[Risk of recurrence of colorectal polyps following endoscopic resection]. / Risques de récidive des polypes colo-rectaux après résection endoscopique.

From 1976 to 1985, 1063 patients (614 men, 449 women, mean age: 63 years) underwent the excision of 1887 adenomatous or villous colonic or rectal polyps. Regular controls by barium enema or total colonoscopy have been proposed to these patients. A first control, performed in 715 patients (67%) after a mean of 27 months, revealed the presence of polyps in 162 of them (23%). A second control performed in 331 of the 535 controllable patients (61%), was positive (presence of polyps) in 82 of them (24%). During the follow-up period, 16 cancerous lesions were observed. Comparing the initial status of the patients with the results of the different controls, 3 risk factors for developing a new colonic or rectal polyp emerged: 1) male sex, 2) the presence of multiple lesions at the initial examination, 3) a recurrence at a previous control.

[Villous tumors of the rectum. Endoscopic treatment using monopolar coagulation]. / Tumeurs villeuses du rectum. Traitement endoscopique par coagulation monopolaire.

UNLABELLED: Many methods are used to treat villous adenomas of the rectum. The best choice between these methods is not well established. Ninety-six patients (47 men, 49 women) treated with endoscopic monopolar coagulation were studied. The mean age was 66 years (range 37-84). The lesions were located in the lower third of the rectum in 27 cases, in the middle third in 35 cases and in the upper third in 34 cases. The circumferential extent of the lesions was less than 1/3 in 70 cases (C1), greater than 1/3-less than 2/3 in 23 (C2) and greater than 2/3 in 3 cases (C3). The follow-up of 2 patients (1 C1 and 1 C2) was not sufficient. Healing was not achieved in 8 of the 94 evaluated patients. Eighty-six patients were totally healed: 68 C1, 16 C2 and 2 C3 with a follow-up of 2 to 132 months (median: 36 months). The treatment was achieved after a mean of 2.1 sessions per patient (range 1-13). CONCLUSIONS: 1) Endoscopic monopolar coagulation of villous adenoma of the rectum is a simple and efficient treatment. 2) This method is complementary to surgery for extensive lesions (C3).

[Epidemiology of rectal cancer: current findings]. / Epidémiologie du cancer du rectum: données récentes.

The exact incidence of rectal cancer in Belgium is not known, due to the absence of an operational national cancer registry. Mortality data however are well documented by death certificates. Annual rectal cancer death rates reach 20 and 13 per 100,000 for men and women respectively in the age category from 45 to 74 years (data from 1981). When similar data obtained for the years 1968 to 1983 are being compared, a significant decrease of rectal cancer mortality can be observed, at a rate of 2.6% annually. Such a decrease is not seen for colon cancer, of which the respective annual death rates are 41 and 33 per 100,000. Absolute figures for the whole Belgian population in 1984 were 3204 deaths due to colorectal cancer, with 2307 cases for colon and 897 cases for rectal cancer. In regions where incidence data are available, it is found that the cumulative risk of colorectal cancer between birth and the age of 75 can reach more than 5% in industrialized countries. Recent incidence data confirm the significant decrease in rectal cancer occurrence.

Phase II trial of medroxyprogesterone acetate in advanced ovarian cancer: an EORTC Gynecological Cancer Cooperative Group Study.

Progestin therapy of ovarian carcinoma in the past has been reported to lead to varying response rates. A multicenter phase II study of high-dose MPA was conducted in 53 patients with epithelial ovarian cancer who had received adequate trials of conventional therapy with cytotoxic agents. Forty-one patients were included for response and toxicity evaluations. Only one partial response has been recorded with a duration of 20 weeks. Stabilization of disease was observed in 7 patients. The present investigation shows that MPA given at the present high dose is not effective in patients extensively pretreated with chemotherapy.

Phase II trial of bleomycin in patients with advanced ovarian cancer: an EORTC Gynecological Cancer Cooperative Group Study.

Bleomycin was administered by continuous i.v. infusion at a dose of 20 mg/m2/day for 7 days to 18 evaluable patients with advanced ovarian epithelial cancer resistant to conventional chemotherapy. The toxicity pattern was no different from that known from earlier studies using continuous infusion of bleomycin with the exception of the occurrence of a life-threatening allergic reaction in one patient, which led to discontinuation of treatment after 3 days. Only one patient showed a partial response for 2 months (5.5%), indicating that the drug has no significant activity in this unfavorable group of patients.

