Elevated sialyl Lewis X-i antigen levels in pleural effusions in patients with carcinomatous pleuritis

The levels of sialyl Lewis X-i antigen (SLX), which is one of the cancer-associated carbohydrate antigens, were evaluated in 83 malignant and 46 benign pleural effusions. SLX levels in pleural effusion due to lung adenocarcinoma were significantly higher than those due to benign diseases (p < 0.0001), lung cancer other than adenocarcinoma (p = 0.0052), and adenocarcinoma originating from other organs (p = 0.0492). According to receiver operating characteristic (ROC) curve analysis, the optimal cut-off level in the discrimination between malignant and benign pleural effusions was 92 U/ml, which gave a sensitivity of 57.1% and a specificity of 77.8%. The cut-off level of pleural effusion in patients with carcinomatous pleuritis might be higher than that of serum (38 U/ml).     

Follow-up study of auditory brainstem responses in hyperbilirubinemic newborns treated with exchange transfusion

Tumor markers have been used for the evaluation of various malignancies though the existence of false positive results in some benign diseases is known. In this study, several established markers including carcinoembryonic antigen, alpha fetoprotein, beta human chorionic gonadotropin, ferritin, CA 19-9 and CA 125 were measured in 60 patients with chronic active hepatitis, 70 patients with cirrhosis and 40 normal subjects in order to evaluate the rate of false elevation of tumor markers in chronic liver disease. Prostate specific antigen and prostatic acid phosphatase levels were also measured in male patients and controls. Serum alpha fetoprotein levels were found elevated in 20% of patients with cirrhosis. The serum CA 19-9 level showed significant elevation in chronic active hepatitis (32%) and cirrhosis (44%). Increase in CA 125 concentration was also remarkable in chronic active hepatitis (23%) and especially in cirrhosis (74%). These results indicate that it is necessary to consider the presence of high false positivity rate of CA 19-9 and CA 125 during clinical interpretation of tumor markers in patients with chronic liver disease.     

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.     

Increased CA-19-9 caused by a splenic cyst: a rare differential diagnosis

Adenocarcinoma of the gastrointestinal tract, particularly primary adenocarcinoma of the pancreas lead to elevation of serum carbohydrate 19-9 (CA19-9) levels. Some benign disorders, like inflammatory diseases also cause CA19-9 tumor marker elevation. An extremely rare entity are benign splenic cysts which express this tumormarker as reported here.     

A patient with allergic bronchopulmonary candidiasis showing a high serum level of soluble interleukin 2 receptors

An 84-year-old man was admitted to Yonezawa City Hospital with fever, cough, hemoptysis and progressive dyspnea. He had complained of wheezing asthmatoid and exertional dyspnea for the previous 10 years, regardless of the season. On admission, chest radiographs revealed a diffuse ground-glass shadow, fibrotic change, and volume reduction. Arterial blood gas analysis showed extreme hypoxemia. A computed tomographic (CT) scan of the chest showed not only faint ground-glass opacities and dense patches in the whole lung field, but also central bronchiectasis. Laboratory tests revealed that both total serum levels of IgE and specific IgE for Candida albicans were elevated. In the bronchoalveolar lavage fluid, lymphocyte, neutrophil and eosinophil percentages were high, and the CD4/CD8 ratio was low. We diagnosed the fibrotic stage of allergic bronchopulmonary candidiasis. During treatment with hydrocortisone and fluconazole, eosinophilia in the peripheral blood was observed, and serum candida antigen was positive. In addition, high serum levels of soluble interleukin 2 receptors were observed in this patient.     

