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Epithelial neoplasms of the vermiform appendix (exclusive of carcinoid). II. Cystadenomas, papillary adenomas, and adenomatous polyps of the appendix.

Forty-two cases of benign epithelial neoplasms of the appendix gleaned from the files of the Laboratory of Surgical Pathology, Columbia University, were studied. The majority were associated with dilatation of the appendix, or "mucocele." Conversely only 50% of all cystically dilated appendices examined had definite underlying adenomatous changes. Thus it is important to distinguish between cystic neoplasms (cystadenomas) and non-neoplastic retention cysts of the appendix. The most frequently found benign epithelial neoplasms were papillary adenomas. Even in the presence of atypia we labeled them benign. Appendectomy is usually adequate treatment for all adenomatous lesions occurring in the appendix. Almost a quarter of the cases reviewed were found to have synchronous or metachronous neoplasms elsewhere in the colon, while several patients harbored multiple colonic neoplasms in addition to the appendiceal adenomas. Thus a patient with an adenomatous lesion of the appendix should undergo a systematic search for other colonic lesions.

Adenoma↗

Arginine metabolism in benign and malignant disease of breast and colon: evidence for possible inhibition of tumor-infiltrating macrophages.

L-Arginine concentrations have been measured in benign and malignant breast and colonic neoplasms and compared with the macrophage content and arginase activity within these tumors. Our study confirmed previous findings of elevated plasma arginine concentrations in malignancy and demonstrated that tissue free-arginine concentrations are substantially higher in malignant (mean 9.8 mumol/g protein) than benign (2.8 mumol/g protein) breast disease. Similarly, malignant colonic neoplasms had a higher free-arginine concentration than benign colonic polyps (14.0 vs. 7.0 mumol/g protein). The macrophage content of the malignant tumors was also significantly higher than in the benign conditions (278 vs 29/high power field in breast disease), but despite this, there was no detectable difference in the arginase activity. These findings suggest that tumor-infiltrating macrophages are not able to produce this enzyme, and/or its activity is inhibited within the tumor cell milieu. The differences observed in the arginine concentrations within these lesions has potentially important implications for the pathway of arginine metabolism and local host antitumor responses.

Arginase↗

[Value of preoperative colonoscopy in colon-rectal neoplasms].

The surgical approach to treat colo-rectal carcinoma is usually based on the findings of barium enema. In 102 patients we reviewed the yield of pre-operative colonoscopy. Barium enema revealed the cancer in 76 of 84 patients (91%), whereas colonoscopy did so in 96 of 102 subjects (94%). In addition, 5 associated cancerous lesions were demonstrated by colonoscopy and none by barium enema. Associated benign lesions were seen in 14 patients. In 5 patients the surgical plan based on the barium enema was modified by the findings at colonoscopy. Eight false negatives to barium enema were correctly diagnosed by colonoscopy. We conclude that colonoscopy yields valuable information, beyond that of barium enema, in patients with colo-rectal cancer.

Adult↗

Hereditary aspects of colorectal adenomas.

BACKGROUND: Inheritance is important to the development of colonic adenomatous polyps and colon cancer. Current knowledge of inherited susceptibility to colonic neoplasms suggests that colon cancer screening strategies should consider familial and genetic risk. METHODS: This report reviews the literature pertinent to adenomatous polyp and colon cancer inheritance and suggests polyp-cancer screening procedures based on inherited or familial risk. RESULTS: Colorectal adenomas and cancer occur in several rare inherited syndromes and more commonly as sporadic cases. Intensive screening protocols have been suggested for the inherited syndromes because of the high associated cancer risk. Recent evidence suggests that inherited susceptibility also may be important in a large fraction of the so-called sporadic cases. Preliminary screening guidelines are suggested for this category based on the number of first-degree relatives affected with colon cancer. CONCLUSIONS: Inherited susceptibility appears to be more important to the pathogenesis of colorectal adenomas and cancer than previously recognized. Screening strategies which consider inherited risk may increase the effectiveness of cancer detection and prevention.

Adenoma↗

Appendectomy, tonsillectomy, and neoplasia.

