[The analysis of tumor growth pattern by endoscopic ultrasonography in patients with depressed type of gastric cancer].
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Biomedical subjects
Publications and source records attributed to Y Takemori.
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The CA 15-3 RIA kit (Centocor Co.) based on a solid-phase radioimmunoassay was evaluated both experimentally and clinically. The results of a basic study of the reproducibility, recovery and dilution were very satisfactory. Serum levels of CA 15-3 were determined in 211 patients with malignancies including 13 breast cancers, 81 patients with benign diseases and 13 controls. Elevated levels of this antigen (greater than 25 U/ml) were observed in 16.7% of esophageal cancers, 9.7% of gastric cancers, 7.9% of colon cancers, 10% of hepatocellular cancers, 10% of biliary tract cancers, 10% of pancreatic cancers, 33% of lung cancers, and 75% of recurrent breast cancers. Thus, in malignant diseases the positivity was low except for recurrent breast cancer. On the other hand, the false-positive rate in benign diseases was only 3.7% and the false-positive cases had a level of 40 U/ml or less. These results indicate that the serum levels of CA 15-3 may have diagnostic value in patients with recurrent breast cancer.
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In order to evaluate the usefulness of serum DU-PAN-2, we determined this antigen in 384 patients with various malignancies and in 215 patients with benign diseases using a sandwich enzyme immunoassay system (Kyowa Medex Co.). Elevated DU-PAN-2 levels (greater than 400 U/ml) were observed in 55% of hepatocellular cancers, 50% of pancreatic cancers, and 43% of biliary tract cancers. On the other hand, most false-positive cases with benign diseases were observed in patients with liver injury, especially in the acute phase of acute hepatitis, chronic active hepatitis, and liver cirrhosis. However, in only a few cases with other benign diseases including pancreatitis, increased levels were found. Moreover, among the pancreatic cancer or biliary tract cancer patients studied, DU-PAN-2 was positive in 7 of the 19 CA 19-9-negative (less than 37 U/ml) patients and 32 of the 68 CEA-negative (less than 5 ng/ml) patients. These results indicate that the assay of DU-PAN-2 by EIA may have diagnostic usefulness in digestive cancer, especially pancreatic cancer or biliary tract cancer.
DU-PAN-2 is a high-molecular-weight glycoprotein defined by a murine monoclonal antibody (MAb) against a pancreatic ductal adenocarcinoma cell line. In order to evaluate the usefulness of this antigen as a tumor marker, we determined the serum level of the antigen by competitive inhibition radioimmunoassay in sera from 139 patients with various malignant tumors, chiefly digestive cancers, 98 patients with different benign diseases and 11 healthy subjects. Values in the healthy subjects were less than 100 U/ml. Levels above 100 U/ml were frequently observed in sera from benign diseases, but levels above 400 U/ml were found in only 6 of the patients with benign diseases. In contrast, levels exceeding 400 U/ml were detected in 72% of patients with pancreatic cancer, 44% of patients with hepatocellular cancer and 40% of patients with biliary tract cancer. The positivity was low in other cancers such as gastric cancer (19%) and colorectal cancer (7%). Serum levels of CEA and CA 19-9 were also determined in cancer patients. Among the pancreatic cancer patients studied, values above 400 U/ml were found in 5 of the 8 CEA-negative patients (less than 5 ng/ml) and 2 of the 3 CA 19-9 negative patients (less than 37 U/ml). These results indicate that determination of the serum DU-PAN-2 can aid in serological diagnosis of cancer of the digestive tract, more particularly of the pancreas.
