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Background and Objective: We have previously reported elevated serum immunoreactive inhibin (INH) levels in patients with ovarian malignancies, particularly granulosa cell and mucinous tumours. The present study was designed to compare INH measurements using a heterologous radioimmunoassay with cross-reactivity for inhibin alpha-subunit derived peptides with measurements obtained using a new ELISA specific for dimeric inhibin-A. It was hypothesized that granulosa cell tumours may secrete significant quantities of inhibin-A whereas mucinous tumours were unlikely to do so because of the lack of a relation between INH and FSH measurements in the latter group., Design: Serum samples obtained from women found to have ovarian cancer were assayed using the heterologous radioimmunoassay (the Monash assay) and using an ELISA specific for dimeric inhibin (the Groome assay) and the results were compared., Patients: Samples for assay were available from 69 normal post-menopausal control women, 12 patients with mucinous tumours of the ovary, 26 with serous tumours, 7 with granulosa cell tumours and 8 with various other ovarian tumours. Patients were post-menopausal or had been subjected to bilateral oophorectomy at the time these samples were collected., Measurements: The Monash and Groome assays were carried out as described previously. The upper limit of normal for post-menopausal women in the Monash assay was 122 U/l and for the Groome assay was calculated to be 32 ng/l., Results: Among the 69 normal subjects, 4 were found to have elevated inhibin levels using the Monash RIA (133-190 U/l) and 4 were found to have elevated levels in the Groome ELISA (45.5-55.3 ng/l). Among 12 patients with mucinous tumours, 10 (83%) had elevated inhibin levels using the Monash assay but only 3 (25%) had elevated levels with the Groome assay (P < 0.005). Among 26 with serous tumours, 15 (58%) had elevated levels in the Monash assay but only 1 (4%) in the Groome assay (P < 0.001). Among 7 samples from patients with granulosa cell tumours, 100% were elevated in the Monash assay and 71% in the Groome assay (NS, non-significant). In a miscellaneous group of tumours all 8 had elevated levels in the Monash assay and 2 in the Groome assay (P < 0.001)., Conclusions: It was concluded that in normal postmenopausal subjects, INH is generally undetectable or present at low levels, consistent with the loss of ovarian function. The majority of granulosa cell tumours appear to secrete significant amounts of dimeric inhibin-A, whereas mucinous tumours secrete predominantly other forms of INH, presumably related to the alpha-subunit. Serous tumours may also secrete inhibin-related peptides but not dimeric inhibin-A. The nature of the inhibin related peptides produced by epithelial ovarian cancers remains to be characterized.

In 180 patients with epithelial ovarian cancer and 214 women with benign pelvic pathologies, serum levels of TATI (cut-off point 21 ng ml-1) and CA 125 (cut-off point 35 U ml-1) were determined. Data were correlated with tumour stage, histological type and tumour grade. Overall, when used as a single marker, TATI showed a sensitivity of 63% and a specificity of 72%, whereas the sensitivity and specificity of CA 125 > 35 U ml-1 were 80% and 82% respectively. A combination of the two markers increased the sensitivity to 91% (TATI > 21 ng ml-1 or CA 125 > 35 U ml-1), whereas the specificity decreased to 65%. TATI was clearly superior in diagnosing mucinous carinomata of the ovaries; the rate of true positive findings was 64% versus 50% for CA 125. Unlike CA 125, TATI levels correlated well with tumour grade. In conclusion, CA 125 remains the single tumour marker of choice in the diagnosis of malignant epithelial ovarian cancer, while TATI appears to be a valuable complementory marker with a higher sensitivity in cases of poorly differentiated and mucinous carcinomata.