Reports in the literature that study the frequency of cancer in individual who have had their tonsils or appendix or both removed are reviewed. Some investigators found a high incidence of solid cancers - in particular, breast and colon neoplasms - in female patients who have had appendectomy, but others disagreed. The association of tonsillectomy and/or appendectomy with the later development of malignant lymphomas is not proven.

Acute Disease↗

Perforated appendicitis and obstructing colonic carcinoma in the elderly.

Two patients admitted with perforated appendicitis and obstructing colonic cancers are presented. The first patient, a 75-year-old man, developed a persistent fecal fistula following appendectomy. Barium enema demonstrated an obstructing hepatic flexure carcinoma. The second patient, a 62-year-old man, recovered uneventfully following appendectomy. Persistent occult blood was found in his stools during follow-up examinations. Three months after surgery, diagnostic colonoscopy revealed a nearly obstructing sigmoid carcinoma. Obstruction of the appendiceal lumen by such lesions as fecaliths, carcinoid tumors, lymphoid hyperplasia, or cecal carcinoma accounts for appendicitis in the majority of patients. These two patients illustrate a less common cause. As many as 3 percent of patients over 40 years of age presenting with appendicitis also have obstructing colonic carcinomas. Elderly patients with appendicitis should be evaluated for colonic neoplasms at a clinically suitable time.

Aged↗

Prevalence of proximal colonic polyps in average-risk asymptomatic patients with negative fecal occult blood tests and flexible sigmoidoscopy.

BACKGROUND: Proximal colonic adenomas were found in 13% to 37% of patients without distal adenomas who underwent colonoscopy. Fiberoptic flexible sigmoidoscopy (FFS) was not performed prior to colonoscopy in all studies except one. The proximal colon at colonoscopy was defined as that portion of the colon proximal to either the descending-sigmoid junction or 60 cm from the anus while withdrawing the colonoscope. These estimates may not reflect exact colonic location when a 60 cm length sigmoidoscope is fully inserted. Therefore, the aim of our study was to determine the prevalence of proximal colonic neoplasms in asymptomatic patients with average risk for colon cancer, aged 50 years and over, with negative fecal occult blood tests and without adenomas at FFS. METHODS: Colonoscopy was performed in 80 patients without and 95 patients with adenomas at FFS. Polypectomy was done using hot biopsy forceps or snare cautery. RESULTS: Twenty-four proximal colonic adenomas (19 < 1 cm and 5 > or = 1 cm) were found in 18 of 80 patients (23%) with normal FFS compared with 39 proximal colonic adenomas (32 < 1 cm and 7 > or = 1 cm), in 28 of 95 patients (29%) with adenomas at FFS (p = 0.31). In patients with normal FFS, there were 20 tubular, 2 tubulovillous, and 2 villous (1 with severe dysplasia) adenomas. In patients with adenomas at FFS, there were 31 tubular, 5 tubulovillous, and 3 villous (1 with severe dysplasia) adenomas. CONCLUSIONS: Proximal colonic adenomas are found in up to one fourth of asymptomatic average-risk patients with negative fecal occult blood test and both with and without adenomas at FFS. The adenomas in both groups have similar size, histology, and location. Severe dysplasia is rarely present.

Adenoma↗

AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis.

The inhibition of apoptosis is a critical event in the development of colorectal malignancies, although the mechanism(s) remain incompletely understood. The anti-apoptotic proto-oncogene, AKT, has been implicated in the molecular pathogenesis of a variety of human malignancies; however, no data exist on the role of AKT in colon carcinogenesis. We therefore evaluated the presence of AKT in human and experimental colon neoplasms by immunohistochemistry. Normal colonic mucosa and hyperplastic polyps exhibited no significant AKT expression, in marked contrast to the dramatic AKT immunoreactivity seen in colorectal cancers (57% positive) and in both human colorectal cancer cell lines examined. Importantly, AKT was also detected in 57% of the adenomas examined, implicating overexpression of this proto-oncogene as an early event during colon carcinogenesis. Moreover, in the rodent-carcinogen model, azoxymethane (AOM)-treatment induced AKT expression in premalignant rat colonocytes. Tumors that evolve via different genetic pathways displayed a lower incidence of AKT overexpression. Indeed, only 22% of mismatch repair defective tumors and 42% of AOM-induced rodent tumors upregulated AKT. Staining with an antibody specific for AKT 2 duplicated findings with the AKT 1&2 antibody, suggesting that AKT 2 was the predominant isoform involved in colon carcinogenesis. Furthermore, utilizing an antibody that specifically recognizes the serine-473 phosphorylated form of AKT, we observed that activated AKT was detectable in the neoplastic but not normal epithelium. In summary, our immunohistochemical analysis indicates AKT overexpression occurs frequently during human colon carcinogenesis, but is less common in colon cancers with microsatellite instability. The early inhibition of apoptosis during sporadic colon carcinogenesis may be related, at least partly, to the overexpression of AKT.

