A case of lung adenocarcinoma associated with remarkably high levels of CA 19-9 and lymphangitis carcinomatosa

A mutant of Methanobacterium thermoautotrophicum with a lesion in membrane Na+-translocating ATPase (synthase) was isolated. The total ATPase activity in permeabilized cells of this mutant was elevated three-fold as compared with the wild-type strain. In contrast to wild-type cells, mutant ATPase was neither inhibited by DCCD nor stimulated by Na+ ions. The methane formation orate of the mutant cells at pH 7.5 under non-growing conditions was nearly twice that of the wild-type strain and was stimulated by sodium ions. On the other hand, the ATP synthesis driven by methanogenesis under the same conditions was lower that of the wild-type under the same conditions, and contrary to the wild-type was not stimulated by Na+ ions. ATP synthesis driven by a potassium diffusion potential in the presence of sodium ions was markedly diminished in the mutant cells. The membrane potential values of the wild-type and the mutant cells in the presence of 10 mM NaCl at pH 7.0 were comparable at energized conditions (-223 mV and -230 mV respectively). The Mg2+-dependent ATPase activity of the 10(5) x g supernatant of broken cells from the mutant cells was 30% higher than in the wild-type. On the other hand, two bands with Mg2+-dependent ATPase activity were identified by native PAGE in this fraction in both wild-type as well as in mutant. These data suggest that the binding of Na+-translocating ATPase (synthase) to the membrane spanning part is changed in the mutant strain.     

Prognostic value of CA 19-9 serum course in pancreatic cancer

BACKGROUND/AIMS: The aim of this study was to determine the sensibility and specificity of a new assay in the diagnosis of pancreatic cancer and predictability of resection rates. In addition, the serum CA19-9 levels was utilised as a prognostic indicator. METHODOLOGY: Serum expression of the tumor marker CA 19-9 was studied in 2119 patients. RESULTS: The discriminating capacity of CA 19-9 between benign and malignant disease was high, especially in patients with pancreatic cancer (n = 347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. The CA 19-9 levels were significantly lower in patients with resectable tumors (n = 126) than in those with unresectable tumors (n = 221, p < 0.0001) (sensitivity 74% versus 90%). The CA 19-9 levels dropped sharply after resection but normalized only in 29%, 13%, and 10% of patients with stage I, II, and III, respectively. In unresectable tumors, no significant decrease in CA 19-9 levels after laparotomy or bypass was found. Among patients with the same tumor stage, the median survival time of those whose CA 19-9 levels returned to normal after resection was significantly longer than those with postoperative CA 19-9 levels that decreased but did not return to normal (stage I: 33 versus 11.3 months; stage II: 41 versus 8.6 months; stage III: 28 versus 10.8 months). In patients with recurrent disease, 88% had an obvious rise in CA 19-9 levels. CONCLUSION: CA 19-9 measurement is a simple test which can be used for diagnostic purposes, as well as the prediction of resectability, survival rate after surgery, and the potential for recurrence.     

A comparative analysis of the serum levels of NCC-ST-439, CEA and CA19-9 in patients with colorectal carcinoma

To investigate the usefulness of NCC-ST-439 (ST439) as a new tumor marker in colorectal cancer, we compared its serum level with the serum levels of CEA and CA19-9. The serum levels of ST439, CEA and CA19-9 from 168 patients were evaluated, of which 124 were primary cases and 44 were recurrent. ST439 was elevated in 31.5% in primary cases and 52.3% in newly-discovered carcinoma patients with confirmed recurrent cases. Following resection of the tumor, ST439 levels decreased rapidly. Similar trends in serial CEA and CA19-9 levels were found. While CEA is more sensitive for the detection of colorectal carcinomas than the other two markers, ST439 is sensitive in the detection of localized carcinomas and recurrent cases with localized lesions or liver metastasis. The results indicate that ST439 is a useful tumor marker not only for diagnosing primary carcinomas, but also for the detection of recurrent cases.     

