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52歳女.von Hippel-Lindau病合併した両側腎細胞癌の1例を報告した.本症例は本邦報告例の第28例目, 下大静脈腫瘍血栓を伴う例としては本邦第1例目と考えられた, We report a case of bilateral renal cell carcinoma with extension into the inferior vena cava associated with von Hippel-Lindau (VHL) disease. A 52-year-old woman was referred to our hospital for further examination of bilateral renal masses which were found on abdominal ultrasound examination. The diagnosis was confirmed with renal angiography, abdominal computed tomography (CT), abdominal magnetic resonance-CT (MRI), cavography and head MRI. Right adjunctive nephrectomy and removal of the tumor thrombus were performed. She has been treated with interferon-alpha after the operation. The analysis of her DNA by using single strand conformational polymorphism revealed a VHL gene abnormality.

1)登録症例は16例で, 全例が適格例であった. 2)副作用は16例中8例に認められたが, 軽度で, 臨床上特に問題はなかった.乳房圧痛, 乳房腫脹等の副作用が50mg群で1例, 80mg群で3例及び100mg群で2例に認められた. 3)有効性に関しては, 各投与群の1例ないし2例において, PR以上の抗腫瘍効果が認められた.又, 排尿困難, 排尿痛, 夜間頻尿の改善がみられた. 4)血清中ホルモンでは, LH, FSH, testosterone及びestradiol濃度の上昇が認められた, A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

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 report a patient who developed a fistula between the right ureter and the right common iliac artery aneurysm. He had had replacement of a synthetic graft for abdominal aortic aneurysm sixteen years previously. The diagnosis was confirmed by angiography, retrograde pyelography and computed tomography. The fistula was treated by right nephroureterectomy and resection of right common iliac artery aneurysm. A brief description of the case is provided and the review of the literature is described.

1)内分泌療法未治療の前立腺癌症例に対し, 375mg/日の用量で単独療法として使用しえる。この際, testosterone産生阻害療法に比し, 「生活の質」が保たれる。2)内分泌療法再燃例に対しても, ある程度その効果が期待できる。3)フルタミドと他の精巣性testosterone阻害剤との併用で, その併用効果が期待できる。4)また, LH-RHアナログの投与によるflare-up現象をフルタミドを併用することにより予防することが可能である, The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1, 125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1, 125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.

A 66-year-old female was admitted to Chiba University Hospital for the evaluation of a left adrenal mass which was incidentally discovered by computerized tomography. The patient had no clinical signs of Cushing's syndrome. Although the plasma ACTH level was suppressed, serum cortisol and urinary 17-OHCS levels were normal. Serum cortisol was not suppressed by dexamethasone and loss of diurnal rhythm of cortisol was observed. Uptake of 131I-aldosterone in the left adrenal gland was noted, but no accumulation was observed in the right one. Left adrenalectomy was performed. The tumor resected was 20 x 22 x 26 mm in size. Pathological diagnosis was adreno-cortical adenoma. Whether slight abnormality of adrenocortical function without clinical symptoms observed in the present case would develop into a clinically typical Cushing's syndrome remains to be solved.

A 20-year-old man was admitted on February 2, 1990 with the chief complaint of pollakisuria, miction pain and macrohematuria. Urinalysis revealed numerous leukocytes and Enterobacter was identified by urine culture. Cystoscopy revealed an edematous region. Contrast film of small intestines demonstrated vesicoileal fistula. Judging from these and the radiographic findings, we made the diagnosis of vesicoileal fistula with Crohn's disease. After medical therapy between February 22 and May 25, urinalysis became normal and we assumed that the fistula had closed. Now, it is about a year since the therapy began, the patient remains well, without urinary and enteric symptoms. Cystoscopy and urinalysis did not reveal recurrence of the fistula. Despite previous reports that vesicoenteric fistulas complicating Crohn's disease require surgical treatment, this case responded to medication, and required no surgical treatment. This case is a reminder of the importance of the principle of therapy.