Similarity and co-expression of tumour-associated antigens recognised by different monoclonal antibodies

The concentration of carcinoembryonic antigen (CEA), CA130, CA125, SLX, CA19-9, SPan1, and tumour-associated glycoprotein 72 (TAG-72) in the culture supernatant of 15 cancer cell lines and in the sera of 58 cancer patients was measured, and the co-expression of these antigens was examined by double determinant immunoradiometric assays. The high correlation coefficient of the concentrations and significant binding in the double determinant assays indicated a close relationship between CA125 and CA130 and between CA19-9 and SPan1. There was variable binding of the 125I-labelled anti-SLX, anti-CA19-9, and anti-SPan1 antibodies to anti-CA130 beads that had been pre-incubated with the culture supernatants, suggesting the presence of the epitopes of SLX, CA19-9, and SPan1 on the molecule expressing CA130. Similarly, the epitopes of SLX, CA19-9, and SPan1 could be present on the molecule expressing CEA. 125I-labelled anti-CA19-9, anti-SLX, and anti-TAG-72 antibodies were bound in variable proportions to anti-CA130 beads or to anti-CEA beads that had been pre-incubated with patients' sera. However, CEA and CA130 were not expressed on the same molecule, either in the culture supernatant, or in patients' sera. In conclusion, the carbohydrate epitopes of CA19-9, SPan1, SLX, and TAG-72 could be present on the molecule recognised by the anti-CA130 or anti-CEA antibody; however, the epitopes of CA130 and CEA did not co-exist on the same molecule.     

Attempted suicide and menstrual cycle. An epidemiologic study

Acute-phase reactant proteins have been considered in searching for new biochemical tumor markers useful at initial diagnosis, staging and monitoring of colorectal cancer. In this study, we aimed to determine the role of acute-phase reactant proteins in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) at the preoperative staging of colorectal cancer. In 22 patients with cancers of the colon and rectum and in 9 control patients without cancer, the serum levels of CEA, CA 19-9, C-reactive protein (CRP), alpha 1-antitrypsin (AAT) and alpha 1-acid glycoprotein (AAG) were measured. While statistical analysis did not show significant correlations between serum CEA, AAT and CRP levels with the stage of disease, the significant correlations between serum CA 19-9 and AAG concentrations with the extent of cancer were detected (p < or = 0.0197 and p < or = 0.0378, respectively). Multivariate discriminant analysis gave a final prognostic model that included serum CA 19-9 and AAG levels with a significance of p < or = 0.0089. The Linear regression analysis also gave a form of (Stage = 0.04667 + 0.0077 x CA 19-9 + 0.0068 x - AAG) for staging. We considered that the serum AAG levels, in combination with serum CA 19-9 concentrations may have an important role in the preoperative staging of colorectal cancer.     

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.     

Clinical usefulness of serum cytokeratin 19 fragment as a tumor marker for lung cancer

Serum soluble cytokeratin 19 fragment (CYFRA) levels were measured in 251 patients with lung cancer and 139 patients with benign lung diseases to determine the clinical usefulness of CYFRA level determination in the diagnosis and monitoring of lung cancer. Serum levels of CYFRA were measured by a 2-step sandwich ELISA method. When the cut-off value was defined as 3.5 ng/ml, which was associated with a specificity of 95% for benign lung diseases, CYFRA had a high sensitivity (53%) in all patients with lung cancer. Both the serum level of CYFRA and its sensitivity increased significantly with the increase in clinical stage. A comparison of areas under receiver operating characteristic curves showed that CYFRA had the most power of discrimination in the diagnosis of lung cancer among markers including carcinoembryonic antigen, squamous cell carcinoma antigen, carbohydrate antigen 19-9, and neuron-specific enolase. A good correlation was found between serial changes in serum CYFRA levels during therapy and clinical responses for 18 patients who underwent chemotherapy and/or radiotherapy. Our findings suggest that CYFRA may be a marker of choice for screening and monitoring of lung cancer, particularly squamous cell carcinoma.     

Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma

50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.     

