The prognostic significance of acute phase proteins in patients with inoperable squamous cell carcinoma of the bronchus.

In 95 patients with inoperable squamous cell carcinoma of the bronchus, nine potential serum "markers" were analysed for their prognostic significance. Lactate dehydrogenase, alpha 1 HS-glycoprotein, ferritin, carcino-embryonic antigen and immunoglobulin E did not prove to be useful as prognostic indices. The erythrocyte sedimentation rate and the acute phase proteins alpha 1 acid glycoprotein, C-reactive protein and prealbumin were correlated with survival. After taking the performance status and tumour stage into account, C-reactive protein still proved to be a strong prognosticator. The clinical relevance of the acute phase proteins signifying a so-called "biochemical status" next to the "clinical status" is discussed.

Catalytic and immunologic activities of placental-like alkaline phosphatase in clinical studies. The value of PLAP in follow-up of ovarian cancer.

Placental-like alkaline phosphatase (PLAP) was measured by its catalytic activity (CA), using an amplified enzyme-linked immunoassay, and by its immunologic activity (IA), using an enzyme-linked immunosorbent assay. In both assays the same monoclonal anti-PLAP antibody was used as the primary reagent. This antibody reacts with the main epitope on PLAP that is common to PLAP of ovarian and testicular origin, as well as of PLAP that is induced by smoking. Determinations of CA and IA of PLAP were carried out in serum samples from 101 patients with epithelial ovarian cancer (49 patients with progressive or recurrent disease, 52 patients with no evidence of disease), 20 patients with testicular cancer (8 non-seminoma testis, 12 seminoma testis) and 61 healthy controls. Smoking status was taken into consideration. The main findings from this study are: 1. In prolonged follow-up of patients who were treated for ovarian cancer, progressive or recurrent disease was never accompanied by rising values of CA or IA of PLAP. Therefore in this study, PLAP was not a good monitor for this disease. 2. In all instances where expression of PLAP was reflected by raised serum levels of these antigens, the measurement of the catalytic activity proved to be a more sensitive parameter than that of the immunologic activity. The value of PLAP measurements in the follow-up of patients with testicular cancer remains to be elucidated.

Biochemical markers in ovarian cancer: possibilities and limitations.

Cancer of the ovary is the commonest cause of death from gynaecological neoplasms. As ovarian tumours are relatively inaccessible, there is a great need for methods to improve early diagnosis and to assist with the management of patients with this disease. In this presentation the state of the art is discussed with regard to the usefulness of the presently recognised 'tumour antigens' and other biochemical markers in ovarian cancer. Of the oncodevelopmental antigens, only alpha fetoprotein and chorionic gonadotropin are well established as good markers in tumours with, respectively, yolk sac and trophoblastic elements. Carcinoembryonic antigen seems from our own experience to be an unreliable marker in cancer of the ovary. In epithelial tumours, which constitute the majority of ovarian malignancies, mostly serous and mucinous cystadenocarcinomas, some tumour products have been described, which may have potential as a marker, for example, ovarian cancer associated antigens, some glycoprotein glycosyltransferases, and also carcinoplacental alkaline phosphatases (CPAP). Recently, in patients with epithelial ovarian tumours attending our institute, multiple biochemical markers have been studied, including CPAP, phosphohexose isomerase, and some acute phase reactant proteins. The preliminary results which will be discussed, show that longitudinal studies of some of these markers could have clinical application in follow-up. It must be concluded that, in spite of all efforts so far, and although some markers may become useful, early detection of ovarian cancer is a goal still to be reached by clinical chemistry in the field of oncology.

Testing facility for hydrogen storage materials designed to simulate application based conditions.

For the daily use of hydrogen storage materials, not only their intrinsic storage properties are important, but also equally important is the performance under practical conditions. Besides the techniques already available for the fundamental characterization of storage materials, there is a growing need to test storage materials under conditions resembling day-to-day use. For that we developed and tested a downscaled hydrogen storage reactor with which it is possible to monitor the hydrogenation behavior under nonideal conditions. Here we present a characterization of the developed reactor setup which enables a fast screening of storage materials. For characterization and calibration purposes, we use the rather well-documented LaNi(5)-Al alloy as reference. The found experimental results agree well with the properties of LaNi(5)-Al as reported in literature. Our results show that this reactor setup enables an efficient screening of new developed storage alloys under realistic conditions and is therefore complementary to the already existing characterization setups.

The frequency of M-components in sera of patients with solid malignant neoplasms.

