Yolk sac tumors and alpha-fetoprotein in first year of life.

Serum alpha-fetoprotein (AFP) levels are normally elevated in the first eight months of life. This is important information when using AFP as a tumor marker for patients in this age group. We report a case of a one-month-old boy with a yolk sac tumor of the testis. After radical orchiectomy and a negative workup for metastatic disease, his AFP level dropped, but remained mildly elevated over the normal range for six months. Using a half-life of five days it was predicted that it would fall into this range in eighty days. Although the elevated levels suggested residual tumor, they did continue to decline each month which led us to pursue some other explanation for this pattern. A literature search revealed the AFP levels are normally elevated in this age group. In retrospect, our patient's AFP was within this range less than sixty days after surgery. Dissemination of knowledge that the normal AFP ranges in young infants are higher than those in older patients will improve the clinical usefulness of AFP as a tumor marker in this age group.

Effect of gynecological operations on the serum concentration of the aminoterminal propeptide of type III procollagen.

Serum concentration of PIIINP (aminoterminal propeptide of type III procollagen), an indicator of connective tissue metabolism, is often increased in advanced gynecological carcinoma and correlates with the tumor growth. Because the healing wound also affects collagen metabolism we measured the serum PIIINP concentration in 15 patients operated on for endometrial carcinoma and in 28 patients operated on for benign gynecological diseases. Serial serum samples were collected for 35-51 days after surgery. In endometrial carcinoma, serum PIIINP level was increased in 53% of the patients before the operation. Postoperatively, the mean PIIINP concentration increased further, remaining at a pathological level throughout the study and with a peak at one week after the operation. In relative terms an abdominal operation for benign disease increased the serum PIIINP concentration as much as in endometrial carcinoma, but the mean level remained within the reference interval. After vaginal operation the increase in PIIINP concentration was not significant. The initially increased PIIINP concentration in endometrial carcinoma is probably caused by the effects of the malignancy on collagen metabolism. Because the relative response of PIIINP to abdominal operation was similar in both groups, the PIIINP response to surgical trauma in patients with malignant disease seems to depend only on the extent of the operation. In this group the transient increase in serum PIIINP concentration does not prevent the use of PIIINP as a tumor marker, since the follow-up examinations for malignancy do not start earlier than two months after operation.

[Case observations on the significance of early pregnancy factor as a tumor marker]. / Kasuistische Betrachtungen zur Bedeutung des Early Pregnancy Factor (EPF) als Tumormarker.

At three patients who have been operated on because of completely different tumours (trophoblast tumour, endodermalsinus tumour of the right ovary and rhabdomyosarcoma as well as adrenal cortex carcinoma) pre-operatively the Early Pregnancy Factor (EPF) could in each case be shown in the serum with the help of the rosette inhibition test. In two cases the EPF already intra-operatively disappeared from the serum. In the third case it could be found until the second day after operation. Since that patient suffered from two histogenetically non-related malignant tumours it was not possible to trace whether the adrenal cortex carcinoma or the rhabdomyosarcoma have been the reason for the EPF-synthesis. The already intra-operative disappearance and the also during further post-operative controls unsuccessful proof of EPF in serum can indicate an opportunity for the early assessment of efficiency of the surgical treatment of tumours which develop EPF or which induce the EPF-synthesis.

Endodermal sinus tumor of the ovary during pregnancy: a case report.

Serum alpha-fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24-year-old female in week 17 of pregnancy. After surgery, chemotherapy was postponed. In week 28 levels of serum alpha-fetoprotein increased, but delivery was delayed until 33 weeks' gestation. After delivery, the patient received four chemotherapy courses (cisplatin, etoposide, and bleomycin). Mother (24 months after last chemotherapy) and child are doing well.

Serum alpha-fetoprotein subfractions identified by Ricinus communis agglutinin I in hepatic malignancies, yolk sac tumor, benign hepatic diseases, and fetal stage.