Overexpression of the c-erbB-2 proto-oncogene has been shown to correlate with relapse and poor prognosis in adenocarcinomas of the breast and stomach. In pancreatic cancer, c-erbB-2 overexpression has been demonstrated using immunohistochemistry, but the relationship between serum c-erbB-2 level and clinical data has not been fully evaluated. In this study, serum c-erbB-2 protein levels were measured in 100 patients with pancreatic adenocarcinomas and in 9 patients with mucin-producing tumors. Immunohistochemical studies for c-erbB-2 protein were performed in 36 patients and 4.0 U/ml in healthy controls (p < 0.001). The positive rate for serum c-erbB-2 was 34% (37/109) in patients with pancreatic cancer and 0% (0/66) in patients with gallstones and in healthy controls (p < 0.001). Immunohistochemical study disclosed that the positive staining rate was 28% (8/29) in common ductal adenocarcinoma specimens, 43% (3/7) in metastasis specimens, and 75% (3/4) in mucin-producing tumor specimens. Clinical evaluation revealed that 59% (22/37) of serum c-erbB-2-positive patients and 33% (24/72) of negative patients had liver or peritoneal metastases (p < 0.01). The mean survival time was 154 days in the c-erbB-2-positive group and 220 days in the negative group (p < 0.05). We suppose that c-erbB-2 is related to metastasis and progression of the disease in patients with advanced pancreatic cancer.

Proteolytic enzymes could be very important in spread of cancer, but the role of the body's natural inhibitors of these enzymes in this process is unknown. One such inhibitor is the serum glycoprotein, alpha-1-proteinase inhibitor (API). In previous studies we showed that the fucose-specific lectin, lotus tetragonolobus, extracted high amounts of API in cancer when patients were unresponsive to treatment. The aim of this study was to determine whether the carbohydrate structure of API is altered in cancer. API was isolated from the sera of healthy women and women with breast or ovarian cancer. By means of high-performance anion-exchange chromatography, cancer API was shown to contain more fucose and less N-acetylglucosamine than healthy API. Further investigation of the purified specimens using a lectin-binding assay suggested that the cancer API was less branched and contained more alpha 2-6 and less alpha 2-3 sialic acid. Observations from both methods were consistent with an increase in bi-antennary chains terminating in alpha 2-6 sialic acid and possibly more alpha 1-6 fucose in the core of the unit. These distinctive changes could have important consequences for the function of API in cancer and may help to develop more precise markers for monitoring pathological progression in this disease.

We compared the tumour marker CA 72-4 and the new markers CASA and CYFRA 21-1 with the established marker CA 125II in follow-up care and control of efficacy of treatment in ovarian cancer in order to determine whether there are differences in recognizing ovarian carcinomas of different histological type. The investigation was done retrospectively on serum samples frozen at -80 degrees C obtained from 262 subjects, among them 50 healthy women, 53 sera with benign gynecological diseases and 159 sera with ovarian cancer, 72 of them at the time of primary diagnosis. We used commercially available kits: CA 125 II: Centocor RIA, CASA: Medac EIA, CA 72-4: Centocor RIA and CYFRA 21-1: Boehringer EnzymunR ELISA. Fixing specificity at 95% versus benign gynecological diseases as a clinically relevant reference group, we found cut-off values of 160 U/mL for CA 125II, 6.5 U/mL for CASA, 6.8 U/mL for CA 72-4 and 2.4 ng/ml for CYFRA 21-1. Based on this specificity we can compare the corresponding sensitivities at the time of primary diagnosis (n = 72): CA 125 II 47%, CA 72-4 47%; CASA 31% and CYFRA 21-1 44%. Regarding histological types of ovarian carcinomas, we found a sensitivity of 50% for CA 125 II and CASA, 36% for CA 72-4 and 33% for CYFRA 21-1 in serous ovarian cancer (n = 53), 21% for CA 125 II and CASA, 36% for CYFRA 21-1 and 43% for CA 72-4 for mucinous ovarian cancer (n = 27). Serous ovarian carcinomas were classified by higher FIGO-stages than mucinous ovarian carcinomas. Additional sensitivities were found at the time of primary diagnosis for the combination of CA 125 II and CA 72-4 and in serous ovarian cancer for CA 125 II and CASA. According to our results, at the time of primary diagnosis the combined determination of CA 125 II and CA 72-4 is useful. If both are negative, determination of CASA can be helpful. For follow-up care and control of efficacy of treatment the preoperative positive or leading marker is sufficient.

