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Pathological features of the colonic tumours induced in rats by the administration of 1,2-dimethylhydrazine.

The parenteral administration of 1,2-dimethylhydrazine to rats caused the development of colonic neoplasms in about 90% of animals by 24--30 weeks of treatment. Usually there were multiple tumours with a mean of 2.7 per rat. The lesions have been classified histologically into adenomata (26% of all tumours) and carcinomata, the latter showing varying degrees of differentiation. No completely anaplastic tumours were seen, and there were none originating in connective tissue. The distributions of the different tumour types along the length of the colon varied. The more benign lesions were situated predominantly in the distal half of the colon, while the poorly differentiated adenocarcinomata were concentrated in the proximal third of the colon. There was good evidence to suggest that adenomata often progressed to frank malignancy in the distal colon. In the proximal part, however, it appeared that tumours frequently developed de novo as poorly differentiated carcinomata. Perhaps regional variations in the kinetic organisation of the normal colonic mucosa somehow influence the nature of the neoplastic change induced by DMH, thus accounting for the differences in tumor distribution. After 24 weeks of DMH treatment there was only a small increase in the mean number of tumours per rat.

Adenocarcinoma↗

New automatic software for virtual colonoscopy: technical aspects.

PURPOSE: To evaluate a new virtual endoscopy software package capable of automatically plotting the path along which to perform endoscopic exploration. MATERIALS AND METHODS: We reviewed the examinations of 50 patients with colonic neoplasms studied by CT colonoscopy by using a single-detector CT scanner (Philips Tomoscan AVE1). The technical parameters used were: slice thickness 3 mm, pitch 1.4, reconstruction interval 2-2.5, 120 kV, 150-200 mA. The images were processed on a separate workstation (Philips Easy Vision 5.1) running an experimental virtual endoscopy software package capable of automatically drawing a line along which to move the virtual endoscope to explore the colon. Reconstruction of the endoscopic images along the path obtained was set at an interval of 15-20 mm between one endoscopic view and the next, to a total of 70 to 120 images. The endoscopic animated image sequence was then saved and evaluated by comparing the starting axial images and the three-dimensional images obtained. RESULTS: The programme plotted the endoscopic path correctly in a single pass in 40 of the 50 cases studied. The overall time spent by the radiologist on image-processing did not exceed 5 minutes. DISCUSSION: The need to reduce the time spent by audiologists on post-processing has led to a gradual improvement in image-processing hardware and software. In the context of virtual endoscopy, one of the main goals is to obtain the path for endoscopic exploration in as short a time as possible. The programme we evaluated successfully fulfils this requirement as, once the image-processing technical parameters have been defined, it plots a path along the entire colon and performs the reconstruction procedures automatically. The time spent by the operator on post-processing does not exceed 5 minutes. CONCLUSIONS: The new programme evaluated in this study facilitates the processing of endoscopic images, reduces radiologist time and may contribute to the widespread use of virtual colonoscopy.

Colonic Neoplasms↗

Streptococcus salivarius meningitis and colonic carcinoma.

Streptococcus salivarius caused fulminant meningitis in an elderly patient. A gastrointestinal diagnostic workup revealed an asymptomatic colonic adenocarcinoma. This first reported instance of S salivarius sepsis associated with a colonic neoplasm is not unexpected, since the organism is bacteriologically similar to S bovis, the prime bacterial indicator of occult malignancy. Exact speciation of streptococcal strains is fraught with technical difficulties, and gastrointestinal investigation may be warranted in an expanded variety of streptococcal infections.

Adenocarcinoma↗

Flexible sigmoidoscopy.

Flexible sigmoidoscopy became available in 1976. To date, studies comparing it with rigid sigmoidoscopy support an increase of 2.5 to six times in the flexible sigmoidoscope's ability to detect polyps, and a two- to threefold increase in detection of colonic neoplasms in the same patients. This paper summarizes the current reported results of flexible sigmoidoscopy to date and describes the instrument and procedure as done at the UCLA Family Practice Residency Program. The flexible sigmoidoscope deserves evaluation for widespread primary care application.

