Leonard S. Gottlieb

Prevention of Colorectal Cancer by Colonoscopic Polypectomy

BACKGROUNDnThe current practice of removing adenomatous polyps of the colon and rectum is based on the belief that this will prevent colorectal cancer. To address the hypothesis that colonoscopic polypectomy reduces the incidence of colorectal cancer, we analyzed the results of the National Polyp Study with reference to other published results.nnnMETHODSnThe study cohort consisted of 1418 patients who had a complete colonoscopy during which one or more adenomas of the colon or rectum were removed. The patients subsequently underwent periodic colonoscopy during an average follow-up of 5.9 years, and the incidence of colorectal cancer was ascertained. The incidence rate of colorectal cancer was compared with that in three reference groups, including two cohorts in which colonic polyps were not removed and one general-population registry, after adjustment for sex, age, and polyp size.nnnRESULTSnNinety-seven percent of the patients were followed clinically for a total of 8401 person-years, and 80 percent returned for one or more of their scheduled colonoscopies. Five asymptomatic early-stage colorectal cancers (malignant polyps) were detected by colonoscopy (three at three years, one at six years, and one at seven years). No symptomatic cancers were detected. The numbers of colorectal cancers expected on the basis of the rates in the three reference groups were 48.3, 43.4, and 20.7, for reductions in the incidence of colorectal cancer of 90, 88, and 76 percent, respectively (P < 0.001).nnnCONCLUSIONSnColonoscopic polypectomy resulted in a lower-than-expected incidence of colorectal cancer. These results support the view that colorectal adenomas progress to adenocarcinomas, as well as the current practice of searching for and removing adenomatous polyps to prevent colorectal cancer.

Randomized Comparison of Surveillance Intervals after Colonoscopic Removal of Newly Diagnosed Adenomatous Polyps

BACKGROUNDnThe identification and removal of adenomatous polyps and post-polypectomy surveillance are considered to be important for the control of colorectal cancer. In current practice, the intervals between colonoscopies after polypectomy are variable, often a year long, and not based on data from randomized clinical trials. We sought to determine whether follow-up colonoscopy at three years would detect important colonic lesions as well as follow-up colonoscopy at both one and three years.nnnMETHODSnPatients were eligible if they had one or more adenomas, no previous polypectomy, and a complete colonoscopy and all their polyps had been removed. They were randomly assigned to have follow-up colonoscopy at one and three years or at three years only. The two study end points were the detection of any adenoma, and the detection of adenomas with advanced pathological features (defined as those > 1 cm in diameter and those with high-grade dysplasia or invasive cancer).nnnRESULTSnOf 2632 eligible patients, 1418 were randomly assigned to the two follow-up groups, 699 to the two-examination group and 719 to the one-examination group. The percentage of patients with adenomas in the group examined at one and three years was 41.7 percent, as compared with 32.0 percent in the group examined at three years (P = 0.006). The percentage of patients with adenomas with advanced pathological features was the same in both groups (3.3 percent).nnnCONCLUSIONSnColonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps. Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening.

A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy

BACKGROUNDnAfter patients have undergone colonoscopic polypectomy, it is uncertain whether colonoscopic examination or a barium enema is the better method of surveillance.nnnMETHODSnAs part of the National Polyp Study, we offered colonoscopic examination and double-contrast barium enema for surveillance to patients with newly diagnosed adenomatous polyps. Although barium enema was performed first, the endoscopist did not know the results.nnnRESULTSnA total of 973 patients underwent one or more colonoscopic examinations for surveillance. In the case of 580 of these patients, we performed 862 paired colonoscopic examinations and barium-enema examinations that met the requirements of the protocol. The findings on barium enema were positive in 222 (26 percent) of the paired examinations, including 139 of the 392 colonoscopic examinations in which one or more polyps were detected (rate of detection, 35 percent; 95 percent confidence interval, 31 to 40 percent). The proportion of examinations in which adenomatous polyps were detected by barium enema colonoscopy was significantly related to the size of the adenomas (P=0.009); the rate was 32 percent for colonoscopic examinations in which the largest adenomas detected were 0.5 cm or less, 53 percent for those in which the largest adenomas detected were 0.6 to 1.0 cm, and 48 percent for those in which the largest adenomas detected exceeded 1.0 cm. Among the 139 paired examinations with positive results on barium enema and negative results on colonoscopic examination in the same location, 19 additional polyps, 12 of which were adenomas, were detected on colonoscopic reexamination.nnnCONCLUSIONSnIn patients who have undergone colonoscopic polypectomy, colonoscopic examination is a more effective method of surveillance than double-contrast barium enema.

