Diagnostic significance of cancer-associated carbohydrate antigen (CA19-9) concentrations in pancreatic juice: analysis in pure pancreatic juice collected by endoscopic aspiration and immunohistochemical study in chronic pancreatitis.

This study evaluated the diagnostic significance of concentrations of the cancer-associated carbohydrate antigen CA19-9 in pure pancreatic juice (PPJ) collected by endoscopic cannulation. We also attempted to elucidate the features and source of the increased CA19-9 concentration found in the pancreatic juice of patients with chronic pancreatitis (CP) by means of immunohistochemical staining. The mean output as well as the mean concentration of CA19-9 in each of the four fractions collected was highest in patients with pancreatic cancer (PC) and also was elevated significantly in patients with CP compared with controls. However, CA19-9 concentrations were not elevated in patients with cholecystolithiasis. When the cutoff value was set as the mean concentration + 2SD of the controls, significantly elevated concentrations of CA19-9 were found in the third fraction (secretory phase) in 90% of the patients with PC and 66% of the patients with CP. Immunohistochemical staining revealed that CA19-9 was expressed more widely in the ductal cells of CP tissues than in those of normal pancreatic (NP) tissues, with CP tissue showing more CA19-9-positive ductal cells per area than NP tissues. In NP tissue, CA19-9 was localized to the apical surface and supranuclear regions (apical type) in all the ductal cells stained by the antigen, while approximately 50% of cases with CP exhibited a cytoplasmic pattern showing a loss of polarity of the antigen expression. Moreover, this cellular localization pattern was more pronounced in the small ducts that had proliferated and aggregated following the destruction of lobules in CP.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol side-chain cleavage enzyme activity and cytochrome P-450 content in adrenal mitochondria of a patient with congenital lipoid adrenal hyperplasia (Prader disease).

An autopsied case with congenital lipoid adrenal hyperplasia (Prader disease) was presented. The cholesterol side-chain cleavage (SCC) enzyme activity in adrenal mitochondria of this case was assayed with [3H]cholesterol as substrate, combined with purified bovine adrenodoxin and adrenodoxin reductase, by measuring the amount of [3H]pregnenolone formed. The cytochrome P-450 content was also measured by recording the difference absorption spectra of carbon monoxide-complexed P-450. The cholesterol SCC enzyme activity in adrenal mitochondria of Prader disease was 0.81 nmol pregnenolone/nmol P-450 per min, which was approximately 10% of that in normal tissue. The content of cytochrome P-450 was 0.074 nmol/mg protein, which was about half of that in controls. These results indicate that there is a cholesterol SCC enzyme deficiency in adrenal mitochondria in this disease.

[A new tumor marker--novel gamma-GTP isoenzyme].

The authors discussed the clinical significance and some properties of the novel gamma-GTP isoenzyme (novel gamma-GTP) which was reported to be specific for sera of hepatocellular carcinoma (HCC) in our previous publications. One or more of specific bands (novel gamma-GTP) such as bands II, II' and I' were electrophoretically detectable in 109 (55%) of 200 patients with HCC, but only in 3% of 279 patients with other hepatobiliary diseases. Novel gamma-GTP was found in 38% of HCC patients with AFP levels below 400 ng/ml. The incidence of novel gamma-GTP was independent of the clinical stage as classified by liver scanning. Even in stage I, where filling defects were not seen, the incidence was 52%. It is concluded that novel gamma-GTP is useful in diagnosis of HCC patients with low levels of AFP or at a relatively early stage. Some properties of gamma-GTP purified from HCC tissues were investigated and compared with those of the normal kidney enzyme. The enzymes from HCC and kidney were identical in enzymatic and immunological properties, whereas a considerable difference was observed in electrophoresis, Con A affinity, effect of neuraminidase and isoelectric point. Respective bands II, II' and I' could be differentiated in Con A affinity and neuraminidase reaction. These results support the possibility that novel gamma-GTP in sera of HCC patients is largely due to a difference in carbohydrate moiety of gamma-GTPs.

[Evaluation of CA 19-9 radioimmunoassay].

A carbohydrate antigenic determinant (CA 19-9) which monoclonal antibody (1116 NS-19-9) recognizes was found by Koprowski et al in 1979. Recently DelVillano et al have developed a forward sandwich radioimmunoassay (RIA) for quantitative measurement of CA 19-9. This CA 19-9 RIA Kit (CENTOCOR) was examined both experimentally and clinically. In the basic study, the standard curve obtained from this assay showed liniality, and the reproducibility of Intra-assay and Inter-assay was good. In the clinical study, using 37 U/ml as the reference value, the CA 19-9 RIA provided excellent sensitivity for pancreatic cancer (84%) and cancer of the biliary tract (69%), and excellent specificity, even among patients with benign gastrointestinal disorders. Moreover, CA 19-9 was suggested to be useful for monitoring of pancreatic cancer. Thus, the data indicate that CA 19-9 RIA can be a useful tumor marker for pancreatic cancer.