Kinetics of tissue proliferation in colorectal mucosa during post-natal growth.

The main developmental event in the colorectal mucosa during post-natal growth is a dramatic increase in the number of crypts of Lieberkühn, resulting from a longitudinal fission of pre-existing crypts. In the present study, the kinetic aspects of this process have been analysed, using extensive gland and cell counts involving the entire colon and rectum of 24 male BD IX rats distributed into four age groups. The number of crypts was found to rise from an average 4652 to 423,800 between birth and adulthood; the corresponding ratios of bifurcating glands were 13.55 and 0.67%, respectively. Crypt production attained its maximum 18 days after birth with an hourly increment of 519 units. The time spent by replicating glands in the bifurcating stage ('fission time') averaged 6.9--10.5 hr. The mean number of epithelial cells per crypt rose from 249 in 4-day old rats to 635 in adults. The estimated total number of epithelial cells in the colon and rectum was one million in newborns and 248 million in adults. The increment in cell number peaked 3 weeks after birth with a value of 310,000/hr. During the first few days after birth, all cells produced in the epithelium were retained. Cell loss thereafter rapidly progressed, reaching 70% of the cell production in 3-week old animals.

Confirmation of the two-step nature of chemical carcinogenesis in the rat colon adenocarcinoma model.

Carcinomas were obtained in the large intestine of BD IX rats using four different dose levels of 1,2-dimethylhydrazine. Analyses of the relationship between dose, number of cells at risk, time, and tumor yield, together with previous observations on the biological behavior of the tumors, indicated that malignant transformation necessitates two distinct and essential changes in the affected cells. The first change is caused by the carcinogen, the effect of which is additive when similar doses are being repeated. This change is transmissible within the renewing mucosa for prolonged periods. The affected cells have no second change does not require carcinogen exposure (although continued presence of the carcinogen can probably contribute to it). It randomly affects cells having undergone the first change, at a rate which is essentially constant, at least within the considered tissue.

Experimental adenomas and carcinomas of the large intestine behave as distinct entities: most carcinomas arise de novo in flat mucosa.

Detailed histologic analyses were performed on tumors of the large intestine obtained in 152 dimethylhydrazine (DMH)-treated rats. Of a total 539 glandular neoplasms, 45 were benign; 494 (92%) were locally invasive; of which 222 (41%) were invading the muscularis propria. One-hundred-forty-one tumors were smaller than or equal to 3mm in diameter. Among those, 127 (90%) were invasive. In addition to macroscopic nodules, several appeared after longer latency periods than did serial sections of flat mucosa. The benign polyps usually appeared after longer latency periods than did carcinomas. A review of the literature indicates that in the majority of rat experiments most or all DMH-induced tumors were frequently reported. All these data constitute strong evidence that most experimental adenocarcinomas do arise de novo in flat mucosa, i.e., without a prior adenoma stage. However, most DMH-induced tumors in mice were reported to be adenomas, either alone or coexisting with carcinomas. It is suggested that "de novo arising carcinomas" and adenomatous polyps, which are both inducible by the same carcinogens, and which can coexist in some experimental systems, nonetheless constitute independent and distinct pathologic entities; they can be separated by genetic susceptibility.

Histogenesis of adenomatous polyps in the human large intestine.

Detailed histologic analyses have been performed in 75, minute, colorectal polyps from familial polyposis patients. All polyps were composed of typical adenomatous tissue, with, in addition, some normal-looking glands still to be found among the neoplastic elements. Bifurcating glands were not observed, and branching patterns were present in 27% of the polyps only. In 86% of the lesions, the number of gland openings along the polyp surface was larger than the number of gland bases observed along the muscularis mucosae. This difference increased with polyp size (r = 0.9043). Those data, together with previous radioautographic observations, suggest that formation of new adenomatous glands mainly results from an infolding of the surface epithelium between normal, preexisting glands. This mechanism sharply contrasts with villous polyps in which papillary projections arise upwards from the mucosal surface.

Relationship between dose, time, and tumor yield in mouse dimethylhydrazine-induced colon tumorigenesis.

