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An 85-year-old man had planned a laparoscopic right nephrouretectomy for a right lower ureteral cancer, pT1, G3. Two months prior to the surgery, he was re-examined because of continuing macrohematuria. He had a 50 mm tumor in his urinary bladder and tumors from the right upper to lower urinary tract by computed tomographic (CT) examination and cystoscopy. He did not have any metastasis. We diagnosed a cT3N0M0 for the right ureteral cancer and a cT3N0M0 for the bladder cancer. A right nephrouretectomy and cystectomy were then performed. The histopathologic examination revealed an urothelial carcinoma with a choriocarcinoma.

20歳女性。患者は以前より不正性器出血を認め, 3ヵ月前より咳嗽も出現していた。今回, 突然の右上腹部痛, 背部痛を主訴に, 腹部CTにて右後腹膜腔の血腫を認め, 著者らの施設へ入院となった。腹部造影CTにて右副腎破裂による後腹膜血腫と考え, 受診後早期より出血性ショックを呈したため, 緊急手術が行われた。右腎摘除および副腎腫瘍を摘出した結果, 病理組織学的に絨毛癌副腎転移と診断され, 胸部CTでは両側肺野に転移巣が確認された。その後, 患者は他院婦人科に転院となり, EMA/CO療法を6コースが施行され, 寛解が得られた。, A 20-year-old woman, who had a history of childbirth, was admitted to the emergency room with an acute abdomen. An abdominal enhanced computed tomography (CT) revealed retroperitoneal hemorrhage, leading to life-threatening, and multiple tumors in the liver. Additionally, chest CT also revealed multiple coin lesions in the lung. These findings strongly indicated a spontaneous rupture of adrenal tumor. We performed exploratory laparotomy. An examination during surgery showed a rupture of adrenal tumor. En bloc resection of adrenal gland, tumor, and the kidney was performed. Pathological finding revealed the adrenal tumor was choriocarcinoma.

68歳男, 絨毛癌への変異を伴った腎盂移行上皮癌を経験した.尿路上皮に発生した絨毛癌は予後不良とされているが, 本症においてはMVC療法及びそれに続くPEB療法が有効であり良好な成績を得た, A 68-year-old male presented to our hospital complaining of gross hematuria. Intravenous pyelography subsequently demonstrated a left non-visualized kidney, and he was admitted for further evaluation. Cystoscopy revealed a bladder tumor around the left ureteral orifice and retrograde pyelography showed a filling defect in the left renal pelvis. The urinary cytology from the left renal pelvis indicated class IV, and the microscopic findings of a bladder biopsy demonstrated grade 1 transitional cell carcinoma. We performed transurethral resection of bladder tumor (TUR-BT) followed by left nephroureterectomy with bladder cuff. The pathological diagnosis was high grade transitional cell carcinoma with choriocarcinomatous component. After the operation, the serum human chorionic gonadotropin-beta (hCG-beta) level was slightly elevated, and the combination chemotherapy with methotrexate, vinblastine and cisplatin (MVC) was administered. Although the serum hCG-beta level fell to 0.1 ng/ml, after two courses of MVC chemotherapy, bilateral pulmonary metastases appeared in the chest X-ray with increasing hCG-beta levels. Salvage chemotherapy with cisplatin, etoposide and bleomycin (PEB) was performed. After two courses of PEB chemotherapy, the serum hCG-beta level fell to within the normal range and all pulmonary metastases disappeared.