[Clinical course of patients with hepatocellular carcinoma after surgical resection, with emphasis on the occurrence of hepatic failure].

Postoperative course including serial changes in values of liver function tests and occurrence of hepatic failure was investigated in 59 patients with hepatocellular carcinoma. Eleven cases out of 59 patients were associated with chronic hepatitis (CH group), while remained 48 cases were with liver cirrhosis (25 cases of group A and 23 of group B in Child's classification). There was no significant difference in survival rate or recurrence rate after operation among these three groups. Hepatic failure within one year after hepatectomy was observed in 9%, 28% and 91% of patients in groups CH, Child's A and Child's B, respectively, and the frequency of occurrence of hepatic failure in Child's B group was significantly higher than those of groups CH and Child's A. Hepaplastin test and serum albumin levels recovered from the decline after hepatectomy in groups CH and Child's A. On the other hand, no recovery was found in Child's B group as well as lower levels before operation and that was thought to be the major reason for the frequent occurrence of hepatic failure in Child's B group.

[Novel gamma-GTP isoenzyme and hepatocellular carcinoma].

The authors discussed the clinical significance and some properties of the novel gamma-GTP isoenzyme (novel gamma-GTP) which was reported to be specific for sera of hepatocellular carcinoma (HCC) in our previous publications. One or more of specific bands (novel gamma-GTP) such as bands II, II' and I' were electrophoretically detectable in 109 (55%) of 200 patients with HCC, but only in 3% of 279 patients with other hepatobiliary diseases. Novel gamma-GTP was found in 38% of HCC patients with AFP levels below 400 ng/ml. The incidence of novel gamma-GTP was independent of the clinical stage as classified by liver scanning. Even in stage I, where filling defects were not seen, the incidence was 52%. It is concluded that novel gamma-GTP is useful in diagnosis of HCC patients with low levels of AFP or at a relatively early stage. Some properties of gamma-GTP purified from HCC tissues were investigated and compared with those of the normal kidney enzyme. The enzymes from HCC and kidney were identical in enzymatic and immunological properties, whereas a considerable difference was observed in electrophoresis, Con A affinity, effect of neuraminidase and isoelectric point. Respective bands II, II' and I' could be differentiated in Con A affinity and neuraminidase reaction. These results support the possibility that novel gamma-GTP in sera of HCC patients is largely due to a difference in carbohydrate moiety of gamma-GTPs.

Factors affecting serum levels of CA 19-9 with special reference to benign hepatobiliary and pancreatic diseases.

In order to elucidate the factors affecting the serum levels of CA 19-9, we analyzed sera of 79 patients with pancreatic cancer and 169 with non-malignant diseases, chiefly consisting of hepatobiliary and pancreatic diseases. Serum CA 19-9 values in patients with pancreatic cancer had no relation to the location of the tumor or presence of jaundice. Similarly, no tendency was observed as to the location and size of tumor or to the grade of differentiation in 12 CA 19-9-negative patients with pancreatic cancer. Serum levels of CA 19-9 in patients with cholelithiasis complicated by cholangitis frequently showed markedly high values, but then rapidly normalized in parallel with the subsiding of inflammation. The behaviour of serum CA 19-9 showed little relation to renal or hepatic failures or to intrahepatic cholestasis. However, slightly elevated levels of the antigen were found in more than half of those patients with fulminant hepatitis showing massive necrosis. In chronic pancreatitis, the prevalence was only 8%; however, an increase was observed at the time of exacerbation in 2 of 5 positive patients. There was hardly any increase in serum levels of CA 19-9 after endoscopic retrograde cholangiopancreatography (ERCP), although serum levels of pancreatic enzymes rose after ERCP in almost all patients. Thus, it appears that CA 19-9 does not easily escape into the bloodstream, unlike pancreatic enzymes.

Serum tumor markers in patients with hepatocellular carcinoma: diagnosis of alpha-fetoprotein -low or -negative patients.

