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1)再燃前立腺癌82例に対する化学療法の効果をみるため新しく提唱した方法(泌尿器科紀要・投稿中)に基づき評価を行った.2)前立腺局所, 骨転移, 軟部組織転移, PAPの4項目を個別に評価し, それを合算して総合評価を行ったところ, PRとstableをそれぞれ19%および27%に認め, 両者は有意な生存期間の延長をみた.3)前立腺局所と骨転移は測定方法が鋭敏なものでないため, 総合評価との一致率が低かった.4)軟部組織とPAPは治療効果を鋭敏に反映した.特にPAPは異常値からの正常化が生存期間を延長する要因として認められた.5)化学療法により自覚症状が改善されることが多いが, 他覚的所見の総合評価とはかならずしも一致しないことが多かった.6)治療効果に影響を及ぼすものとして, 既治療の内容, performance state, 年齢, 病変数, stageがあったが, 初回治療時の組織学的分化度は関係がなかった.7)新しく提唱された評価方法の妥当性が認められた, Effect of chemotherapy for relapse of prostatic cancer was evaluated with new response criteria, in which four objective parameters including the prostate, bone metastasis, soft tissue metastasis and the serum acid phosphatase level estimated by radioimmunoassay or enzyme immunoassay were judged separately and then summarized to evaluate the response as complete response (CR), partial response (PR), stable and progressive disease (PD). Eighty-two patients were included in the study. Rate of PR and stable were 19% and 27%, respectively, and these two groups showed longer survival than those with PD. Evaluation of prostate and bone showed tendency to be discrepant with total judgement. Evaluation of soft tissues and prostatic acid phosphatase reflected the effect of chemotherapy. Chemotherapy often improved subjective symptoms but the effect did not parallel the total judgement in many cases. Factors influencing response of chemotherapy were mode of pretreatment, performance status, age, number of affected areas and clinical stage, but the grade at initial treatment was not correlated to response. The new criteria used in this study was valid for evaluation of response in prostatic cancer.

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.

An 82-year-old man was seen with the complaints of gross hematuria and dysphagia in September 1979. An invasive bladder tumor was found and TUR-Bt (Transitional cell carcinoma, G2, pT3NXMO ) was performed. Fluoroscopic examination revealed a large esophageal cancer (Undifferentiated squamous cell carcinoma, T2NXMO ) and irradiation was performed (Linac 4, 600 rads). The patient's condition aggravated rapidly and he died in February 1980. A 76-year-old man irradiated for an esophageal cancer (Linac 6, 540 rads) (undifferentiated squamous cell carcinoma, T1NXMO ) in March 1981. Eleven months later, bladder cancer was found and treated with TUR-Bt (Transitional cell carcinoma, G2, PTlmNXMO ) followed by intravesical instillation of carboquone and adriamycin. The patient was alive 1 year and 9 months after the diagnosis of the esophageal cancer. Sixteen cases of double cancer of the esophagus and urinary bladder were found in the Japanese literature. Eighteen cases including the above 2 cases were males and their ages ranged from 51 to 82 years. Sixteen bladder cancers were transitional cell carcinoma and 15 esophagus cancers were squamous cell carcinoma. Of 9 cases whose clinical course were described in detail, 3 were synchronous and 6 were metachronous. Radical surgery was performed for one or both of the two cancers in 5 cases, 4 of which were metachronous. Indication of surgery for the metachronous second cancer does not differ significantly from sporadic cancer when the first cancer has been managed successfully. However, the treatment for the synchronous double cancer of this type of combination is often forced to be restricted, since the prognosis of esophageal cancer is poor and surgical risk may be increased by two radical surgeries in such elderly patients.

The efficacy of cytotoxic agents in the treatment of prostatic cancer is difficult to evaluate because objective, measurable lesions, such as lung, liver, skin, subcutaneous and nodal metastasis are often not found. However, most of the patients with advanced prostatic cancer have bone involvement and elevated serum acid-phosphatase in addition to the primary tumor. Exact clinical trials on such cases, especially phase II studies can not be performed without appropriate evaluations of these three parameters. The criteria of these three parameters offered by various study groups are reviewed and the relevant response criteria are proposed. A stable category was thought to be useful to evaluate the efficacy on the patients with progressing disease. In our proposal, overall assessment of response involves all objective parameters including these three parameters as well as both measurable and unmeasurable disease described in the WHO handbook for reporting results of cancer treatment.

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.

