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PubMed1978

Dose response to intrarectal administration of N-methyl-N-nitrosourea and histopathologic evaluation of the effect of two retinoids on colon lesions induced in rats.

Male F344 rats, 8 weeks of age, were given 16 intrarectal administrations of N-methyl-N-nitrosourea (NMU) at one of three dose levels over a period of 8 weeks. Five days after the final NMU instillation, rats were placed on one of three diets: chow with gelatin beadlets, chow with beadlets containing 0.024% 13-cis-retinoic acid, or chow and beadlets with 0.006% of the trimethylmethoxy phenyl analog of retinoic acid ethylamide. Groups of 20-40 rats were killed at 22-26 weeks after the first carcinogen treatment. The number of rats with colon carcinoma and the number of tumors per rat were dose related. In addition, "blind" histopathologic evaluation of four predesignate colon locations revealed a dose-related incidence of microscopic preinvasive and invasive colon carcinomas. The feeding of diets containing these two retinoids did not significantly alter the incidence of these parameters of carcinogenesis or the mean histopathologic score at predesignated colon locations for preinvasive or invasive neoplastic lesions. Over 90% of the colon neoplasms induced were invasive tubulopapillary adenocarcinomas. The diameters of the tumors correlated significantly with degrees of invasion of the colons. Only 1 tumor (a signet ring carcinoma) metastasized to the peritoneal cavity. Only 2 of 300 rats treated with NMU had tumors at sites other than the colon.

Adenocarcinoma↗
PubMed1976

Air contrast colon examination in patients with colostomies.

A readily feasible technique for producing an excellent air contrast examination of the colon in patients with colostomies is described. The technique employes no special equipment and is easily tolerated by patients. Indications for the examination include a symptomatic patient with a negative conventional enema or suspicious single column examination. The surprisingly high incidence of both benign and malignant coexisting colonic neoplasms is reviewed.

Aged↗
PubMed1997

New rodent models for studies of chemopreventive agents.

Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc1638 mice). These mice develop multiple gastrointestinal lesions, including adenomas and carcinomas, focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice on a Western-style diet, which has higher fat content and lower calcium and vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min mice were treated with sulindac, which markedly reduced the incidence of intestinal tumors. A third new rodent model containing a targeted mutation in the gene Mcc (mutated in colorectal cancer) recently became available for chemoprevention studies. These mice develop multiple types of neoplasms including adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the forestomach, and tumors in other organs including lung, liver, and lymphoid tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in significantly increased gastrointestinal lesions. These nutrient modifications also have been given to normal mice, demonstrating without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style diets also have now induced modulation of cell proliferation in other organs including mammary gland, pancreas, and prostate. These findings help develop new preclinical rodent models to aid the analysis of genetic and environmental factors leading to neoplasia, as well as new methods for evaluating the chemopreventive efficacy of specific nutrients and pharmacological agents.

Animals↗
PubMed1981

Direct metastatic spread of right colonic adenocarcinoma to duodenum--barium and computed tomographic findings.

Contiguous involvement of the duodenum from primary right-sided colonic neoplasms is relatively uncommon. More rarely, metastatic involvement of the duodenum occurs after resection of a primary carcinoma of the right colon. Until recently, the radiological assessment of this pathologic process has been limited to barium gastrointestinal imaging techniques. Three cases of primary right colonic tumors metastasizing to the duodenum are presented, and barium studies are correlated with CT findings in 2 of these cases.

Adenocarcinoma↗
PubMed1988

Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers.

We studied 670 persons in 34 kindreds by flexible proctosigmoidoscopic examination (60 cm) to determine how frequently colorectal adenomas and cancers result from an inherited susceptibility. Kindreds were selected through either a single person with an adenomatous polyp or a cluster of relatives with colonic cancer. The kindreds all had common colorectal cancers, not the rare inherited conditions familial polyposis coli and nonpolyposis inherited colorectal cancer. Likelihood analysis strongly supported the dominant inheritance of a susceptibility to colorectal adenomas and cancers, with a gene frequency of 19 percent. According to the most likely genetic model, adenomatous polyps and colorectal cancers occur only in genetically susceptible persons; however, the 95 percent confidence interval for this proportion was 53 to 100 percent. These results suggest that an inherited susceptibility to colonic adenomatous polyps and colorectal cancer is common and that it is responsible for the majority of colonic neoplasms observed clinically. The results also reinforce suggestions that first-degree relatives of patients with colorectal cancer should be screened for colonic tumors. This evidence of an inherited susceptibility to a cancer with well-recognized environmental risk factors supports the hypothesis that genetic and environmental factors interact in the formation and transformation of polyps.