Suspected extragonadal germ-cell cancer syndrome presenting with an orbital mass and elevation of serum CEA, CA 19-9 and CA50 levels

Patients with extragonadal germ-cell cancer syndrome (EGCCS) represent a subgroup of patients with poorly differentiated carcinoma or adenocarcinoma of an unknown primary site for whom potentially curative therapy is available. We report the case of a young man presenting an orbital tumor and high serum levels of CEA, CA 19-9 and CA50 for whom an initial diagnosis of metastatic poorly differentiated carcinoma was made. Suspecting EGCCS, he was treated as for a germ-cell tumor. While in treatment, he underwent residual orbital mass resection, and the histologic diagnosis was embryonal carcinoma based on alpha-fetoprotein immunoperoxidase staining. We discuss the rare location at diagnosis, the impressive increase in the commonly considered gastrointestinal markers that he showed, and the potential utility of these markers for such patients.     

Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients

It is unknown whether the addition of aspirin might increase both the efficacy and the potency of clopidogrel, a potent and selective ADP blocker. For that purpose, the efficacy of clopidogrel (1-20 mg/kg, p.o.) administered orally to rabbits alone or in combination with aspirin (0.1-10 mg/kg, p.o.) was determined in several experimental models. A potent synergistic effect of the clopidogrel/aspirin association was demonstrated with regard to collagen-induced platelet aggregation measured ex vivo. Similarly, aspirin potentiated the antithrombotic activity of clopidogrel measured with regard to experimental thrombosis induced by a silk thread or on stents placed in an arteriovenous shunt, thrombus formation following electrical stimulation of the rabbit carotid artery and with regard to 111In-labeled platelet deposition on a stent implanted in an arteriovenous shunt or on the subendothelium following air drying injury of the rabbit carotid artery. A similar potentiating effect of aspirin was obtained with regard to myointimal proliferation (restenosis) in the femoral arteries of atherosclerotic rabbits which occurred as a consequence of stent placement. The clopidogrel/aspirin combination showed only additive-type effects on bleeding time prolongation induced by ear transection in the rabbit, therefore showing that combined inhibition of cyclooxygenase and ADP's effects provide a marked enhanced antithrombotic efficacy. Such a combination may provide substantial protection against platelet aggregation leading to thrombotic occlusion at sites of endothelial injuries and coronary artery stenosis in humans.     

Hepatobiliary cystadenocarcinoma without ovarian stroma and normal CA 19-9 levels. Unusually prolonged evolution

Hepatobiliary cystadenoma and cystadenocarcinoma are rare tumors of the liver. The differential diagnosis of cystadenoma includes other cystic neoplasms, nonneoplastic cysts, and even on some occasions parasitic liver involvement. It has been suggested that elevated serum level of the tumor marker CA 19-9 may be of value in distinguishing between cystadenoma with ovarian stroma and hydatid disease. We report the unique case of a male patient with a hepatobiliary cystadenocarcinoma without ovarian stroma of prolonged evolution characterized by a normal CA 19-9 serum level, low cyst fluid CA 19-9, and a very weak CA 19-9 expression on cyst epithelium.     

Marked increase in serum CA 19-9 level in patients with alcoholic cirrhosis: report of four cases

We report four cases of marked increase in serum carbohydrate antigen (CA 19-9) levels in patients with severe alcoholic cirrhosis without any evidence of gastric or pancreatic carcinoma. Brief reports were obtained from two hepatology units of four cirrhotic patients, three of them with alcoholic hepatitis. In the four cases, improvement of liver function and disappearance of jaundice were associated with a decrease to normal serum CA 19-9 levels. These observations show that a marked increase in serum CA 19-9 level in patients with severe hepatic dysfunction is not diagnostic of pancreatic or gastric carcinoma.     

Lymph node inflammatory pseudotumor. Description of a case

A case of inflammatory pseudotumor of lymph node in a 56-year-old man is described. The awareness of this benign reaction pattern is of great importance for differential diagnosis with many nodal lesions.     

Unexpected increase of the CA 19-9 tumour marker in patients with endometriosis

The purpose of this study was to investigate whether the ovarian function of women with endometriosis could be identified by serologic concentration of the oncofetal antigen CA 19-9 before, during and after treatment for 6 months with danazol. A total of 15 women with endometriosis, 20-40 years old, were studied. The serum CA 19-9 antigen was measured by immunoradiometric assay. The measurement of CA 19-9 was repeated during the last 15 days of a 6-month therapy period with danazol and after 3 months from the end of the therapy in only seven women. It was found that: 1) Eight out of 15 women (53.3%) showed higher CA 19-9 values than the upper normal limit. 2) Danazol caused a significant decrease in the antigen values which remained stable after the cessation of therapy. This data suggests that endometriosis should be classified among other diseases which cause an increase in the serum levels of CA 19-9 and that ovarian function is related to antigen levels.     