Colonic Neoplasms↗

A bitter diterpenoid furanolactone columbin from Calumbae Radix inhibits azoxymethane-induced rat colon carcinogenesis.

The modifying effect of dietary administration of a diterpenoid furanolactone columbin isolated from the crude drug Calumbae Radix (the root of Jateorhiza columba MIERS, Menispermacea) on azoxymethane (AOM)-induced was investigated in male F344 rats. Animals were initiated with AOM (three weekly subcutaneous injections of 15 mg/kg body weight) to induce colonic neoplasms. They were fed the experimental diets mixed with columbin (4, 20, and 100 ppm) for 4 weeks, starting 1 week before the first dosing of AOM and thereafter maintained on the basal diet without columbin. Additional experimental groups included the AOM alone group, the columbin alone group (100 ppm in diet for 4 weeks), and the untreated control group. Dietary feeding of columbin (4, 20, and 100 ppm) during the initiation phase of AOM-induced colon carcinogenesis reduced the incidence and multiplicity of colonic adenocarcinoma and the inhibition by feeding of 20 ppm (incidence: 20%, P=0.0242 and multiplicity: 0.20+/-0.40, P<0.02) and 100 ppm (incidence: 10%, P=0.0029 and multiplicity: 0.10+/-0.30, P<0.002) columbin was significant when compared with the AOM alone group (incidence: 55% and multiplicity: 0.55+/-0.50). Also, columbin administration in diet lowered the number of argyrophilic nucleolar organizer regions protein per nucleus in non-lesional colonic crypts and the blood polyamine content, which are reflected in cell proliferation activity. These results indicate chemopreventive ability of dietary columbin against chemically induced colon tumorigenesis when fed during the initiation phase, providing a scientific basis for chemopreventive ability of columbin against human colon cancer.

Animals↗

Comparative microsatellite analysis in discerning origin of disseminated tumor: the case of a patient with malignant ascites and a history of multiple tumors.

The origin of metastatic carcinoma is now always easily resolved on the basis of conventional dinical and pathological parameters, particularly in patients with more than 1 primary tumor. When 1 of the tumors is a renal cell carcinoma, the clinical picture is further confounded by the tendency of these tumors to be locally silent, to metastasize to unusual sites, and to disseminate long after removal of the primary tumor. We compared tumors for loss (ie, deletion) of loci on chromosomal arms 3p, 5q, 11q, and 18q in a patient with a malignant ascites fluid, a remote history of renal and colonic neoplasms, and a strong clinical suspicion of disseminated gastrointestinal adenocarcinoma. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. Even though the clinical picture suggested a gastrointestinal origin, comparison of genetic alterations clearly showed that the malignant ascites represented recurrence of the renal cell carcinoma. The malignant ascites and the primary renal cell carcinoma showed identical patterns of allelic loss at all loci tested. In contrast, the malignant ascites and colonic adenoma showed discordant patterns of allelic loss. Comparative microsatellite analysis provides a rapid genetic approach for discerning the origin of metastatic tumor spread. This may be a useful diagnostic adjunct when tumor origin is not clear on clinical or morphological grounds. In some instances, it may even provide a reasonable alternative to an extensive and costly conventional work-up.

Adenoma↗

Ferritin content in human cancerous and noncancerous colonic tissue.

Tumor tissue samples from 25 patients with adenocarcinoma of the colon, twelve related samples of normal colons as well as five serum specimens from the same patients were analyzed for ferritin. The average ferritin content of the tumor tissue was 788 ng/mcp with a range of 47-1,745 ng/mcp. The average ferritin content of normal colon mucosa was 115 ng/mcp with a range of 32-230 ng/mcp. Two specimens of metastatic colon cancer taken from the retroperitoneal space and liver, respectively, contained 3,867 and 2,827 ng/mcp of ferritin. The ferritin content of the tumor tissue was higher than that of the normal colon in 8 of 9 patients who had specimens obtained from both sites. The amount of ferritin found in tumor tissue was independent of sex, age, and the site of the original tumor. This study shows that the ferritin content of colon neoplasms is elevated and indicates that the tumor tissue may be the direct source of elevated serum levels of ferritin previously observed in cancer patients.