1975年1月～1989年12月に根治的腎摘除術およびリンパ節郭清術をおこなった86例を集計した.1) 15例にリンパ節転移を認めた.2)リンパ節転移陽性率はpT, gradeと有意に相関し, またrapid typeに多かった.3) slow typeではリンパ節転移は局所に限局し, 予後も良好であったので, リンパ節郭清術の治療効果があったと考えられた.rapid typeでは静脈血栓や遠隔転移を有する症例が多く, このような症例ではリンパ節郭清術の意義を見出せない, Between January, 1975 and December, 1989, 86 patients with renal cell carcinoma received radical nephrectomy associated with lymphadenectomy at our institutions. Pathological examination revealed lymph node metastasis in 15 patients (17.4%). The incidence of lymph node metastasis increased in accordance with the aggravation of tumor stage (p less than 0.01) and grade (p less than 0.05). Patients with a rapidly growing tumor showed higher incidence of lymph node metastasis than patients with a slow growing tumor (p less than 0.01). Regional lymph node metastases were found in 3 of the 41 patients with a slow growing tumor. Since these 3 patients are surviving with no evidence of disease for 38.7 months on average, the regional lymphadenectomy was considered to have been effective for their survival. Nine of the 25 patients with a rapid growing tumor had progressive lymph node metastasis. Four of them had apparent tumor thrombi as well as lymph node metastasis, and 2 of them had distant metastasis. These patients showed poor prognosis even after operation. Lymphadenectomy was of no value to the patients with apparent tumor thrombi and/or distant metastasis.

A 65-year old man presented with a seven-month history of macrohematuria and left back pain. Abdominal ultrasonography, enhanced computed tomographic (CT) scanning, magnetic resonance imaging (MRI), selective renal angiography and vena cavography revealed a left renal tumor extending into the inferior vena cava and right atrium. Surgery was performed using the cardiopulmonary bypass and the whole tumor was resected grossly except for the tumor invading into the lumbar vein. The patient recovered promptly but died from cancer metastasis six months after operation.

前立腺癌に対するRU 23908の有効性および安全性を検討するため, stage C, Dの前立腺癌患者47例に1日1回150または300 mg経口投与による早期第2相臨床試験を行った.対象病巣に対する効果では, 総合効果判定は40例中CR+PRが34例, 部位別効果は原発巣では40例中CR+PRが35例, 骨転移では22例中10例, リンパ節転移では6例中5例, 肺転移は1例のみにみられCRであり, PAP判定では34例中CR+PRは33例であった.臨床症状に対する改善率は骨疼痛8/9例, 排尿障害25/30例, P.S. 15/33例であった.副作用は調査症例数47例中29例にみられ, 中止例は7例あった.特殊な副作用として間質性肺炎が試験期間の12週以後の継続投与期間も含めて6例に認められ, その他2例では出現の可能性が否定できないと判定された, To investigate the efficacy and the safety of RU23908 for the treatment of prostatic cancer, an early phase 2 study with the oral administration of 150 or 300 mg daily was performed in 47 patients with stage C or D prostatic cancer at 15 institutions from April 1987 to June 1988. Forty patients were evaluable for efficacy. Concerning the effect on the object lesion, the results of the overall evaluation revealed that complete or partial response (CR + PR) was obtained in 34 of the 40 cases (85.0%). As to the effect classified by site, CR + PR were observed in 35 out of the 40 cases with primary lesion (87.5%), in 10 of the 22 cases with bone metastasis (45.5%), in 5 of the 6 cases with lymph node metastasis (83.3%) and CR was observed in one case with lung metastasis. In the PAP evaluation, 33 out of the 34 cases were judged to be CR + PR (97.1%). The improvement rate of clinical symptoms was 88.9% for bone pain, 83.3% for dysuria and 45.5% for performance status. Adverse reactions were observed in 29 of the 47 cases (61.7%) investigated and 7 cases (14.9%) were withdrawn. During the study period of 12 weeks and the subsequent period of continued administration, 6 cases (12.8%) and 2 possible cases of interstitial pneumonia were diagnosed. From the above results, the treatment of prostatic cancer with RU23908 150 mg/day or 300 mg/day in combination with surgical castration showed an excellent clinical effect compared to conventional endocrine therapy, but has a problem of safety. Therefore, this drug may be expected to be a highly useful therapeutic drug, if safely is improved in the future by reviewing the dose.