We report a case of pure choriocarcinoma of the left testis in a 27-year-old male. He consulted a physician with left back pain in August, 1990. Intravenous pyelography (IVP) revealed left hydronephrosis. Abnormal computerized tomography (CT) revealed para-aortic lymph node swelling. The chest X-ray revealed bilateral multiple coin lesions. The genital examination revealed a left testicular nodule 8 mm in diameter. Left high inguinal orchiectomy was performed. Histopathological diagnosis was pure choriocarcinoma. After 4 courses of the PVB (cisplatin, vinblastine, bleomycin) therapy, tumor regression rate of the pulmonary metastases was 41.9%. He was transferred to our hospital on December 3, 1990 and was admitted 3 days later. "COMPE" chemotherapy, consisting of cisplatin, vincristine, methotrexate, peplomycin, and etoposide, was administered. After seven courses of "COMPE" chemotherapy, he achieved a partial response (the regression rate of the pulmonary metastases and the retroperitoneal lymph node metastasis were 78.8% and 69.1%, respectively) and the residual masses in the lungs and the retroperitoneum were removed. Necrosis and xanthogranulomatous fibrosis were found in the resected material. The patient showed no evidence of disease one year after thoracotomy.

A 32-year-old Japanese male consulted a clinic complaining of gynecomastia. Right painless scrotal swelling was also detected. Right high orchiectomy was performed, then the surgical specimen was histopathologically confirmed as choriocarcinoma and mature teratoma. The imaging revealed cerebral, pulmonary, retroperitoneal metastases. After 3 courses of combination chemotherapy with cisplatin, etoposide and peplomycin (PEP therapy), the brain metastasis completely disappeared and the serum titer of the tumor markers such as beta-HCG became normal. The regression rates of lung and retroperitoneal metastases were 68% and 27%, respectively. Therefore, retroperitoneal lymph node dissection was performed. After the 5th course of PEP therapy, lung metastases disappeared completely. Until the present, no evidence of disease has persisted. The PEP therapy, which is a salvage therapy for refractory testicular cancer, was performed as first-line chemotherapy in this case. It was an excellent modality against choriocarcinoma, along with the surgical treatment.

A case of extragonadal germ cell tumor is reported. A 41-year-old man, an elementary school teacher, was referred to our department with left abdominal pain and gynecomastia on September, 1985. Laboratory examinations revealed markedly high levels of LDH, AFP and HCG-beta. IVP and abdominal CT disclosed dislocation of the left kidney and the large left retroperitoneal mass. The mass was supplied by the left lumbal arteries on the aortogram. Chest X-ray film showed multiple coin lesions in the bilateral lung fields. By percutaneous needle biopsy, the histological finding of the tumor showed choriocarcinoma. No abnormal findings were found in either testicle by the physical and ultrasonic examinations. This case was diagnosed as extragonadal choriocarcinoma with lung metastasis. After 3 courses of chemotherapy (PVB regimen), resection of the retroperitoneal residual mass and lymphadenectomy were performed. Postoperatively, the chemotherapy, CISCA II - VB IV regimen, was repeated. The patient was discharged after 7 months hospitalization. Now, 35 months after operation, tumor markers, chest X-ray and abdominal CT showed no evidence of recurrence of the tumor.

