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[Colo-rectal precancerous conditions: anatomo-pathologic and clinical aspects].

The authors, after emphasizing the value presently ascribed to the conception of "epithelial displasia" as initial histologic and cytologic alteration, common to all groups of patients with high risk of development of colorectal cancer, review the mani precancer lesions of large intestine. As a conclusion, they affirm the main target one presently aims at for the screening in groups with high risk is to precociously identify the stage of transformation of epithelial displasia into carcinoma, so as to be able to set up a timely treatment.

Adenoma↗

Immunohistochemical analysis of p53 overexpression in human colonic tumors.

The progression from benign adenoma to colorectal cancer is underscored by an accumulation of genetic defects involving the activation of protooncogenes and the inactivation by point mutations and deletions of tumor-suppressor genes. Altered p53 has been one of the most commonly observed of these defects. By using a monoclonal antibody, PAb1801, it was possible to detect the accumulation of an altered p53 protein in standard sections of colon-preserving histopathological criteria. We analyzed biopsies from benign and malignant colorectal tumors fixed in 70% ethanol, and detected cells positive for p53 in 65% of 34 carcinomas and 24% of 84 adenomas, but none in the normal-appearing adjacent mucosa. No correlation was found between degree of differentiation of adenocarcinomas and p53 immunodetection. Abnormal p53 protein expression in adenomas ranged from sparsely stained to focally intensive areas. Overexpression of p53 was detected in more tumors taken from the left side of the colon than from the right side. Adenomas with greater villous content and severe dysplasia had a greater tendency to overexpress mutated p53. Cases of multiple synchronous adenomas showed different patterns of p53 expression but more positivity was found in adenomas from patients with a synchronous adenocarcinoma. Immunodetection of p53 in 11 biopsies from the same tumors alternatively fixed in 70% ethanol or formalin gave comparable results for adenocarcinomas but was not consistent for adenomas. Fifty-four archival formalin-fixed paraffin-embedded colorectal tumors were also stained with PAb1801. p53 was detectable, sometimes with a weaker intensity, in 50% of 18 adenocarcinomas and 22% of 36 adenomas, and most of these showed severe dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Synchronous multiple colorectal adenocarcinomas.

BACKGROUND: The object of the present work was to characterize clinical features and the quality of preoperative examinations in patients with synchronous colorectal carcinomas, and to compare the incidence of associated benign polyps with our findings in patients with a single malignant lesion. METHODS: A retrospective evaluation of 225 patients with primary colorectal carcinoma revealed 9 cases (4.0%) of synchronous colorectal carcinomas. RESULTS: The synchronous colorectal carcinomas were located in the same anatomical segment in 7 patients and were divided into different segments in 2 patients. The accuracy of preoperative diagnosis was 55.6% by endoscopy alone and 66.7% by double contrast barium enema (DCBE) alone, while the rate was 77.8% when colonoscopy and DCBE were combined. There was a higher incidence of associated benign polyps in the group with synchronous colorectal carcinomas (55.6%) versus 28.7% for a single carcinoma (P < 0.05). The main reason why multiple lesions could not be identified preoperatively was that the distal lesions prevented examination of the proximal lesions. CONCLUSIONS: At the time of surgical resection, it is important to ascertain preoperatively whether or not a second lesion exists. If synchronous polyps are present in patients with synchronous colorectal carcinomas, they should be ablated to reduce the risk of metachronous colorectal carcinoma.

Adenocarcinoma↗

The significance of synchronous carcinoma and polyps in the colon and rectum.

The relationship of colorectal carcinoma with polyps was studied retrospectively in 1202 patients. The incidence of synchronous carcinoma (SC) and metachronous carcinoma (MC), prognosis, and recurrence patterns were studied. Synchronous polyps (SP) were found in 36% of the patients. SC was found in 4.4% of the patients, and MC developed in 3.5% of patients. The incidence of SC and of MC increased with SP, and varied according to number, size, and histologic features of the polyps. The adjusted 5-year survival rate was improved in patients with SP compared with those without SP, both overall (79% versus 64%, respectively) and by Dukes' Stage B (87% versus 73%, respectively) and Dukes' Stage C (56% versus 39%, respectively). The pattern of relapse was the same for the SP and non-SP groups. Subtotal colectomy is recommended for colorectal carcinoma and SP in good-risk patients.

