた死亡例は22例(29.7%)であった.うち前立腺癌死は全体の12.1%(9/74例)であった, Seventy-four new cases of prostatic carcinoma treated between 1981 and 1985 were analyzed. The patients were between 40 and 86 years old with a mean age of 72.2 +/- 7.7 years. More than 70% of the patients had clinical stage C and D carcinoma. All cases proved histologically to be adenocarcinoma of the prostate. Eighteen patients had well differentiated, 21 moderately differentiated and 35 poorly differentiated adenocarcinoma. Various hormonal treatments were performed as the initial treatment in 88.9% (64/72) of the cases. Among them, 37 cases were treated by estrogen and 22 cases by luteinizing hormone releasing hormone analogues. Fourteen of 64 patients (21.9%) who received hormonal treatment discontinued the therapy within 10.1 +/- 9.1 months because of relapse of the disease or no therapeutic response. Salvage therapy following hormonal treatment were chemotherapy (9/14) and radiation therapy (4/14). During the 5-year follow up 12.1% (9/74) of the patients died due to prostatic carcinoma.

9施設565例の初診時年齢は70歳代をピークとする分布を示した.来院時症状は排尿困難が72.2%と最も多く, 癌性疼痛を訴える例が13.6%あった.検査法では, アルカリ性ホスファターゼ, 前立腺生検, IVP, 骨シンチグラフィー, 尿道膀胱造影, 前立腺酸性ホスファターゼ, 酸性ホスファターゼなどが広く施行されていた.臨床病期では, A1 6.2%, A2 3.7%, B 14.9%, C 20.7%, D1 7.4%, D2 43.7%であり, 進行病期のものが多かった.組織学的分化度は, 高, 中, 低分化癌が, それぞれ20.4%, 33.3%, 32.7%であった.初診時年齢が低いほど, 分化度の低い癌がやや多くなる傾向がみられた.また進行病期のものほど, 低分化癌の占める割合が増加していた.治療として内分泌療法が多く行われ, 方法としてほぼ全例にホルモン剤が投与され, その約半数に除睾術が併用された.臨床病期や組織学的分化度を考慮し, 手術療法, 放射線療法, 化学療法や複数の治療を組み合わせた治療法もある程度は試みられていたが, 年齢による制約がみられた.臨床病期別実測5年生存率は, 病期A1 89.2%, A2 66.1%, B 72.7%, G 51.0%, D1 47.5%, D2 28.0%であった.D2において低分化癌の実測5年生存率は16.0%であり, 高中分化癌より悪かった, Five hundred and sixty-five patients with prostatic cancer, who first visited 9 institutions in Japan between 1981 and 1985, were analyzed. The peak of age distribution was in the seventies. As clinical symptoms, disturbance on micturition was the most frequent and pain caused by metastasis was a complaint in approximately one tenth of the cases. Alkaline phosphatase measurement, prostatic biopsy, intravenous pyelography, bone scintigraphy, cystourethrography, and measurements of serum prostatic acid phosphatase and serum acid phosphatase were performed on more than 80% of the patients. The clinical stage was stage A1 in 6.2%, A2 in 3.7%, B in 14.9%, C in 20.7%, D1 in 7.4%, and D2 in 43.7%. According to the histological grade, well, moderately and poorly differentiated adenocarcinoma were observed in 20.4, 33.3 and 32.7%, respectively. Increased ratio of high grade to low grade was noticed in the lower age group as well as in the advanced stage. In this series, endocrine therapy was still accepted in most of the patients. Almost all were treated with hormonal medication and half of them had undergone bilateral orchiectomy. Surgery, radiation, chemotherapy or multidisciplinary therapy were attempted judging from the clinical stage and histological grade. However, old age restricted the therapeutic modality. Actuarial survival rate at 5 years for stage A1, A2, B, C, D1 and D2 was 89.2, 66.1, 72.7, 51.0, 47.5 and 28.0%, respectively. In the patients with stage D2, the 5-year actuarial rate of poorly differentiated adenocarcinoma was lower than that of well or moderately differentiated adenocarcinoma, even though more intensive therapy was given to the former.

