Norman Zamcheck

Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.

One‐hundred‐ninety‐four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high‐dose (6000 rads) radiation therapy alone, to moderate‐dose (4000 rads) radiation + 5‐fluorouracil (5‐FU), and to high‐dose radiation plus 5‐FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5‐FU‐containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5‐FU and 6000 rads plus 5‐FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

Carcinoembryonic antigen assay in cancer of the colon and pancreas and other digestive tract disorders.

In a study of 279 persons, carcinoembryonic antigen (CEA) was detected in the sera of 32 of 35 patients with carcinoma of the colon, 13 of 13 patients with carcinoma of the pancreas, and 6 of 14 patients with other gastrointestinal cancers, confirming previous work which associated circulating CEA with GI tract malignancies. Six of 8 patients with bronchogenic carcinomas also gave positive assays. Seventy-nine assays on 40 young normal controls were negative. Twenty-four of 46 selected patients with severe alcoholic liver disease and 7 of 13 selected patients with uremia also gave positive results, thus requiring careful interpretation of the assay as presently performed on such patients pending further studies.

Influence of Gastric Acidity on Bacterial and Parasitic Enteric Infections: A Perspective

Abstract In the early twentieth century various investigators believed that patients with reduced gastric acid secretion were especially susceptible to bacterial enteric infections. Since many bact...

Carcinoembryonic antigen in breast cancer patients: Serum levels and disease progress

Serum CEA was evaluated in 69 patients with breast cancer and 17 with benign breast disease. Serum CEA was elevated (above 2.5 ng/ml) in 6 of 22 patients (27%) with primary cancer without clinical evidence of distant metastases, and in 37 of the 47 (79%) who had metastatic disease. Sixteen of 17 patients (94%) with benign cystic disease had values less than 2.5 ng/ml (1 was 2.9 ng/ml). Fourteen patients with metastases undergoing chemo‐ and hormonal therapy were studied by serial CEA estimations for 3 to 18 months, with a mean of 14 months. The trends of serial CEA values correlated with response to treatment.

Effect of Diet upon Intestinal Disaccharidases and Disaccharide Absorption

The administration of a carbohydrate-containing diet for 24 hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of maltase was similarly increased, but lactase activity was unaffected. The sucrose-containing diet led to a greater increase in sucrase than maltase activity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase activity of mixed homogenates from casein-fed and sucrose-fed rats or fasted and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding. Adrenalectomized rats maintained on 1.0% salt intake had sucrase and maltase levels comparable to those of controls. Steroid administration did not significantly increase their activities. The response to sucrose feeding was similar in both control and adrenalectomized rats, indicative of the absence of steroidal control on sucrase and maltase activity in the adult animal. Studies using intestinal ring preparations indicated that sucrose hydrolysis by the intact cells proceeded more rapidly when animals were fed sucrose. Additional corroboration of the physiologic significance of the increased enzyme levels in homogenates was afforded by intestinal perfusion studies. Sucrose hydrolysis increased twofold and fructose absorption fourfold in animals fed sucrose when compared to either fasted or casein-fed rats.

Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum.

The median survival of all patients with hepatic metastases from colorectal cancer referred to the Sidney Farber Cancer Institute during a five-year period was 12.5 months. Two major factors influenced survival. The first was extent of disease at presentation. The second was the histologic grade of the cancer. The median survival of patients presenting with the least disease, characterized by less than four liver nodules visible on liver scan (n=38), normal liver size on physical examination (n=60), normal liver function test results (n=30), and normal performance status (n=91), was between 18 and 24 months, regardless of treatment. The median survival of those few patients (n=13) who had objective responses to a variety of treatments, most of whom also had minimal disease at presentation, was also 24 months. Patients whose tumors were poorly differentiated or who had abnormal performance status or weight loss of greater than 10 per cent at presentation survived only six months (median). Those with four or more liver nodules, hepatomegaly (greater than 16-cm vertical span on physical examination), or abnormal liver function test results, survived ten, eight, and 12 months (median), respectively. It is concluded that a significant group of patients survived longer than would have been predicted by earlier literature surveys after the diagnosis of colorectal cancer metastatic to the liver. It is suggested that future therapeutic trials, using survival as a measure of response of patients with liver metastases from colorectal cancer, must be prospectively controlled before selection factors can be differentiated from significant therapy effect.