Using Ricinus communis agglutinin I (RCA-I) affinity crossed-line immunoelectrophoresis, alpha-fetoprotein (AFP) subfractions were studied in sera from patients with primary hepatic cancer (PHC), hepatic metastasis of gastric cancer (HMGC), yolk sac tumor (YST), acute or chronic hepatitis or hepatic cirrhosis. Fetal AFP subfractions were also examined in amniotic fluids or in culture fluids of fetal tissues. RCA-I non-reactive subfraction was commonly found in PHC, HMGC, YST, benign hepatic diseases, and fetal stage. RCA-I weakly reactive (WR) or strongly reactive (SR) subfraction was noted only in malignant diseases. RCA-I has a specific affinity to terminal galactose in oligosaccharide, and the presence of sialic acid on galactose residue(s) inhibits the affinity with RCA-I. Therefore, common AFP subfraction non-reactive with RCA-I was assumed to be galactosialyl form, while RCA-I WR and SR subfractions found only in malignancies were monogalactosyl and digalactosyl, respectively. Clinically this approach to detect the RCA-I WR or SR subfraction facilitates a differential diagnosis of AFP-producing malignancies and benign conditions.

[An early combined endodermal sinus tumor of the ovary that was diagnosed due to torsion of serous cystadenoma--a case report].

Reported is a rare case of a 2.5cm endodermal sinus tumor (EST) that was included within a 11 x 10.5 cm serous cystadenoma. A 24-year-old female suddenly complained of abdominal pain caused by having undergone an intestinal torsion of a left ovarian tumor. After a unilateral salpingo-oophorectomy the serum AFP was 219.8 ng/ml. The patient then received two cycles of cis-platinum, vinblastine and bleomycin combination chemotherapy. After one cycle, the serum AFP decreased to a normal level and the woman has remained free of disease 6 months after the discovery of her tumor. In this case, fortunately, this torsion of a serous cystadenoma enabled us to find the EST at a very early stage.

[Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for sialyl TN antigen: (2). Evaluation of clinical significance. STN Study Group].

The clinical significance of serum sialyl Tn antigen as a tumor marker was evaluated using "STN Otsuka" kits. Results indicated that the antigen was frequently elevated in sera from patients with ovarian cancers (43.1%, 140/325), including serous cystadenocarcinoma (51.6%, 63/122), mucinous cystadenocarcinoma (55.6%, 30/54), endometrioid carcinoma (56.5%, 13/23), and mesonephroid carcinoma (40.0%, 6/15). The positive frequency of sialyl Tn antigen in patients with ovarian carcinoma was less than the frequency of CA 125 (75.5%, 194/257) or sialyl SSEA-1 (47.2% 83/176). However, the false positive rate of sialyl Tn antigen in patients with benign gynecological disorders (3.7%, 15/401) was much lower than the false positive rates of other antigens; such as CA 125 (48.4%, 155/320) and sialyl SSEA-1 (19.2%, 51/266). The serum level of sialyl Tn antigen reflected the clinical activity of the disease quite well in patients with ovarian cancers. The sialyl Tn antigen was concluded to be a useful serum tumor marker for ovarian cancers.

Second-look laparotomy in endodermal sinus tumor: a report of two patients with normal levels of alpha-fetoprotein and residual tumor at reexploration.

The role of second-look laparotomy in the management of patients with endodermal sinus tumor of the ovary is controversial. We report two women who converted to a normal alpha-fetoprotein (AFP) level during treatment with combination chemotherapy, yet were found to have residual endodermal sinus tumor at second-look laparotomy. In view of the limited experience with this rare disease, we continue to recommend second-look laparotomy for patients who have completed chemotherapy for endodermal sinus tumor of the ovary, regardless of the serum AFP level.

An improved sensitive assay method for the heterogeneity of alpha-foetoprotein: possible application for early differential diagnosis.