Using indirect immunoperoxidase staining, we examined the distribution of blood group substances and related antigens, including Le(a), A, B, H type 2, and Le(x), in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in metastatic lesions of 32 lymph nodes and 9 liver specimens. The compatible expression rate of A/B/H type 2 antigens was 33.3% (3/9) in proximal normal colon, but only 6.1% (2/33) in distal normal colon. Compatible expression was observed in 14 of 25 carcinomas in the proximal colon (56.0%), but these antigens in distal colon cancers reappeared with a high positive rate, 62.9% (39/62). The rate of H type 2 accumulation with the deletion of A and/or B antigens was 6.9% (6/87). Incompatible expression was not observed in colorectal cancer. Le(a) and Le(x) antigens were expressed in normal mucosa and primary carcinoma throughout the colon. Le(a) and Le(x) in primary carcinoma that showed A/B deletion with/without H type 2 accumulation was expressed more than in carcinoma with A/B/H type 2 compatible expression (88.2% vs 71.7% for Le(a); 94.1% vs 88.7% for Le(x), respectively). In 16 of 32 patients (50.0%), A/B/H type 2 antigen expression in metastatic lesions had disappeared or was decreased compared with that in primary carcinoma, followed by metastasis to regional lymph nodes. These results suggested that: (a) A/B/H type 2 blood group substances in the distal colon behave as tumor-associated antigens in colorectal carcinoma. (b) Most frequently, A/B/H type 2 antigens expressed in primary carcinoma were weakened or had disappeared in metastatic lymph nodes. Further investigation of the biological function of carbohydrate chains, such as those of blood group substances and related antigens on cancer cell surfaces may lead to a solution of the problem of the metastatic behavior of tumor cells.

Serum samples from 82 patients with epithelial ovarian cancer, previously assayed for CA125, were assayed for circulating colony-stimulating factor 1 (CSF-1). An elevated CSF-1 concentration (> 450 U ml-1 or > 5.42 ng ml-1) was significantly associated with a worse survival (P = 0.02). The predictive value of raised CSF-1 levels was retained whether the first available sample for all patients (n = 82) or the first sample at the start of chemotherapy (n = 41) was considered. Mean CSF-1 levels (n = 14) dropped significantly during six courses of platinum-based chemotherapy (P = 0.02). Although an elevated CA125 concentration appeared to be a prognostic indicator in the total population (n = 82), it was not related to prognosis in the group of patients from whom samples had been drawn at the start of chemotherapy. In a Cox proportional hazards model, CSF-1, but not CA125, was significantly associated with outcome following adjustment for stage, grade and degree of surgical clearance.

Levels of CA-125 were determined pre- and postoperatively in 13 patients with fallopian tube cancer. Values before surgery were significantly higher (Median 1220 IU/ml, 90-5000 IU/ml) compared with postoperative levels (Median 194 IU/ml, 67-880 IU/ml) (P = 0.0052). Correlation analysis with FIGO stage and grading failed to show any statistical significance, but a trend for a positive correlation with FIGO stage and preoperative values could be observed. The CA-125 antigen is expressed by fallopian tube carcinoma and should therefore be used in diagnosis and follow-up.

Circulation within the bloodstream of mucin derived from mucin-producing adenocarcinomas has been documented infrequently but has been associated with vascular occlusion, organ infarction, and hyperviscosity. The nature of the mucin and the therapeutic role of plasmapheresis in this condition has not been reported. A 64-yr-old female, who had undergone a mastectomy 3 yrs previously for an infiltrating mucinous breast adenocarcinoma, presented with dementia. A blood film showed marked rouleaux and a bluish background. No abnormal bands were detected on plasma protein electrophoresis. Blood, serum and plasma viscosity were above the range of readability of the viscometer. A bone marrow biopsy showed replacement with tumor similar to the original. Repeated plasmaphereses substantially reduced viscosity and temporarily improved her mental state. Post mortem revealed numerous infarcts with eosinophilic mucoid material in the lumen of many small vessels. That the offending plasma constituent was a sialomucin was suggested by mucin stains of the tumor and peripheral blood, a plasma sialic acid level 10 x normal and a substantial fall in viscosity after in vitro treatment of plasma with neuraminidase.