Adult↗

Increased content of chondroitin sulfate proteoglycan in human colorectal carcinoma metastases compared with the primary tumor as determined by an anti-chondroitin-sulfate monoclonal antibody.

To determine if the amount of chondroitin sulfate proteoglycan (CSPG) in human colorectal tumor tissue correlates with the tumor's aggressiveness we immunochemically determined the CSPG levels in colorectal carcinomas at different stages. A total of 50 specimens--4 polyps, 15 stage B tumors, 9 stage C tumors, 12 stage D tumors, 7 liver metastases, and 3 lymph node metastases--were examined. Tumor tissues were extracted with 4 M guanidine hydrochloride containing protease inhibitors. The extracts were serially diluted and blotted onto nitrocellulose membranes. Reactivity of a chondroitin sulfate-specific mouse monoclonal antibody (CS-56) was determined by biotinylated goat antimouse Ig and avidin-biotin-peroxidase complex. After comparing tissues from tumors at different stages (classified by the presence or absence of metastasis), we could not find a positive or negative correlation between the amount of CSPG in primary colorectal carcinoma tissues and the tumor's metastatic potential. However, the metastatic foci in the liver or lymph node contained higher amounts of CSPG than the primary tumors did. Immunohistochemical staining of colon carcinoma tissue with CS-56 revealed that CSPG is predominantly localized in fibrotic portions in the tumor tissues. Two-year follow-up studies indicated that a high level of CSPG in primary tumors was not predictive of recurrence.

Adenocarcinoma↗

The role of colonoscopy and flexible sigmoidoscopy in screening for colorectal carcinoma.

Six hundred thirty-two patients were referred to the Colorectal Clinic from February 1983 to February 1986 for screening with the Pentax 65 cm flexible sigmoidoscope. Forty-nine of these patients (8 percent) had adenomatous polyps. There were 27 males and 22 females. The mean distance examined by the 65 cm flexible sigmoidoscope was 55 cm. Five patients were excluded from analysis, leaving 44 patients who underwent colonoscopy to the cecum. At the time of colonoscopy, 15 of the 44 patients (34 percent) had one or more adenomatous polyps beyond reach of the 65 cm flexible sigmoidoscope. The remaining 29 patients who underwent colonoscopy had no polyps beyond reach of the 65 cm flexible sigmoidoscope. Thirty adenomatous polyps, one invasive carcinoma of the ascending colon, and one hyperplastic polyp were found in these 15 patients. In summary, 34 percent of patients found to have adenomatous polyps within reach of the 65 cm flexible sigmoidoscope harbored one or more adenomatous polyps in the proximal colon at the time of colonoscopy. A positive 65 cm flexible sigmoidoscope examination requires colonoscopy to identify and remove proximal premalignant lesions, thereby aborting the polyp-cancer sequence.

Colonic Neoplasms↗

Screening and prevention of colorectal cancer in Haining County.

From September 15, 1977, to April 15, 1978, 450, 477 persons over the age of 7 years were screened for schistosomiasis; a subgroup of 198,950 over 30 years were screened for colorectal cancer. Seventy-five malignant colorectal tumors were discovered in the latter group, a positive rate of 37.69 per 100,000 (seven were colonic cancers, 14 rectal cancers, 20 polyps with cancerous change, and 34 carcinoids). Of this group, 2701 had various types of polyps and 5242 had definitive diagnostic schistosomiasis. History, physical examination, and an occult blood test are simple, useful methods for detecting late colorectal cancer but are of no value in preventive screening of early cases. While digital rectal examination is an important, effective method of diagnosing rectal cancer, the positive rate is one tenth that of rectoscopy. It cannot be used for mass screening because the examining finger cannot tolerate such constant use and is too short to discover higher tumors. The sequence of colorectal cancerous change found in our center was from normal intestinal epithelium to tumorigenic polyps or colorectal ulcer, to polyps with anaplastic change, to polyps with local cancerous change, to adenocarcinoma. Cancer was seen more frequently in villous and adenomatous polyps; these are called precancerous stages of colorectal cancer. No relationship between schistosomiasis and colorectal cancer was found.

