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A 73-year-old male presented with melena and severe anemia. An esophagogastroduodenoscopy(EGD)and colonoscopy( CS)revealed no source of hemorrhage. Multiple small intestinal tumors were observed on abdominal ultrasound(US). CT also showed mesenteric lymph node metastases and multiple lung and liver metastases. Since active bleeding was suspected, we performed an emergency surgery. The small intestine including 2 tumors and 2 mesenteric lymph node metastases were resected. On histopathological examination, choriocarcinoma was diagnosed. The blood hCG level was remarkably elevated. The primary lesion could not be detected. Chemotherapy containing cisplatin(CDDP)and irinotecan(CPT-11)was initiated; although the blood hCG level was temporally lowered, the patient died of liver failure 8 months after the surgery.

Case: A 32 year-old man was diagnosed with retroperitoneal choriocarcinoma with metastasis to the lungs and liver. One cycle of modified BEP regimen did not sufficiently decrease the hCG. Therefore, we chose the GETUG 13 protocol of dose dense chemotherapy. After 6 days of cisplatin administration(3 cycles), he was diagnosed with acute hyperuricemia and kidney injury. He was treated with intravenous hydration and rasburicase. The hyperuricemia improved after a few days.

A 62-year-old man was admitted to our hospital because of appetite loss. Computed tomography(CT)revealed thickness of the gastric wall, multiple liver tumors, and lung nodes. Upper gastrointestinal endoscopy revealed an easy bleeding type 2 tumor at the gastric antrum. We performed distal gastrectomy to control bleeding from the gastric tumor. Histological findings from the gastric lesion indicated primary gastric choriocarcinoma(PCG). Combination chemotherapy using hepatic arterial infusion chemotherapy for synchronous liver metastases and S-1 was administered for 5 months after the operation. CT revealed that the liver metastases decreased remarkably. On the other hand, lung metastases increased. Irinotecan and cisplatin were administered. Liver metastases did not increase, as observed using imaging studies. The patient died 17 months after the operation for cachexia. PCG is a highly aggressive tumor that is often associated with liver metastasis. It is important to control liver metastasis from PCG.

We experienced a case of primary gastric choriocarcinoma(PGC)treated by curative operation after neoadjuvant chemotherapy with S-1/CDDP. Gastric endoscopy was carried out on this 43-year-old woman with epigastric discomfort and revealed an ulcerative lesion in her stomach. Choriocarcinoma in the gastric lesion was pathologically shown by endoscopic biopsy, so we diagnosed the patient without another primary lesion as PGC. The patient was initially treated by five courses of neoadjuvant chemotherapy with S-1/CDDP due to the metastases of Virchow and intraabdominal lymph nodes, and then a curative operation could be performed because of disappearance of the lymph node metastases by neoadjuvant chemotherapy. The patient was continuously treated by S-1 after gastrectomy but was dead due to the multiple metastases of the liver and adrenals, and the multiple recurrences of lymph nodes four months after the surgery. Further therapeutic strategy by chemotherapies against PGC is needed to ameliorate the prognosis.

A 53-year-old woman with choriocarcinoma (high-risk gestational trophoblastic disease: FIGO score 17) was treated with paclitaxel (175 mg/m(2)) and carboplatin (AUC=5). The patient was treated with an EMA/CO regimen as initial chemotherapy, but she developed EMA/CO-induced interstitial lung disease after the 3rd course of treatment. After high-dose steroid therapy, she received combination chemotherapy with paclitaxel and carboplatin. Her hCG-/b dropped to <0.1 ng/mL after 11 courses of the chemotherapy. A paclitaxel+carboplatin regimen is potentially effective for high-risk GTD, but a more effective combination or schedule with a platinum-taxane regimen should be explored.

The success of choriocarcinoma treatment in Japan is over 90% at the present time. As for the first contribution, chemotherapeutic progress contributed to this success greatly. The next contribution is establishment of the registration system of administration of the hydatidiform mole patients, since the course of choriocarcinoma in most cases is hydatidiform mole --> invasive mole --> choriocarcinoma. When treatment is begun by preventive measures for benign tumors at the very onset of the invasive hydatidiform mole, there are fewer choriocarcinoma onsets. Moreover, discovery of choriocarcinoma in the initial stages contributes to a better prognosis. However, following abortion or normal childbirth, different measures may be necessary. No problems were found with patients once treated for invasive hydatidiform mole in connection with current problems involving post-treatment pregnancy or delivery. However, in cases of pregnancy or abortion after choriocarcinoma treatment done with multi-cancer agents strongly, heart malformations are seen in some newborns, and how to preserve egg cells may pose a problem at the time of anti-cancer agent administration.

A 25-year-old man who suffered from cough, sputum, and swelling of left scrotal contents was admitted to our hospital. We found testicular choriocarcinoma with multiple lung, liver, and brain metastases. The patient received 5 courses of VIP therapy (cisplatin, etoposide, ifosfamide) and 1 course of high-dose chemotherapy (carboplatin, etoposide, cyclophospamide) with peripheral blood stem cell transplantation. One year later, the patient underwent surgery for resection of lung metastasis after 1 course of chemotherapy (cisplatin, etoposide). Pathological diagnosis showed a remnant of choriocarcinoma. Three years and three months after surgery, no recurrence of the choriocarcinoma has been found.

