[Exfoliative cytodiagnosis by isoperistaltic total intestinal irrigation in neoplasms of the colon].
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Adult↗
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Utility of preoperative fiberoptic flexible sigmoidoscopy in the evaluation of patients with suspected gynecologic malignancy.
BACKGROUND: Fiberoptic flexible sigmoidoscopy (FFS) is routinely requested preoperatively as part of evaluation of pelvic masses to exclude colonic involvement by the tumor or concurrent colonic neoplasm. The aim of our study was to evaluate the utility of preoperative FFS in patients with suspected gynecologic malignancy. METHODS: FFS, performed using a 60 cm sigmoidoscope, evaluated (1) presence of bowel involvement by the tumor, (2) extrinsic compression by the tumor, and (3) presence of colonic neoplasms. FFS findings were correlated with surgical findings. RESULTS: A total of 107 women underwent preoperative FFS and subsequent surgery. Eleven patients (11%) had lower gastrointestinal symptoms. At surgery, 63% of pelvic tumors were malignant and 37% were benign. The most common abnormality at FFS was colonic polyps in 23 patients (21%). Colonic adenomas were found in 11 patients (10%). Extrinsic compression by the tumor without mucosal abnormalities was seen in 15 patients (14%). The most common intraoperative finding was tumor adhering to the bowel in 18 patients requiring dissection, but only 1 patient required bowel resection. Eight of these 18 patients had preoperative lower gastrointestinal symptoms. All 15 patients with extrinsic compression at FFS had tumor adhering to the bowel. CONCLUSIONS: Pelvic masses cause extrinsic compression at FFS in 14% of patients. This is suggestive of tumor adherent to the bowel at surgery. However, bowel resection is rarely required because of tumor involvement. Most patients with bowel adherence by tumor have lower gastrointestinal symptoms. Colonic adenomas are found in one tenth of patients, mostly in patients older than 50 years of age. Preoperative FFS does not change the surgical management of pelvic tumors. Screening FFS is indicated in all patients with pelvic tumors over age 50, as in persons with average risk, but is otherwise unnecessary in evaluation of pelvic masses.
Adult↗
Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin.
The modulating effects of dietary feeding of two flavonoids, diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing diosmin (1000 ppm), hesperidin (1000 ppm) or diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.
Animals↗
Altered methylation of versican proteoglycan gene in human colon carcinoma.
We show for the first time that DNA isolated from human colon carcinoma tissue exhibits a selective hypomethylation of versican gene, which encodes a large chondroitin sulfate proteoglycan. The degree of methylation of CpG sequences of versican gene locus, as determined by isoschizomeric endonucleases and Southern hybridization, is about three times lower than that found in either normal colon or ulcerative colitis tissues. Hypomethylation can be observed in both benign and malignant colonic neoplasms; however, there is no correlation with increased expression since versican mRNA levels do not significantly vary between normal and neoplastic tissues. We further show that versican gene locus from malignant tissue, but not from normal or ulcerative colitis tissues, contains Hind III hypersensitive sites which also comprise hypomethylated CpG sequences. Analysis of versican methylation status in colon carcinoma cells and benign mesenchymal cells derived from human colon suggests that the changes observed in vivo derive from demethylating events involving host stromal cells rather than tumor cells themselves. These findings demonstrate that changes in versican gene methylation are specific for colonic neoplasms, that these changes may precede malignant transformation, and that inflammation and tissue remodelling alone are not enough to generate these changes in proteoglycan gene methylation and nuclease hypersensitivity.
Blotting, Southern↗
Enhancing effect of ethanol or saké on methylazoxymethanol acetate-initiated large bowel carcinogenesis in ACI/N rats.