The presence of specific gamma-glutamyl transpeptidase isoenzyme (gamma-GTPI) and variant alkaline phosphatase (VAALP) were concurrently determined, and levels of basic fetoprotein (BFP) and carcinoembryonic antigen (CEA) in addition to alpha-fetoprotein (AFP) were measured in 144 hepatocellular carcinoma (HCC) patients in order to evaluate the diagnostic value of these tumor markers with respect to AFP-low or -negative patients and the tumor stage. Serum AFP levels below 400 ng/ml, commonly seen in sera of hepatobiliary diseases other than HCC, were noted in 42% of the patients. The diagnostic usefulness was increased by combination assay of these markers except for CEA. A definitive diagnosis of HCC could be made in 78% of the patients by a combination of gamma-GTPI, VAALP and AFP. Moreover, a diagnosis of malignancy could be made in 87% of cases by the inclusion of BFP. The prevalence of BFP and CEA increased in proportion to the tumor stage, whereas that of AFP and gamma-GTPI were independent of stage and were high even in patients in comparatively early stages. Furthermore, secreting type markers such as AFP and gamma-GTPI were relatively useful for diagnosis of HCC when the lesions were still small.

[Evaluation of the measurement of serum carcinoembryonic antigen (CEA) levels using monoclonal antibody].

We measured serum carcinoembryonic antigen (CEA) levels in 164 cancer patients, 153 patients with benign diseases and 45 healthy controls using monoclonal antibody and compared CEA levels by monoclonal antibody (m-CEA) with those by polyclonal antibody (p-CEA). There was a good correlation between m-CEA and p-CEA, especially in cancer patients. The positively of m-CEA was almost the same as that of p-CEA in cancer patients. But, false-positive cases by m-CEA were less common than by p-CEA in non-cancerous patients. Thus, the measurement of m-CEA was not less useful than that of p-CEA.

Segmental hepatic iron deposition due to peripheral portal vein tumor thrombus: MR features.

We report a case of segmental hepatic iron deposition in the parenchyma peripheral to a tumor-thrombosed intrahepatic portal vein. On MR imaging, especially fast low-angle shot image, the liver parenchyma was demonstrated as a hypointense area with segmental and wedge-shaped configuration. Absence of portal blood flow may cause such segmental hepatic iron deposition.

Hepatocellular carcinomas with excessive copper accumulation: CT and MR findings.

Results of orcein staining and findings obtained with non-contrast-medium-enhanced computed tomography (CT) and magnetic resonance (MR) imaging (T1- and T2-weighted images) were compared for 53 histologically confirmed hepatocellular carcinomas (HCCs). HCCs were 5 cm in the largest diameter. Three lesions with diffuse and strong orcein staining were highly attenuating on nonenhanced CT images. Electron x-ray microanalysis of one of them revealed copper. The high attenuation value at nonenhanced CT may have been due to the abundant copper-binding protein in the cancer cells. The difference between orcein staining results and attenuation patterns at CT was statistically significant (chi 2, P less than .001). It could not be concluded that the paramagnetic effects of copper in HCC had an influence on signal intensity on MR images. The difference between orcein staining results and signal-intensity patterns on T1- and T2-weighted images was not statistically significant.

Measurement of sialylated stage-specific embryonic antigen-1 in pure pancreatic juice for the diagnosis of pancreatic cancer.

The diagnostic significance of measuring sialylated stage-specific embryonic antigen-1 (SLX) in pure pancreatic juice was evaluated in 20 patients with pancreatic cancer, 43 with chronic pancreatitis, 13 with cholecystolithiasis, and 15 control individuals. Four fractions of pure pancreatic juice were collected sequentially from the pancreatic duct by endoscopic cannulation. The SLX levels in all four fractions of pure pancreatic juice were significantly higher in patients with pancreatic cancer than in controls. On the other hand, patients with chronic pancreatitis or cholecystolithiasis did not have SLX levels that significantly differed from those of controls in any fraction. When the cut-off value was set as the mean concentration +2 times the standard deviation of the control values, the positive rates of SLX in the first fraction (washout phase) and the third fraction (secretory phase) of pure pancreatic juice from pancreatic cancer were 55% (11/20) and 40% (8/20), respectively. Although the false positive rates in the first fraction were high in chronic pancreatitis (30%) and cholecystolithiasis (31%), such high SLX levels in the third fraction were found only in one (2%) patient with chronic pancreatitis and in one (8%) with cholecystolithiasis. The specificities of the test for pancreatic cancer in the first fraction and the third fraction were 70% (39/56) and 96% (54/56), respectively. These results indicate that the measurement of SLX in the third fraction of pure pancreatic juice is useful as a specific marker for pancreatic cancer.