A 32-year-old woman, gravida 4, para 2, visited Teikyo University Hospital with complaints of abnormal uterine bleeding and lower abdominal pain. Urine hCG level was 1,024 x 10(3) IU/l. MRI examination showed a vascular, rich solid mass 10 cm in diameter at the posterior region of the uterus. Under the clinical diagnosis of choriocarcinoma, she underwent total hysterectomy with right salpingooophorectomy. The ovarian choriocarcinoma was confirmed by pathologic examination. Additional chemotherapy was planned using the combined regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovin. After 2 min of etoposide administration (100 mg/m2), the patient complained of acute dyspnea, which was caused by bronchospasms and cutaneous flushing. Etoposide infusion was immediately stopped, and anti-anaphylaxic treatment was done by administering hydroxyzine hydrochloride. Five min after the episode had occurred, the patient recovered. This episode was thought to have been induced by etoposide, but etoposide was a key agent for choriocarcinoma. Thus, we devised a modified chemotherapy using etoposide as follows. The regimen was hydrocortisone 100 mg i.v. q6 h and promethazine hydrochloride 50 mg i.m. q6 h for 24 h before infusion of etoposide. The etoposide concentration was diluted to 50%, and the drug administration rate reduced by half. With the modified regimen, the patient showed no anaphylaxic symptoms. The few reports on anaphylaxic reactions to chemotherapeutic agents induced by side effects must be taken into account when we use these drugs.

Four cases with non-seminomatous testicular tumor in stage III completed chemotherapy with POMB/ACE. Of these 4 cases, metastasis to retroperitoneal lymph nodes was found in all of them. In addition, metastasis to the lung was noted in 3, and to the left supraclavicular lymph nodes in one. After orchiectomy, 5 courses of POMB/ACE therapy were given to each of the 4 cases. Tumor marker returned to normal value in all of the cases after 3-4 courses of treatment, with disappearance of metastasis to the lung and supraclavicular lymph nodes. However, the response rate in metastasis to retroperitoneal lymph nodes was CR in one case, and PR in 3. Therefore, retroperitoneal lymph nodes were excised in all 3 cases. Histologically, 2 of the 3 were found to have necrotic tissues. The remaining one patient had teratoma. An additional 1-3 courses of POMB/ACE therapy were given to these 3 cases. These 4 cases are alive without recurrence 6 years and 4 months, 5 years and 8 months, 4 years and 9 months, and 2 years 9 months, respectively, after orchiectomy. Thus POMB/ACE therapy is considered to be a useful method in the treatment of advanced testicular tumor.

A twenty-six-year-old male patient with advanced choriocarcinoma originated from mediastinum was treated by high-dose chemotherapy with peripheral blood stem cell (PBSC) transplantation. He had massive tumors in the cervical, mediastinal and bilateral lung fields. After 3 kur of PVeBV therapy (CDDP 60 mg x day 1-3, etoposide 160 mg x day 1-3, BLM 30 mg x day 1, VBL 12 mg x day 1), he obtained complete remission. PBSC was collected at the time of hematopoietic recovery and high-dose chemotherapy with PBSC transplantation was conducted because of the high possibility of recurrence. The hematopoietic recovery was rapid, and the patient remained well with no sign of recurrence for 24 months.

A 27-year-old female was admitted to Sendai National Hospital complaining of continuous slight genital bleeding for about one and a half year after incomplete abortion. At first visit, urinary hCG was elevated to 32,000 IU/l and ultrasonography revealed a heterogeneous tumor in the uterus body. After abdominal simple total hysterectomy, the sample was diagnosed pathologically as a uterine choriocarcinoma. The patient was treated with 2 courses of MTX, but this regimen was not so effective. Because of persistent elevation of urinary hCG, 2 courses of etoposide were performed and hCG was rapidly reduced to within LH level. Etoposide (25 mg/day per os) was given to the patient for about three months since hospitalization and now complete remission has been obtained.

The choriocarcinoma was one of the most curable malignant neoplasms. This is chiefly because the effective chemotherapy was introduced and the sensitivity of hCG was improved. But about 10-20% cases with choriocarcinoma were drug resistant or recurrent cases. And now, the treatment of these refractory choriocarcinomas were one of the most important clinical problems. We describe a new combination chemotherapy for these refractory choriocarcinomas in this paper. This high dose 5-FU + Act-D protocol was effective for drug resistant cases with MEA protocol.

Methylprednisolone was given to 8 patients receiving CDDP-containing chemotherapy. Of 8 patients, 7 patients achieved complete relief of nausea and emesis and 1 patient obtained partial elimination of symptoms. All these patients had consistent history of severe nausea and emesis before the methylpredisolone trial. At present, a potential effect of methylprednisolone on chemotherapy has not been known. In a case of testicular cancer the titer of tumor markers decreased straight on a table of logarithms.