Adenoma↗

The true incidence of synchronous cancer of the large bowel. A prospective study.

The reported incidence of synchronous primary cancers and polyps associated with single cancers of the large bowel is varied. In a prospective study over a 5 year period, 166 patients with primary colorectal cancer had either total colonoscopy preoperatively or total colonoscopy within 6 months of surgical resection. One hundred seventy-eight cancers were detected. Synchronous cancers were found in eight patients (5 percent), and benign neoplastic polyps were demonstrated in 46 patients with single cancers (28 percent) and in 112 patients with synchronous primary cancers (38 percent). Of significance is that seven of eight (88 percent) synchronous cancers would not have been included in the standard resection for the index primary cancer. Similarly 31 of 46 neoplastic polyps (67 percent) were not in the same surgical segment as the primary cancer. Total large bowel evaluation, preferably using colonoscopy, is essential in all patients with cancer of the large bowel.

Adult↗

Pathologic risk factors of occult malignancy in endoscopically unresectable colonic adenomas.

BACKGROUND: With the advent of new endoscopic and laparoscopic techniques, the likelihood of colonoscopically unresectable adenomas harboring occult malignancy influences management. While prior studies have evaluated polyp size and morphology in assessing the risk of malignancy, the relative risk of cancer based on the presence or absence of high-grade dysplasia has not been systematically studied. METHODS: For all lesions preoperatively diagnosed as adenomas without invasive cancer, multivariate logistic regression analysis was performed to elicit independent variables associated with malignancy in the resected specimen. RESULTS: One hundred patients underwent a colectomy for preoperatively diagnosed adenomatous lesions. Multivariate logistic regression analysis revealed size, degree of dysplasia, and left-sided location to be independent predictors of malignancy. CONCLUSIONS: In colonic adenomas which are not amenable to simple colonoscopic resection, the most useful predictors of the lesion harboring a malignancy are polyp size and the presence of high-grade dysplasia, and these factors can help determine management.

Adenoma↗

Serum retinol level in patients with colorectal premalignant and malignant lesions.

Serum retinol levels were determined by a fluorometric method in patients with colorectal cancer or polyps and those with inflammatory bowel disease. Serum retinol levels in patients with benign or malignant colorectal polyps and stage B cancer (modified Dukes' classification) were similar to those found in controls. By contrast, serum retinol levels were significantly lower in patients with Dukes' stage C or D. Among cancer patients that were followed after surgical treatment serum retinol levels did not differ significantly from those found in controls. Patients who died of metastases during follow-up possessed very low serum retinol levels. These findings suggest that a decreased serum retinol level in cancer patients is a consequence rather than a precursor of the neoplastic process. Furthermore, this study suggests that the marked decrease in serum retinol level might be an indicator of poor prognosis in colorectal cancer patients after surgery.

Adult↗

Patterns of proliferative changes in crypts bordering colonic tumors: zonal histology and cell cycle marker expression.

Proliferative crypt changes have been noted in mucosa bordering colonic carcinomas, but their biological significance is disputed. We anticipated that zonal patterning of histological changes and cell cycle marker expression would provide clues to the pathogenesis of these border changes. 81 specimens were examined including carcinomas, adenomatours polyps, adenomas with early carcinoma, flat adenomas and aberrant crypt foci. The spatial distribution and frequency of micro-architectural features, and mucosal thickness were determined in a border domain of 150 300 sequential crypts/specimen. Immunocytochemical expression of Ki67 and p53 antigens in crypts also was semi-quantitatively examined. We found that in 100% of carcinomas two histologically abnormal zones (Proximate and Middle) separated tumor from normal mucosa. Differences in the feature frequency between zones were statistically significant (p<0.05). Both zones showed mild increases in crypt cell expression of Ki67, with a statistically significant relationship to zonal patterning (p<0.005). Weak expression of p53 only appeared in rare cells. Crypt elongation with mucosal thickening (1.9x normal, p<0.001) in the Proximate and Middle zones distinguished carcinomas from border changes in all benign lesions, except flat adenomas. Since this change occurs in all cases of carcinoma, there is no correlation with tumor stage or grade. Also in carcinomas, elaborate complexes of attached crypts (connected crypt structures) were characteristic of the Middle zone, so that proximate zone was always architecturally simpler. We conclude, that despite continuous carcinoma growth, the invaded border mucosa maintains a prototypical zonal organization of molecular and histological crypt changes This spatially organized reaction pattern is likely to reflect an interplay between regulated growth and destructive processes in response to advancing carcinoma. Compared to the edges of benign colonic tumors, the edges of carcinomas are distinctive and consistent enough to be diagnostically useful.