Effects of ethanol or saké on intestinal carcinogenesis by methylazoxymethanol (MAM) acetate were examined in two experiments. In the first experiment, 39 male ACI/N rats were given two weekly intraperitoneal injections of MAM acetate (25 mg/kg body wt) and divided into two groups, with Group 1 being given 10% ethanol and Group 2 being given distilled water. The incidence of colonic cancer in Group 1 (15/17, 88%) was higher than in Group 2 (9/16, 56%, p = 0.040). Differences in the incidences of rectosigmoidal colonic neoplasms were even more marked (59% vs. 19%, p = 0.019) and their proportion of the total number of large intestinal neoplasms was greater in Group 1 (36%) than in Group 2 (15%, p = 0.046). In the second experiment, 97 female ACI/N rats were divided into 6 groups, with the animals of Groups 1-5 being given MAM acetate (2 times, 25 mg/kg body wt). Rats in Group 6 received saline. The rats received isocaloric drinks: Group 1, saké; Group 2, 50% saké; Groups 3 and 6, 15% ethanol; Group 4, 7.5% ethanol; and Group 5, nonalcoholic water. Incidences of rectosigmoidal colonic neoplasms in Groups 1, 2, and 3 (53%, 46%, and 50%) tended to be higher than in Group 5 (38%). Their proportions of the total number of large intestinal neoplasms in Groups 1 (68%) and 2 (67%) were slightly greater than in Group 5 (45%). The results suggest an enhancing effect of ethanol or saké on rectosigmoidal colonic carcinogenesis.
Alcoholic Beverages↗
Absence of p53 gene mutations in rat colon carcinomas induced by azoxymethane.
The K-ras and p53 genes are two of the most frequently mutated genes found in the human colonic tumors. Since azoxymethane (AOM) induced rat colonic neoplasms are similar to human colonic tumors in their histological features and proliferation characteristics, the rat has been used as an experimental model to study the pathogenesis of colon cancer in humans. Although the presence of K-ras point mutations has been reported in AOM induced rat colonic tumors, there are no reports describing the frequency for mutation of the p53 gene in these tumors. In this study, colon adenocarcinomas induced in rats by AOM were examined for the presence of point mutations in exons 5-8 of the p53 gene, using a combination of single strand conformation (SSCP) analysis, immunohistochemistry and direct DNA sequencing. SSCP analysis showed no differences in banding patterns between the normal mucosa and any of the 20 adenocarcinomas analyzed. Nuclear p53 immunoreactivity was absent in all tumors examined. Since p53 point mutations predominate in malignant colonic tumors, five adenocarcinomas with the greatest local invasiveness were analyzed by direct DNA sequencing of exons 5-8 of the p53 gene. Direct DNA sequencing did not reveal mutations in any of the adenocarcinomas analyzed, within the coding region of p53 gene that were sequenced. The results from the present study indicate that point mutations in the p53 gene, at least in the coding region (exons 5-8) are not involved in the development of colon cancer induced by AOM in the rat.
Adenocarcinoma↗
Changes in serum lipids related to the presence of experimental colon cancer.
People at risk from coronary heart disease and large bowel cancer are drawn from the same urbanised, industrialised Western populations. Whilst changes in blood lipids are well recognised in heart disease, little is known of their role in large bowel cancer. This study investigates serial alterations in blood lipids in the 1,2-dimethylhydrazine (DMH) rat model of colon cancer. Eighty Wistar rats received a 5 weekly regimen of DMH. At week 10, and at 5 weekly intervals until week 40, random groups of 10 rats were killed and blood taken for total and free cholesterol, phospholipids, triglycerides and liver enzymes. All colonic neoplasms were histologically classified either as adenomas or carcinomas with groups being allocated into tumour-free (n = 16) or tumour-bearing (n = 54), the latter group being further sub-divided into animals with adenoma alone (n = 8) and those with carcinoma (n = 46). Results were considered both sequentially and according to tumour status. Sequential results showed that with increase in colonic neoplasms with time there were accompanying increases in free and % free cholesterol and in phospholipids (P less than 0.001). There were no changes in total cholesterol, triglycerides or liver enzymes. Results according to tumour status showed that whilst there was no difference in total cholesterol or triglycerides between tumour-free and tumour-bearing rats, there was a significant increase in free (P less than 0.01) and % free cholesterol (P less than 0.001) and a decrease in phospholipids in the tumour-bearing animals (P less than 0.001). There was no difference in any serum lipid between tumour-free and adenoma-bearing rats. In animals with carcinoma, while there was no difference in total cholesterol or triglycerides, there was an increase in free (P less than 0.005) and % free cholesterol (P less than 0.001) and a decrease in phospholipids (P less than 0.001) compared to tumour-free rats. The data show for the first time a clear relationship between blood lipids and the presence or absence of large bowel cancer.
