Shigeaki Kaseki

Surgical indications for resection in pulmonary metastasis of choriocarcinoma

One hundred and twenty‐two patients with choriocarcinoma were treated from 1965–1977. Pulmonary metastasis was noted in 82 of the 122 patients. In 21 cases, open thoracotomy and lobectomy were performed in conjunction with chemotherapy. Fifteen patients achieved complete remission and six patients died. It became evident that the factors with the greatest effect on the outcome of the surgical treatment are the preoperative hCG values and the extent of pulmonary metastasis. The following are the authors established criteria for the operative intervention of pulmonary metastasis of choriocarcinoma (modifying Thomfords principles): (1) The patient must be a good risk for surgical intervention. (2) That the primary malignancy is controlled, (the uterus has already been resected, or no angiographical evidence of tumor in pelvic cavity). (3) There is no evidence of metastatic disease elsewhere in the body. (4) Roentgenologic evidence of pulmonary metastasis is limited to one lung. (5) The urinary hCG value is below 1000 miU/ml.

Intracranial metastasis of choriocarcinoma. A clinicopathologic study

In an attempt to improve the diagnosis and treatment of intracranial metastases of choriocarcinoma, the authors carried out a clinicopathologic investigation of 36 patients with choriocarcinoma metastasized in the brain. Analysis on the autopsy findings of 30 cases with documented intracranial metastases of choriocarcinoma proved neurosurgical resectability in most cases. After initiation of the clinical use of dactinomycin in 1965, 5 of 10 patients in the surgically treated group, and 1 of 17 in the group without surgery, survived for more than 6 months after development of neurologic symptoms. Intracranial metastases of choriocarcinoma should be treated as follows: (1) if symptoms of increased intracranial pressure progress to a life‐threatening situation, removal of tumor or, at least, decompression should be immediately performed; (2) multidrug chemotherapy supplemented by whole‐brain irradiation should be started within several days after surgery; and (3) if symptoms are not present, chemotherapy combined with irradiation is the first treatment of choice.

Criteria of complete remission from trophoblastic neoplasia with the use of human chorionic gonadotropin (hCG) excretion pattern as a parameter

The excretion pattern of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) was observed in the urine of 77 patients with trophoblastic neoplasia, 109 with complete remission from trophoblastic neoplasia, and 94 with no trophoblastic neoplasia, when the anti‐β‐subunit hCG system radio‐immunoassay (anti‐β‐subunit RIA), which specifically measured hCG was used. The sensitivity of anti‐β‐subunit RIA was limited to urinary hCG 16 mIU/ml from the specificity of the anti‐β‐subunit serum. Luteinizing hormone in the urine of patients with complete remission and in normal menstrual, post‐menopausal, and castrated women was less than 16 mIU/ml in most cases. The excretion pattern of urinary hCG in the patients undergoing treatment for trophoblastic neoplasia was more clearly comprehended with the anti‐β‐subunit RIA as compared with the anti‐hCG RIA. The criteria for judgment of complete remission were that the hCG value dropped to less than 16 mIU/ml and that cellular response was not observed at least in the last two courses.

Histopathologic classification of uterine choriocarcinoma.

Histopathologic features of uterine choriocarcinoma were studied to establish new criteria for grading malignancy of the disease. Thirteen items of histopathologic findings concerning the degree of differentiation and the forms of masses of trophoblasts (Trs), the manner of Tr invasion, and host response of surrounding tissues were studied with relationship to prognosis in 70 patients with uterine lesions (alive, 49; dead, 21). Chi‐square test results were examined for each item in relation to prognosis of the patients. Four items were thought to have significance and were selected as criteria: (1) island formation; (2) massive proliferation of intermediate‐type Trs; (3) rectangular infiltration of Trs to surrounding muscle fibers; and (4) atypia of Trs at the end‐point of tumor invasion. A discriminant analysis was carried out (under the standardization of tumor extension and the historical staging of treatment). From the results obtained in discriminant analysis, scores were given to the four items that existed in the specimen. New criteria for grading malignancy are proposed based on scoring these four items. The algebraic sum of the scores had a possible range of +4 to −16. Patients with scores of −9 and above had a low‐grade malignancy with a mortality rate of 7%. Patients with scores of −10 and lower had a mortality of 69% and were classified as having tumors of high‐grade malignancy.

Rh-D factor in trophoblastic tumors: a possible cause of the high incidence in Asia.

thickening previously referred to as unsoftened segments in 71% of 881 pregnancies between 14 and 30 weeks’ gestation. They observed a significant change in the configuration of these segments within a 30-minute period and concluded that uterine contractions were the cause. Because the majority of amniocenteses considered difficult (more than one attempt necessary or fluid initially blood tinged) occurred in patients with a prominent uterine contraction, these authors modified their procedure by waiting for an observed contraction to relax before selecting a needle path. This case report is presented as a representative example of a phenomenon seen repeatedly in our laboratory and to indicate an approach to dealing with this problem. If the initial aspiration returns either blood or no fluid, the ultrasound sector scanner is used to assess the situation before the needle is advanced or withdrawn, the trajectory is changed, or a second amniocentesis site is selected. The unpredictable occurrence of a myometrical contraction in response to an inserted needle with a consequent shift of amniotic fluid spaces is a strong reason for performing amniocentesis in the ultrasound suite and in particular with real-time monitoring equipment available.

Sandwich-type enzyme immunoassay for human chorionic gonadotropin

We have developed a sandwich-type enzyme immunoassay for human chorionic gonadotropin (hCG), in which antibody Fab’-β-D-galactosidase complex and an antibody-immobilized silicone rubber solid phase were used. Despite the fact that this assay system cross-reacted about 40% with human luteinizing hormone (LH) that contains an immunologically very similar subunit to that of hCG, it proved to be highly sensitive with hCG measurable at levels as low as 0.3 mlU per assay tube. Using 25 μl of serum sample or 100 μl of urine sample, hCG levels in serum (10–1000 mlU/ml) or in urine (3–300 mlU/ml) could be determined with the same degree of precision as in radioimmunoassay without sample interference with the assay. The coefficients of variation in within-run, and between-run were 9.2–13.3%, and 4.2–18.8%, respectively. Values obtained with enzyme immunoassay correlate well with those of radioimmunoassay (r = 0.961, slope = 1.129, y-intercept = 3.7 mlU/ml for 35 serum samples) and hemagglutination assay (r = 0.954, slope = 0.951, y-intercept = 1.8 mlU/ml for 88 urine samples).

Operative procedure and indications for surgical management of pulmonary metastasis of choriocarcinoma.

From 1961 to 1977, thoracotomy was performed on 19 patients with pulmonary metastasis of choriocarcinoma in Nagoya University with regard to the role of thoracotomy in management of pulmonary metastasis of choriocarcinoma. Our surgical indications for the disease are: 1) the patients must be a good risk for surgical intervention. 2) The primary malignancy be controlled. 3) Evidence of pulmonary metastasis be limited to the lung. 4) The urinary human chorionic gonadotropin (hCG) titers should be controlled at low levels below 1000 mIU/ml by preoperative chemotherapy. At levels below 200 mIU/ml, the indication for surgery will be assessed by the cellular response to chemotherapeutic agents. As an operative procedure, in view of a low incidence of lymph nodes metastases, extended pulmonary surgery appears to be unnecessary providing that the gross pulmonary lesion is removed by partial resection of the lung or lobectomy. Postoperative adjuvant chemotherapy is required to induce a complete remission of the choriocarcinoma.