Adenocarcinoma↗

[Multiple colorectal polyps and risk of cancer].

The malignancy rate ("severe cellular atypia' and "invasive carcinoma' in adenomas and associated carcinoma) was determined in a retrospective study on 95 patients, aged 28 to 97 years (median age 65 years), with colonoscopy findings showing multiple (more than 8) colorectal polyps. It amounted to 22% to 100% in patients with 8 and up to more than 50 polyps in the colorectum. The malignancy rate was "only' 3.7% to 11.8% based on the number of polyps in the individual patients and thus was about the same as in patients with an isolated or few polyps. Thus, malignancy rate increases with number of polyps (by far the majority adenomas). Endoscopy showed the presence of gastric polyps in eleven of the 95 patients (11.6%) with multiple colorectal polyps. With the exception of one "borderline lesion' they were benign, showing no definite tendency towards malignancy. After endoscopic ectomy of the multiple polyps surgical treatment (procto-mucosectomy, segment resection, hemicolectomy or colectomy) was necessary in 37 patients (39%).

Adenoma↗

Flexible sigmoidoscopy as a screening procedure for asymptomatic colorectal carcinoma in patients with inguinal hernia.

In patients about to have hernia repair, preoperative screening studies for early colorectal cancer using the rigid proctosigmoidoscope and barium enema have previously shown minimal cost effectiveness and poor patient acceptance. Flexible sigmoidoscopy may be more acceptable to patients and of greater diagnostic value. Between October 1980 and December 1983, 100 consecutive asymptomatic male surgical patients were examined using the Olympus 60 flexible proctosigmoidoscope. All patients were admitted for elective hernia repair. Age ranged from 21 to 88 years (mean 59.7). All patients with stool positive for occult blood on admission were excluded from this study. In addition, patients with any gastrointestinal symptoms, history of colorectal disease, or family history of colorectal polyps or carcinoma were excluded. Examinations were done under direct supervision of an attending surgeon (W.W. or C.S.C.). Of the 22 patients who had one or more benign polyps, three had villous adenomas. Two additional patients had carcinoma. Results of examination were completely normal in 63, while 13 patients were found to have hemorrhoids or diverticular disease. There were no complications and the procedure was well tolerated by all patients.

Adenoma↗

Sialomucins and carcinoembryonic antigen in the evolution of colorectal cancer.

We have explored the merit of a simultaneous study of sialomucin content and carcinoembryonic antigen (CEA) expression in the identification of early malignancy in adenomas. One hundred and thirteen colorectal adenomas were investigated by histochemical and immunocytochemical techniques. We compared adenomas from 'high risk' patients having synchronous carcinoma and 'low risk' groups with incidental polyps only. Twenty-three metaplastic and eight inflammatory polyps were also included. Our data suggest that size and dysplasia are not always closely related and that synchronous adenomas seem to carry a higher malignant potential than incidental polyps irrespective of size. The degree of O-acylation of sialic acids appears to be a sensitive indicator of early malignant change: loss of O-acylation was seen in all II adenomas with highly atypical foci ('focal carcinoma') but noted in only four of the remaining polyps with lower grade dysplasia (P less than 0.005). By contrast the intensity of staining for CEA was a gradual phenomenon and showed no statistically significant increase with the onset of malignancy. Inflammatory polyps showed staining characteristics similar to normal mucosa. Metaplastic polyps, however, revealed increased expression of CEA and reduced O-acylation with increased size which may reflect a disorder of growth and differentiation. Finally, by comparing these profiles of staining with those of normal mucosa, 'transitional' mucosa adjacent to carcinoma and carcinoma, we further illustrate a progression of changes occurring in colonic mucosa in carcinogenesis.

Adenocarcinoma↗