Neurobiological basis of creativity

We have used a previously described model of bilateral radiation-induced lung disease in the rat (Ward et al., Radiat. Res., 136, 15-21, 1993) to study the role of hyaluronan in this process. Hyaluronan was measured in the bronchoalveolar lavage fluid, serum and lung tissue of rats after gamma irradiation or sham irradiation. Four weeks after irradiation, during peak alveolitis (12-fold increase in protein in the lavage, 7-fold increase in lavaged cells) hyaluronan was elevated 5.5-fold in serum and 1.5-fold in the bronchoalveolar lavage fluid. Histochemical staining demonstrated hyaluronan was in the intra-alveolar edema fluid but was not increased in the alveolar walls; hyaluronan, measured by high-performance liquid chromatography, also was not elevated in lavaged lung tissue. Hyaluronan was not increased in bron-choalveolar lavage fluid, serum or lung tissue during pulmonary edema (2 weeks) or fibrosis (6 to 20 weeks). The administration of methylprednisolone significantly decreased the alveolitis, including the increase in hyaluronan in the alveolar space and serum, but did not suppress fibrosis. It appears that hyaluronan is a marker of inflammation and cannot be used as a serum marker to predict the onset of radiation pneumonitis. Furthermore, an increase in interstitial hyaluronan does not appear to be a necessary precursor in the evolution of radiation fibrosis.     

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.     

Diagnosis of pleural effusions. Experience with clinical studies, 1986 to 1990

OBJECTIVES: To identify in patients with pleural effusion which procedures are most useful in separating malignant from nonmalignant pleural effusions and to identify which procedures most commonly lead to a definitive diagnosis. DESIGN: Prospective consecutive case series. SETTING: Pulmonary referral hospital in Prague, Czech Republic. PATIENTS: One hundred seventy-one adults between ages 18 and 70 years with a pleural effusion and a Karnofsky score of 70 or above. INTERVENTIONS: All patients underwent history, physical, pleural fluid cytologic study, laboratory evaluation of serum and pleural fluid, pleural biopsy, bronchoscopy, and lung scan and/or pulmonary arteriogram. RESULTS: In this series in which 45% of the patients had malignant effusions, 19% had paramalignant effusions, and 36% had benign diseases, the pleural fluid cytologic study was the best for establishing a diagnosis. The pleural fluid carcinoembryonic antigen (CEA) levels above 10 had a high specificity (90%) for malignancy but had low sensitivity (37%). The pleural fluid CEA level was increased only in 19% of patients with paramalignant effusions. Although there were statistically significant differences in the mean results on several biochemical tests of pleural fluid, none were very accurate in separating malignant from benign disease. CONCLUSION: From this study, we conclude that patients with an undiagnosed pleural effusion should be evaluated in an individualized stepwise manner. If malignancy is strongly considered, the initial three steps should be relatively noninvasive and include clinical evaluation and cytologic study.     

Allergic bronchopulmonary aspergillosis in a patient with no symptoms of asthma until after bronchial lavage

An asymptomatic 56-year-old man was admitted to our hospital because of an abnormal shadow on a chest X-ray film. Allergic bronchopulmonary aspergillosis was diagnosed on the basis of five findings: eosinophilia, immediate skin reactivity to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, a high concentration of IgE in serum, and central bronchiectasis. He had no symptoms of asthma at the time of diagnosis, but did a few days after he underwent bronchial lavage. We speculate that the asthma attack was related to the bronchial Lavage as follows: First, drainage of mucus plugs by bronchial lavage may have exposed the bronchial epithelium, which had already been sensitized, to aspergillus antigens. Second, the scattered antigen may have dose-dependently stimulated the bronchi. Third, the infection may have increased bronchial responsiveness to the antigen. Symptoms of bronchial asthma are not necessary for the diagnosis of allergic bronchopulmonary aspergillosis.     

Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured preoperatively in 24 patients with colorectal cancer. IL-1 beta was not elevated, IL-6 and IL-8 were markedly elevated, and GM-CSF was slightly elevated. TNF-alpha was not detected in most patients. Serum IL-6 levels correlated closely with serum IL-8 levels and with serum carbohydrate antigen (CA) 19-9 levels. Serum IL-6 levels were significantly higher in patients whose tumors exceeding 5.0 cm in diameter or spreading circumferentially. Serum IL-8 levels showed significant differences according to histological type, being lower in well differentiated adenocarcinoma compared to other types. Serum levels of IL-6 and IL-8 were significantly higher in patients with liver metastasis than in those without liver metastasis and serum levels of both these cytokines were also significantly higher in patients with lung metastasis than in those without lung metastasis. These results suggest that IL-6 and IL-8 may play an important role in the hematogenous metastasis of colorectal cancer.     

Evaluation of eosinophilic cationic protein levels in patients with eosinophilic pneumonia

We investigated the significance of eosinophilic cationic protein (ECP) as a biological indicator of disease activity in patients with eosinophilic pneumonia (EP). ECP levels were measured in serum and bronchoalveolar lavage fluid (BALF) samples from patients with EP or other diffuse interstitial lung diseases and from healthy subjects. Also we performed immunohistochemical staining of lung tissue sections from patients with EP using anti-EG 2 antibody, and computed the correlation between the number of EG 2-positive cells in lung tissues and ECP levels in serum and BALF from patients with EP. Levels of ECP in serum and BALF samples from patients with EP were significantly elevated compared to the levels in samples from other interstitial lung-disease patients and healthy subjects. Additionally, changes in serum ECP levels reflected the clinical courses for EP patients. Approximately 90 percent of the infiltrated eosinophils in tissue sections from patients with EP were EG 2-positive and activated. The number of EG 2-positive cells in lung tissues correlated significantly with levels of ECP in serum and BALF samples from patients with EP. These findings suggested that ECP levels in serum and BALF reflect the degree of eosinophil activation in lung tissues and the degree of disease activity in patients with EP. We concluded that ECP may serve as a useful biological indicator in EP.     

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.     

Birthmarks to worry about. Cutaneous markers of dysraphism

CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.     

Induced expression of the Candida albicans multidrug resistance gene CDR1 in response to fluconazole and other antifungals

Squamous cell carcinoma (SCC) antigen (Ag) present and expressed in normal epithelium and epithelial tissues is used primarily as tumor marker of SCC of the uterine cervix. In this review, we considered factors interfering in vitro with the collection of samples and assay procedures, benign and malignant nongynecological diseases which may be the cause of elevated serum levels of SCC Ag. Contamination with skin or saliva strongly influences SCC Ag levels. SCC Ag is elevated in several benign lesions, including pulmonary (tuberculosis, adult respiratory distress syndrome, pulmonary infiltration with eosinophilia, sarcoidosis, bronchogenic cyst) and skin (eczema, pemphigus, erythroderma epidermitis, psoriasis) diseases. Elevations are observed in SCC malignancies of the head and neck, esophagus, skin, lung, urothelium, anal canal and vulva.     

Physical and genetic localization of the gene encoding the AP-2 transcription factor to mouse chromosome 13

This retrospective study assessed 46 patients with advanced ovarian cancer who had elevated preoperative serum CA 125 (>35 U/ml) and who had another serum CA 125 assay 6-9 days after surgery. Preoperative CA 125 levels were similar in patients with residual disease below 20 mm and in those with larger residuum. The postoperative decline of serum CA 125 was significantly higher in patients with small residual disease at any preoperative serum CA 125 value. By taking 60% as the cutoff of CA 125 decline, the diagnostic accuracy of this parameter in discriminating between patients with residual disease below or above 20 mm improved progressively when we considered patients with increasing preoperative antigen values. However, even in the subset of patients with preoperative serum CA 125 above 400 U/ml, 2 of the 20 patients with less than 20 mm residual disease had a percentage reduction of antigen levels lower than 60%, whereas 5 of the 10 patients with larger than 20 mm residuum had a CA 125 decline higher than 60%. Therefore, we believe that the perioperative changes of CA 125 levels have a limited clinical relevance in the management of patients with ovarian cancer.