Pharmacokinetics of GM1 ganglioside following parenteral administration.

The pharmacokinetic parameters of monosialotetrahexosylganglioside (GM1) have been determined in healthy volunteers at 3 dose levels: 100, 200, 300 mg. Each dose was administered to separate groups of 12 volunteers. GM1 levels were determined in plasma, urine, and faeces by a method based on the property of the cholera toxin beta subunit to react specifically with GM1 ganglioside. A non-compartmental model was applied to determine standard pharmacokinetic parameters. The average AUC increased with dose (1002 +/- 121.2, 1306 +/- 146.1, 3155 +/- 121.6 micrograms mL-1 h after 100, 200, 300 mg, respectively). Plasma clearance was less than 3 mL min-1 and the distribution volume was close to the plasma volume (on average between 4.3 and 7.2 L). Mean residence time was about 43 h for all doses. GM1 was not detected in urine, while in faeces the amount of GM1 determined was similar to the baseline values obtained before dosing.

Combined determination of serum CA 19-9 and tissue polypeptide antigen: why no improvement in pancreatic cancer diagnosis?

CA 19-9 and tissue polypeptide antigen (TPA) were determined in the sera of 28 control subjects, 29 patients with pancreatic cancer, 26 with chronic pancreatitis and 62 with benign and malignant extra pancreatic diseases in order to compare their usefulness in diagnosing pancreatic cancer, to verify whether the combined assessment of the two indices could improve the results given by a single parameter and to speculate on the role of liver dysfunction in increasing their serum levels. The sensitivity, specificity and accuracy of CA 19-9 and TPA in diagnosing pancreatic malignancy were: 76, 85 and 61% for CA 19-9 and 79, 52 and 32% for TPA. The receiver-operating characteristic curves showed that CA 19-9 and TPA similarly discriminate pancreatic cancer from controls and chronic pancreatitis, while CA 19-9 is more useful than TPA in differentiating pancreatic malignancy from benign and malignant extra pancreatic abdominal diseases. TPA did not seem to add further information as compared to CA 19-9 alone when both markers were combined. Liver dysfunction may contribute to increasing serum levels of both markers.

Tissue polypeptide antigen, galactosyltransferase isoenzyme II and pancreatic oncofetal antigen serum determination: role in pancreatic cancer diagnosis.

The clinical usefulness of tissue polypeptide antigen, galactosyltransferase II and pancreatic oncofetal antigen was evaluated in detecting pancreatic cancer and in differentiating this malignancy from chronic pancreatitis and other diseases (mainly of the liver and biliary tract) which may enter in differential diagnosis. TPA seems to be the most sensitive among these indices in detecting pancreatic cancer and appears to discriminate this malignancy quite satisfactorily from chronic pancreatitis. It is also frequently pathological in a number of other diseases and is influenced by the presence of liver dysfunction. GT II and POA do not grossly differ from TPA in specificity, but they appear to be less sensitive. Both are frequently pathological in hepato-biliary diseases. All these markers seem, therefore, to be of limited value in the diagnosis of pancreatic cancer.

Pancreolauryl test in chronic pancreatitis.

The pancreolauryl test was performed in 30 subjects with chronic pancreatitis, in order to evaluate its behavior in relation to the duration of the clinical history and the presence of pancreatic calcifications, diabetes mellitus, jaundice, and pancreatic pseudocysts. A significant inverse linear correlation was found between the onset of symptoms and FDL test values. While calcifications and diabetes were present in patients with both normal and abnormal test results, those with pseudocysts or jaundice always had pathological results.

CA 19-9 and carcinoembryonic antigen in pancreatic cancer diagnosis.

CA 19-9 (Centocor, Malvern, PA) and carcinoembryonic antigen (CEA), two recently developed immunoradiometric assays utilizing monoclonal antibodies, were evaluated in the sera of 139 subjects in order to assay their individual and combined value in pancreatic cancer diagnosis and to assess the influence of jaundice. Sensitivity, specificity, and accuracy in detecting pancreatic cancer were 69%, 85%, and 54% for CA 19-9; and 28%, 78%, and 6% for CEA, respectively. Combined evaluation gave the highest specificity (95%) when both, and the highest sensitivity (79%) when at least one, gave pathologic results. The receiver-operating characteristic curves demonstrated that CA 19-9 is more discriminating than CEA, for any serum value. A correlation between serum bilirubin and CA 19-9 was demonstrated in pancreatic and extrapancreatic disease. CEA determination, performed using monoclonal antibodies, seems to be unsatisfactory as compared to CA 19-9 in pancreatic cancer diagnosis, and combined assessment does not improve the results of CA 19-9 alone. Jaundice may influence serum CA 19-9 in pancreatic and extrapancreatic diseases.

