Giuseppe Del Favero

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.

Natural history of gallstones in non-insulin-dependent diabetes mellitus : a prospective 5-year follow-up

This prospective study was undertaken to assess the natural history of gallstones in patients with non-insulin-dependent diabetes. Four hundred forty outpatients with diabetes mellitus were studied; 81 of these had gallstones diagnosed by ultrasound. On the basis of the information they gave, they were divided into two groups: A, asymptomatic; and B, symptomatic (previous episode(s) of biliary pain) at recruitment. Five years after diagnosis, the patients were recalled and questioned about their symptoms. Three of 81 could not be traced and eight had died from diseases not related to gallstones. Seventy were finally evaluated, 47 belonging to group A, 23 to group B. The cumulative percentage of initially asymptomatic patients who presented with biliary pain or complications during the follow-up was 14.9% (4.2% for complications). Of group A patients, 17% underwent cholecystectomy (one prophylactic, six elective and two emergency). One patient (2.1%) died after operation of obstructive jaundice. Of group B patients, 47.8% had biliary symptoms or complications (8.7% cholecystitis); 21.7% were operated (17.4% elective, 4.3% emergency cholecystectomy). Since few patients with asymptomatic gallstones and non-insulin-dependent diabetes mellitus develop pain or complications over time, prophylactic cholecystectomy is probably not advisable.

Development and Validation of an Endoscopic Classification of Diverticular Disease of the Colon: The DICA Classification

Background: A validated endoscopic classification of diverticular disease (DD) of the colon is lacking at present. Our aim was to develop a simple endoscopic score of DD: the Diverticular Inflammation and Complication Assessment (DICA) score. Methods: The DICA score for DD resulted in the sum of the scores for the extension of diverticulosis, the number of diverticula per region, the presence and type of inflammation, and the presence and type of complications: DICA 1 (≤3), DICA 2 (4-7) and DICA 3 (>7). A comparison with abdominal pain and inflammatory marker expression was also performed. A total of 50 videos of DD patients were reassessed in order to investigate the predictive role of DICA on the outcome of the disease. Results: Overall agreement in using DICA was 0.847 (95% confidence interval, CI, 0.812-0.893): 0.878 (95% CI 0.832-0.895) for DICA 1, 0.765 (95% CI 0.735-0.786) for DICA 2 and 0.891 (95% CI 0.845-0.7923) for DICA 3. Intra-observer agreement (kappa) was 0.91 (95% CI 0.886-0.947). A significant correlation was found between the DICA score and C-reactive protein values (p = 0.0001), as well as between the median pain score and the DICA score (p = 0.0001). With respect to the 50 patients retrospectively reassessed, occurrence/recurrence of disease complications was recorded in 29 patients (58%): 10 (34.5%) were classified as DICA 1 and 19 (65.5%) as DICA 2 (p = 0.036). Conclusions: The DICA score is a simple, reproducible, validated and easy-to-use endoscopic scoring system for DD of the colon.

Clinical Utility of TPS, TPA and CA 19-9 Measurement in Pancreatic Cancer

UNLABELLED The aims of this study were to (1) evaluate the diagnostic utility of a new tumor marker, TPS, with respect to TPA and CA 19-9 in patients with pancreatic cancer; (2) ascertain the reliability of the markers in predicting survival, and (3) evaluate the effect of liver dysfunction on the results. CA 19-9, TPA and TPS were measured in the serum of 19 control subjects, 42 patients with pancreatic cancer, 29 with chronic pancreatitis, and 52 with extrapancreatic diseases. CA 19-9 was confirmed to be the best serological indicator of pancreatic cancer, while TPA and TPS lacked both sensitivity and specificity. Pancreatic cancer patients with liver metastases had higher mean CA 19-9 and TPA, but not TPS, values than pancreatic cancer patients without metastases. A shorter survival time was associated with the presence of liver metastases and with higher serum tumor marker levels. CA 19-9, TPA and TPS were found to be correlated with liver function test results (ALT, ALP and bilirubin). IN CONCLUSION (1) TPS adds no significant information to that obtained using CA 19-9 in the diagnosis of pancreatic cancer; (2) CA 19-9 and TPA, but not TPS, are influenced by the presence of liver metastases; (3) the main factor to influence survival is advanced disease, which is in turn associated with higher tumor marker levels, and (4) liver dysfunction can influence not only CA 19-9 and TPA, as already described, but also TPS.

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.