Adenomatous Polyposis Coli↗
PubMed1992

Pulmonary metastases of colonic carcinoma. Distinction from pulmonary adenocarcinoma.

Pulmonary metastases may develop in patients with colonic carcinoma. Histopathologic separation of a solitary colonic metastasis from a primary pulmonary adenocarcinoma may be problematic. With the use of a polyclonal antibody to carcinoembryonic antigen, a monoclonal antibody to cytokeratin (CAM 5.2), and a monoclonal carcinoembryonic antigen antibody (D-14), we compared 23 colonic carcinomas metastatic to the lung with 24 primary pulmonary adenocarcinomas. Both carcinomas manifested similar histologic features. However, foci of "dirty necrosis" were common in all but one of the colonic neoplasms, and foci were observed in only four of the primary lung carcinomas. The polyclonal carcinoembryonic antigen antibody did not distinguish metastatic colonic carcinoma from primary pulmonary adenocarcinoma. All colonic tumors stained with D-14, while three primary pulmonary adenocarcinomas stained diffusely, and eight stained focally. Staining with D-14 will not absolutely distinguish colonic from pulmonary adenocarcinoma. However, positive D-14 staining and the presence of dirty necrosis should identify most colonic carcinomas. True-negative D-14 staining practically excludes a colonic origin.

Adenocarcinoma↗
PubMed2000

Overexpression of intestinal trefoil factor in human colon carcinoma cells reduces cellular growth in vitro and in vivo.

BACKGROUND & AIMS: Intestinal trefoil factor (ITF) has a role in gastrointestinal mucosal integrity and the repair of damaged mucosa. However, little is known about its role in tumors. To analyze the role of ITF in colon carcinomas, overexpression of the ITF gene in colon carcinoma cells was used. METHODS: Human colon carcinoma cell lines LoVo and SW837, expressing no endogenous ITF, and WiDr expressing a low level of ITF were stably transfected with an expression vector harboring human ITF complementary DNA. The effects of ITF overexpression on in vitro growth, morphology in collagen gel, response to epidermal growth factor (EGF), mitogen-activated protein kinase (MAPK) activity, and growth in nude mice were assessed. RESULTS: Overexpression of ITF in LoVo and SW837 resulted in significantly reduced growth in vitro and in vivo. In collagen gels, the ITF-expressing LoVo clones formed smaller, more dispersed colonies. EGF-induced phosphorylation of MAPKs was modestly reduced in the ITF-expressing clones. The growth of WiDr was modestly suppressed only in vivo by ITF overexpression. CONCLUSIONS: Overexpression of ITF suppressed the growth of colon carcinoma cells. ITF may function as an inhibitory factor for the growth of colonic neoplasm.

Animals↗
PubMed1989

Enhanced carcinogenesis in the proximal small intestine of the rat following rumenectomy.

Various techniques have been used to enhance carcinogenesis in experimental animals. This study examines the effects of the excision of the forestomach (rumen), a squamous epithelial pouch of the rat, on the incidence and distribution of intestinal neoplasms induced by 1,2-dimethylhydrazine (DMH). Thirty-four male Sprague-Dawley rats were randomly assigned to control and experimental groups. The experimental group was subjected to an excision of the rumen while the control group underwent a gastro-rumenotomy and closure. Following a two week recovery period, each animal was weighed and injected with DMH (20 mgm/kg body wt) on a weekly basis for 22 weeks. At 24 weeks, the 32 surviving rats were sacrificed and the number, location, and histology of the neoplasms in the intestinal tract of each rat were noted. Rumenectomy resulted in a statistically increased incidence of neoplasms in the proximal small bowel (mean of 1.3 +/- 0.01 neoplasms/rat) when compared with the control group (mean of 0.1 +/- 0.2 neoplasms/rat) (p less than 0.001); but did not influence the incidence, distribution, or histology of colonic neoplasms between control and experimental animals. All neoplasms of the proximal small bowel when examined histologically were classified as invasive adenocarcinomas. The colon contained adenomata and carcinoma in situ, as well as adenocarcinomas. It is therefore concluded that excision of the rumen of the rat stomach selectively promotes malignant formation in the proximal small bowel following repeated injections of DMH.