Animals↗

Endoscopy for hematochezia in patients under 50 years of age.

The optimal strategy for evaluating rectal bleeding in young persons is unknown. This study examines the prevalence of adenomatous neoplasms identified at endoscopy for rectal bleeding. Retrospective cross-sectional analysis was made of patients under 50 years of age undergoing elective outpatient colonoscopy or flexible sigmoidoscopy for hematochezia. In all, 570 patients (309 F/261 M) met our inclusion criteria. The prevalence of neoplasms was 3.8% (95% CI 1.2-8.5%) among persons under 30, 2.8% (95% CI 0.9-6.3%) among persons age 30-39, and 10.9% (95% CI 7.4-15.4%) among persons age 40-49. The prevalence of neoplasms was higher in persons over age 40 (relative risk 3.43, 95% CI 1.70-6.94). Six of seven advanced neoplasms were identified in persons over age 40 (relative risk 7.4, 95% CI 0.89-60.7). In conclusion, the prevalence of colonic neoplasms in patients 40-50 years old with hematochezia is substantial. Among those persons younger than 40 years, the prevalence of colonic neoplasms is significantly lower.

Adolescent↗

Beta-Catenin mutations in a mouse model of inflammation-related colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sodium sulfate.

In a previous study, we developed a novel mouse model for colitis-related carcinogenesis, utilizing a single dose of azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in drinking water. In the present study, we investigated whether colonic neoplasms can be developed in mice initiated with a single injection of another genotoxic colonic carcinogen 1,2-dimethylhydrazine (DMH), instead of AOM and followed by exposure of DSS in drinking water. Male crj: CD-1 (ICR) mice were given a single intraperitoneal administration (10, 20 or 40 mg/kg body weight) of DMH and 1-week oral exposure (2% in drinking water) of a non-genotoxic carcinogen, DSS. All animals were killed at week 20, histological alterations and immunohistochemical expression of beta-catenin, cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) were examined in induced colonic epithelial lesions (colonic dysplasias and neoplasms). Also, the beta-catenin gene mutations in paraffin-embedded colonic adenocarcinomas were analyzed by the single strand conformation polymorphism method, restriction enzyme fragment length polymorphism and direct sequencing. The incidences of colonic neoplasms with dysplastic lesions developed were 100% with 2.29+/-0.95 multiplicity, and 100% with 10.38+/-4.00 multiplicity in mice given DMH at doses of 10 mg/kg or 20 mg/kg and 2%DSS, respectively. Although approximately half of the mice given DMH at a dose of 40 mg/kg bodyweight were dead after 2-3 days after the injection, mice who received DMH 40 mg/kg and 2%DSS had 100% incidence of colonic neoplasms with 9.75+/-6.29 multiplicity. Immunohistochemical investigation revealed that adnocarcinomas, induced by DMH at all doses and 2%DSS, showed positive reactivities against beta-catenin, COX-2 and iNOS. In DMH/DSS-induced adenocarcinomas, 10 of 11 (90.9%) adenocacrcinomas had beta-catenin gene mutations. Half of the mutations were detected at codon 37 or 41, encoding serine and threonine that are direct targets for phosphorylation by glycogen synthase kinase-3beta. The present results suggests that, as in the previously reported model (AOM/DSS) our experimental protocol, DMH initiation followed by DSS, may provide a novel and useful mouse model for investigating inflammation-related colon carcinogenesis and for identifying xenobiotics with modifying effects.