A simple, rapid and highly sensitive high-performance liquid chromatographic method for the determination of N-acetyl- and N-glycolylneuraminic acids in serum and urine is described. The neuraminic acids, released by hydrolysis of serum and urine, are converted in dilute sulphuric acid with 1,2-diamino-4,5-dimethoxybenzene, a fluorogenic reagent for alpha-keto acids, to highly fluorescent derivatives. The derivatives are separated isocratically within 8 min by reversed-phase chromatography using a Radial-Pak cartridge C18 column and detected fluorimetrically. The limit of detection is 40 fmol (12 pg) for both neuraminic acids in 10-microliters injection volume [0.3 nmol (90 ng)/ml) of serum or urine]. This sensitivity permits the precise determination of the neuraminic acids in 5 microliters of serum or urine. The method was applied to the determination of the neuraminic acids in sera from normal subjects and cancer patients, normal urine and rat serum.
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.
The carbohydrate antigenic determinant (CA 19-9) EIA kit (FUJIREVIO INC) was examined both experimentally and clinically. In the basic study, the standard curve showed linearity from to 240 U/ml, and the intra-and interassay reproducibility was good. Serum levels of CA 19-9 were determined by EIA in 246 cancer patients and 180 patients with benign diseases, and CA 19-9 levels by EIA were compared with those by RIA in concurrent measurement. There was an excellent correlation between the two. The positive of CA 19-9 EIA was almost the same as that of CA 19-9 RIA in cancer patients. False-positive cases by CA 19-9 EIA were somewhat more numerous than those by CA 19-9 RIA in patients with benign diseases, especially liver diseases. However, CA 19-9 assay by EIA is simple and has an excellent reproducibility and accuracy, as does that by RIA. Thus, the CA 19-9 EIA is a very useful assay.
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A simple, rapid and highly sensitive high-performance liquid chromatographic method for the determination of alpha-keto acids in serum and urine is described. In dilute hydrochloric acid, alpha-keto acids are converted by 1,2-diamino-4,5-dimethoxybenzene into highly fluorescent quinoxalinone derivatives. The derivatives are isocratically separated simultaneously within 14 min by reversed-phase chromatography on a Radial-Pak cartridge C18 and detected fluorimetrically. The limits of detection are 10-300 fmol in an injection volume of 10 microliters (40-1200 pmol/ml of serum or urine). This sensitivity permits precise determination of several alpha-keto acids in 5 microliter of serum or urine from healthy persons, and also the determination of phenylpyruvic acid in normal urine which cannot be simultaneously determined by other methods.
A 57-year-old woman was referred to our hospital because of epigastric tumor on Jan. 16, 1980. Two advanced gastric carcinomas were recognized in the antrum and the corpus by X-ray and endoscopic examinations. The biopsy diagnosis was poorly differentiated adenocarcinoma. She was treated with FT-207 suppositories and subcutaneous injection of OK-432 without operation because of a suspicion of ascites and Virchow's metastasis. After five months, the tumor of the corpus disappeared, and, after nine months, that of the antrum changed to a scarlike lesion. On July 30, 1981, total gastrectomy with extended nodal dissection was performed. Histological examination revealed complete absence of carcinoma cells in the stomach and regional lymph nodes.
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.
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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.
Carcinoembryonic antigen (CEA) is important as one of the tumor markers, and enzyme-immunoassay using monoclonal anti-CEA, which is based on the Sandwich method and unnecessary for the treatment of CEA-extract from serum, was tried in this study. The standard curve obtained from this assay showed lineality on low CEA level. Sensitivity could allow to detect CEA below 5 ng/ml of CEA. Correlation between radioimmunoassay and this EIA was not found in especially high CEA-concentration. Reproducibility respect of Intra-assay and Inter-assay had good results. CEA value yielded by dilution of sample serum coincided with nearly expected value; this result indicated that dilution test was effective. CEA value determined by the assay to be necessary for treatment of extract was higher than that by the assay without treatment. Though the number of test samples used for assay of CEA in serum from various diseases were small, we considered it would be appropriate to set up a normal value range in 0.44-3.16 ng/ml (mean +/- 2 SD) and cut off value at 3.9 ng/ml (mean +/- 3 SD). We have been interested in cancer-specificity on monoclonal antibody, but we could not so for evaluate effects of the assay using monoclonal antibody.
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