Colorectal tumor yield and volume data were obtained using 355 CF1 mice serially sacrificed up to 84 weeks following various dose levels of the carcinogen 1,2-dimethylhydrazine dichloride (DMH). Several conclusions were reached: (a) With increasing doses of DMH, there was an increased tumor yield and decreased latency period. (b) With repeated doses, there was a rapidly cumulative tumor yield. (c) New tumors continued to accumulate in the colon and rectum even at long intervals after the DMH treatments. This was substantiated by a positive correlation between the number of tumors per colon and the delay after DMH. In addition, when several tumors were present in the same mouse, their sizes were graded rather than uniform. These observations are consistent with a 2- or multi-step carcinogenesis mechanism. The latter implies that DMH induces a permanent transmissible alteration within some cells which thereafter will be at risk for further alterations capable of initiating cancer growth.

Significance of the karyorrhectic index in 1,2-dimethylhydroazine carcinogenesis.

Specimens from the liver, kidney, stomach and various intestinal segments of BD IX male rats were analyzed for mitotic index (MI) and the proportion of karyorrhectic figures (karyorrhectic index, KI) at various intervals after a s.c. injection of 1,2-dimethylhydrazine. In the intestinal specimens, a severe drop in MI (maximum after 12--14 h) and rise in KI (maximum after 6 h) were observed, with all karyorrhectic figures found in the proliferative compartment of the mucosa. Within the large intestine, there was a good correlation between the KI of each segment and its susceptibility to further tumor development.

Cell proliferation of pericryptal fibroblasts in the rat colon mucosa.

The turnover of pericryptal fibroblasts in the rat colon mucosa was analysed after in vivo incorporation of tritiated thymidine. Thirty-six rats were serially killed one hour to 21 days after intraperitoneal injection of the radionuclide. At one hour, the labelling index of pericryptal fibroblasts was only 2.44%; labelled fibroblasts were slightly predominant along the lower two-thirds of the crypts. Within 24 hours, most underwent at least one cell division. No migration was observed and a significant proportion of labelled fibroblasts was still present after three weeks. It is concluded that those fibroblasts constitute a slowly renewing cell population. The data failed to confirm the hypothesis of an 'en bloc' migration of fibroblasts in synchrony with the epithelial cells.

[An animal model for tumors of the large intestine]. / Een voorbeeld van dikke darmkanker bij dieren.

Dimethylhydrazine (DMH) and its derivatives induced in many animal species tumors of the large intestine with a great specificity and reproductibility. Oour personal observations using rats BD IX injected weekly with DMH are summarized in this presentation. The induced tumors appear as invaded tumors already at the microscopic stade. Their growth is best described by a Gompertz function. The number of induced tumors increases with time as a non linear function. This model is very useful for the study of the biology of human tumors with a low development.

Histogenesis of colon glands during postnatal growth.

The development of colon mucosa during postnatal growth was analyzed in male BD IX rats using histological and radioautographic methods. Newborn animals already exhibited clearly recognizable crypts of Lieberkühn. DNA synthesis activity predominated in the lower two thirds of those crypts, as it constantly did during subsequent growth and in adult colons. The height of crypts at birth was already half the adult size. There was, in contrast, a dramatic increase in their number (more than 1,000% from birth to the 10th week, as observed on transverse sections). The mechanism by which new glands derive from the mucosal epithelium implies a longitudinal fission of preexisting glands.

Tritiated thymidine incorporation into epithelial cells of normal-appearing colorectal mucosa of cancer patients.

A radioautographic analysis of the number and position of labeled epithelial nuclei after in vitro incorporation of tritiated thymidine ([3H]TDR) was carried out with 30 specimens of histologically normal colorectal mucosa from 26 patients, of whom 13 were being treated for rectal or sigmoid cancer and 13 were controls. A higher mean labeling index was found in the cancer than in the control group (9.8% +/- 1.2 and 7.9% +/- 0.9, respectively). Because of wide individual variations, this difference was not statistically significant. However, a highly significant upward shift of the proliferating cell compartment was observed in the cancer group, resulting in a specific modification of the [3H]TDR labeling pattern in 6 of 17 specimens. DNA synthesis predominated in the middle or middle and upper thirds of the crypts of Lieberkühn rather than in the lower third as observed in controls. The patchy alteration of epithelial cell renewal frequently accompanying colorectal cancer was suggestive of a defect in the regulatory control mechanism. This in vitro [3H]TDR incorporation assay could provide a valuable discriminatory parameter in studies of high-risk populations.