A combination of lectin-affinity electrophoresis and antibody-affinity blotting was used for the qualitative determination of molecular species of alpha-foetoprotein. Concanavalin A and erythrophytohaemagglutinin were used as lectins. This method was able to quickly discriminate between the molecular species of alpha-foetoprotein of recurrent ovarian yolk sac tumour and those of non-malignant liver diseases and cord sera at term, using only 3 microliters of sera containing 200 micrograms/l of alpha-foetoprotein. The results indicate that this assay method might be useful for the differential diagnosis of recurrent yolk sac tumour from drug- or blood transfusion-induced liver diseases and for the monitoring of the serum alpha-foetoprotein level of patients with yolk sac tumour producing less than 200 micrograms/l of alpha-foetoprotein.

Analysis of lectin affinity immunoelectrophoretic profiles of serum alpha-fetoprotein from patients with yolk sac tumors and carcinomas of the gastrointestinal tract: correlations with molecular structures.

Profiles of concanavalin A (Con A) and lentil agglutinin (LCH) affinity immunoelectrophoresis were compared for serum alpha-fetoprotein (AFP) from patients with yolk sac tumors and carcinomas of the gastrointestinal tract, in order to find some correlations between peaks of AFP subfractions detectable by two different lectins, and to investigate whether or not it is possible to prove that the binding of AFP to LCH is weakened to some extent if a fucosylated sugar chain has, in addition, a bisect N-acetylglucosamine (GlcNAc) attached to the beta-linked mannose. The results obtained with our improved techniques tend to indicate that a Con A-reactive AFP subfraction (peak a) corresponds to an LCH strongly reactive AFP (peak A), while a Con A-nonreactive AFP (peak b) corresponds to an LCH weakly reactive AFP (peak B). the authors consider the present data sufficient to support the above explanation.

The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumour activity.

The therapeutic antitumour activity and host toxicity of cis-platin (CDDP), which was administered with selenium (sodium selenite) was studied on the growth of a human yolk sac tumour grown in nude mice. Treatment consisted of CDDP single agent chemotherapy (3 weeks) or preliminary PVB combination chemotherapy (CDDP + vinblastine + bleomycin, 2 weeks). Selenium was co-administered from day 1 to 5 with each therapeutic regimen. The administration of CDDP alone caused significant reduction in tumour burden but at higher doses there was significant host toxicity. The co-administration of selenium together with CDDP (CDDP: selenium, molar ratio = 3.5:1) did not affect the anti-tumour activity of CDDP but it did cause a decrease of parameters of host toxicity including lethality, increasing the 50% lethal dose (LD50) from 9.3 mg kg-1 to 17.5 mg kg-1. The parameters of host toxicity which were altered by selenium co-administration were nephrotoxicity, myeloid suppression and weight loss. Our study suggested that selenium co-administration allows higher doses of CDDP with reduction of apparent toxicity, resulting in a higher therapeutic index and possibly indicating a potential increase in the utilization of CDDP in clinical cancer chemotherapy.

Ataxia-telangiectasia and endodermal sinus tumor of the ovary: report of a case.

Ataxia-telangiectasia, an inherited disorder characterized by progressive cerebellar ataxia and telangiectasias, is often associated with primary immunodeficiency and high incidence of malignancies, mostly of the lymphoreticular type. Endodermal sinus tumor is a rare germ cell tumor of the ovary characterized by an extremely rapid growth and poor prognosis. Both these diseases are associated with an abnormal production of alpha-fetoprotein. Primary tumors of the ovary in patients with ataxia-telangiectasia are extremely rare and the association of an endodermal sinus tumor and ataxia-telangiectasia has never been reported in the literature. This case report serves to focus on the particular problems encountered in the diagnosis and management of two diseases both characterized by the same serum marker.

Successful treatment of pure endodermal sinus tumors in adult men.

Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.

Half-life of alpha-fetoprotein in patients with a teratoma, endodermal sinus tumor, or hepatoblastoma.

To evaluate the AFP-concentration postoperatively and/or during chemotherapy treatment, a retrospective study was carried out on 14 patients with a teratoma, endodermal sinus tumor (EST), or hepatoblastoma. Eleven patients were operated. Eight of the 11 patients showed postoperatively a linear decline in their AFP concentration. The half-life was about 6 days. In the group of patients that underwent a noncomplete resection, both a linear and a nonlinear declining pattern was seen. The patients that underwent a complete resection showed only a linear decline in the AFP concentration. No relationship was found between the reduction pattern of the AFP and the development of recurrences. The development of a recurrence was accompanied by an increasing AFP concentration.

