A. Panucci

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 extra‐pancreatic diseases. Cancer 57:1576–1579, 1986.

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.

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 elastase 1 in chronic pancreatic disease

SummaryElastase 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.

Tissue polypeptide antigen (TPA) in pancreatic cancer diagnosis.

Tissue polypeptide antigen (TPA) is a protein produced by rapidly growing tissues, such as placenta and neoplasms (Bj6rklund et al., 1976; Bjorklund, 1978). Increased serum levels of this antigen have been observed in a variety of malignant diseases of different origin: i.e. lung, breast, stomach and colorectal cancer (MenendezBotet et al., 1978; Schlegel et al., 1981). They have also been detected in several acute and chronic inflammatory conditions, especially liver cirrhosis and acute hepatitis (Bj6rklund, 1980). Only the occasional report appears in the literature on TPA measurements in pancreatic cancer (Andriulli et al., 1983). Moreover few data are available on the utility of serum TPA assay in the differential diagnosis between pancreatic cancer and chronic pancreatitis (Panucci et al., 1984). The aim of the present investigation was to evaluate the role of TPA in detecting pancreatic malignancy and its value in distinguishing pancreatic cancer from other pancreatic and benign extra-pancreatic gastrointestinal conditions. A total of 106 subjects were studied: 29 control subjects (19 male, 10 female, age range, 37-66 years) who were healthy members of the medical staff and blood donors; 28 with pancreatic cancer of duct cell origin (Cubilla & Fitzgerald, 1978) (20 male, 8 female, aged 43-71) always histologically confirmed; staging was: T,NoMo (3), T2N1Mo (6), T2N1M, (9), T3AM, (10); 24 with chronic pancreatitis (22 male, 2 female, aged 26-64) (7 with calcified chronic pancreatitis) diagnosed on the basis of the following examinations: abdominal x-ray for pancreatic calcifications, pancreatic ultrasonography, endoscopic retrograde pancreatography, CAT scanning. The diagnosis of chronic pancreatitis was always histologically confirmed on surgical biopsies. Twenty five were affected by gastrointestinal extra-pancreatic diseases of a nonmalignant nature (11 male, 14 female, aged 37-81): liver cirrhosis (6 cases), primary biliary cirrhosis (1), gallstones (4), common duct stones (3), benign stenosis of the papilla of Vater (2), chronic gastritis (4), duodenal ulcer (3), irritable colon (2). Diagnosis was made on the basis of the clinical picture and on the results of specific radiological and histological procedures. Serum TPA determination was performed by an RIA procedure (Prolifigen RIA kit, AB Sangtec Medical, Bromma, Sweden). The intra-assay (no = 15, mean= 125.5, s.d. =6.2 UI-) and interassay (no =7, mean= 122.6, s.d. = 12.3 U -1) coefficients of variation were 4.9% and 10.0% respectively. Serum specimens were always frozen at -20°C immediately after collection, and the

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.

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.

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.

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.

Pancreolauryl test in chronic pancreatitis.

SummaryThe 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.