博士論文, 絨毛癌細胞に対する,より効果的な加温条件を求めるため,種カの条件下でのBeWo株の細胞増殖およびβ HCG産生の変化を検討した.1.加温条件の違いによる効果について培養4日目に39℃,41℃,43℃に加温した.43℃,1時間施温時の効果は,39℃,120時間加温時と同程度でかつ41℃,24時間加温時より大きく,加温効果が43℃にて著しく増強することが明らかとなった.2.加温時期の違いによる効果について対数増殖期の4日目,5日目,6日目に43℃,1時間または3時間加温した.増殖抑制は4日目が最大で,加温開始時期が遅れるにつれて加温効果の減少が認められた.3.MTXと併用した場合の加温効果について培養4日目からMTX10^^Mを48時間添加し,加温(43℃,1時間)開始の時期は,MTX添加開始から除去後10時間までの種々の時期に設定した.その結果,併用効果はMTX添加開始後24時間から除去後4時間以内が最大であり,またβ HCGの産生は細胞増殖抑制効果の大きい穫高値を持続し,増殖抑制効果が小さくなるにつれて漸減することが示された.以上の結果,BeWoの熱感受性は43℃で急激に増大し,他の細胞株と同様の加温効果が期待できると思われる.またBeWoは対数増殖期の各時期およびMTX添加および除去後の時間により熱感受性が異たっており,細胞増殖速度の減少およびMTXによる細胞周期の変化が熱感受性の重要た因子となることをうかがわせた.また加温のみでは,β HCGの産生先進が認められなかったのに対し,MTXと併用した場合には,β HCGの産生光進が高値で持続した.これは,MTXによる効果と加温による効果が各々異なる機序により引き起こされることを示している., In order to elucidate the effect of hyperthermia, gestational choriocarcinoma cell line (BeWo) was studied with respect to cell growth and hormone (β-HCG) production in various conditions of hyperthermia. 1. BeWo was heated in the 39.0-43.0℃ temperature range on Day 4. The cell growth was reduced significantly at 43℃ for I hour. The same effect was observed at 39℃ for 120 hours. And this effect was more severe than that at 41℃ for 24 hours. 2. BeWo was heated at 43℃ on Day 4, Day 5, and Day 6 during the logarithmic growth phase. Maximum suppression of the cell growth was observed on Day 4, and the effect was reduced with the length of time that heat application was delayed. 3. MTX (10^M) was added for 48 hours beginning on Day 4, and heat (43℃ for I hour) was applied at various points during or after MTX exposure. Heat showed an adjuvant effect with MTX when heat was applied between 24 hours after administration of MTX and 4 hours after removal of MTX. These findings strongly suggest that the heat sensitivity of BeWo is greatly related to the cell cycle. Elevated HCG production was not observed following heat alone, but observed following simultaneous heat and MTX administration. To elucidate the mechanism involved here, further studies will be needed.

A case of pure choriocarcinoma of the testis in a 62-year-old male is reported. The patient consulted his family physician with an enlarged but painless right scrotal containment in November, 1980. Initial diagnosis was right hydrocele testis and chronic epididymitis, and he was treated with antibiotics. However, the tumor continued to enlarge. Right high orchiectomy was performed on March, 15, 1981 under the diagnosis of suspected right testicular tumor. The resected specimen was 10 X 7 X 6 cm and elastic hard. The cut surface was dark reddish with hemorrhagic foci. Serial sections of the entire testis were made and their histopathological examinations revealed the tumor to be a classical pure choriocarcinoma of the testis. The plasma beta-HCG level was remarkably elevated, but the alpha-fetoprotein level was normal. Anticancer chemotherapy (CDDP 125 mg, MTX 20 mg, ADM 50 mg, and EDX 500 mg) was performed in eight courses after the operation. Multiple metastatic foci were present in both lungs during the treatment, and his condition gradually deteriorated. Therefore, he was transferred to our hospital. Aggressive anticancer treatment could not be given because of his poor general condition, and he died on May, 16, 1982 of carcinomatosis. The autopsy revealed multiple nodular metastasis of the tumor to bilateral lungs, bilateral adrenal glands and right kidney. There was no metastasis to the lymph nodes. The metastatic lesions, macrospically dark reddish with hemorrhagic foci, were histopathologically pure choriocarcinoma.