1,2-Dimethylhydrazine↗
Fecal occult blood testing in hospitalized patients.
We have evaluated the diagnostic value of the fecal occult blood test (FOBT) in hospitalized patients. We reviewed the medical records of patients who had a positive FOBT not associated with a large gastrointestinal bleed, and who had a subsequent complete evaluation of their gastrointestinal (GI) tract. Of the 50 subjects who met the study criteria, 21 had various GI symptoms and 13 reported weight loss. Patients taking medications that may influence the FOBT result were distributed as follows: 15 were taking nonsteroidal antiinflammatory drugs, eight were taking iron supplementation, three were using steroid drugs, and three were taking anticoagulant drugs. Nonneoplastic lesions were found in 47 patients. Neoplastic lesions were discovered in 11 patients: seven had adenomatous polyps, two had colorectal cancer, one had gastric cancer, and one had duodenal cancer. Only two of seven patients with adenomatous polyps had lesions > 1 cm. In the study population, the positive predictive value of FOBT for finding colonic neoplasms was 18% and for any GI neoplasm it was 22%. Our data indicate that in hospitalized patients (a) the yield of colonic neoplasms from FOBT is approximately 50% less than that in healthy outpatients, and (b) a positive FOBT test is unlikely to lead to the detection of GI malignancy in the absence of suggestive clinical findings.
Adult↗
[Potentialities of colonic fluorography in the diagnosis of small neoplasms of the colon].
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Colon↗
Increased epithelial cell proliferation in the colon of patients with acromegaly.
To gain insight into the possible physiological mechanisms responsible for the increased incidence of colonic neoplasms in patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly. Seven patients had newly diagnosed acromegaly and 23 were studied during follow-up. Serum growth hormone and insulin-like growth factor-1 (IGF-1) were determined on two separate occasions. During diagnostic endoscopy, mucosal biopsies were obtained for immunohistochemical determination of sigmoidal epithelial cell proliferation, expressed as labeling index (LI). Duodenal and fecal bile acid analyses were performed using gas-liquid chromatography. Results were compared with normal ranges of the laboratory. An increased overall LI was found in 54% of the patients. Increased LI of the luminal, middle, and basal crypt compartments was found in 11, 64, and 28%, respectively. Similarly, comparisons of the mean +/- SEM of the overall LI and the LI of the middle and basal compartments between acromegalic patients and a control group showed overall LI 10.0 +/- 0.8% versus 5.7 +/- 0.6% (P < 0.001), middle LI 12.1 +/- 1.2% versus 5.0 +/- 0.6% (P < 0.001), and basal LI 17.1 +/- 1.3% versus 10.8 +/- 1.3% (P < 0.01). Duodenal and fecal bile acid proportions were within the normal ranges of the laboratory. There was a positive correlation between growth hormone and overall LI (r = 0.55, P < 0.01) by least square regression analysis. There was no correlation between duodenal bile acid composition and hormone levels. The proportion of secondary bile acids in feces correlated with growth hormone (r = 0.55, P < 0.05) as well as with IGF-1 (r = 0.59, P < 0.05). With multiple regression analyses, only a relation between overall LI and IGF-1 (P = 0.007) remained to hold true. Increased epithelial cell proliferation, most probably due to a direct stimulatory effect of especially IGF-1, contributes to the increased risk of colonic neoplasms in acromegaly.
Acromegaly↗
Value of digital fluoroscopy for the diagnosis of pneumatosis coli.
Two cases are presented of benign pneumatosis coli diagnosed on digital fluoroscopic barium enema examinations, in which the gas-filled cysts in the colonic wall were only recognized by postprocessing of the images (i.e. increasing the brightness and contrast settings) at the computer workstation. When digital barium enemas are performed, we therefore recommend image postprocessing to evaluate polypoid lesions in order to differentiate pneumatosis coli from true colonic neoplasms.
