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Serial carcinoembryonic antigen (CEA) titers were measured in 38 patients receiving chemotherapy for metastatic carcinoma of the colon, pancreas, and stomach. CEA levels were initially elevated (over 2.5 ng/ml) in 26 patients (12/20 colonic, 8/10 pancreatic, 6/8 gastric). Seventeen patients had rising serial CEA values during therapy; 13 had evidence of tumor progression, 3 had stable disease, and 1 had no measurable disease. Nineteen patients had stable CEA levels which were either persistently elevated (11 patients) or normal (8 patients). Ten of 11 patients with elevated CEA levels developed tumor progression. In 8 patients with consistently normal CEA levels, 6 (colon) had no evidence of progressive tumor, and 2 (1 pancreatic and 1 gastric) eventually died of metastatic disease. CEA levels decreased in 2 patients with colon carcinoma during remission from chemotherapy. A rising CEA titer often presages clinical deterioration, although elevated CEA levels may remain stable despite progressive disease. Persistently normal CEA, however, is a favorable prognostic sign. The limited effectiveness of chemotherapy for gastrointestinal cancer in this series precludes any definitive conclusion regarding the effect of chemother-apeutically induced tumor regression on CEA levels, although there is suggestive evidence that CEA correlates with remission.

Repeated determinations of serum CEA levels in untreated advanced gastrointestinal cancer patients with initially elevated values showed day to day variations of ±35%. If there was no intervening chemotherapy, all such patients who were followed over long term showed progressively increasing CEA levels. With chemotherapy there was a general correlation between changes in serum CEA levels and clinically measured changes in tumor mass. Among patients who showed objective improvement, 75% had reduction in serum CEA levels (> 35%) and 87% had either reduced or unchanged levels. Among those who showed objective progression, 65% had increases in serum CEA levels (> 35%) and 80% had either increased or unchanged levels. Paradoxical reductions in CEA levels were observed in some patients approaching terminal status. Among 80 patients being followed with serial CEA determinations after potentially curative resections of large bowel cancer and normal postoperative CEA levels, 6 have again showed clinical evidence of malignant disease and in 5 of these there was concurrent elevation of serum CEA. Serial serum CEA determinations appear to have some value for following the course of gastrointestinal cancer patients after surgery or chemotherapy, but these determinations must be interpreted in the context of the over-all clinical picture.

The in vitro blastogenic responses of lymphocytes from peripheral blood leukocytes (PBL) and lymph-node leukocytes (LNL) of cancer patients were examined simultaneously in paired studies. The lymph nodes were obtained at the time of surgical tumor extirpation from the area draining or adjacent to the tumor, but were determined to be tumor-free. There was an inverse relationship between the responses of PBL and LNL to tumor cells (TC). In those subjects where the PBL responses to TC were positive (stimulation index >3), the responses of LNL were usually negative and significantly lower. In those subjects where the LNL responses to TC were positive, the PBL responses were usually negative and significantly lower. A positive response by LNL to TC correlated with a significantly higher mixed lymphocyte culture response among LNL than among PBL. There was no correlation of these responses to TC with the PBL or LNL responses to phytohemagglutinin. There was a trend for the PBL response to TC to be higher than that of the LNL in patients with gastrointestinal cancer and melanoma and lower than that of LNL in patients with breast and squamous cell carcinoma. Stage of disease and age also influenced these results.

Some 99,000 new cases of cancer of the colon are expected next year, an incidence rate higher than that for both cancer of the lung and cancer of the breast. Evidence from geographic pathology suggests that some environmental factors play a strong role in its etiology. Data obtained in the 1959 survey of one million people by the American Cancer Society and followed since, has failed to show correlation with any of the large number of factors listed. It is suggested that the etiology is one of multiple factors. The synergistic effect of exposure to asbestos and cigarette smoking in the production of bronchogenic carcinoma is demonstrated by data on cohorts of insulation workers. There was also a modest increase in the number of deaths from gastrointestinal cancer in asbestos workers, but smoking did not seem to act in synergistic fashion at that site, except perhaps in the esophagus. Deaths from cancer occurred almost entirely after a period of 20 years or more from initial exposure. The death rate from cancer tended to increase with duration of exposure, but a distinct rise over the expected was seen in those who had been exposed less than one year to amosite dust.