C-JUN and CPP32 (CASPASE 3) in human pancreatic cancer: Relation to cell proliferation and death

Introduction There is strong evidence that tumor growth is not only a result of uncontrolled cell proliferation but also of decreased apoptosis. Aims To ascertain the expression of c-Jun in specimens of pancreatic duct cancer and to evaluate its correlation with CPP32, apoptotic index, and proliferation index (MIB-1). Methods Tissue samples were collected from 23 patients with pancreatic duct cancer who had not received chemotherapy nor radiation therapy before surgery. In these specimens we determined the expression of c-Jun protein, CPP32, and MIB-1 by immunohistochemical method. Apoptosis was studied by the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick end labeling method. Results CPP32/caspase3 was expressed in 83% and c-Jun in 87% of primary lesions. Three of 23 samples were completely negative for c-Jun, and 4 of 23 were negative for CPP32. Three of 4 specimens negative for CPP32 showed low or negative c-Jun. A significant correlation was found between CPP32/caspase3 and c-Jun (r = 0.51;p < 0.01) and between c-Jun and MIB-1 (r = 0.57;p < 0.004). No correlation was found between CPP32, c-Jun, MIB-1, and apoptotic index. Conclusions The positive correlation between the expression of c-Jun and CPP32 and the absence of both in the same specimens suggest that a common factor or common factors induce the expression of both genes. Pancreatic cancer tissue with an increased percentage of proliferating tumor cells showed also a strong expression of c-Jun, which supports the hypothesis that this oncogene may be involved in the growth of pancreatic cancer. We hypothesize that under different extracellular stimuli both death and proliferation are activated in neoplastic cell, probably under the control of transcription factor AP-1.

Hepatic changes and serum ferritin in pancreatic cancer and other gastrointestinal diseases: the role of cholestasis

Serum ferritin, prealbumin, pseudocholinesterase, α-1-antitrypsin and caeruloplasmin were determined in control subjects and patients with pancreatic cancer, chronic pancreatitis or extra-pancreatic disease mainly of gastrointestinal origin, in order to investigate the different hepatic changes which influence serum ferritin in chronic pancreatic and other digestive diseases. Increased circulating ferritin was found in pancreatic cancer and extra-pancreatic disease when compared to controls. Correlations were detected between ferritin and the other proteins investigated and between ferritin and total bilirubin, alkaline phosphatase and alanine aminotransferase. Multiple regression analysis demonstrated that cholestasis accounts for 45% of circulating ferritin, the acute-phase response accounted for 18% and decreased liver function accounted for 11%. We conclude that the increase in serum ferritin in chronic pancreatic and other gastrointestinal diseases largely depends on liver changes, with cholestasis probably playing a primary role.

Serum phospholipase A2 activity in chronic pancreatic diseases.

This study was performed to investigate the phospholipase A2 (PLA2) serum activity in patients with chronic pancreatic disease. PLA2, elastase-1, total, and pancreatic isoamylase were evaluated in 40 control subjects, 28 patients with pancreatic cancer, 51 with chronic pancreatitis, and 36 with extrapancreatic diseases, mainly of gastrointestinal origin. Elastase-1, PLA2, and pancreatic isoamylase were increased in 56%, 25%, and 15% of patients with pancreatic cancer, and in 40%, 31%, and 41% of subjects with chronic pancreatitis. All four enzymes gave pathological values in a number of patients with extrapancreatic diseases. We conclude that the diagnostic efficacy of phospholipase A2 in chronic pancreatic disease is similar to that of other well known pancreatic enzymes, with an unsatisfactory sensitivity and specificity.

Is CA 242 Really a New Tumour Marker for Pancreatic Adenocarcinoma

CA 242, a sialylated carbohydrate epitope situated on the same macromolecule as CA 50 has been proposed as a new tumour marker for pancreatic cancer (PC). The aims of the present study were: (1) to evaluate serum CA 242 versus CA 19-9 in PC patients, and (2) to assess whether these markers can predict tumour spread or patient survival. We studied 59 healthy controls, 27 PC patients, 12 chronic pancreatitis cases, 107 with extra-pancreatic gastrointestinal tumours, 30 with benign jaundice and 24 with benign extra-pancreatic gastrointestinal diseases. Mean CA 242 values were significantly higher in PC than in any other group; CA 19-9 showed a similar pattern. The best diagnostic efficacy (ROC curves analysis) in diagnosing PC was 86% for CA 242 and 84% for CA 19-9, using cut-off values of 60 and 80 U/ml, respectively. In PC, serum levels of both markers were unrelated to tumour spread or size; in PC patients with high levels of CA 242 or CA 19-9 survival was significantly shorter. CA 242 and CA 19-9 were correlated both when considering all the patients together (r = 0.962, p < 0.001) and PC alone (r = 0.880, p < 0.001). Given the very close relationship between CA 242 and CA 19-9, we tested for cross-reactivity between CA 242 antigen and CA 19-9 antibody: CA 242 antigen with CA 19-9 antibody produced a similar curve to CA 242 antigen and its corresponding antibody. In conclusion, CA 242 showed similar diagnostic values to CA 19-9 in assessing PC patients; both seem unrelated to tumour size or spread, but seem to predict survival. Their remarkably similar behaviour is due to cross-reactivity between CA 242 antigen and CA 19-9 antibody, so CA 242 cannot, in our opinion, be considered a new tumour marker for PC.