Biomedical subjects
Publications and source records attributed to N Zamcheck.
Preoperative serum CEA values showed prognostic usefulness and correlated with established histopathologic prognostic parameters. CEA levels provide an additional useful prognostic index of a complex immunopathologic process. The best prognostic appraisal of the individual patient can be achieved by a complete assessment of all participating factors.
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Plasma carcinoembryonic antigen (CEA) and serum enzyme levels of phosphohexose isomerase (PHI), gamma-glutamyl transpeptidase (psi-GTP), and lactate dehydrogenase (LDH) were measured in 147 patients with malignancy. Levels were higher in patients (particularly with G.I., breast and lung cancers) than in normals or in patients with cancer in clinical remission. Elevations of CEA and of all three enzymes in blood were most frequent in patients with hepatic metastases. CEA elevations correlated directly with PHI levels. Seventy-eight percent of patients with metastatic G.I. cancer could be identified by CEA (greater than 5 ng/ml) alone, as well as 38% with breast cancer and 85% with lung cancer; but only 17% of other cancers could be identified by CEA alone. CEA or one or more enzymes was elevated in 64% of metastatic breast cancer patients, 92% of lung cancer and 41% of other cancers, but enzyme measurement did not increase identification of G.I. cancer over that achieved by CEA alone. These findings suggest that circulating levels of CEA, PHI, psi-GTP and LDH may reflect a direct contribution from the malignant tissue and/or liver malfunction secondary to liver replacement.
Monthly serial postoperative CEA determinations, three-monthly system review plus physical examination, and a battery of six-monthly laboratory and radiologic tests were compared in order to evaluate each in detection of recurrent colorectal cancer. Twelve of the 33 patients studied prospectively developed recurrent disease. In this study CEA was found not to be a substitute for careful clinical follow-up, but if used in a serial manner it was a useful adjunct for detection of early recurrent cancer, especially intra-hepatic and retroperitoneal disease recurring in patients with elevated pretreatment CEA levels. The other laboratory and radiologic tests employed were often useful to confirm progressing disease, but they did not reveal any first evidence of recurrent disease.
Carcinoembryonic antigen (CEA) activity was assayed in plasma and in pure pancreatic juice from eight patients with carcinoma of the pancreas, 28 patients with pancreatitis, and 13 controls with no demonstrable pancreatic disease. Juice specimens were obtained via direct transduodenal cannulation of the pancreatic duct. The mean pancreatic juice CEA activities in controls, pancreatitis, and pancreatic carcinoma were 8.1 ng/ml, 18.6 ng/ml, and 309 ng/ml, respectively. Pancreatic juice CEA activity in patients with cancer of that organ was significantly higher than in those with pancreatitis or in controls. None of the 32 subjects with both pancreatic juice CEA activity less than 30 ng/ml and plasma CEA less than 2.5 ng/ml had pancreatic cancer. Three of the four patients with CEA elevations in both fluids above these levels harbored this malignancy. These findings suggest that combined measurement of CEA activity in plasma and pancreatic juice may help in diagnosing pancreatic disease.
Through persistent clinical research efforts, the CEA test has developed into a useful although complex disease monitor for colorectal cancer. Although improved or prolonged survival from its use has not been demonstrated, CEA monitoring may allow more knowledgeable patient management. Several reports indicate that postoperative serial CEA assays may identify patients with early recurrence, especially when assays are done frequently. Patients with elevated pretreatment CEA levels usually showed progressively rising titers before other objective evidence of recurrence was apparent. A progressively rising CEA titer correlated well with recurrent cancer, but a normal CEA could not be used as proof of its absence. Persistently elevated CEA titers post-treatment was caused either by persistent disease or by nontumor-related factors. The CEA assay was not a substitute for clinical follow-up but was an adjunct in the diagnosis of eary recurrence. Patients with elevated CEA levels caused by localized disease treated by radiation therapy demonstrated a marked fall in serial CEA levels if all CEA-producing tumor was localized within the radiation portal. The use of pretreatment CEA values plus the pattern of CEA reponse to irradiation may help in the selection of fulguration versus abdominoperineal resection as primary treatment for rectal cancer. Persistently low serial CEA titers after irradiation therapy correlated with disease control. The use of frequent serial CEA assays in patients treated with chemotherapy compared well with other parameters as a monitor of disease progression or regression. When used with other clinical parameters, serial CEA trends appeared to be a useful adjunct in assessing the effectiveness of chemotherapy. A fall in circulating CEA or the stabilization of a rising titer after starting chemotherapy usually indicated an effective regimen, whereas a rising CEA titer may signal may signal the need to initiate or to change chemotherapy.
In an attempt to identify new tumor markers in human colon carcinoma, we produced antisera in rabbits tolerant to normal human tissue antigens and immunized with zinc glycinate-treated extracts of liver metastases from a colon carcinoma. These antisera reacted with carcinoembryonic antigen and with an additional component present in the tumor extracts but not detected in the extracts of normal tissues. The new component, the zinc glycinate marker (ZGM), had an alpha2 mobility on immunoelectrophoresis, was soluble in 1 M perchloric acid, and had a molecular weight of approximately 2X10(6), as indicated by its elution pattern on Sepharose 6-B chromatography. It differed from alpha fetoprotein, nonspecific cross-reacting antigens (NCA, NGP, or CCA III), ferritin-like molecules, and blood group substances A, B, H, Lewis a, and Lewis b. The ZGM was similarly identified in saline or zinc glycinate extracts of 11 of 23 carcinomas of the colon. With routine hematoxylineosin staining, no histologic differences were apparent between tumors bearing the antigen and those without it.