Adenocarcinoma↗
PubMed1987

Immunohistochemical studies of blood group substance H in colorectal tumors using a monoclonal antibody.

With the use of a murine monoclonal antibody with specificity for human blood group substance H, the distribution of this antigen on colorectal carcinomas and adenomatous polyps has been studied by immunohistochemistry. All of the 20 carcinomas studied were found to express H substance regardless of their location in the colon, their pathologic grade, or their clinical stage. Adenomas were variably positive for H substance, and expression of the antigen appeared to correlate with the degree of dysplasia seen on microscopic examination. Normal colonic mucosa, nonadenomatous polyps, and nonepithelial colonic neoplasms studied failed to express H substance. The results suggest that detection of H substance expression may be useful in the diagnosis of colonic malignancies and dysplastic premalignant lesions.

Adenocarcinoma↗
PubMed1993

Human papillomavirus 16 DNA in NIH3T3 cells transformed by colonic cancer cellular DNA.

Human papillomavirus (HPV) 16 DNA is closely associated with human cancers. It has been identified as an aetiological agent in cervical cancers and, recently, in colonic neoplasms. To further understand the role of HPV 16 DNA in colorectal carcinogenesis, NIH3T3 cells were transformed with high molecular weight DNA from colonic cancer cells and the expression of HPV 16 DNA detected. Both human Alu and HPV 16 DNA sequences were found in the type II foci of CC-M2T cells by Southern blot hybridisation. Additionally, 100% tumorigenicity in nude mice was seen. This study shows the transfection of HPV DNA from colonic cancers into NIH3T3 mouse cells and suggests that HPV type 16 might be associated with the malignant transformation of colonic cells.

3T3 Cells↗
PubMedDate not supplied

Expression of adhesion molecules in the host response to colon carcinoma.

Expression of the adhesion molecules LFA-1, ICAM-1, and VCAM-1 was studied in five resected colon carcinomas, one villous adenoma, and normal colon mucosa to determine whether expression of these markers is increased in response to tumor. Frozen tissue samples were stained by a labeled avidin-biotin technique using primary antibodies to LFA-1 (CD11a), CD2, CD4, CD8, CD20, CD68, HLA-DR, ICAM-1 (CD54), and VCAM-1. For each marker, the number of positive mononuclear cells was graded semiquantitatively, and stromal and endothelial cells were scored as either positive or negative. Overall grade of inflammation was increased in tumor compared with normal mucosa in five cases. Cells positive for LFA-1, CD2, CD4, CD8, and CD20 were increased in the tumors in the same cases. ICAM-1 was expressed in vessels, inflammatory cells, and stromal cells in normal mucosa. It was markedly increased in tumor stroma in all six cases. VCAM-1 was negative in normal mucosa, and focally expressed in tumor vessels and stroma. We conclude that increased expression of adhesion molecules occurs around colon neoplasms, particularly in stromal cells, and may be a mechanism for the recruitment of activated leukocytes as part of the inflammatory response to colon carcinomas.

Adenoma, Villous↗
PubMed2004

Mucocele of the appendix: a report of five cases.

Mucocele of the appendix is an uncommon disorder, characterized by a cystic dilatation of the lumen. It is often diagnosed clinically from signs and symptoms of acute appendicitis or, if it is asymptomatic, as an incidental finding during ultrasonography, computed tomography, and radiographic examinations of the gastrointestinal tract, or laparotomy. The incidence of mucocele ranges from 0.2% to 0.3% of all appendectomy specimens. We report five cases of appendiceal mucocele (all women, aged 19-90 years), who were admitted from January 1993 to January 2003 to our hospital. These cases represent 0.29% of the 1720 appendectomies performed during this period. Three of the patients were symptomatic and had appendectomies. The final diagnosis for mucocele was given at laparotomy. No colon neoplasms were identified during surgery, and subsequent colonoscopic examinations were also negative. The other two patients were asymptomatic of appendiceal tumor. Colonoscopy revealed two colonic malignant tumors in one patient and an adenocarcinoma of the sigmoid colon in the other. Mucocele of the appendix was diagnosed pre-operatively by ultrasound and computed tomography. One of the two patients underwent a right hemicolectomy and sigmoidectomy; the other one underwent an appendectomy, cecostomy and sigmoidectomy. Four of the patients recovered and are doing well today; one patient died on the twenty-fifth postoperative day. The most common symptom of mucocele is abdominal pain, although many patients may be asymptomatic. Mucocele is often associated with concomitant colon cancer, thus patients with this tumor should be systematically checked for other colonic lesions.