Aged↗
Microsatellite instability is uncommon in intestinal mucosa of patients with Crohn's disease.
Patients with long-standing inflammatory bowel disease have an increased risk for colorectal carcinoma. Microsatellite instability occurs in colonic neoplasms and has been reported in colonic tissues from patients with ulcerative colitis. Patients with Crohn's disease also have an increased risk for colorectal cancer, although it is lower than that associated with ulcerative colitis. This study was designed to determine whether microsatellite instability occurs in Crohn's disease, and whether it occurs with similar frequency to that observed in ulcerative colitis. In all, 177 tissue samples from 33 patients with Crohn's disease were evaluated for microsatellite alterations. Microsatellite instability occurred in five different tissue samples from one of 33 Crohn's disease patients. Four of the five tissue samples showed microsatellite instability at more than one locus. We conclude that microsatellite instability is less common in Crohn's disease than ulcerative colitis and may reflect differences in cancer risk between these two forms of inflammatory bowel disease.
Adenocarcinoma↗
Colon cancer secreted protein-2 (CCSP-2), a novel candidate serological marker of colon neoplasia.
Cancers of the colon and rectum are the second leading cause of cancer death among adult Americans. When detected at early stages, colon cancer is highly curable. Colonoscopy, an effective but invasive screening test, has been limited in its public acceptance. The goal of this study was to identify novel serum markers of colon cancers and precancerous colon adenomas as potential candidates for noninvasive detection of early colon neoplasms. Employing expression microarrays, we identified colon cancer secreted protein-2 (CCSP-2) as a novel transcript whose expression is generally absent in normal colon and other normal body tissues, but that is induced an average of 78-fold in Stage II, III, and IV colon cancers, as well as in colon adenomas and colon cancer cell lines. These findings were validated by real-time PCR analysis in an independent panel of colon cancer cases. Moreover, CCSP-2 was shown to encode a secreted protein that circulates stably and is detectable in the blood of mice bearing human cancer xenografts transfected with epitope-tagged CCSP-2. As a novel secreted protein that is markedly induced in colon adenomas and cancers, CCSP-2 is a novel candidate for development as a diagnostic serum marker of early stage colon cancer.
Amino Acid Sequence↗
Analysis of adenocarcinoma of the colon and rectum: detection of human papillomavirus (HPV) DNA by polymerase chain reaction.
OBJECTIVE: The aim of the present work was to evaluate the presence of human papillomavirus genotypes in malignant and normal mucosa of the colon and rectum in order to determine if a relationship exists between HPV infection and colon neoplasms. MATERIALS AND METHODS: Thirty normal colon tissues and 54 sporadic adenocarcinomas were screened for HPV positivity using nested-PCR. Detection of viral types 6, 11, 16, 18, 33, 34 and 51 was performed by the LIS-SSCP (Low Ionic Strength-Single Strand Conformational Polymorphism) procedure. RESULTS: Significant differences in high risk HPV infection were found between normal samples and adenocarcinomas (P < 0.001). Among the cases, an inverse association between HPV infection and Dukes staging was also found (P = 0.020). Finally, there was no significant association between HPV and some classical clinicopathological features, although a gradient of infection form rectum to cecum was evident. CONCLUSION: The present study demonstrates that HPV may infect the glandular mucosa of the colon and suggests a possible association between HPV and colorectal cancer.
Adenocarcinoma↗
Phase I trial of sulindac plus 5-fluorouracil and levamisole: potential adjuvant therapy for colon carcinoma.