Background: Inhibin is an ovarian hormone that inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. Women with granulosa-cell tumors of the ovary have elevated serum inhibin concentrations, but whether the concentrations are increased in women with other ovarian tumors is unknown., Methods: We measured serum inhibin and FSH concentrations before surgery in 212 postmenopausal women with suspected ovarian cancer and after surgery in 210 of them., Results: Eighteen of the 22 women (82 percent) with mucinous carcinomas (mucinous cystadenocarcinomas and mucinous borderline cystic tumors) of the ovary had elevated serum inhibin concentrations, whereas only 9 of the 53 women (17 percent) with serous carcinomas (serous cystadenocarcinomas and serous borderline cystic tumors) had elevated levels. Serum inhibin concentrations were also elevated in 2 of 12 women (17 percent) with clear-cell carcinomas, 4 of 26 women (15 percent) with undifferentiated carcinomas, 3 of 3 women (100 percent) with granulosa-cell tumors, and 5 of 27 women (19 percent) with other ovarian cancers. The serum concentrations of inhibin were increased in 2 of 28 women (7 percent) with nonovarian pelvic cancers and 11 of 41 women (27 percent) with benign ovarian diseases. All women but one with initially elevated serum inhibin concentrations had low values one week after surgery. Serum inhibin concentrations correlated negatively with serum FSH concentrations (P = 0.05) in women with granulosa-cell tumors but not in women with other tumors, suggesting that the inhibin secreted by tumors in the latter group has decreased biologic activity., Conclusions: Serum inhibin concentrations are elevated in most postmenopausal women with mucinous carcinomas of the ovary and in some women with other types of epithelial ovarian tumors. The concentrations fall after tumor removal.

The use of antibiotics in patients with necrotizing pancreatitis is indicated since bacterial complications are the most common cause of death in this condition. Olfloxacin was studied in six patients regarding its permeation into pancreatic juice and bile and into pancreatic tissue in cases of chronic pancreatitis and pancreatic carcinoma. The peak concentrations in pancreatic juice (3.7 mg/l) and bile (12.9 mg/l) were found 20 minutes after i.v. administration of 3 mg/kg ofloxacin, these are 79 and 275% of the corresponding serum level, respectively. Pancreatic tissue concentrations varied between 54 and 333% of serum values in relation to the removal time of specimens and to the stage of inflammation. After three days and five days of ofloxacin treatment with doses of 2 x 200 mg daily even in pancreatic necroses concentrations were detected between 0.8 and 3.7 mg/kg wet weight. This suggests that in all pancreatic compartments analyzed, sufficient antibacterial ofloxacin levels above the MIC of relevant germs were found. Therefore, from a pharmacokinetic point of view, ofloxacin could be a potentially effective drug in prophylaxis and therapy of bacterial infections of the pancreas.

When a significantly lower follicle stimulating hormone (FSH) level was found in patients with epithelial ovarian carcinoma, it was decided to analyze the influence of hormonal factors on prognosis. Thirteen factors were tested for prognostic significance in 35 women with epithelial ovarian carcinoma. Age, FIGO-stage, histopathological grade, residual tumor, treatment, gonadotrophins and steroid hormones were tested. By univariate log-rank testing a significantly shorter survival time was found for patients with ascending FIGO-stage, residual tumor mass, estradiol < 0.10 nmol/l, progesterone < 2.0 nmol/l and DHEAS < 1300 nmol/l. In the Cox model the independently significant prognostic factors found were residual tumor mass (P < 0.001) with a risk estimate of 2.65, progesterone (P < 0.05) with a risk estimate of 0.29 for a progesterone level > 2.0 nmol/l and total testosterone (P < 0.03) with a risk estimate of 0.29 for a total testosterone level > 1.15 nmol/l. The present findings, together with the assumption that an elevated gonadotrophin level may induce ovarian tumor growth (the gonadotrophin theory), earlier findings of estrogen and progesterone receptors in human ovarian cancer, and the in vitro demonstration of gonadotrophin-growth-stimulation of human malignant epithelial tumors, justify a thorough investigation of the interaction between steroid hormones and receptors, gonadotrophins, tumor bulk and survival in future research protocols.