Adenocarcinoma↗
PubMed1996

Five primary synchronous neoplasms of the gastrointestinal tract.

Multiple primary malignant neoplasms in a single patient have been well documented in the literature over the past hundred years. The lesions can be limited to a single organ or involve multiple organ systems. It is relatively common for patients with colorectal carcinoma or carcinoid tumors to have more than one primary neoplasm. Colonic lesions can be synchronous or metachronous in presentation and colonic or extracolonic in location. We present a patient with five primary synchronous neoplasms of the gastrointestinal tract, involving the stomach, small bowel, and colon. The patient had no evidence of metastatic disease and underwent resection of all the lesions. This case illustrates the need for a thorough search for additional neoplasms in the treatment of patients with cancer.

Adenocarcinoma↗
PubMed1996

Familial risk and colon cancer.

Familial occurrence in excess of that expected by chance is common among cases of colon cancer. Only a small fraction of these familial cases arise from well-described syndromes. There are epidemiologic, colonoscopic, genealogic data base and large prospective studies that characterize the familial occurrence and risk for common colon cancer. Kindred studies suggest that common familial occurrence arises from inherited susceptibility of a mild to moderate magnitude. The responsible genes are yet to be identified, though a number of candidate genes have been suggested. Clinical features, especially age at diagnosis and number of first-degree relatives with colon cancer, already allow stratification of familial risk. Risk stratification is important for colon cancer screening, as some higher-risk persons should probably have more intensive screening. Research is needed to identify the genes or their polymorphisms that give rise to common inherited susceptibility for colon cancer, to examine how susceptibility genes interact with environmental factors and give rise to colonic neoplasms and to verify suggested screening approaches that incorporate familial risk.

Adult↗
PubMed1996

The modulation of choline phosphoglyceride metabolism in human colon cancer.

Colorectal cancer has a high incidence of morbidity and mortality in the North American population. Elevated levels of plasmalogens have been reported in some neoplastic tissues including colon tumors, but the mechanism for this increase has not been defined. Since changes in plasmalogen level are usually associated with changes in the other phospholipid subclasses, a general increase in all phospholipid subclasses may also be found in colonic neoplasms. In this study, the levels of the major phospholipids, including their plasmalogen and diacylphospholipid subclasses, were found to be elevated in human malignant colonic tissues. Since phosphatidylcholine is the most prominent type of phospholipid found in both malignant and control tissues, the mechanism for its accumulation during malignancy was investigated. Decreases in phospholipase C and D activities were observed in tumor samples, but an enhancement of the CTP: phosphocholine cytidylyltransferase activity was also detected. Immunoblotting analysis revealed that the elevated cytidylyltransferase activity was caused by a three-fold increase in the level of enzyme protein during tumor development. Based on these enzyme studies, we conclude that the high level of phosphatidylcholine in colon tumors resulted from a decrease in its turnover and an increase in its expression.

Colon↗
PubMed2001

Total colectomy with ileorectal anastomosis leads to appreciable loss in quality of life irrespective of primary diagnosis.

Total colectomy with ileorectal anastomosis (TC) is a well-accepted procedure for many colonic pathologies but data on faecal incontinence and related quality of life after TC are lacking. The aims of this study were to assess the long-term bowel frequency, degree of incontinence and quality of life with respect to faecal incontinence and to compare them with the outcome for TC for different diagnostic groups. We identified 54 patients who had undergone TC at Singapore General Hospital and interviewed them using two questionnaires: the faecal incontinence quality of life (FIQL) scale and the Wexner faecal incontinence score (WS). The patients were allocated in 3 groups based on the primary diagnosis leading to operation, i. e. slow-transit constipation or megacolon (STC), colonic neoplasm (CA) and complicated pan-colonic diverticular disease (DD). Median bowel frequencies for STC and DD groups were 2.5/day; for CA, it was 3.5/day (p=0.042). There was no significant difference in the FIQL score and WS between the groups. Eleven patients had some degree of faecal incontinence based on WS. Many patients (20.4%) with perfect continence had fear of faecal leakage affecting their quality of life. In conclusion, patients with frequent stools do not need to have incontinence to suffer from the fear of it. The primary pathology leading to TC made no difference to the faecal incontinence or bowel urgency problems.

Adult↗