Summary 1. A correlative study was made of the roentgen findings of 1714 gastrointestinal cancer suspects who had negative exfoliative cytologic examinations. All were proven to be clinically free of cancer. The negative cytologic examination, properly performed, significantly excluded the presence of cancer of the digestive tract, with the exception of the pancreas and biliary tract. 2. Notable benign conditions clinically simulating malignancy are esophagitis, gastric ulcer, antral gastritis, large gastric rugae, biliary and pancreatic diseases, ulcerative colitis, diverticulitis, and polyps of the colon. 3. Diagnostic cytologic inaccuracy for the various malignancies of the esophagus, stomach, and colon is approximately 10 per cent. The incidence of diagnostic error for benign conditions (including those considered premalignant) of the gastrointestinal tract is a fraction of 1 per cent. A negative cytologic report has definite clinical value.

Summary Miniature Geiger counter tubes were passed into the esophagus, stomach, and rectum of patients previously given 500 μc. of radioactive phosphorus intravenously to evaluate this method in the detection of gastrointestinal malignant neoplasia. To test the esophagus and rectum, the counter was placed at the tip of a plastic probe and passed through the esophagoscope and sigmoidoscope. The gastric counter was inserted in the distal end of a controllable tip gastroscope for scanning under direct vision. Of 62 esophageal tests, 25 of the patients had cancer, 5 benign lesions, and 32 were normal control subjects. There was an accuracy of 92 per cent in cancer, and an over-all accuracy of 95 per cent. In 46 gastric tests, 22 patients had cancer, 11 had benign ulcer, 2 had benign tumor, and 11 were normal control subjects. The accuracy in gastric cancer was only 73 per cent, largely due to technical difficulties. Over-all accuracy was 83 per cent. Rectal testing was carried out only in 5 patients, 4 of whom were correctly evaluated. Although the Geiger counter probe technique cannot be used as a survey method in the diagnosis of gastrointestinal cancer, it is highly accurate in detecting cancer of the esophagus and rectum, and seems quite valuable in differentiating obscure and equivocal findings. The method is technically difficult in the stomach, but seems to be useful in the differentiation of small cancerous and precancerous lesions.

The incidence of hepatocellular carcinoma is rising in many countries, including the United States. Approval of sorafenib (Nexavar) as the first targeted therapy for treatment of advanced hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. The approval was based on two large randomized phase III trials from the Western and Eastern hemispheres that showed an overall survival benefit compared with placebo in patients with well-preserved liver function. The exact indication for sorafenib is unclear, however. The U.S. Food and Drug Administration (FDA) authorized use of sorafenib for "unresectable HCC", an indication which is very broad, vague, and confusing. Less is known about the effects of sorafenib in patients with decompensated liver disease, or of sorafenib in combination with local therapy or in a transplant setting. Prospective trials are lacking in these areas. We will review current data on use of sorafenib in HCC.

Summary The fluorinated pyrimidines are capable of producing significant but limited regressions in a small proportion of patients with gastrointestinal cancer. No significant difference in regression rates was noted among the major types of gastrointestinal cancer. Frequent toxic reactions to therapy included nausea, vomiting, diarrhea, stomatitis, esophagopharyngitis, dermatitis, alopecia, and leukopenia. 5-Fluorouracil was decidedly less toxic when administered by a slow intravenous infusion than when given by rapid intravenous injection; its effectiveness in inducing objective regressions in patients with advanced carcinoma of the large bowel was greater when administered by the rapid intravenous method. The optimal regression rate with 5-fluorouracil seems to be achieved by treating to the point of mild to moderate drug toxicity. Treatment seems to be more successful in patients with malignant neoplasms of a high degree of anaplasia and patients with hepatic metastasis. Preliminary observations suggest that 5-FUDR holds some therapeutic advantage over 5-fluorouracil both in relation to the severity of leukopenia accompanying therapy and in relation to the rate of objective regressions obtained. This apparent advantage of 5-FUDR must be confirmed by further observations.