The frequency of M-components was studied by agar gel electrophoresis in sera from 807 patients, 467 (57%) females and 340 (43%) males with histologically proven solid malignant neoplasms.M-components were found in the sera of 40 male and 20 female patients. Apart from two known cases of multiple myeloma and one case of Waldenström's macroglobulinaemia, none of the patients were found to be suffering from these diseases. The frequency of M-components increased with age, and this was more evident in males. Twenty-two of 60 patients with M-components did not exhibit abnormalities on immunoelectrophoresis. Of the 35 remaining patients, 27 had an abnormal component of the IgG class, 6 of the IgA and 2 of the IgM class. M-components were found in the sera of patients with a wide variety of neoplasms. There appeared to be no evidence of an increased frequency of M-components in the sera of patients with solid malignant neoplasms compared with normal adult population.

Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP.

During the last 6 1/2 years, serum AFP has been determined by radioimmunoassay in 387 patients with germ cell tumors of the gonads and extragonadal sites. The histological appearances of all these neoplasms were carefully reviewed. Highly elevated levels of serum AFP were noted in patients with tumors containing endodermal sinus (yolk sac) tumor elements irrespective of the location of the neoplasm or presence or absence of metastatic disease. There was good correlation between the presence and quantity of endodermal sinus (yolk sac) tumor elements within the primary tumor or its metastases and elevated levels of serum AFP. All patients with tumors composed of pure seminoma or dysgerminoma, and teratoma, had normal serum AFP levels. Slightly elevated levels of serum AFP up to 60 ng/mg (upper limit of normal 20 ng/ml) were noted in a few patients with testicular tumors composed of pure embryonal carcinoma, whereas patients with tumors composed of or containing endodermal sinus (yolk sac) tumor elements had serum AFP levels that could be measured in 100's or 1000's of ng/ml. Serum AFP was elevated only in patients with active disease. Serum AFP was determined in 81 patients with gonadal tumors of non germ cell origin and was normal in all these patients. Serum AFP is a very good tumor marker in patients with germ cell tumors composed of or containing endodermal sinus (yolk sac) tumor, irrespective of their location. Serial serum SFP determinations can be used for diagnostic purposes, for monitoring the results of treatment, and for early detection of metastases and recurrences. Serial serum AFP determination is a useful procedure in all patients with germ cell neoplasms and is highly recommended.

Alpha-1 antitrypsin (AAT) and alphafoetoprotein (AFP) in sera of patients with germ-cell neoplasms: value as tumour markers in patients with endodermal sinus tumour (yolk sac tumour).

Serum alphafoetoprotein (AFP) and serum alpha-1 antitrypsin (AAT) were determined in 24 patients with germ-cell neoplasms of the gonads and extragonadal sites and in two patients with hepatocellular carcinoma. In the majority of the patients serial determinations were performed. All seven patients with testicular seminoma and four patients without evidence of active disease had normal levels of serum AAT and AFP. The remaining 13 patients with germ-cell neoplasms had tumours containing endodermal sinus tumour (yolk-sac tumour) elemetns. All these 13 patients had elevated levels of serum AFP and the levels were high or very high in most cases. Nine of these 13 patients had raised serum AAT, although the elevation above normal levels was only slight in a number of cases. When serial determinations were performed serum AAT levels frequently followed the pattern of serum AFP levels, but the AAT levels were frequently within normal limits and therefore the interpretation of the results was difficult, and much less reliable as compared with those for serum AFP. The elevation of serum AAT levels following the recurrence of the tumour was found to occur much later and was much less marked than elevation of serum AFP, which occurred early, showed a large rise and was a reliable marker of tumour recurrence in patients with germ-cell neoplasms containing endodermal sinus tumour elements. It is therefore considered that, although there is good evidence that serum AAT is produced by endodermal sinus tumour elements, serum AAT is not a useful monitor of disease activity in these patients, especially when compared with serum AFP, the value of which is well recognized. Serum AAT may be a useful tumour marker in patients with hepatocellular carcinoma, and this aspect should be investigated further.

Serum alphafetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk sac) tumor and mixed germ cell tumor of the ovary.

Serum AFP was determined serially by radioimmunoassay in 13 patients with ovarian germ cell tumors and in one patient with bilateral pure gonadoblastoma. There were 4 patients with pure dysgerminoma, one with pure endodermal sinus tumor (EST) and 8 with mixed germ cell tumors, all containing EST. The patients with dysgerminoma and gonadoblastoma had normal serum AFP at all times. All patients with tumors containing EST had raised serum AFP, although in most cases it was first determined between 1 and 3 weeks after operation and there was no evidence of metastases. Serum AFP became normal 5 to 7 weeks after operation and began to rise when disease recurred. Serum AFP determinations detected presence of recurrent disease long before it became detectable by other methods. Serum CEA was determined serially by radioimmunoassay in 8 of these patients, including 2 who dies with metastases, and was normal on all occasions.

Comparison of enzyme immunoassay and dextran-coated charcoal techniques for progesterone receptor determination in human breast cancer cytosols.