The CA 195 levels in ovarian cyst fluids from malignant mucinous tumours (median 2,300,000 U/ml) were significantly higher than the levels in benign mucinous tumours and malignant non-mucinous tumours (medians of 26,800 and 1,700 U/ml, respectively, p = 0.039 and 0.011). Also, the carcinoembryonic antigen (CEA) and tumour-associated trypsin inhibitor (TATI) levels in cyst fluid from mucinous tumours were much higher than those in non-mucinous tumours. Pretreatment serum CA 195 levels were found to be elevated (> 10.5 U/ml) in 72% of the patients with malignant mucinous tumours (n = 25), compared with 35% in malignant non-mucinous tumours and 28% in benign mucinous tumours. The positivity rate shown for serum CA 195 in malignant mucinous tumours was higher than that measured for serum TATI, CA 125 or CEA (60, 53 and 42%, respectively). Measurement of serum CA 195 can be valuable in the clinical management of patients with mucinous ovarian cancer.

The serum levels of CA 125 (cutoff limit, 65 U/ml), CA19.9 (cutoff, 40 U/ml), CA 15.3 (cutoff, 32 U/ml), CA72.4 (cutoff, 3.8 U/ml), and TATI (cutoff, 22 ng/ml) were preoperatively measured in 90 patients with epithelial ovarian cancer and in 254 patients with benign ovarian pathology. CA125 had a sensitivity of 75.6%, a specificity of 86.6%, and a diagnostic accuracy of 83.7% for epithelial ovarian cancer; CA19.9 had a sensitivity of 35.6%, a specificity of 81.1%, and a diagnostic accuracy of 69.2%; CA15.3 had a sensitivity of 57.1%, a specificity of 93.9%, and a diagnostic accuracy of 84.6%; CA72.4 had a sensitivity of 70.7%, a specificity of 91.8%, and a diagnostic accuracy of 86.2%; and TATI had a sensitivity of 47.3%, a specificity of 95.3%, and a diagnostic accuracy of 82.9%. CA 125 was the most sensitive marker for nonmucinous tumors, while CA19.9 and CA72.4 were the antigens more frequently expressed by mucinous malignancies. The sensitivities of serum CA 125 (81.1% vs 50.0%; P = 0.01) and TATI (55.2% vs 18.8%; P = 0.02) were higher in patients above 50 years of age than in younger patients while specificities were quite similar in both age groups. The association of serum CA125 and CA19.9 had a significantly higher sensitivity (93.2% vs 81.1%; P = 0.03) and a slightly lowered specificity (78.9% vs 86.0%; P = 0.46) than CA125 assay alone in the differential diagnosis of ovarian masses in patients above 50 years of age.

We have studied platelet aggregation in fourteen pre- and post-menopausal women treated with cyclic adjuvant CMF chemotherapy for mammary cancer with positive axillary nodes, previously operated. Aim of the investigation is to evaluate the effect of chemotherapy on platelet aggregation. The obtained results demonstrate that CMF therapy does not modify platelet aggregation in both pre- and post-menopausal patients.

The levels of CA 125 (reference values [RV]s = 35 U/mL and 65 U/mL), CA 19.9 (RV = 40 U/mL), CA 50 (RV = 20 U/mL) and CA 195 (RVs = 10.5 U/mL and 15 U/mL) were measured in blood samples collected before laparotomy from 71 patients with ovarian carcinoma and 204 patients with benign ovarian pathology as controls. CA 125 levels greater than 35 U/mL were observed in 53/61 patients with non-mucinous carcinomas and in 6/10 with mucinous ones, while antigen levels above 65 U/mL were detected in 50/61 patients with non-mucinous malignancies and in 6/10 with mucinous ones; therefore mucinous tumors expressed this antigen less frequently than non-mucinous ones. Elevated CA 19.9 levels were found in 15/61 patients with non-mucinous malignancies and in 8/10 with mucinous ones. Raised CA 50 levels were observed in 13/50 patients with non-mucinous cancers and in 7/8 with mucinous ones. CA 195 values were greater than 10.5 U/mL and 15 U/mL respectively in 20.0% and in 15.0% of 40 patients with non-mucinous tumors, while antigen levels were above 10.5 U/mL and 15 U/mL respectively in 75.0% and 62.5% of 8 patients with mucinous carcinomas. Therefore, CA 19.9, CA 50 and CA 195 highly correlated with mucinous histotype. The results of CA 195 and CA 19.9 determinations were very similar because of the closely related: structures of the two epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