Recent advances in intensive care procedures have improved the therapeutic results of choriocarcinoma treatment. The mortality of patients with choriocarcinoma, which was 100% in 1958, has gradually decreased, and finally fell to about 10% in 1983. These favorable results have been mainly due to the progress made in chemotherapy, including combined administration of methotrexate and actinomycin-D. However, recent progress has been chiefly dependent on intensive care procedures, involving so-called multidisciplinary treatment, including surgical treatment for pulmonary or intracranial metastatic foci and whole-brain irradiation. When the treatment results for choriocarcinoma were compared between metastatic and non-metastatic cases, the mortality, which had decreased for both groups with time, had already reached 0% in non-metastatic cases, although it was still about 20% in metastatic cases. These results have made it clear that the most important aspect is how to treat choriocarcinoma metastatic foci. With the goal of finding some form of treatment that will help to attain complete cure of choriocarcinoma, we present here details of recent progress made in choriocarcinoma treatment.

The combination chemotherapy consisting of methotrexate (MTX), actinomycin D (ACD), and an alkylating agent was applied to the high risk patients refractory to MTX and/or ACD. The remission rate of the high risk group was about 70% and that of low risk patients was 100%. It is important to seek an effective chemotherapy for patients refractory to the above combined chemotherapy; therefore, we tried out the following regimens: (1) Quadritherapy with MTX, ACD, CPM and vincristine; (2) CHAMOMA protocol; (3) cis-platinum, bleomycin and vinblastine therapy; (4) ultra high dose MTX therapy and (5) the combination chemotherapy without MTX. The last regimen was designed based on the experimental data chemotherapy using nude mice.

Advances in the management of gestational trophoblastic tumor have been made during the last three decades. Individualization of the therapy is one of the major advances. A number of risk factors has proved to predict accurately the prognosis of each patient. A few systems were currently in use, but difficult in putting them to practical use in the different geographical areas. At National Taiwan University Hospital from 1965 to 1979, 65 patients treated by chemotherapy were analyzed with respect of various prognostic factors. The score was assigned according to the mortality rate of each item to each prognostic factor, and thus established a scoring system which is suitable for the use in Taiwan. After establishment of our scoring system, 51 patients from 1980 to 1986 were treated according to the system and the appropriate therapeutic regimens. The outcome of these patients and toxicity of the different therapeutic regimens are presented.

A case of choriocarcinoma responding well to cis-diamminedichloroplatinum (CDDP) was reported. A 24-year-old male was admitted to our hospital with chief complaints of upper abdominal discomfort and gynecomastia. Physical findings on admission included solid tumors in the upper abdomen and bilateral inguinal regions. The chest X-ray picture showed numerous coin lesions, and abdominal ultrasound examination revealed a widespread metastasis in the retroperitoneum. Blood chemical analysis pointed out the high levels of LH, HCG, and beta-subunit of HCG. The pathological diagnosis of the biopsied inguinal mass was choriocarcinoma. The patient was treated with CDDP, vincristine and bleomycin according to the protocol of Einhorn. After three courses of this therapy, serum HCG level was normalized and pulmonary metastatic lesions were diminished, although abdominal ultrasound examination showed remnants of the decreased tumor masses. The patient was transferred to the urological department for further cytoreductive therapy.

The patient was a 26-year-old male. He was admitted to our hospital with a chief complaint of hemoptysis, cough and left scrotal mass on May 9,1984. Chest X-ray film, LAG and CT revealed multiple lung, lymph node and cerebral metastases. Based on a diagnosis of testicular neoplasm, orchiectomy was performed on May 14,1984. PVB chemotherapy (Cis-diamminedichloro-platinum, Vinblastine and Pepleomycin) was administered. Because he got worse, however, he was treated with another combination chemotherapy, consisting of Methotrexate (MTX, 100 mg/m2 intravenous push (i.v.), 200 mg/m2 12-h infusion, day 1. The dose of MTX was increased with each course. Maximum dose of MTX was 900 mg/m2/day), Vincristine (1.0 mg/m2 i.v. day 1.) Actinomycin D (10 micrograms/kg i.v. days 3.4.5), Cyclophosphamide (600 mg/m2 i.v. day 3.), Adriamycin (30 mg/m2 i.v. day 8.) and Melphalan (6 mg/m2 p.o. day 8.). After 6 courses of this regimen, distant metastases disappeared or were reduced to under one tenth, and complete remission was obtained without severe side effects. The patient was in good health on March 30, 1985.

The patient was a 29 years old male. He was attended to our hospital with a chief complaint of a right scrotal mass on August 20, 1983. Based on the diagnosis of testicular neoplasm, orchiectomy was performed on September 7, 1983. After surgery, the patients, HCG and alpha-fetoprotein (AFP) values of still remained high. Pathological diagnosis was mixed tumor (choriocarcinoma, Embryonal carcinoma, and malignant cystic teratoma). From September 22, VAB-4 combination therapy was performed and complete remission was obtained without severe side effects. The patient was in good health with normal HCG and AFP values on January 20, 1984.