[The role of CEA, CA 19-9 and TPA in the diagnosis of pancreatic cancer. Evaluation by discriminant analysis]. / Ruolo del CEA, CA 19-9 e TPA nella diagnosi di carcinoma pancreatico. Valutazione con l'analisi discriminante.

In order to assess the relative value of CA 19-9, Tissue Polypeptide Antigen (TPA) and Carcinoembryonic Antigen (CEA), evaluated alone and in combination, in diagnosing pancreatic malignancy, serum CA 19-9, TPA and CEA were determined in 25 control subjects (CS), 26 pancreatic cancer (PC), 23 chronic pancreatitis (CP) and 21 benign extra-pancreatic diseases (EPD). The three markers were able to allocate the subjects correctly in 56.8% of the cases (CS 100%, PC 73.1%, CP 17.4%, EPD 28.6%). Sensitivity, specificity and diagnostic accuracy in detecting pancreatic cancer were respectively: 77%, 91% and 68% for CA 19-9; 92%, 75% and 67% for TPA; 50%, 84% and 34% for CEA; 73%, 91% and 64% for the three parameters evaluated simultaneously. CA 19-9 and TPA appear to be useful indices of pancreatic cancer with a satisfactory specificity when related to chronic pancreatitis; their diagnostic value seems to be comparable and better than that of CEA; the combination of these markers does not improve the results obtained by CA 19-9 or TPA alone.

Serum elastase 1 and immunoreactive trypsin in chronic pancreatic disease: is there any relationship with trypsin inhibitors?

In order to investigate modifications of serum levels of elastase 1, immunoreactive trypsin, alpha 1-antitrypsin and alpha 2-macroglobulin in chronic pancreatic disease, and to speculate on the possible relationships among these parameters, the enzymes and inhibitors were assayed in the sera of 33 control subjects, 34 pancreatic cancer, 28 chronic pancreatitis and 36 extra-pancreatic diseases. An increase of elastase 1, alpha 1-antitrypsin and alpha 2-macroglobulin was detected in pancreatic cancer, chronic pancreatitis and extra-pancreatic diseases; no changes were found for serum immunoreactive trypsin. Multiple regression analyses showed that only 7% of elastase 1 was explained by inhibitors with alpha 1-antitrypsin playing a major role. Inhibitors did not influence immunoreactive trypsin. Our data indicate that the variations of the serum levels of proteases and antiproteases in chronic pancreatic disease are probably independent of each other.

Carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) in pancreatic cancer. Role of age and liver dysfunction.

In order to ascertain the clinical usefulness of CA 19-9 in detecting pancreatic cancer in comparison with CEA, and to verify the influence of age and liver dysfunction on serum levels of these two antigens, serum CA 19-9 and CEA were assessed in 32 control subjects, 32 patients with pancreatic cancer, 26 with chronic pancreatitis and 43 with gastrointestinal extra-pancreatic diseases. Sensitivity, specificity and diagnostic accuracy of CA 19-9 and CEA in detecting pancreatic cancer were: 69% and 44%, 91% and 75%, 60% and 19% respectively. Linear correlations were observed between the age of the subjects on the one hand and CA 19-9 or CEA on the other. Significant relationships were also noticed between alanine-amino-transferase or bilirubin serum levels and CA 19-9 values. Serum CA 19-9 seems to be a better diagnostic tool than CEA in the assessment of pancreatic cancer; nevertheless the influence of liver dysfunction and age to some extent limits the diagnostic value of CA 19-9.

Is tissue polypeptide antigen more accurate than serum CEA for diagnosing pancreatic cancer?

Tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) were determined in the sera of 36 control subjects, 30 patients with pancreatic cancer, 35 with chronic pancreatitis and 25 with non-pancreatic digestive disease to evaluate their role in detecting pancreatic malignancy. Abnormal values of TPA and CEA were found in 28 and 19 of 30 patients with pancreatic cancer, and in four and seven of 35 patients with chronic pancreatitis, respectively. Raised titres of TPA were observed more often than equivalent serum CEA in simulated pancreatic diseases. The receiver-operating (ROC) characteristic curves showed that TPA was more discriminating than CEA in detecting pancreatic cancer. Specificity was enhanced when both titres were abnormally high and sensitivity when one titre was raised, but the diagnostic accuracy of TPA alone has not improved, which satisfactorily discriminates pancreatic cancer from chronic pancreatitis.