It was previously reported that sera from ovarian cancer patients contained abnormal forms of alpha-1-proteinase inhibitor (API) that predicted unresponsiveness to chemotherapy. These molecules were detected by extracting the sera with the fucose-specific lectin, lotus tetragonolobus, and analysing the extracts by electrophoresis. In a new study of ovarian cancer, we report that API cannot be extracted by lotus from fresh sera, unless the specimens are subjected to repeated cycles of freezing and thawing. Furthermore, increases in lotus-extractable API in the pretreated sera are also associated with a poor response to chemotherapy. This would suggest that lotus is extracting the same molecules in both studies. It seems likely that the discrepancy between the two studies is due to the length of time the specimens were stored prior to analysis. We present evidence suggesting that the API extracted by lotus is present in serum as soluble complexes, the detailed composition of which is unclear. The change in the properties of API in cancer may be very important with respect to tumour spread.

Serum levels of TAG 72 were measured in 726 serum samples from patients with benign and malignant gynaecological conditions in order to evaluate the clinical usefulness of TAG 72 alone or in combination with other tumour markers. Sixty-six per cent of patients with ovarian cancer showed abnormal concentrations of TAG 72 antigen. A good correlation was also found between serial TAG 72 values and the clinical course of disease during chemotherapy and follow-up. In cervical and endometrial cancer abnormal TAG 72 values occurred in 23% and 14% of cases, while none of the patients with breast cancer had abnormal TAG 72 levels. Among patients with benign disease only one out of 12 patients (8%) with benign ovarian tumours and one of 15 patients with uterine fibromyomatosis (7%) showed high TAG 72 serum levels. However, the determination of TAG 72 did not increase the sensitivity of CA 125 and squamous cell carcinoma antigen (SCC), in ovarian and cervical cancer, respectively. The systemic administration of recombinant interferon alpha-2b to 15 patients with ovarian cancer and different basal levels of TAG 72 did not increase serum levels of the antigen.

The levels of CA125 (reference values [RVs] 35 U/mL and 65 U/mL), CA15.3 (RV = 32 U/mL), Mucin-like carcinoma associated antigen (MCA; RV = 15 U/mL), CAM26 (RV = 75 U/mL) and CAM29 (RV = 15 U/mL) were preoperatively assayed in blood samples drawn from 42 patients with ovarian carcinoma and 101 patients with benign ovarian pathology undergoing laparotomy at the Department of Gynecology and Obstetrics of the University of Pisa. With 65 U/mL as RV, CA125 had a sensitivity (SE) of 80.9% and a specificity (SP) of 89.1% for ovarian carcinoma; with 35 U/mL as RV, CA125 had a SE of 85.7% and a SP of 66.3%; CA15.3 had a SE of 57.1% and a SP of 96.0%; MCA had a SE of 59.5% and a SP 86.1%; CAM26 had a SE of 21.4% and a SP of 96.0%, CAM29 had a SE of 64.3% and a SP of 97.0%. The association of CA125 with each of other antigens did not improve the SE of CA125 assay alone in the detection of patients with ovarian carcinoma. In conclusion, the present data showed that the measurement of CA15.3, MCA and CAM26 did not give any additional information with respect to CA125 assay in the diagnosis of ovarian carcinoma. The good SE and the very good SP and diagnostic accuracy of CAM29 could suggest further investigation in order to evaluate the role of this antigen in the management of patients with this malignancy.

