In studies of cell proliferation in the intestine of animals during the past few years, observations have been made that suggest points of interest concerning cell renewal in humans. In rodents, proliferating jejunal and colonic epithelial cells have mean generation times of about 12 to 18 hours, DNA synthesis (S phase) times of 5 to 8 hours, and premitosis (G2) and mitosis (M) times of 1 to 2 hours (1-3). Also, although many epithelial cells undergo a second generation cycle soon after mitosis, some cells appear to remain longer in interphase before dividing again (3). The rate of disappearance of labeled cells from the mucosa has also been shown to vary in different portions of the gastrointestinal tract in a number of species; e.g., more labeled cells are present in the colon and stomach 1 week after injection of H3-thymidine than in the duodenum or jejunum (4).In man, studies of mitotic indexes and radioautographic studies with H3-thymidine have suggested turnover times of intestinal epithelial cells in the order of several days (5-7). In the present study, we have measured the mean generation time and the phases of the proliferative cycle of human colonic and rectal epithelial cells after the administration of H3-thymidine. The results describe cell renewal and give data on the rate of disappearance of labeled cells from the mucosa of the human colon and rectum. METHODSTwo patients with colostomies were studied. Both had resections of the descending colon for carcinoma of the rectum and liver metastases. The colostomies were composed of normal mucosa of the transverse colon. A * Supported in part by U. S. Public Health Service grants A-3165 and C-3697, and by The John A. Hartford Foundation, Inc., New York, N. Y. third patient with a carcinoma of the rectum 8 cm proximal to the anal orifice was studied. Although all patients had carcinoma and known metastases, and had recently lost weight, they were fairly well-nourished at the time of these studies. Figure 1. The zone of rapid epithelial cell proliferation is located in the lower and middle third of the colonic crypts. In Figure 1A, labeled proliferating cells are seen blended 767

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The authors reviewed all cases of non-Hodgkin's lymphoma primarily involving the gastrointestinal tract treated at Memorial Hospital during the period from 1949-1978. Complete clinical records were available in 104 cases. Slides of original pathology specimens were available in 81 cases. Tumors were classified by Rappaport, Lukes-Collins and modified Kiel classifications. All patients were staged retrospectively, using modified Ann Arbor staging. The primary tumor was in the stomach in 76 patients, in the small bowel in 15 and in the large bowel in 13. The life-table survival for all patients at five years was 44% and for the 81 Stage I and II patients it was 53%. We found a trend toward improved survival for patients treated in the last decade (P = 0.05). Using Cox regression analysis, survival was found to be correlated with stage (P less than 0.0001) and involvement of adjacent structures (P = 0.007). For Stage I patients, resection and radiation therapy were equally effective alone in controlling local tumor even though factors responsible for the selection of either treatment could not be identified. For Stage II patients, resection combined with radiation therapy controlled local disease better than either treatment alone. For Stage II, patient survival was correlated with the pattern of nodal involvement (P less than 0.0001). Neither the choice of treatment (resection, radiation therapy, or resection with radiation therapy; P = 0.17) nor the involvement of resected margins (P = 0.22) affects survival. Among 81 Stage I and II patients, 68% had recurrences outside the primary field of treatment and 60% outside the abdomen. Systemic multiple modality therapy should be considered for patients at high risk for recurrence.

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