1,2-Dimethylhydrazine↗

Colitis-related rat colon carcinogenesis induced by 1-hydroxy-anthraquinone and methylazoxymethanol acetate (Review).

Patients with long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer (CRC) compared to the general population. For investigation of the mechanisms and prevention of UC and UC-related CRC, establishment of a promising animal model for such disease is important. 1-hydroxyanthraquinone (1-HAQ) present in certain medicinal plants such as Rubia tinctorum L. is a genotoxic and rodent colon carcinogen. Long-term feeding of 1-HAQ induced hyper-cell proliferation in rat colonic crypts with ulcerative changes, crypt abscess, severe inflammation and erosion before the occurrence of tumors, which are similar to those found in human UC. In addition, 1-HAQ has a synergistic effect with methylazoxymethaol (MAM) acetate on colon carcinogenesis. The polymerase chain reaction-single strand conformation polymorphism analysis revealed no mutations in Ki-ras and p53 in colonic neoplasms induced by MAM acetate + 1-HAQ, MAM acetate alone or 1-HAQ alone. Also, no mutations of APC were found in these tumors. These findings are similar to those found in human ulcerative colitis-associated colon cancer in contrast with sporadic colon cancers. A previous study revealed that induced colonic tumors had beta-catenin mutation with high frequency, suggesting tumor development by activation of the beta-catenin-Tcf signaling pathway. Increased expression in TNF-alpha and IL-1alpha was found in these induced colonic neoplasms, and the expression was more remarkable in colonic mucosa of rats exposed to MAM acetate + 1-HAQ, MAM acetate or 1-HAQ when compared with that in untreated rats. Thus, these cytokines may act as growth factors in rat colon carcinogenesis by MAM acetate and 1-HAQ and the synergistic effect of 1-HAQ with MAM acetate might be related to the biological effects of the cytokines expressed in the inflammatory conditions induced by 1-HAQ.

Animals↗

Does scant hematochezia necessitate the performance of total colonoscopy?

BACKGROUND AND STUDY AIMS: Controversy exists as to whether all patients with lower intestinal bleeding need to undergo total colonoscopy. This study compares the prevalence of colonic neoplasms in patients reporting scant hematochezia with the prevalence in controls. PATIENTS AND METHODS: Structured interviews were carried out with 4265 consecutive patients referred for colonoscopy. Of these, 468 patients had scant hematochezia, 299 had occult rectal bleeding and 57 reported dark rectal bleeding. Patients with scant hematochezia were matched for age and sex with those having no risk factors for colorectal neoplasms. For all groups, we determined the prevalence of adenomas and cancers below and above 50 cm. RESULTS: Colonic neoplasms were found in 18 % of patients with scant hematochezia and in 7.5 % of controls. However, most of these tumors were located within the reach of a sigmoidoscope. Compared with controls, patients with scant hematochezia had no increased risk for proximal neoplasms (odds ratio [OR] = 1.2), while this risk was significantly increased in patients with occult rectal bleeding (OR = 3.1) and patients who had observed maroon-colored blood in their stool (OR = 4.8). CONCLUSIONS: Flexible sigmoidoscopy appears to be a sufficient work-up for young patients who have observed trace amounts of bright red blood on the surface of their stool.

Adenoma↗

Methionine dependence in skin fibroblasts of humans affected with familial colon cancer or Gardner's syndrome.