Copper, zinc and copper/zinc ratio in chronic pancreatitis and pancreatic cancer.

Serum copper and zinc levels and their ratio were evaluated in 48 control subjects, 29 patients with pancreatic cancer, 46 with chronic pancreatitis and 32 with extra-pancreatic diseases, with the purpose of ascertaining modifications in chronic pancreatic disease. Hepatic involvement and age were also investigated as possible factors influencing results. Cu/Zn ratio was found to be significantly increased in pancreatic cancer (2.66 +/- 0.16, mean +/- SE) as compared to controls (1.39 +/- 0.06, p less than 0.001), chronic pancreatitis (1.82 +/- 0.09. p less than 0.001) and extra-pancreatic diseases (1.81 +/- 0.18, p less than 0.001), but without practical clinical value. Serum zinc levels appear to decrease with age, while copper and Cu/Zn ratio increase. However, covariance analysis demonstrated that age does not play an important role in influencing copper and Cu/Zn ratio. A decreased liver synthetic function, at least in part age-related, seems to be an additional factor in decreasing serum zinc values.

Serum deoxyribonuclease and ribonuclease in pancreatic cancer and chronic pancreatitis.

Serum ribonuclease (RNase) and deoxyribonuclease (DNase) were investigated in 18 control subjects, and in 22 patients with pancreatic cancer, 13 with chronic pancreatitis and 29 with extrapancreatic diseases in order to assess their clinical usefulness in pancreatic cancer diagnosis and to evaluate whether modifications were consensual and/or age-related. Increased DNase and RNase values were found not only in a notable proportion of pancreatic cancer, but also in chronic pancreatitis and extra-pancreatic diseases. Thus the clinical value of both enzymes in pancreatic cancer diagnosis is negligible. DNase does not seem to be strictly age-dependent, whereas serum RNase does. Elevated levels of the two enzymes, when present, were consensual, suggesting that factors involved in such an increase were partially common to both.

Serum elastase 1 in chronic pancreatic disease.

Elastase 1 and immunoreactive trypsin were assessed by a RIA technique in the sera of 29 control subjects, 24 pancreatic cancer patients, 22 patients with chronic pancreatitis and 31 with extra-pancreatic diseases to ascertain and compare their usefulness in chronic pancreatic disease diagnosis. Increased levels of elastase 1 were detected in 60.9% of pancreatic cancer and in 61.1% of chronic pancreatitis patients; low values were found in only two subjects with pancreatic disease. A close correlation between the two enzymes was found in patients suffering from pancreatic cancer and chronic pancreatitis. These data suggest that serum elastase 1, as well as immunoreactive trypsin, is of limited value in chronic pancreatic disease diagnosis; increased levels of the two enzymes always occur simultaneously; low immunoreactive trypsin values together with normal elastase 1 serum levels are detectable in a number of patients with chronic pancreatitis and severe exocrine insufficiency.

CEA and ferritin in chronic pancreatic disease: a comparative evaluation.

CEA and ferritin were determined in 90 subjects with the aim of comparing their value in the diagnosis of pancreatic malignancy. Ferritin was shown to be more sensitive than CEA in detecting pancreatic cancer patients (68.4% and 57.9%, respectively) all of whom were, however, in an inoperable stage. In contrast, CEA showed a higher specificity as compared to ferritin (77.4% and 47.2%, respectively), the latter being frequently increased in inflammatory conditions such as chronic pancreatitis. The simultaneous assessment of CEA and ferritin showed the highest sensitivity when either parameter was found to be pathological and the highest specificity when both were. The receiver-operating characteristic curves demonstrated that CEA is more discriminating than ferritin for all serum values. Neither ferritin nor CEA may be considered a practically suitable marker of pancreatic cancer.

CA 19-9 in the differential diagnosis between pancreatic cancer and chronic pancreatitis.

CA 19-9 serum concentration was determined by a immunoradiometric technique in 130 subjects to evaluate its role in differentiating pancreatic cancer from chronic pancreatitis. Two threshold values were chosen, 17 and 37 U/ml. With the former, sensitivity, specificity and diagnostic accuracy were 86.7, 62.3 and 49.0 respectively, with the latter 73.3, 87.0 and 60.3%. The receiver-operating characteristic curves demonstrated a satisfactory discriminating capacity of CA 19-9 as regards pancreatic cancer and chronic pancreatitis; in contrast, the discrimination was poor for other gastrointestinal diseases, mainly of a malignant nature.