Polyunsaturated fat, cholesterol and large bowel tumorigenesis

The possibility that the disposition of cholesterol, which is influenced by the quality of dietary fat, may be associated with either vascular lipidosis or colon cancer was evaluated in this study. Rats were fed diets containing cholesterol plus a) saturated fat, 20% coconut oil, to elevate serum cholesterol and promote vascular lipidosis or b) polyunsaturated fat, 20% safflower oil, to minimize serum cholesterol elevations and retard the development of vascular lipidosis. The relationships of these diets to gastrointestinal tract tumors induced by 1,2,‐dimethylydrazine (DMH) was evaluated. Serum cholesterol levels in rats fed the coconut oil diet and given DMH were markedly elevated and were associated with moderate to severe vascular and aortic sudanophilia. Conversely, rats fed the safflower oil diet and given DMH had modest elevations in serum cholesterol levels and minimal vascular and aortic sudanophilia. Significantly, greater numbers of large bowel tumors induced by DMH were found in rats fed the safflower oil diet than in those fed the coconut oil diet. It was suggested that the polyunsaturated fat diet promoted the decrease in serum cholesterol levels concomitant with an increase in fecal neutral and acid sterols, which in turn augmented tumorigenesis by DMH in these animals compared with those fed the saturated fat diet. Thus, in the animal model used, the interaction of dietary fat (quality or quantity) with endogenous or dietary cholesterol determines whether or not diet will be a contributing factor in a) the development of vascular lipidosis or b) augmentation of small and large bowel tumorigenesis.

Cirrhosis and hepatoma occurring at Boston city hospital (1917-1968)

Cirrhosis and hepatoma at Boston City Hospital have progressively increased in frequency, especially cirrhosis associated with chronic alcoholism. Alcoholic cirrhosis or fatty nutritional cirrhosis (FNC) increased from 31% (1917‐1926) to 61% (1955‐1968) of all types of cirrhoses. One third of 98 subjects dying of hepatoma had FNC. The occurrence of hepatoma associated with postnecrotic cirrhosis increased twofold and threefold in subjects with hemochromatosis. Chronic alcoholism was considered the pathogenetic agent implicated in the production of FNC, hemochromatosis, and post‐necrotic cirrhosis in 56 of our 98 patients dying of hepatoma. An average of 8 years ensued from the onset of alcoholic cirrhosis to the appearance of hepatoma in 23 alcoholic patients.

CEA levels in patients with colorectal polyps

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 (≥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 ((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.

Pulmonary Alveolar Microlithiasis, or Calcinosis of the Lungs

PULMONARY alveolar microlithiasis is a rare and extraordinary disease in which microscopic stones are found within the pulmonary alveoli. The lungs, which are heavy and stony hard, cut with the greatest of difficulty. As far as can be determined this disease was first described by Friedreich1 in 1856; its present name was originally used by Puhr2 in 1933. The case presented below is the third to appear in the English language. Case Report A 45-year-old Scottish chauffeur was first seen on January 2, 1942, because of abnormal pulmonary shadows on routine x-ray examination of the chest. He had been a .xa0.xa0.

Granular-cell myoblastoma of stomach and colon

Summary1. Two cases of granular-cell lesions (myoblastoma) involving stomach and colon, respectively, are reported.2. The biologic nature of the lesion with reference to histogenesis is reviewed.3. In our opinion, granular-cell myoblastoma, rather than developing as a neoplasm of muscle origin, is a tumor of neural origin arising from Schwann cells, and the term granular-cell neuroma is appropriate.

The Effects of Iron Deficiency and the Quality and Quantity of Fat on Chemically Induced Cancer

Iron deficiency has been shown to affect a number of systems including the immune system, the gastrointestinal system, the erythron, and the utilization of at least one essential nutrient and perhaps others. A number of studies have indicated that in irondeficient animals and humans there is decreased killing by polymorpholeucocytes (1,2), but phagocytosis may not be altered. Additionally, in iron-deficient humans, it is shown to depress the response of T cells to mitogens.(3)

Augmentation of ethanol absorption by mono- and disaccharides.

Assessment of the influence of nutritional substrates on the disposition of ingested ethanol from the blood requires, first, an understanding of the influence that these may exert upon ethanol absorption from the gastrointestinal tract. In this report, the effects of various carbohydrates on the intestinal absorption of ethanol were studied. When carbohydrates (50 mM) were perfused simultaneously with ethanol (50 mM) in vivo in the rat small bowel, ethanol absorption increased up to 34% (P less than 0.005) above controls receiving ethanol alone. Of the monosaccharides, fructose, 3-O-methylglucose, glucose, or galactose added to an ethanol perfusate, only glucose or galactose increased ethanol absorption over control animals receiving ethanol alone. Of the disaccharides tested, sucrose and maltose, but not lactose, enhanced ethanol absorption. Addition of varying concentrations of maltose to an ethanol perfusate augmented ethanol absorption in a direct proportion to the quantity of glucose absorbed, rather than to the quantity of maltose hydrolyzed. Augmentation of ethanol absorption by carbohydrates appears to be dependent upon sugar-active transport. Ethanol, dissolved in intraluminal water, may cross the mucosa in water absorbed during sugar-active transport. This quantity of ethanol is absorbed in addition to that which normally crosses the mucosa by diffusion down its concentration gradient.