1975年から1989年までに, 臨床病期A2-G 90例に病期診断骨盤リンパ節郭清を行い, 非再発率を検討した.1)リンパ節転移頻度は, 臨床病期および原発巣の組織学的分化度の低分化傾向と共に増大した.2) pN0-1に対し, 根治的治療法として, 前立腺全摘除術, または放射線療法を行い, 良好な成績をみた.したがって, 現時点では本病期は治癒的病期とみなした.3) pN2以上には内分泌療法を行い, 病期D2よりは良い傾向をみた.以上より, 病期D1においてはpN1は根治的治療法, pN2以上には内分泌療法の適応と考えた, Between 1975 and 1989, 90 patients with prostate cancer in clinical stage A2 to C underwent pelvic lymphadenectomy. Median follow-up period was 38 months. Almost all of the patients with pN0-1 (49) and 4 of pN2 were treated by curative treatment, such as radical prostatectomy (7) or radiation therapy (45). The remaining pN2 (26), pN3 (4) and pM1 LYM (6) received endocrine therapy. Pelvic lymph node metastasis were noticed in 50 cases (56%). Rates of positive node and degree of nodal extension were related to clinical stage and histological grade. Disease-free survival of the patients with pN0-1 was better than that of the patients with more than pN2. There was no difference in disease-free survival between the patients with pN0 and pN1. We concluded that the patients with pN0 and pN1 were the candidates for curative therapy and recommend that the patients with more than pN2 be treated with endocrine therapy.

初回治療として内分泌療法を施行した病期D2前立腺癌120例について, PAP, γ-SmおよびPSA値と予後およびマーカー併用の有用性を検討した.1)治療前マーカー値の高低と予後とは, PAP, γ-SmおよびPSA共関連が認められなかった.2) PAPおよびγ-Smにおいては, 内分泌療法後3ヵ月および6ヵ月の時点で, マーカーが異常値にとどまるものの予後は正常化したものより不良であった.ただし, 1ヵ月後ではこの関連がみられなかった.3)内分泌療法後3ヵ月の時点で, PAPが正常化したもののうち癌死例があるが, これらの大多数はγ-Smは異常値にとどまっていた.したがって, 両マーカーの併用により, よりよく予後を推測できる.4)低分化腺癌で, 内分泌療法後3ヵ月でマーカー正常化の有無は予後に差があり, 正常化したものは中分化腺癌で異常値のままのものと同じ予後であった.このことにより, 組織学的分化度は経過を腫瘍マ, ーカーにて観察することでより有用となることを確認した, Prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PSA) were examined on 120 cases of stage D2 prostate cancer between 1979 and 1989. All patients received endocrine therapy as the first treatment; castration and immediate administration of estrogen or antiandrogen (101), LH-RH analogs (13), estrogen (3) and antiandrogen (3). The actuarial survival rates were calculated by the cause-specific survival method. Pretreatment levels of PAP, gamma-Sm and PSA did not influence prognosis. After start of treatment, the relationship between the changes of the markers and prognosis were examined. At 1 month after the start of the treatment, normalization of PAP or gamma-Sm was not reflected in the following course. On the contrary, at 3 and 6 months, groups with normalization of PAP or gamma-Sm showed better prognosis than those with elevated levels. The same tendency of PSA was obtained at 6 months after start of treatment. In patients with normalized PAP at 3 months, abnormal gamma-Sm showed worse prognosis than normalized gamma-Sm. Therefore, the significance of determination on the two markers was manifested. As histological grade influenced the following course, poorly differentiated adenocarcinoma with normalized PAP at 3 months showed better prognosis than those with elevated levels. In conclusion, it is worthwhile to measure multiple markers for predicting the prognosis of stage D2 prostate cancer treated with endocrine therapy.

1971年より1987年までに千葉大学泌尿器科において内分泌療法を施行したstage D2前立腺癌175例のうち, 5年以上制癌状態のもの18例と, 治療に反応せず, あるいは当初制癌されたが再燃し3年以内に癌死したもの35例との宿主側, 腫瘍側因子の比較を行った.両群間に有意差を認めたものは, 骨疼痛, 貧血, 組織学的分化度, 骨転移の拡がり, 内分泌療法の反応性であった, To clarify factors affecting prognosis following endocrine therapy, stage D2 patients who died from prostatic cancer within 3 years and those under well-controlled state longer than 5 years were compared with respect to background factors and response to endocrine therapy. Thirty-five and 18 cases, respectively, were studied. Differences between the two groups were bone pain, anemia, tumor grade, number of bone metastasis, and response to endocrine therapy. Performance status in long-term survival groups tended to be better than that in short-term cancer death groups.