The serum levels of sialyl SSEA-1 antigen, a type 2 chain carbohydrate antigen detected using the monoclonal antibody FH-6, were elevated in 47.2% of patients with epithelial ovarian cancer, with the percent positivity increasing with the clinical stage. Of the histological type, it is interesting to note the relatively high sensitivity in patients with mucinous adenocarcinoma and clear cell carcinoma in contrast with the CA 125 antigen levels. Although the percentage of patients with ovarian cancer who had elevated sialyl SSEA-1 antigen levels is lower than that observed with elevated CA 125 antigen levels, the false-positive rate is significantly low in the sialyl SSEA-1 test. Serial sialyl SSEA-1 antigen levels obtained during follow-up were strong predictors of clinical outcome. The combined determination possible with sialyl SSEA-1 and CA 125 did not markedly increase the detection rate because of the overlap in the positivity. However, increased levels of both serum sialyl SSEA-1 antigen and CA 125 antigen indicated the presence of malignancies in pregnant women associated with ovarian tumors.

Seriated ferritin assays were carried out on 95 patients affected by primitive ovarian epithelial tumour over a period of three years (1979/82), by radioimmunometric assay for human spleen ferritin. Ferritin was elevated in endometrioid tumours and in the presence of active progressing disease and chemotherapy did not influence these values. The ferritin/sideremia ratio was high in the case with pathological levels. Studying the glicosilation of this protein a significant amount of ferritin was not bound to concavallin A, suggesting direct release of this protein by tumour cells.

Three hundred and one gastric cancer patients have been examined preoperatively to investigate their gastric acid secretions after stimulation by tetragastrin, and serum gastrin stimulation by a test meal, as well as for skin reactions and an evaluation of their serum glycoproteins. The results have indicated that their gastric secretions and serum gastrin response were found to be reduced, according to the advancement of their cancer, and that the gastric acid secretion of patients with signet ring cell carcinoma was higher than that of patients with other histological carcinomas. Gastric acid secretions of patients with an ulcerated type of cancer, that is, type IIc and type III in an early cancer stage and type IIc of an advanced Borrmann V type, was higher than in patients with other types, and there were significant correlationships between gastric secretions and PHA skin test and gastric secretions and the IAP and the sialic acid.

Serum concentrations of the vitamins A and E were measured in 38 postmenopausal women with either malignant, borderline, or benign epithelial ovarian tumors or with a normal ovary. No statistically significant differences were found in the levels of the vitamins between the various groups. The levels of both vitamins in the ovarian vein were also measured in malignant and benign ovarian tumors. The concentration of vitamin A in the ovarian vein of a patient with a malignant tumor was lower than in the peripheral vein, although the difference was not significant. The findings indicate that the vitamin A and E are not of great importance to the metabolism of epithelial ovarian cancer.

Serum levels of immunosuppressive substance (IS) were determined in 99 patients with gastric cancer and in 32 healthy individuals. The serum IS levels in the patients (769.6 +/- 314.8 micrograms/ml) were significantly higher than those in the healthy individuals (549.7 +/- 104.7 micrograms/ml). A multivariate analysis on the correlation between serum IS levels and clinicopathological findings in the patients disclosed that there was a close correlation between the serum IS levels and the depth of invasion, in particular, the prognostic serosal invasion, metastasis to the distal lymph nodes and peritoneal dissemination. There was, however, no correlation between the serum IS level and hepatic metastasis. Serum IS levels were higher in patients with well-differentiated adenocarcinoma than in those with poorly differentiated adenocarcinoma or signet ring cell carcinoma. A serum IS level higher than 1000 micrograms/ml indicates the possibility that the tumor is only palliatively resectable because of involvement of the distal lymph nodes or peritoneal dissemination.

Plasma levels of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) were measured in 253 patients with gynecologic malignancies and in 317 patients with benign gynecologic diseases. Plasma concentrations of each of these antigens were elevated in a significantly (p less than 0.001) greater number of patients with invasive gynecologic cancers than in the control population. Carcinoembryonic antigen was the most commonly elevated marker, followed by AFP and hCG. Prior to therapy, over 85% of patients with ovarian or cervical cancer had elevated plasma levels of one or more antigens. Specifically, CEA was most often elevated in patients with mucinous adenocarcinomas of the ovary and endocervix. Alpha-fetoprotein was most often increased in patients with germ cell or stromal tumors of the ovary and in patients with large-cell nonkeratinizing cervical cancers. In contrast, hCG concentrations were highest in patients with serious cystadenocarcinomas of the ovary and in patients with keratinizing squamous cell carcinomas of the cervix. Plasma antigen levels were directly related to tumor differentiation and stage of disease, and generally returned to normal eight to 12 weeks following therapy. Effective plasma and tumor antigen screening during initial evaluation of patients with gynecologic tumors should help to identify the most appropriate antigen for immunodetection procedures and for serial plasma determinations following therapy.