絨毛癌は,化学療法に奏効する代表的疾患であり,Methotrexate(MTX), Actinomycin-D(ACD),Cyclophosphamide(CPM)の3剤同時併用療法(MAC)により,その予後は改善されてきたが,なお寛解率は60-70%にとどまっており,MACに抵抗性を示す症例の治療法の確立がいそがれるところである。そこで我々は,ヌードマウス継代難治性人絨毛癌を用い治療実験を行い,その結果を臨床応用し,難治性絨毛癌の治療法の確立をめざした。ヌードマウスは,BALB/cA,6～7週齢,雌を用い,Barrier system内にて飼育。実験腫瘍として当科で確立したCC-HM-1(HM),実験動物中央研究所より恵与を受けたCC-1-JCK(JCK)の2種類を用いた。制癌剤投与は,MTX, ACD, CPM, Vincristine(VCR)の4剤を各々1/3LD_量を用い,単独,2剤併用,3剤併用各種組み合わせにて腹腔内へ投与,腫瘍重量変化より効果を判定した。JCKに対しては,ACD+CPM (AC)及びACD+CPM+VCR(VAC),HMに対してはMTX+ACD+VCR(MOA)の腫瘍抑制効果が強く,腫瘍の消失をみたものもあった。このAC, VAC, MOAをそれぞれ臨床応用したところ,AC, VACについては,難治性絨毛癌4例中2例に寛解がえられた。MOA療法は難治性絨毛癌2例,未治療の絨毛癌3例計5例に用い,全例に寛解がみられている。MOA療法については,現在存在するMACに抵抗性を示す難治性絨毛癌症例に対する治療法として有用であることが判明した。, The remission rate of choriocarcinoma has remarkably improved by the introduction of combination MAC chemotherapy consisting of methotrexate (MTX), actinomycin D (ACD), and cyclophosphamide (CPM). However, a rational chemotherapy against choriocarcinoma has not been established and the remission rate of MAC-resistant choriocarcinoma is 60-70 % at present time. Therefore, we attempted to study using xenografted human choriocarcinoma cell lines transplanted in nude mice the most effective combin

絨毛癌の治療成績は, 有効な制癌剤の開発や, 新たな多剤併用化学療法, 積極的な手術療法, 放射線療法などによる集学的治療により, 飛躍的に向上している. さらに, 絨毛性疾患登録管理制度の普及が絨毛癌の早期発見早期治療を可能にしたということも, その一因であろう. 静岡県では, 昭和52年度より絨毛性疾患登録管理制度を実施しており, 今回, 過去12年間の登録成績に検討を加え, 併せて最近の傾向から, 今後の問題点についても触れてみた. 1) 過去12年間に, 胞状奇胎1,925例, 侵入胞状奇胎68例, 存続絨毛症70例, 絨毛癌48例が発生し登録され, その登録率は97.4%であった. 2) 登録開始初期には, 胞状奇胎は, 毎年180例前後発生していたものが, その後の出生数の減少に伴い, 最近では年間140例前後にまで減少している. また, 侵入胞状奇胎, 存続絨毛症はさほど減少していないが, 絨毛癌に限ってみれば, その発生数は明らかに減少傾向にあり, とくに最近では激減してきている. 3) 絨毛癌および臨床的絨毛癌を先行妊娠別にその年度推移について検討してみると, 登録初期には胞状奇胎後に発生した絨毛癌がその多くを占めていたが, その後の胞状奇胎後発症例の減少により, 絨毛癌は減少してきている. しかし, 胞状奇胎以外の妊娠後に発生する絨毛癌は決して減少しておらず, 最近ではその占める比率が上昇してきた. なかでも正常分娩後産褥期に発症した症例が多くみられ, 自験例によれば, 早期診断例では治療期間が短期となり, 早期発見が, その予後を左右する因子の一つであることが判明した. 以上のように絨毛癌は著減したが, 胞状奇胎を先行妊娠としない絨毛癌についてはこの登録管理制度の外にあるため, 決して減少しておらず, 早期診断に手間取る例もある. 今後, 絨毛癌の治療成績をさらに向上させるには, 正常分娩症例にも管理の目を向ける必要があろう.

In this report, two cases of metastatic renal tumor are described. The first case is a 58-year-old female who had branchiogenic carcinoma. She had found a left neck tumor, before asymptomatic macrohematuria developed. The second case is a 25-year-old female who had choriocarcinoma. She had no urological symptoms. In both cases, unilateral nephrectomy was performed. Seventy nine cases of metastatic renal tumor in survivals have already been reported.