58歳女にみられた膀胱海綿状血管腫の例を報告した.自験例の治療法としては, MRI及び経尿道的超音波検査の所見よりTURを選択した, We report a case of cavernous hemangioma of the urinary bladder treated with transurethral resection (TUR). A 58-year-old woman was admitted to our department with the chief complaint of macroscopic hematuria. Cystoscopy revealed a red sessile tumor 2 cm in diameter, at the internal urethral orifice. The tumor had a mostly low signal intensity, partly high signal intensity, on T1-weighted, coronal magnetic resonance (MR) images. Computed tomography and T2-weighted MR images did not delineate the tumor. TUR was performed, and the specimen was pathologically diagnosed as cavernous hemangioma of the urinary bladder. A brief description of the case is provided and the literature is reviewed.

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.

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

We report a case of bilateral renal cell carcinoma with extension into the inferior vena cava associated with von Hippel-Lindau (VHL) disease. A 52-year-old woman was referred to our hospital for further examination of bilateral renal masses which were found on abdominal ultrasound examination. The diagnosis was confirmed with renal angiography, abdominal computed tomography (CT), abdominal magnetic resonance-CT (MRI), cavography and head MRI. Right adjunctive nephrectomy and removal of the tumor thrombus were performed. She has been treated with interferon-alpha after the operation. The analysis of her DNA by using single strand conformational polymorphism revealed a VHL gene abnormality.

We report a case of cavernous hemangioma of the urinary bladder treated with transurethral resection (TUR). A 58-year-old woman was admitted to our department with the chief complaint of macroscopic hematuria. Cystoscopy revealed a red sessile tumor 2 cm in diameter, at the internal urethral orifice. The tumor had a mostly low signal intensity, partly high signal intensity, on T1-weighted, coronal magnetic resonance (MR) images. Computed tomography and T2-weighted MR images did not delineate the tumor. TUR was performed, and the specimen was pathologically diagnosed as cavernous hemangioma of the urinary bladder. A brief description of the case is provided and the literature is reviewed.

The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1, 125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1, 125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.

We report a patient who developed a fistula between the right ureter and the right common iliac artery aneurysm. He had had replacement of a synthetic graft for abdominal aortic aneurysm sixteen years previously. The diagnosis was confirmed by angiography, retrograde pyelography and computed tomography. The fistula was treated by right nephroureterectomy and resection of right common iliac artery aneurysm. A brief description of the case is provided and the review of the literature is described.

A 66-year-old female was admitted to Chiba University Hospital for the evaluation of a left adrenal mass which was incidentally discovered by computerized tomography. The patient had no clinical signs of Cushing's syndrome. Although the plasma ACTH level was suppressed, serum cortisol and urinary 17-OHCS levels were normal. Serum cortisol was not suppressed by dexamethasone and loss of diurnal rhythm of cortisol was observed. Uptake of 131I-aldosterone in the left adrenal gland was noted, but no accumulation was observed in the right one. Left adrenalectomy was performed. The tumor resected was 20 x 22 x 26 mm in size. Pathological diagnosis was adreno-cortical adenoma. Whether slight abnormality of adrenocortical function without clinical symptoms observed in the present case would develop into a clinically typical Cushing's syndrome remains to be solved.

A 20-year-old man was admitted on February 2, 1990 with the chief complaint of pollakisuria, miction pain and macrohematuria. Urinalysis revealed numerous leukocytes and Enterobacter was identified by urine culture. Cystoscopy revealed an edematous region. Contrast film of small intestines demonstrated vesicoileal fistula. Judging from these and the radiographic findings, we made the diagnosis of vesicoileal fistula with Crohn's disease. After medical therapy between February 22 and May 25, urinalysis became normal and we assumed that the fistula had closed. Now, it is about a year since the therapy began, the patient remains well, without urinary and enteric symptoms. Cystoscopy and urinalysis did not reveal recurrence of the fistula. Despite previous reports that vesicoenteric fistulas complicating Crohn's disease require surgical treatment, this case responded to medication, and required no surgical treatment. This case is a reminder of the importance of the principle of therapy.