CA 19-9 in evaluating the response to chemotherapy in advanced pancreatic cancer

BACKGROUND/AIMS: The determination of serum carbohydrate antigen 19-9 (CA 19-9) level is useful in managing pancreatic cancer. However, the usefulness of this marker in evaluating the response to chemotherapy has not been fully established. MATERIALS AND METHODS: Serial changes of serum CA 19-9 levels were studied during chemotherapy in 66 pancreatic cancer patients who showed CA 19-9 level of 100 U/ml or greater before treatment. We investigated the relationship between patient survival and reduction in serum CA 19-9 level after treatment. RESULTS: When a responder was defined as a patient whose serum CA 19-9 level was reduced by more than 50% of the pre-treatment level within 2 months after treatment, CA 19-9 response was observed in 9 (13%) of the 66 patients. Median survival times of CA 19-9 responders and non-responders were 141 and 88 days, respectively. Based on Cox regression analysis, the relative risk of cancer death in CA 19-9 responders for non-responders was 0.47 (95% confidence interval, 0.21 to 1.05). CONCLUSIONS: CA 19-9 reduction may be useful for assessing the efficacy of chemotherapy for advanced pancreatic cancer.     

Evaluation of CA 15-3 serum levels in breast cancer patients

A case of opacity in the fetal gallbladder was diagnosed by ultrasound. The lesion resolved spontaneously in the postnatal period. Careful follow-up ultrasound examinations are necessary for fetal cholelithiasis in the pre- and postnatal periods, and conservative management is mandatory.     

Laparoscopic resection of a benign true cyst of the spleen with the harmonic scalpel producing high levels of CA 19-9 and carcinoembryonic antigen

BACKGROUND: Oral ingestion of immunoglobulins in humans has been shown to be effective as prophylaxis against enteric infections. However, its therapeutic effect in children with infectious diarrhea has hitherto not been proven. We treated children with rotavirus diarrhea with immunoglobulins extracted from immunized bovine colostrum (IIBC) containing high titers of antibodies against four rotavirus serotypes. METHODS: In this double blind placebo-controlled trial, 80 children with rotavirus diarrhea were randomly assigned to receive orally either 10 g of IIBC (containing 3.6 g of antirotavirus antibodies) daily for 4 days or the same amount of a placebo preparation. The daily stool output (grams/kg/day), intake of oral rehydration solution (ml/kg/day), stool frequency (number of stools/day) and presence of rotavirus in stool were monitored for the 4 days during treatment. RESULTS: Children who received IIBC had significantly less daily and total stool output and stool frequency and required a smaller amount of oral rehydration solution than did children who received placebo (P < 0.05). Clearance of rotavirus from the stool was also earlier in the IIBC group compared with the placebo group (mean day, 1.5 vs. 2.9, P < 0.001). No adverse reactions from the colostrum treatment were observed. CONCLUSIONS: Treatment with antirotavirus immunoglobulin of bovine colostral origin is effective in the management of children with acute rotavirus diarrhea.     

Giant splenic cyst with high serum concentration of CA 19-9. Failure of treatment with percutaneous transcatheter drainage and injection of tetracycline

BACKGROUND: Recently, several cases of nonparasitic true splenic cyst with high serum concentration of carbohydrate antigen (CA 19-9) have been reported. CASE: We report a giant splenic cyst presenting with high serum concentration of CA 19-9 in a 21-year-old man without a history of previous trauma. Imaging techniques showed a huge monolocular cyst of the spleen, and laboratory data showed increased serum CA 19-9 levels (326 U/ml; normal, < 37 U/ml). Serologic test was negative for parasitic infection. These findings led us to the diagnosis of epithelial splenic cyst. Percutaneous transcatheter drainage and injection of tetracycline were performed for 2 weeks. The cyst shrank, and the serum CA 19-9 level decreased favorably. However, cystic fluid reaccumulated in a month. CONCLUSIONS: The accumulation of cystic fluid in splenic epithelial cysts may be attributable not only to the secretion of the lining cells but also to influx from the splenic sinuses.     