Epidemiological studies indicate that nonsteroidal anti-inflammatory agents may reduce colorectal cancer incidence and mortality. Moreover, sulindac has been shown to attenuate the growth and progression of colonic neoplasms in an experimental model of colon carcinoma and in patients with familial adenomatous polyposis. To determine whether sulindac (300 mg/day) would increase toxicity associated with 5-fluorouracil (5-FU) and levamisole, 15 patients with advanced colorectal cancer were treated. Median treatment duration was 3 (range, 0.6-6.0) months, and median age was 56 years (33% >/= 60 years). All patients had failed prior 5-FU-based therapy, had measurable disease, and were evaluable for toxicity. Grade III/IV granulocytopenia occurred in four patients; three patients had received prior pelvic irradiation resulting in a predisposition to myelosuppression. Two patients developed grade III anemia, and occult gastrointestinal bleeding was suspected in one. No other grade II or greater gastrointestinal or other nonhematological toxicity occurred. One patient had a partial response, 3 patients had disease stabilization, and 10 patients progressed on study. Our results indicate that sulindac does not significantly increase short-term toxicity associated with 5-FU and levamisole. To determine whether sulindac increases the efficacy of adjuvant chemotherapy, we propose a phase III randomized trial in patients with lymph node-positive colon cancer.
Adult↗
Regional chemoprevention of carcinogen-induced tumors in rat colon.
BACKGROUND & AIMS: Rat colon neoplasms are distributed 60% in the distal colon (DC) and 40% in the proximal colon (PC), similar to distribution of colon cancers in the industrialized world. The effects of chemopreventive agents that affect colon tumor incidence on the distribution of colon tumors were studied. METHODS: Colon tumor distribution, numbers, and volumes were measured in the DC and PC of rats administered azoxymethane (15 mg/kg subcutaneously 2x) as an initiating agent and fed diets containing various chemopreventive agents. RESULTS: In control rats, azoxymethane-induced tumor incidence in the DC exceeded that in the PC, but tumor volume was greater in the PC than the DC. Ellagic acid showed no chemopreventive effect and maintained the PC-DC colon tumor gradient. Oltipraz, a modestly effective chemopreventive agent, principally reduced the incidence of DC tumors. DL-d-difluoromethylornithine also greatly altered tumor number in the DC compared with the PC. In contrast, piroxicam (400 ppm) reduced PC tumors by 82% but DC tumors only by 57%. With all regimens, tumor volume remained greater in the PC than the DC. CONCLUSIONS: Chemopreventive agents have a selective regional effect on colon tumorigenesis in the rat. Elucidation of the mechanism for these differences may help clarify the modes of action of chemopreventive agents in colon cancer.
Animals↗
Carcinoma of colon after ureterocolic anastomosis: implantation on calyceal mucosa.
Two cases are reported of the development of mucoid adenocarcinoma of the colon in young patients, nineteen and thirty-four years after ureterocolic anastomosis for benign conditions. One patient showed implantation of the colonic neoplasm on the mucosa of an upper calyx in the obstructed kidney. Patients who have undergone ureterocolic anastomosis have a greatly increased risk of the development of large-bowel neoplasms. When suspected, radiologic examination of the colon using a water-soluble contrast material, together with rectosigmoidoscopy or colonoscopy, is essential. Because of the serious nature of this complication, it is suggested that the recent trend to return to the use of large bowel in urinary diversion may be hazardous, especially in the young patient with a benign disease.
Adenocarcinoma, Mucinous↗
Inguinal hernia is not a sign of colon cancer: results of a prospective screening trial.
BACKGROUND: It has been suggested that patients with an inguinal hernia harbour an increased risk for colorectal cancer. METHODS: In a prospective clinical trial, we compared the prevalence of colonic neoplasms in 100 cases with inguinal hernia and 100 controls without inguinal hernia. The number, size, histology type, and the location of all colorectal lesions found during a screening flexible sigmoidoscopy were recorded. RESULTS: Not a single case of colorectal cancer was detected in the patients with inguinal hernia pending surgical repair. In the asymptomatic control subjects, one Dukes A and one Dukes B1 colon cancer were detected. Polypectomy was performed in 15% and 17% of the case and control subjects, respectively. During a 5-year period following the initial screening procedure, none of the case or control subjects was diagnosed with colon cancer. CONCLUSIONS: The decision for or against performing an endoscopic procedure in a patient with inguinal hernia should be guided by the general principles of screening for colorectal cancer. The mere presence of an inguinal hernia does not automatically increase the risk of colorectal cancer.
Adenoma↗