[Clinical observation of twelve cases of testicular cancer].

Twelve cases of testicular cancer were treated at our Department of Urology between 1984 and 1985. The mean age of the patients was 35.2 years old. Eight of them were pure seminoma in histology, other cases were non-seminomatous germ cell tumors (NSGT). Seven cases were of stage I testicular cancer, 3 cases were of stage IIA, and 2 cases were of stage IIB. Patients with stages I and IIA seminoma were given radiation to the ipsilateral iliac and bilateral paraaortic caval nodes to the crura of the diaphragma. Two patients with stage IIB seminoma were treated with PVB therapy and retroperitoneal lymph node resection. Chemotherapy containing CDDP was effective to reduce the tumor size. Two cases were of stage I NSGT, one case was treated with high orchiectomy only, and the other case was treated with chemotherapy after high orchiectomy. Chemotherapy and retroperitoneal lymph node resection were given to two patients with stage IIA NSGT. Abnormally elevated values of lactate dehydrogenase were observed in cases with a primary tumors weight larger than about 100 g. Six of the 8 cases of pure seminoma had slightly elevated beta-human chorionic gonadotropin levels. Two cases with bilateral testicular cancer were found among the 12 cases so that necessity of meticulous palpation of remaining testis was felt. Recurrent change was not observed in any of the 12 cases so that testicular cancer is considered to be an almost curable disease.

[Histopathology of testicular germ cell tumors].

The most common type of testicular tumor is the germ cell tumor, which shows peculiar histological and biological features. The histopathology of germ cell tumors of the testis is illustrated here according to the WHO classification except for extremely rare polyembryoma and teratoma with malignant transformation. The tumors are divided roughly into 2 groups, one histological type including seminoma, spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma and teratoma, and more than one histological type including many possible combinations of one histological type. Seminoma and spermatocytic seminoma show some similar features to the germ cell line, while embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma show differentiation toward a variety of structures appearing at any stage of embryogenesis instead of the original testicular tissue. The histology of the metastatic disease may or may not be the same as that of the primary lesion. The reasons for the occurrence of histological differences between primary and metastatic tumors is discussed. Two major tumor markers of the germ cell tumor, HCG and AFP, are analyzed using immunohistochemical procedure, and the significance of immunostaining for these markers in clinicopathological study is stressed.

Affinity chromatography used in distinguishing alpha-fetoprotein in serum from patients with tumors of hepatic parenchyma and of germ cells.

We used affinity chromatography on concanavalin A Sepharose to study the serum alpha-fetoprotein of 10 patients with histologically proven germ-cell tumors and 12 patients with primary liver cancer. Less than 50% of the fetoprotein from germ-cell tumors bound to concanavalin A, as compared with more than 80% of the alpha-fetoprotein from primary liver cancers.

[Modified VAB-3 combination chemotherapy of stage IV endodermal sinus tumor of the ovary].

A case of pure endodermal sinus tumor (EST) of the ovary with huge multiple liver metastases was treated with modified VAB-3 protocol. Serum alpha-fetoprotein (AFP) before treatment was 137,775 ng/ml. A complete clinical response was achieved with rapid shrinkage of liver metastases and normalization of serum AFP. Second-look laparotomy preformed 17 months after the start of chemotherapy revealed no evidence of disease. VAB-3 combination chemotherapy, which was proved to be very effective in the treatment of metastatic testicular cancer, also seems to be effective in the treatment of advanced EST of the ovary. This is believed to be the first detailed report of the successful management of advanced EST of the ovary.

Endodermal sinus tumour of the ovary: serum alpha fetoprotein dynamics and immunohistochemical localization of marker in tumour tissue.

The apparent successful treatment of endodermal sinus tumour of ovary is reported. The patient, after surgery and adjuvant chemotherapy, has remained in remission, and the serum alpha fetoprotein has been less than 10 micrograms/1 over a period of 9 months.