Pancreatic juice collected from 10 patients without evidence of malignant disease of the pancreas or other organs was pooled, extracted, and fractionated by Sepharose 6-B and Sephadex G-200 gel filtration. The carcinoembryonic antigen (CEA) activity in the material was demonstrated and studied by: a) radioimmunoassay, b) competitive binding to antibodies against CEA, c) precipitin inhibition, and d) Ouchterlony analysis. The immunochemical identity of the active material to CEA purified from liver metastases of colon cancer was demonstrated.
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Circulating carcinoembryonic antigen (CEA) levels and their relation to liver function test values were studied in 29 jaundiced patients with benign extrahepatic biliary tract obstruction and inflammation. During the obstructive and inflammatory phase, 15 (52%) of the patients had CEA levels greater than 2.5 ng/ml. Elevated CEA levels were associated more frequently with common bile duct stones (and cholangitis) than with gallbladder stones (and cholecystitis) alone, although this difference was not statistically significant. The former often had values greater than 5.0 ng/ml. The highest values were found in two patients with liver abscesses. T'HE CEA levels returned to normal following relief of obstruction in seven of ten patients and increased in two patients who had progressive inflammation. Serum alkaline phosphatase and bilirubin levels were significantly higher in the patients with elevated CEA levels (p smaller than .05). Serum alkaline phosphatase levels showed a significant positive correlation with CEA levels (p smaller than .02). Patients with obstructive jaundice and elevated CEA levels do not necessarily have cancer.
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Despite nonspecificity for the diagnosis of colon cancer, the assays for CEA widely studied to date may be useful in the management of patients with colorectal cancer by aiding detection of colonic cancer and especially of widespread metastases to the liver. Use of serial quantitative measurements may also be useful in determining persistence of residual or metastatic tumor after apparently complete surgical resection, in enabling detection of recurrence at an earlier stage than may be otherwise possible, and in helping to evaluate the effects of chemotherapy, provided that the assays are used only in context with complete clinical and laboratory findings, including cancer staging, histopathologic findings, assessment of liver status, and with appreciation of methodologic complexities. Both the further investigation of the clinical use of CEA and the intensified search for more specific markers are encouraged by the findings to date.
Preoperative plasma CEA levels were measured in 93 selected patients with histologically defined colorectal adenomata removed at fibroptic colonoscopy in order to determine whether CEA levels are elevated in patients with colonic polyps, or vary with different histologic patterns. None of the patients had inflammatory bowel disease, previous history of carcinoma, or evidence of liver disease. Fifteen percent of the patients had elevated CEA levels (greater than or equal to 2.5 ng/ml; Hansen method), and two-thirds of these were between 2.5 and 4.0 ng/ml. Increased association of elevated CEA levels was noted with old age, villous adenomas (2- to 4-fold), and increased tumor size (greater than 2.3-cm diameter; 2-fold), but not with foci of dysplasia or carcinoma in situ as such. One-half (7/14) of the patients with elevated CEA levels showed the following: two patients had villous tumors with carcinoma in situ, one had a villous adenoma, two had mixed villous and tubular adenomas (with a high proportion of villous pattern), and two were subsequently shown to have carcinoma elsewhere in the colon. It is uncertain that the polyps were the source of the elevated circulating CEA levels; other factors including smoking and patient selection need to be considered. This preliminary study suggests that patients with colorectal adenomata and elevated circulating CEA may be at higher risk for the development of carcinoma. Further follow-up studies of the malignant potential of the polyp-bearing colon are essential.
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The results of histopathologic study and the preoperative circulating carcinoembryonic antigen levels were correlated with each other and with the postoperative clinical course in 45 surgically treated patients with cancer of the colon. Histopathologic evaluation of the tumor included the depth of bowel wall involvement according to the Dukes classification, the histologic differentiation of cells on the basis of Broders' grades of malignancy, evidence of lymphocyte and plasma cell infiltration within and surrounding the primary tumor, and evidence of blood vessel, lymphatic, and perineural invasion. All these parameters, including the serum carcinoembryonic antigen level, had prognostic value. Low serum carcinoembryonic antigen levels in patients with colonic cancer suggested tumor localized within the bowel wall; the highest values were found in patients with tumors that had spread beyond the bowel wall. An inverse correlation was noted between the degree of tumor differentiation and carcinoembryonic antigen levels in the same patient. Carcinoembryonic antigen levels tended to be elevated when blood vessel, lymphatic, and perineural invasion was present. An inverse correlation was also noted between the preoperative carcinoembryonic antigen level and the degree of lymphocyte and plasma cell infiltration in the primary tumor. Round cell infiltration was interpreted as an indication of the host's immune response against the tumor. Thus, on the basis of clinical follow-up of the patients it is concluded that all morphologic parameters evaluated have prognostic value, that preoperative serum carcinoembryonic antigen levels have prognostic value, that all prognostic parameters correlate with each other appropriately, and that the combined parameters are more reliable than any single one alone.