We have compared a new enzyme immunoassay for progesterone receptors (Abbott PgR-EIA, monoclonal) with our standard radioligand binding-assay (PgR-RBA). For both assays cytosols were freshly prepared from human breast cancer specimens that had been stored frozen for up to 1 year, and predominantly tissues were used which contained critically low amounts of progesterone receptors. A highly significant correlation was observed between the PgR-EIA and PgR-RBA (Spearman: Rs = 0.85, n = 100). Using a cut-off point of 10 fmol PgR/mg protein, 87% of the values were in accordance with each other (52% negative, and 35% positive in both assays), whereas 13% scored positive (median: 16, range 11-38 fmol PgR/mg protein) in one assay and negative (median: 7, range 0-10 fmol PgR/mg protein) in the other. Also in cytosols from human ovarian and endometrial carcinoma tissues immunoreactive PgR could be detected, and significant correlations with PgR-RBA were observed (Rs = 0.94, n = 6) for both tissues.

Biochemical aids in the monitoring of patients with ovarian cancer.

A study of possible biochemical markers of tumor recurrence and progression was made in 93 patients with ovarian cancer followed longitudinally for up to 2 years during treatment by moderate or aggressive chemotherapy regimens. A panel of potential indicators was tested; the combination of serum albumin, C-reactive protein, alpha 1-acid glycoprotein, and phosphohexose isomerase levels was found to provide information that is useful as an adjunct to the clinical assessment of patients with advanced disease. However, the system could not detect a small tumor burden. The level of beta 2-microglobulin may have value in those patients whose tumor is associated with an increase of this analyte (77%), but it would appear to reflect a large tumor mass. Serum CEA, carcino-placental alkaline phosphatase, transferrin, and prealbumin were not found to be helpful.

Alpha-foetoprotein and carcinoembryonic antigen in germ cell neoplasms.

Serum alpha-foetoprotein (AFP) and serum carcinoembryonic antigen (CEA) levels were measured, serially whenever possible, in 70 patients attending the Institute of Radiotherapy, Rotterdam, on account of testicular (65) or ovarian (4) germ cell tumours or, in one case, an endodermal sinus (yolk sac) tumour in the mediastinum. In 15 patients the disease was active; in the others it was in remission. Patients with active disease had raised serum AFP levels which correlated well with disease activity; no patient without evidence of active disease had raised serum AFP levels. None of the patients with active disease was found to have raised serum CEA levels. There was no correlation between serum AFP and CEA levels in patients with germ cell neoplasms, but good correlation between serum AFP levels and disease activity. Serum CEA levels did not correlate with disease activity, and serial determinations would therefore not be useful in monitoring progress in this group of diseases.

The value of a sensitive assay of carcino-placental alkaline phosphatase (CPAP) in the follow-up of gynecological cancers.

Using a sensitive enzyme immunoassay, carcinoplacental alkaline phosphatase (CPAP) was determined in sera of 1266 patients with gyneocological cancers. All these patients were referred after initial surgical treatment elsewhere. There were 95 patients with evidence of disease at the time of the study and 1171 without evidence of disease. Of the 95 patients with active disease, 47 were treated for ovarian carcinoma, 36 for carcinoma of the cervix and 12 for endometrial carcinoma. Raised levels of CPAP were seen in 40% of patients with ovarian carcinoma, in 22% with carcinoma of the cervix and in 41% in the small group with endometrial carcinoma. In patients without evidence of disease, raised levels of CPAP were seen in 12% of patients with carcinoma of the cervix, in 6% of endometrial carcinoma and only in 2% of patients with carcinoma of the ovary. Therefore it was considered that in the latter group CPAP studies would prove of some value. In the group of patients with carcinoma of the ovary and evidence of disease, raised levels of CPAP were seen almost exclusively in patients with epithelial tumors. It is considered that CPAP may be of value as a tumor marker in this group of patients. When compared with CEA, CPAP tends to give fewer false positives and correlates better with the presence of disease.

Delayed alloimmunisation by random single donor platelet transfusions. A randomised study to compare single donor and multiple donor platelet transfusions in cancer patients with severe thrombocytopenia.

The effects of single-donor (SD) and multiple-donor (MD) platelet transfusions in 34 cancer patients with severe thrombocytopenia and haemorrhages were compared in a randomised study. Platelet recovery values in both groups were similar after the first transfusion. After the second transfusion platelet recovery values were significantly better in those receiving SD transfusions. Platelet recovery values gradually declined with subsequent MD transfusions. These results suggest early alloimmunisation in the MD transfused patients only. MD transfusions were estimated to be no longer effective after about nine transfusions. Platelet recovery values were better indicators of early sensitisation than was the lymphocytotoxicity test. Restriction of the number of donors per transfusion may postpone the development of refractoriness to random-donor platelet transfusions in thrombocytopenic patients.