Adenocarcinoma↗

Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel tumorigenesis: the inhibition correlates with suppression of cell proliferation and lipid peroxidation and with induction of phase II drug-metabolizing enzymes.

In our previous short-term experiment, Citrus auraptene inhibited the development of azoxymethane (AOM)-induced aberrant crypt foci, which are precursor lesions for colorectal carcinoma. In the present study, the possible inhibitory effect of dietary administration of auraptene was investigated using an animal colon carcinogenesis model with a colon carcinogen AOM. Male F344 rats were given s.c. injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce colon neoplasms. They also received diets containing 100 or 500 ppm auraptene for 4 weeks in groups of "initiation" feeding, starting 1 week before the first dosing of AOM. The diets containing auraptene were also given to rats for 38 weeks in groups of "postinitiation" feeding. At the termination of the study (38 weeks), dietary administration of auraptene caused dose-dependent inhibition in AOM-induced large bowel carcinogenesis. Auraptene feeding during the initiation phase reduced the incidence of colon adenocarcinoma by 49% at 100 ppm (P = 0.099) and 65% at 500 ppm (P = 0.0075). Auraptene administration during the postinitiation phase inhibited the incidence of colon adenocarcinoma by 58% at 100 ppm (P = 0.021) and 65% at 500 ppm (P = 0.0075). Also, the multiplicity of colon carcinoma was significantly reduced by initiation feeding at a dose level of 500 ppm (P < 0.01) and postinitiation feeding at a level of 100 and 500 ppm (P < 0.05 and P < 0.01, respectively). Feeding of auraptene suppressed the expression of cell proliferation biomarkers (ornithine decarboxylase activity and polyamine content) in the colonic mucosa and reduced the production of aldehydic lipid peroxidation [malondialdehyde and 4-hydroxy-2(E)-nonenal]. In addition, auraptene increased the activities of Phase II drug-metabolizing enzymes (glutathione S-transferase and quinone reductase) in the liver and colon. These findings suggest that the inhibitory effects of auraptene on AOM-induced colon tumorigenesis at the initiation level might be associated, in part, with increased activity of Phase II enzymes, and those at the postinitiation stage might be related to suppression of cell proliferation and lipid peroxidation in the colonic mucosa.

Aldehydes↗

Clusterin as a biomarker in murine and human intestinal neoplasia.

Early detection of colorectal cancer is critical for the management of this disease. Biomarkers for early detection of several cancers have been developed and applied clinically in recent years. We have sought to discover candidate biomarkers without the restricted choice of markers placed on microarrays, and without the biological complications of genetic and environmental heterogeneity. We have compared by cDNA subtraction two genetically matched sets of mice, one developing multiple intestinal neoplasia (C57BL/6J-ApcMin) and the other tumor-free (C57BL/6J). One prominent candidate biomarker, clusterin, was then subjected to a series of validation steps. In situ hybridization and immunohistochemistry were used to analyze clusterin expression at a cellular level on a series of murine intestinal and human colonic neoplasms. Elevated clusterin expression was characterized within certain regions of murine and human tumors regardless of tumor stage, location, or mode of initiation. The cells showing high clusterin levels generally lacked differentiation markers and adenomatous polyposis coli antigen. Tumor cells undergoing apoptosis expressed low levels of clusterin. Its specific expression patterns and correlation with cellular events during tumorigenesis make it a useful diagnostic tool in the mouse and a potential contributor to the set of biomarkers for early detection of human colon cancer.

Alkylating Agents↗

High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer.