成人睾丸精細胞性腫瘍患者110例中19例にhCG陽性例を認め, 臨床的検討をおこなった.1)セミノーマ65例中2例, 非セミノーマ45例中17例がhCG陽性であった.2) hCG陽性19例のうち絨毛癌を確認できたものは10例, 確認できなかったものは9例であった.3) hCG陽性例において原発巣と転移巣の組織型を比較したところ, 不一致例が多く睾丸腫瘍の組織診断のむつかしさを示した.4)血中hCG濃度と絨毛癌の有無については, 絨毛癌の証明されたものでは3, 000 mIU/ml以上と高値を示し, 絨毛癌の証明されなかったものは1, 000 mIU/ml以下と低値であった.5) hCG陽性例は絨毛癌組織の有無にかかわらず陰性例に比べ進行例が多いために予後が悪かった.6) hCG陽性例でも予後はstageに関係し, stage 1の予後はよく2, 3で悪い傾向がうかがえた, The outcome of clinical therapy of testis tumor presenting with positive human chorionic gonadotropin (hCG) in our hospital is reported. Of 110 patients with adult germ cell testis tumor, 19 (17.3%) had elevated hCG levels in serum or urine. Two (3.1%) of the 65 patients with seminoma and 17 (37.8%) of the 45 non-seminoma patients had positive hCG. Chorionic elements were confirmed at primary and/or metastatic sites in 10 (52.6%) of these patients, and in not a few cases different histologic features were seen at the two sites. Many patients with chorionic elements had high hCG levels (more than 3, 000 mIU/ml) in serum, while patients in whom no chorionic elements were detected had low hCG levels (below 1, 000 mIU/ml). The hCG-positive group seemed to have a poor prognosis because they were mostly in an advanced stage at their first visit to the hospital, and no difference in prognosis was found between the patients with chorionic elements and those without. The advanced group had a poor prognosis irrespective of their hCG levels.

A 24-year-old man with a large abdominal mass in addition to the left lymph node swelling was referred to our clinic. Neither testicular nodulus nor overt evidence of tumor development in the scrotal cavity was confirmed by careful palpation and testicular biopsy. Values of lactate dehydrogenase, alpha-fetoprotein, human chorionic gonadotropin (HCG) and beta-HCG in the serum were markedly elevated. The specimen removed from the left cervical lymph node demonstrated mixed type of choriocarcinoma and embryonal carcinoma. A partial response near complete remission was achieved following the VAB-6 combination therapy (cyclophosphamide, vinblastine, actinomycin D, bleomycin, cis-platinum). The patient has been in good health with normal tumor markers and abdominal CT findings.

The results of cytological examinations of two choriocarcinomas and one material of incomplete abortion are discussed about the points of differential diagnosis of these diseases. The specimens for the cytological examinations were obtained by scraping from the cut surfaces of the surgically removed materials. The smears revealed many number of abnormal cells which are distributed as scattered single cell or gathering. The abnormal cells had large and thick cytoplasm and hyperchromatic nuclei which were lobulated or multinucleated and they were diagnosed as atypical trophoblasts. In the background, there were necrotic materials and abundant red blood cells. These findings of the cytological examinations were diagnostic for choriocarcinoma. On the other hand, another smears obtained from the materials of uterine curettages also revealed hyperchromatic cells resembled to those found in choriocarcinoma. Then the patient was suspected a choriocarcinoma at first based on the results of cytological examination. However, the later histological examination of the resected uterus did not show any malignancies and the case was finalmy diagnosed as incomplete abortion. This experience lead us to the conclusion that the establishment of definite diagnosis of choriocarcinoma or abortion is difficult by a cytological examination amone., 論文