Reduced growth in methionine-deficient, homocysteine-, folic acid-, and vitamin B12-supplemented medium, a characteristic of tumor and transformed cell lines, was investigated in skin fibroblasts of patients affected with hereditary colon neoplasms. The presence or absence of this phenotype was studied in 37 cell lines from either low-risk subjects or members of families with Gardner's syndrome (GS) or familial colon cancer (FCC). Growth constants of skin fibroblasts of the low-risk group were not significantly different in the presence of methionine (Kme) or absence of methionine (Kho) (0.106 +/- 0.011 and 0.098 +/- 0.011, respectively). However, growth constants of skin fibroblasts of both GS and FCC were significantly reduced in the absence of methionine. In GS, Kho = 0.086 +/- 0.006 and Kme = 0.120 +/- 0.006 (P less than .01). In FCC, Kho = 0.048 +/- 0.007 and Kme = 0.084 +/- 0.009 (P less than .01). Thus the growth of skin fibroblasts from both GS and FCC was methionine dependent. This phenotype was expressed in skin fibroblasts of an individual several years before any clinical manifestation of GS. In all populations studied the phenotype was independent of the age or sex of the individuals, aging of the cell lines, low serum concentration, and acute carcinogen treatment. In addition, there is a significant correlation (r = -0.85, P less than .001) between the disorganization of actin cables of the skin fibroblasts and the ratio of the growth constants. These data constitute the first report demonstrating methionine dependence in cell lines that are not derived from transformed cells, tumor cells, or fetal cells but are derived from skin fibroblasts of patients with hereditary colonic neoplasms. Inasmuch as these cells are not target cells related to colon cancer, the phenotype appears to be the expression of an inherited autosomal dominant genotype related to the oncogenic transformation.

Adolescent↗

The clinical value of Haemoccult and Fecatwin in the detection of colorectal neoplasia in hospital and general practice patients.

Four hundred and fifty asymptomatic general practice patients and 330 hospital inpatients had their stools tested for occult blood with the Haemoccult and Fecatwin methods. In general practice, 9/64 (14%) of patients with a positive result had a colonic neoplasm (three carcinomas, one Dukes' Stage A, two Dukes' Stage C, six adenomas) and in hospital 12/142 patients (8%) were found to have colonic tumours, (nine carcinomas, two Dukes' Stage A, two Dukes' Stage B, five Dukes' Stage C and three adenomas). The overall detection rates for colonic neoplasia were 2% in general practice and 3.4% in hospital. In 2 years of follow-up, none of the general practice patients have presented with colonic symptoms. Two hospital patients with colonic carcinomas produced negative tests with both methods. Out of the total of 21 colonic neoplasms, nine were detected by Fecatwin alone, but this trend in favour of the more sensitive test did not reach the 5% level of statistical significance. In contrast, the number of false positive results were significantly greater with Fecatwin than Haemoccult. From our data it would appear that the Fecatwin method warrants assessment in a full controlled trial of its value as a population screening test for colonic cancer.

Adenoma↗

Non-life-threatening sepsis: report of two cases.

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.

Adenocarcinoma↗

Biological variability of fecal calprotectin in patients referred for colonoscopy without colonic inflammation or neoplasm.

OBJECTIVE: Fecal calprotectin concentration in stool has recently been proposed as a marker of colonic neoplasm and inflammation, but the intraindividual day-to-day variability has so far received little attention. The present study was undertaken to determine the biological variability of fecal calprotectin in patients referred for colonoscopy. METHODS: A prospective design was applied. In each of 14 consecutive patients submitted for colonoscopy, eight stool samples were collected before the endoscopy. A detailed questionnaire was used. Calprotectin was measured by quantitative enzyme-linked immunoassay, and standard deviation for the within-patient variability was estimated from one-way analysis of variance. RESULTS: In absence of colonic neoplasm and inflammation, two populations of patients emerged: one (36%) with remarkably low and stable fecal calprotectin values all within the recommended cut-off of 50 microg/g, and one (64%) with labile values also beyond this limit. In this latter group. fecal calprotectin was 70 microg/g (mean) (single tests ranged from 9 to 461), and SD within patients was 52 microg/g, showing considerable day-to-day variation. History, concurrent diseases, or findings at colonoscopy could not explain labile values. A similar pattern was observed for spot variation in one stool sample from healthy volunteers, suggesting that factors other than disease contribute to the significant intraindividual biological variation of fecal calprotectin. CONCLUSIONS: Day-to-day variation of fecal calprotectin is considerable in patients without colonic inflammation or neoplasm, for whom the pattern of stabile low fecal calprotectin may seem to be a valid negative predictor. The origin and pattern of fecal calprotectin excretion deserve further attention.

Adult↗