Fifty-nine patients with ovarian carcinoma were studied with particular reference to abnormalities of the coagulation mechanism. The notable findings were the high incidence of episodic thrombocytosis (73%) and the relation of these peaks of thrombocytosis to periods of expected maximum tumour break-down. The incidence of pulmonary embolism for the series was 44%, with the majority occurring in the group demonstrating significant thrombocytosis; in this latter group, pulmonary embolism constituted the major cause of death. The abnormalities in coagulation are discussed, together with pragmatic significance and methods of control.

Mitomycin-C (MMC) is an alkylating agent which has shown significant activity in gynecologic cancers, both in vivo and in vitro. We determined the delivery of MMC to target tissue by comparing plasma and tumor tissue concentrations of MMC as measured by high-performance liquid chromatography (HPLC) in five patients with cervical cancer. In a companion study, we measured MMC concentrations in plasma and selected tumors of female rats given an equivalent dose. In patients, the mean terminal half-life and total body clearance rates of MMC were 40 min and 275 ml/min/m2, respectively. The mean cervical tumor to plasma concentration of MMC was 1.26 +/- 0.34 (mean +/- SE, n = 4). In female rats, the terminal half-life and total body clearance rates of MMC were 28.4 min and 270 ml/min/m2, respectively. Tissue concentrations of MMC in rats were lower than plasma concentrations measured at corresponding times. The highest concentrations were found in lung and uterus (including cervix) with lower concentrations in ovary and liver. The mean half-life for elimination of MMC from tissues of rats was 20.3 +/- 2.8 min (mean +/- SE, n = 6). Based on similar pharmacokinetic parameters in rats and patients, the rat appears to be a suitable model for the disposition of MMC in human patients. The near equivalent drug concentrations found in tumor and plasma of patients suggests that the in vitro tests conducted at concentrations based on plasma level may be relevant to cervical tumor tissue, as well.

Human placental lactogen (HPL or HCS), the beta subunit of human chorionic gonadotropin (beta-HCG), and carcinoembryonic antigen (CEA) were measured by a specific radioimmunoassay in plasma of 65 patients with ovarian cancer. Fifty-one patients had epithelial tumors, while 14 had germ cell tumors. It was found that 47 patients (72 per cent) had high levels of plasma HPL, 29 patients (45 per cent) had high levels of plasma beta-HCG, and 34 patients (52 per cent) had high levels of plasma CEA, but there was no correlation between these protein marker levels in different patients. Twenty of these patients were studied before and after operation and during chemotherapy and/or radiotherpy. There was no consistent correlation between these marker levels and the course of the disease. These data suggest that measurement of HPL, beta-HCG, and CEA in sera of patients with ovarian cancer is not of value in assessing the clinical status of the patients or in determining the effect of therapy.

The trace element spectrum of gastric tissue and whole blood specimens from gastric cancer and peptic ulcer patients was recognized with pattern recognition technique in order to obtain the chemical information of gastric cancer. Thirty specimens were obtained from cancer patients in each of the 58 gastric tissues and 54 whole blood specimens. Five pathological types were divided into two groups: peptic ulcer and dysplasia as the ulcer group; well-differentiated, undifferentiated and mucinous carcinoma as the cancer group. The accuracy of recognizing the several spectra was 90%: nine trace element spectra (Cu, Zn, Ni, Co, Cr, Cd, Mn, Fe and Mg) for the tissue specimens from the cancer and ulcer groups; six (Cu, Zn, Mn, Co, Cr and Cd) for dysplasia and well-differentiated adenocarcinoma tissues; five (Cu, Ni, Cr, Cd and Fe) for the whole blood specimens from these two groups and six (Cu, Zn, Cr, Cd, Fe and Ni) for the whole blood specimens from dysplasia and peptic ulcer (including 10 normal individuals). The data were treated by non-linear mapping method and calculated by TRS-80 III type microcomputer.