DNA methylation abnormalities occur consistently in human neoplasia including widespread hypomethylation and more recently recognized local increases in DNA methylation that hold potential for gene inactivation events. To study this imbalance further, we have cloned and localized to chromosome 19 a portion of the human DNA methyltransferase gene that codes for the enzyme catalyzing DNA methylation. Expression of this gene is low in normal human cells, significantly increased (30- to 50-fold by PCR analysis) in virally transformed cells, and strikingly elevated in human cancer cells (several hundredfold). In comparison to colon mucosa from patients without neoplasia, median levels of DNA methyltransferase transcripts are 15-fold increased in histologically normal mucosa from patients with cancers or the benign polyps that can precede cancers, 60-fold increased in the premalignant polyps, and greater than 200-fold increased in the cancers. Thus, increases in DNA methyltransferase gene expression precede development of colonic neoplasia and continue during progression of colonic neoplasms. These increases may play a role in the genetic instability of cancer and mark early events in cell transformation.

Animals↗

Symptomatic colonic lipoma: differential diagnosis of large bowel tumors.

Symptomatic colonic lipomas, although unusual, continue to present difficulties in the preoperative differential diagnosis between malignant and benign colonic neoplasm. Although new imaging techniques are available, they are frequently diagnosed at laparotomy, and definitive histology is required. Local excision is adequate treatment, but segmental excision may be necessary when there is doubt about the diagnosis, or when a complication occurs.

Adult↗

The angiographic diagnosis of colonic carcinoma.

Carcinoma of the colon is a common cause of chronic iron deficiency anaemia in elderly patients and is conventionally diagnosed by either barium enema or colonoscopy. Occasionally these studies are inconclusive and individuals may proceed to further imaging, including angiography. Between December 1991 and October 1996, 337 patients were referred for visceral angiography to determine the cause of chronic gastrointestinal bleeding. In seven of these individuals (two males and five females with an age range of 65-74 years), all of whom had been investigated by barium enema and colonoscopy, both reported as showing no cause for bleeding, an arteriographic diagnosis of colonic carcinoma was made. Four of these demonstrated patchy areas of increased vascularity whilst three were predominantly hypovascular. Early venous drainage was seen in five. Marked irregularity and truncation of vasa rectae was present in six; more subtle irregularity was visible in one. The mural veins were irregular with or without truncation in five of the six patients in whom they were visualized. The marginal artery was angiographically involved in only two cases and in one of these the tumour was irresectable. It is important to recognize that a previous 'normal' colonoscopy and barium enema does not exclude a colonic neoplasm, even if advanced, and that this diagnosis may be made angiographically. Confusion with other pathologies, such as angiodysplasia, should be prevented by close scrutiny of vasa rectae at the site of arteriographic abnormality, which will usually demonstrate vascular irregularity and truncation highly suggestive of malignancy.

Aged↗

Incidence and odds ratio of appendicitis as first manifestation of colon cancer: a retrospective analysis of 1873 patients.

BACKGROUND AND AIM: Obstruction of the lumen of the appendix is the major cause of appendicitis. Tumors could obstruct this lumen and cause appendicitis in the elderly. The association between appendicitis and colon cancer has not been sufficiently investigated, and this study was designed to clarify this association. METHODS: This was a retrospective study. Patients diagnosed with acute appendicitis from January 1998 to December 2003 at the Taipei Veterans General Hospital were surveyed. Patients found to have colon cancers immediately or subsequently after appendectomy were included and analyzed. RESULTS: A total of 1873 patients were diagnosed as having appendicitis of whom 16 were found to have colon cancer. The incidence of appendicitis associated with colon cancer was 0.85%. The time from appendectomy to the recognition of colonic cancer was at a median delay of 5.8 months. From the Taiwan Cancer Research Annual Report, the incidence of colon cancer was 31.91/100,000 in the year 2000. The odds ratio of colon cancer incidence had a 38.5-fold increase among patients older than 40 with acute appendicitis. CONCLUSIONS: In patients over 40 years who present with symptoms of acute appendicitis the possibility of a coexistent colonic neoplasm should always be kept in mind. These patients should undergo colonoscopy 6 weeks after surgery to exclude the possibility of a coexistent colorectal cancer.

Acute Disease↗

[Clinico-endoscopic diagnosis of cancer of the large intestine].