CYFRA 21-1 serum levels in women with adnexal masses and inflammatory diseases

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin marker CYFRA 21-1 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic marker in women suffering from ovarian cancer. In order to determine the specificity of the CYFRA 21-1 test, we have investigated CYFRA 21-1 serum levels in several benign conditions. This retrospective study comprises 37 patients suffering from ovarian cancer FIGO stages Ia-III. Sera from patients with benign ovarian cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases respectively. With a sensitivity of 41% and a specificity of 95%, CYFRA 21-1 was not suitable as a screening marker for ovarian cancer. Although CYFRA 21-1 was able to discriminate between ovarian cancer and benign adnexal tumours (univariate regression model, P = 0.0001), CYFRA 21-1 did not reveal additional information to CA 125 in a multivariate regression analysis (P = 0.06). CYFRA 21-1 serum levels were elevated in benign conditions such as liver cirrhosis, but not in endometriosis and inflammatory diseases. In ovarian cancer patients, elevated CYFRA 21-1 serum levels before therapy were associated with a poor overall and disease-free survival (log-rank test, P = 0.02 and log-rank test, P = 0.005 respectively). CYFRA 21-1, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.     

Tumor markers CA 125 and CA 19-9 in cord blood and during infancy: developmental changes and use in pediatric germ cell tumors

Tumor markers CA 125 and CA 19-9 are elevated in a variety of malignancies in adult patients, but only little is known of their biology during gestation or infancy. We have addressed the developmental pattern of these carbohydrate antigens in pediatric patients by measuring their serum levels in 133 cord blood samples from the second through third trimester of gestation and in 39 infants aged less than 1.5 y. The serum concentrations of both markers revealed developmental changes, the levels being higher at earlier gestation (wk 24 through 37) than at term or during infancy. The clinical value of the markers was evaluated by monitoring 26 children with germ cell tumors; 14 benign and 2 immature teratomas, and 11 malignant germ cell tumors. Patients with immature sacrococcygeal teratomas showed constant and prolonged elevations of serum CA 125 and CA 19-9. In contrast, all but two children with mature teratomas had normal marker levels; these two patients with abnormally high serum CA 125 and CA 19-9 values for the first 4 postoperative weeks had a benign ovarian and ventricular teratoma, respectively. Of the 11 children with malignant germ cell tumors, serum CA 125 or CA 19-9 concentration was elevated in four patients at diagnosis and declined to normal within 2 wk after institution of therapy. Malignant recurrence in two patients was not associated with a reelevation of the CA 125 level. Taken together, our results demonstrate a developmentally regulated pattern of serum CA 125 and CA 19-9. The carbohydrate markers were usually inferior to alpha-fetoprotein in monitoring of germ cell tumors, but may be a useful adjunct in the follow-up of immature teratomas.     

Circulating form of human vascular adhesion protein-1 (VAP-1): increased serum levels in inflammatory liver diseases

Vascular adhesion protein-1 (VAP-1) is a dimeric 170-kDa endothelial transmembrane molecule that under normal conditions is most strongly expressed on the high endothelial venules of peripheral lymph nodes and on hepatic endothelia. It is a glycoprotein that mediates tissue-selective lymphocyte adhesion in a sialic acid-dependent manner. In this study, we report the detection of a soluble form of VAP-1 in circulation. We developed a quantitative sandwich ELISA using novel anti-VAP-1 mAbs and used it to determine the levels of soluble VAP-1 (sVAP-1) in the serum of healthy individuals and in patients with inflammatory diseases. In healthy persons, circulating sVAP-1 concentrations were 49 to 138 ng/ml. Immunoblotting studies revealed that the apparent molecular mass of dimeric sVAP-1 is slightly (approximately 10 kDa) higher than that of transmembrane VAP-1 under nonreducing conditions. In contrast, the electrophoretic mobilities of monomeric sVAP-1 and transmembrane VAP-1 were similar after reduction and boiling. Adhesion assays showed that the circulating sVAP-1 modulates lymphocyte binding to endothelial cells. Inflammation can cause an elevation of serum sVAP-1 levels, because sVAP-1 concentrations in patients with certain liver diseases were two- to fourfold higher than those in normal individuals. In contrast, rheumatoid arthritis and inflammatory bowel diseases were not associated with elevated levels of sVAP-1. These findings indicate that there is a functionally active, soluble form of VAP-1 in circulation and suggest that the serum level of sVAP-1 might be a useful marker of disease activity in inflammatory liver diseases.