A statistical analysis was made by computer on 511 cases of testicular tumor experienced at 14 facilities in Japan between 1970 and 1979. The age distribution of the patients had two peaks, one under 3 years (15%) and the other between 25 and 34 years (32%). Forty percent of the patients were office workers and 76% were college graduates. Fifty percent of the patients had 0 to 1 sibs. The blood type distribution was similar to that for the whole Japanese population. Six percent of the patients had a past history of trauma, and no relation with cell type was detected. Sixty nine percent of the patients were married and 31% were not married. Sixty seven percent of the patients over 30 had seminoma, and 78% of the patients under 29 years old had non-seminoma. Seminoma was rare in patients under 9 years old. Histologically, 75% were simple type, and 25% were mixed type. Forty three percent of the cases were seminoma and 57% were non-seminoma. Of the stage I cases, 78% and 57%, and of the stage III cases 7 and 28%, respectively, were seminoma and non-seminoma, many of the non-seminoma being at high stage. The 5-year survival rate for the 75 patients under 9 years old was 96%, and that for the 341 patients over 15 years was 70%, the survival rate for the patients under 9 years being significantly higher. The 5-year survival rate for stage I, II and III seminoma was 100, 65 and 0%, respectively, while that for non-seminoma was 93, 56 and 8%, respectively. The survival rate for stage I was higher for seminoma cases than for non-seminoma cases. No difference was detected between survival rate for stage II or III between seminoma and non-seminoma. The survival rate for seminoma did not differ with the time when the surgery was performed, but for the patients with non-seminomatous tumors, the survival rate was higher for the patients operated within one month than those operated later. The survival rate was not related to the weight of the extracted testicle. The 5-year survival rate for the patients with normal body temperature was 78% whereas that for the patients who had fevers was 32%. The 5-year survival rate for the patients not accompanied by abdominal tumors was about 80%, whereas that for the patients with palpated abdominal tumors was 42%.(ABSTRACT TRUNCATED AT 400 WORDS)

黄体形成ホルモン分泌刺激ホルモン(LHRH)誘導体Buserelin (Hoe766)の前立腺癌に対する有効性と安全性, 内分泌動態に検討を加えた.試験1の単回投与は前立腺癌3例と前立腺肥大症7例, 試験2および3は病期BないしDの前立腺癌それぞれ40例, 70例を対象とした.試験1の単回投与で本剤がLHRHと同様の動態を示し, 試験2の3ヵ月間投与で至適用量を検討したところ, 500 μg×3/日が初期導入として優れていた.3ヵ月間投与後の有効率は従来の治療法である去勢あるいは抗男性ホルモン剤と遜色がなかった.本剤の長期投与の評価対象は経時的に減少し, 特に病期Dの減少率が高かったが, 組織分化度別の減少率はほぼ一定であった.副作用は本剤投与後3ヵ月以内に発現し, 中止に至った3例を除く6例は本薬の主作用によるもので症状も軽度であった.心血管系や肝障害などは見られなかった.以上より本剤は合併症の多い高齢者の前立腺癌に対し, 短期, 長期とも副作用の少ない有用性の高い薬剤であると結論できた, Seventy three patients with prostatic carcinoma (PC) and 7 patients with benign prostatic hypertrophy (BPH) in 12 institutes subcutaneously received single and multiple doses of Hoe 766, and clinical efficacy, safety and endocrine effects of drug were examined. In a single doses study, six doses were subcutaneously administered to 7 BPH and 3 with PC. Gonadotropin and testosterone levels in the blood were increased following all these doses. In a multiple study, 7 kinds of doses were given to 40 patients with PC. The optimum doses of subcutaneous injection was decided to be 500 x 3 micrograms/day based on gonadotropin and testosterone suppression. Objective response by NPCP's criteria was observed in 35.3% (complete response 5.9%, partial response 29.4%) following 3 months of Hoe 766 treatment. Adverse reactions were observed in 9 cases (12.8%): Treatment was discontinued in 3 cases (eruption in 2, nausea and vomiting in 1), and continued in 6 cases (8.6%) without any treatment required. Buserelin was thus considered to be an effective, safe drug to treat prostatic carcinoma.