The Use of Preoperative Plasma CEA Levels for the Stratification of Patients After Curative Resection of Colorectal Cancers

One hundred forty-five patients with colorectal cancer were analyzed in order to correlate the preoperative plasma carcinoembryonic antigen (CEA) levels with the sites and times of disease recurrence. The median follow-up periods of these patients was 50 months (range 36–72 months). Twenty-one patients were found to have metastases at the time of their operation. None of the seven patients whose primary tumors were classified as Dukes/Kirklin A have had tumor recurrence. Seventeen per cent of the patients with Dukes/Kirklin B tumors have had tumor recurrences, and 63% of the patients with Dukes/Kirklin C colorectal primary tumors have had tumor recurrence. No correlation was found between preoperative CEA values and subsequent risk of tumor recurrence or times to recurrence among the patients with Dukes/Kirklin B colorectal primary cancers. In Dukes/Kirklin C patients, however, elevated preoperative CEA values predicted a higher risk of tumor recurrence. Ninety per cent of the patients (19/21) with preoperative CEA levels greater than 5.0 ng/ml have had relapses, with a median time of 17 months before disease recurrence. Only 39% (9/23) of the patients with Dukes/Kirklin C lesions and CEA levels less than 5 ng/ml have had relapses and there is insufficient follow-up data as yet to determine the median survival time. If those patients whose Dukes/Kirklin C primary tumors were poorly differentiated on histologic examination are excluded, the contrast between patients having CEA levels greater than 5.0 ng/ml and those having CEA levels less than 5 ng/ml is even more marked. Sixteen of the 18 remaining patients whose CEA levels were greater than 5.0 ng/ml prior to curative resection have had relapses as compared with only three of 15 patients whose preoperative CEA values were less than 5. We conclude, therefore, that CEA is an important factor in stratifying patients after curative resection of their Dukes/Kirklin C colorectal tumors.

Carcinoembryonic antigen (CEA) levels in benign gastrointestinal disease states

Elevated circulating CEA levels occur in patients with benign gastrointestinal and hepatic disorders. These are usually less than 10 ng/ml. Of clinical importance is the influence of liver disease on the interpretation of CEA. At least 50% of patients with severe benign hepatic disease have elevated CEA levels, most often active alcoholic cirrhosis, and also chronic active and viral hepatitis, and cryptogenic and biliary cirrhosis. Patients with benign extrahepatic biliary obstruction may have increased plasma CEA, the highest in patients with coexistent cholangitis and especially liver abscess. The liver appears to be essential for the metabolism and/or excretion of CEA. Hence, liver work‐up is needed to assess any patient with an elevated CEA. A damaged liver may further augment elevated CEA levels due to cancer. The increased circulating CEA observed in some patients with active ulcerative colitis tends to correlate with severity and extent of disease and usually returns to normal with remission. CEA levels also may be mildly elevated in patients with pancreatitis and in adults with colonic polyps. Smoking may contribute to the increased CEA levels seen in patients with alcoholic liver disease and pancreatitis. Therefore, in interpreting mildly elevated circulating CEA levels in patients with GI tract diseases, one must consider benign as well as malignant etiologies.

Prognostic factors in colon carcinoma: Correlation of serum carcinoembryonic Antigen Level and Tumor Histopathology

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.

Correlation of plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer

A review of patients operated on for colorectal cancer disclosed poorly differentiated histologies in those whose preoperative and postoperative carcinoembryonic antigen (CEA) levels were no elevated, even in the presence of metastatic disease. CEA was therefore, of little prognostic value or predictive of disease recurrence in these patients. The amount of CEA in tumor tissue of 17 patients with poorly differentiated colorectal cancer was estimated with the immunoperoxidase staining technique and was correlated with histology and plasma CEA levels obtained during various stages of disease. Five tumors did not stain negatively for CEA and all had predominantly poorly differentiated histologies. In all of these patients metastatic disease developed but not elevated plasma CEA levels. In contrast 12 tumors stained positively for CEA and were found to contain either differentiated areas or signet ring cells. Serial plasma CEA levels correctly monitored the postoperative course of all 12 patients. Six of these had a relapse and all were detected by serial increases in plasma CEA. The remaining six were disease free greater than 48 months after resection and had normal plasma CEA levels. Among poorly differentiated tumors, those that contain glandforming areas or signet ring cells can be assumed to produce CEA and plasma CEA levels can be used effectively for monitoring. On the other hand, undifferentiated tumors which do not stain for CEA identify those patients whose plasma CEA levels do not provide a useful monitor.