For the fundamental study of the targeting cancer chemotherapy against choriocarcinoma using the anti-human chorionic gonadotropin beta subunit (hCG beta) antibody-conjugated-liposome containing anticancer drugs, we evaluated the specific accumulation of the antibody to the choriocarcinoma tissue and the uptake of liposome by choriocarcinoma cells. In vivo, the mice bearing human choriocarcinoma were injected anti-hCG beta antibody (30 micrograms/body) and the localization of the antibody in the tumor and other mouse organs were investigated by the PAP method. The antibody specifically accumulated to the choriocarcinoma tissue within 4 hours after the injection of the antibody, and gradually increased. In vitro, cultured BeWo cells were exposed to the liposome containing adriamycin, the antibody conjugated liposome containing adriamycin or the adriamycin alone, respectively, for 2 hours. Then the uptake of the adriamycin by the tumor cells was studied under fluorescent microscopy. The nuclear accumulation of adriamycin was clearly observed in the tumor cells exposed to the liposome containing adriamycin or the antibody conjugated liposome containing adriamycin, whereas only faint cytoplasmic accumulation of the adriamycin without any nuclear accumulation was observed in the cells exposed to the adriamycin alone. These results indicate that the liposome is a good carrier of anticancer drugs for immunotargeting chemotherapy.

The results of cytological examinations of two choriocarcinomas and one material of incomplete abortion are discussed about the points of differential diagnosis of these diseases. The specimens for the cytological examinations were obtained by scraping from the cut surfaces of the surgically removed materials. The smears revealed many number of abnormal cells which are distributed as scattered single cell or gathering. The abnormal cells had large and thick cytoplasm and hyperchromatic nuclei which were lobulated or multinucleated and they were diagnosed as atypical trophoblasts. In the background, there were necrotic materials and abundant red blood cells. These findings of the cytological examinations were diagnostic for choriocarcinoma. On the other hand, another smears obtained from the materials of uterine curettages also revealed hyperchromatic cells resembled to those found in choriocarcinoma. Then the patient was suspected a choriocarcinoma at first based on the results of cytological examination. However, the later histological examination of the resected uterus did not show any malignancies and the case was finalmy diagnosed as incomplete abortion. This experience lead us to the conclusion that the establishment of definite diagnosis of choriocarcinoma or abortion is difficult by a cytological examination amone.

絨毛癌の治療成績は早期発見, 早期治療, さらに化学療法の進歩, また手術療法, 放射線療法, 免疫療法を併用した集学的治療などにより飛躍的に向上している. しかし, 手術療法に限つていえば, 転移病巣に対する手術療法の適応, 時期などの具体的取り扱いには一定の方針がないのが現状である. そこで昭和53年より昭和62年までの10年間に当科において治療した絨毛癌16症例に関して, 当科の治療成績及び絨毛癌転移病巣に対する手術療法を検討し, 一定の治療方針を求めた. 1) 絨毛癌16症例中死亡例は2例で, 14症例に寛解をみ, その寛解率は87.5%であつた. 2) Bagshawe予後スコアによる分類では high risk 9例, medium risk 5例, lowrisk 2例であった. 3) 16症例中死亡例2例を含む14症例に転移病巣を認め, そのうち10症例に症状の軽減, tumor reductionによる化学療法の効果増強, 再発防止の目的で, 化学療法併用のもと, 手術療法を施行したところ, 10例全例とも寛解し再発もみていない. 4) 16症例中死亡例2例を含む14症例に肺転移を認め, その内9症例に肺葉切除術を施行し全例寛解した. 肺葉切除術施行例の寛解までに要した化学療法平均コース数は6.0であるのに対し, 化学療法のみの5症例の平均使用コース数は9.6であった. 5) 16症例中3症例に脳転移を認め, 脳腫瘍血腫除去術施行した2症例は寛解したが, 化学療法のみで手術を行わなかった1症例は死の転帰をとった. 以上より肺, 脳転移を示す絨毛癌症例の転移病巣に対する積極的手術療法は症状軽減, tumor reductionによる化学療法の効果増強, 再発防止の三目的が明確であれば, 集学的治療の一環として有効であると思われた.