An analysis of vulvar carcinoma (ICD No. 176.0) from the California Tumor Registry data, 1942–1969, was performed. While the incidence rate for vulvar cancer has increased slightly from 1.8 (1960) to 2.2 (1969) per 100,000 population (age-adjusted), the absolute and relative survival rates for vulvar carcarcinoma in California for localized lesions have declined drastically (85% 5-year relative survival in 1942–1954 versus 75% 5-year relative survival in 1955–1969), and localized lesions have increased from 7 to 23% for these time periods, respectively. The reason for this decline appears to be a decline in the use of radical vulvectomy, radiation therapy and adjuvant radiation therapy. For all stages of vulvar cancer, the 5-year relative survival rates have increased from 66% (1942–1954) to 70% (1955–1969). A further study of these data by the FIGO classification scheme is in progress. The rarity of vulvar cancer in the nonwhite races is emphasized.

Dr. Ellison cites the dramatic improvement in curability of cancer when it is discovered in an asymptomatic stage and discusses exfoliative cytologic technics and other methods to detect gastrointestinal cancer. Dr. F. Jackson Stoddard points out that application of existing methods of diagnosis and treatment can virtually eliminate death from cancer of the cervix and reduce the mortality rate of endometrial cancer to 10 per cent or less. Dr. Donald J. Ferguson examines the indications for biopsy of breast lesions and the significance of the histologic findings. Dr. Laurence F. Greene stresses the importance of rectal examinations to discover prostatic carcinoma and describes corroborative and definitive evidence for this diagnosis. Dr. Edward J. Beattie, Jr. compares the accuracy of procedures for diagnosis of lung cancer and the merits of different modes of treatment.

SummaryThe ether, neutral, and phenolic fractions of the urine of normal individuals and of patients with carcinoma of the breast, cervix, gastrointestinal tract, and with various leukemias were analyzed polarographically. Reducible compounds were found in all the fractions. In the urine phenolic fraction the ratio (of the number of polarographically reducible compounds with an E1/2 more negative than—0.5 V vs SCE to that more positive than—0.5 V) was significantly different for male and female patients with gastrointestinal cancer as compared to normal persons of both sexes. There was no difference in this ratio between the neutral urine fraction of normal persons and cancer patients. The ether fraction of the urine of males with gastrointestinal cancer had a much higher ratio (number of compounds with an E1/2 more negative than—0.5 V vs SCE/number of compounds with E1/2 more positive than —0.5 V) than that of the same fraction of normal males. Finally a significant difference was found in the ratio (of ...

ConclusionsThe low plasma levels of vitamin A of patients with cancer of the gastrointestinal tract probably are not due to a decreased capacity of the livers of those patients to store the vitamin.

DEDICATION The authors wish to dedicate this article to the late Dr. Gordon P. McNeer, for many years Chief of the Gastric and Mixed Tumor Service of Memorial Hospital for Cancer and Allied Diseases, and a pioneer in the surgical treatment of gastrointestinal cancer. Dr. McNeer’s illness and untimely death prevented him from participating in the prepara- of this article, but we wish gratefully to acknowledge his previous guidance and counsel.

In a controlled double blind study involving 116 patients with far-advanced gastrointestinal cancer, dexamethasone at dosages of 0.75 and 1.5 mg four times daily produced improved appetite and sense of well-being in comparison to placebo treatment. This symptomatic palliation, however, was not accompanied by weight gain or improved performance status. Survival of the steroid treated patients was essentially identical to that of the placebo treated patients. Cancer 33:1607–1609, 1974.

Inositol was found by Gavin and McHenry1 to prevent the development of a special type of biotin fatty liver, but no such lipotropic activity was demonstrated against thiamin fatty livers. Abels et at.2 found that inositol accounted for the lipotropic property of a lipocaic preparation when given to patients with gastrointestinal cancer. Inositol administered preoperatively, reduced the average concentration of fat to 46% of that of almost uniformly fatty infiltrated livers of untreated patients. Shay3 could demonstrate no reduction in the size of fatty livers in diabetics nor any changes in the blood cholesterol by the daily administration of 1.2 g of inositol. However, Russakoff and Blumberg4 reported reduction in the blood cholesterol and cure by inositol in doses of 1 g per day, in a patient with a diermatological condition associated with a disturbed fat metabolism.Further studies seemed to be in order and inositol was therefore subjected to animal experimental studies similar to those made with other...