Appearance of the clinical signs of large-intestinal cancer usually demonstrates advanced stages of the process. Endoscopic polypectomy, along with screening and active follow-up of patients, can be one of the measures for identification and prevention of tumours in early terms.

Adult↗

The relationship between faecal bile acids and the development of experimental colon cancer.

Human metabolic studies have suggested a positive association between dietary intake, faecal bile acid excretion and the development of colon cancer. Similar investigations in experimental models of this disease have also implicated faecal bile acids but in both animals and man the results remain equivocal. This study sequentially examines the outputs and concentrations of faecal bile acids in dimethylhydrazine (DMH) treated groups of rats (n = 10), killed at 5-weekly intervals from the 10th to 40th week following the first injection. The sequential results showed that both the output and concentration of faecal bile acids decreased with time and accompanied an increase in both the incidence and numbers of colonic neoplasms over the 40 weeks of the study. When the animals were grouped according to the histological classification of their tumours, the faecal bile acids did not differ between animals with and without tumours. Further, when the latter group were sub-divided into those with adenomas alone and those with carcinomas, faecal bile acid outputs and concentrations did not differ between them, nor when they were compared with the tumour-free animals. The results of this study do not support a role for faecal bile acids in the dimethylhydrazine-induced model of experimental colon cancer in rats.

Animals↗

Screening for colonic neoplastic lesions using flexible sigmoidoscopy in employees of a nuclear research center and members of collective settlements.

It has been shown that screening of average risk individuals reduces the incidence of colorectal cancer. The most effective method for screening has yet to be determined in terms of cost-effectiveness, but approximately two-thirds of colorectal neoplastic lesions are within the reach of the flexible sigmoidoscope. It has been estimated that a single such examination at the end of the sixth decade may reduce the colorectal cancer incidence by 60%. As part of a screening program for colon cancer, short colonoscopy was performed on 399 employees of a nuclear research center and 228 members of a collective settlement (kibbutz). The examinations were carried out on individuals aged > or = 40 years by two experienced endoscopists. The splenic flexure or transverse colon was reached in 95% of the procedures. Neoplastic lesions were found in 24 (6.0%) and 8 (3.5%) screenees (not significant) in the Nuclear Research Center and kibbutz populations respectively. Polyps <1 cm in diameter were significantly more common in the Nuclear Research Center population but larger polyps and cancers were not. In 47 Nuclear Research Center screenees with a family history positive in a first-degree relative, findings increased to 14.9% (P = 0.016). A family history of malignancy was found in 33.8% of kibbutz members but in only 11.8% of Nuclear Research Center employees. There was no evidence to suggest that working at the Nuclear Research Center increased the risk of colonic neoplasms. We conclude that flexible sigmoidoscopy is a valuable screening tool, especially for individuals with a first-degree relative with cancer. The yield of neoplastic lesions in the Israeli Nuclear Research Center and kibbutz populations is similar to that of the general population in the western world. Compliance rates are high in well-defined populations.

Adult↗

Histogenetic relationship between carcinoids and mucin-secreting carcinomas of colon as revealed by heterotransplantation.

Heterotransplantation of a human colonic neoplasm with classical morphologic characteristics of a carcinoid was sucessful in the cheek pouches of unconditioned, adult golden hamsters after a short sojourn in cell-impermeable chambers in rats. Although no mucin-secreting cells were detected in the donor carcinoid, the cheek pouch transplants exclusively exhibited mucinsecreting tumour cells of signet-ring type consistent with adenocarcinoma. This transplantable tumour, designated GW-77, has retained this appearance as well as expansive growth characteristics in xenogeneic hosts for a period of 4 years.These findings represent strong biological evidence consonant with views, based upon morphological findings, advocating a histogenetic relationship between colonic carcinoid and adenocarcinoma. It is believed that colonic adenocarcinoma has a selective advantage over carcinoid for serial propagation in an alien environment, indicating the less differentiated nature of its cellular components. Since the donor carcinoid cells failed to exhibit argentaffin reactions, these conclusions may be limited only to the nonreactive forms of carcinoid.

Adenocarcinoma, Mucinous↗