Electron microscopic studies were carried out in pursuit of the difference and interrelationship between the changes of the basement membrane of renal glomerulus and the changes of the basement membrane of renal arteriole in experimental hypertension. The changes of the basement membrane of arteriole and basement membrane like material of mesangium and lacis show their occurrence at about the same time and their progress in the same degree. The changes first observed are the beads-like thickening and reticular change of the basement membrane of vascular wall and also the increase of basement membrane like material in mesangium and lacis. These changes are followed by the deposit of dense material and fibrin on the vascular wall and the increase of basement membrane like material of mesangium and lacis so as to compress their cells and tear them to pieces. About this stage, the thickening of the basement membrane of glomerular capillary loop is intensified and moreover the wrinkle and tortuosity of the basement membrane of glomerular capillary loop and the collapse of glomerular capillary lumen became remarkable. The above findings suggest that the basement membrane of renal arteriole and the basement membrane like material of mesangium and lacis are interrelated, and may be the portions in the kidney most liable to changes and injury in hypertension., Acta medica Nagasakiensia. 1975, 19(1-4), p.59-81

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.

Effect of chemotherapy for relapse of prostatic cancer was evaluated with new response criteria, in which four objective parameters including the prostate, bone metastasis, soft tissue metastasis and the serum acid phosphatase level estimated by radioimmunoassay or enzyme immunoassay were judged separately and then summarized to evaluate the response as complete response (CR), partial response (PR), stable and progressive disease (PD). Eighty-two patients were included in the study. Rate of PR and stable were 19% and 27%, respectively, and these two groups showed longer survival than those with PD. Evaluation of prostate and bone showed tendency to be discrepant with total judgement. Evaluation of soft tissues and prostatic acid phosphatase reflected the effect of chemotherapy. Chemotherapy often improved subjective symptoms but the effect did not parallel the total judgement in many cases. Factors influencing response of chemotherapy were mode of pretreatment, performance status, age, number of affected areas and clinical stage, but the grade at initial treatment was not correlated to response. The new criteria used in this study was valid for evaluation of response in prostatic cancer.

An 82-year-old man was seen with the complaints of gross hematuria and dysphagia in September 1979. An invasive bladder tumor was found and TUR-Bt (Transitional cell carcinoma, G2, pT3NXMO ) was performed. Fluoroscopic examination revealed a large esophageal cancer (Undifferentiated squamous cell carcinoma, T2NXMO ) and irradiation was performed (Linac 4, 600 rads). The patient's condition aggravated rapidly and he died in February 1980. A 76-year-old man irradiated for an esophageal cancer (Linac 6, 540 rads) (undifferentiated squamous cell carcinoma, T1NXMO ) in March 1981. Eleven months later, bladder cancer was found and treated with TUR-Bt (Transitional cell carcinoma, G2, PTlmNXMO ) followed by intravesical instillation of carboquone and adriamycin. The patient was alive 1 year and 9 months after the diagnosis of the esophageal cancer. Sixteen cases of double cancer of the esophagus and urinary bladder were found in the Japanese literature. Eighteen cases including the above 2 cases were males and their ages ranged from 51 to 82 years. Sixteen bladder cancers were transitional cell carcinoma and 15 esophagus cancers were squamous cell carcinoma. Of 9 cases whose clinical course were described in detail, 3 were synchronous and 6 were metachronous. Radical surgery was performed for one or both of the two cancers in 5 cases, 4 of which were metachronous. Indication of surgery for the metachronous second cancer does not differ significantly from sporadic cancer when the first cancer has been managed successfully. However, the treatment for the synchronous double cancer of this type of combination is often forced to be restricted, since the prognosis of esophageal cancer is poor and surgical risk may be increased by two radical surgeries in such elderly patients.

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.

The efficacy of cytotoxic agents in the treatment of prostatic cancer is difficult to evaluate because objective, measurable lesions, such as lung, liver, skin, subcutaneous and nodal metastasis are often not found. However, most of the patients with advanced prostatic cancer have bone involvement and elevated serum acid-phosphatase in addition to the primary tumor. Exact clinical trials on such cases, especially phase II studies can not be performed without appropriate evaluations of these three parameters. The criteria of these three parameters offered by various study groups are reviewed and the relevant response criteria are proposed. A stable category was thought to be useful to evaluate the efficacy on the patients with progressing disease. In our proposal, overall assessment of response involves all objective parameters including these three parameters as well as both measurable and unmeasurable disease described in the WHO handbook for reporting results of cancer treatment.