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Consider colonoscopy for young patients with hematochezia.

BACKGROUND: Hematochezia is a common complaint in adult patients aged <50 years. Most studies of lower endoscopy for rectal bleeding have concentrated on older patients or have failed to mention the location of lesions. OBJECTIVE: To determine the findings of complete colonoscopy in adults younger than 50 years with rectal bleeding. METHODS: Data were retrieved from medical records and included demographics, indications, endoscopic findings, and histology. Lesions were labeled according to location: proximal to the splenic flexure or distal to (and including) the splenic flexure. Excluded were those with a history of colitis, colorectal cancer, polyps, anemia, significant weight loss, severe bleeding, or strong family history of colorectal cancer. RESULTS: The study included 223 patients with rectal bleeding aged <50 years who had undergone a colonoscopy. Normal findings were recorded for 48 (21.5%). Four (1.8%) were diagnosed with cancer in the distal colon, and 22 (9.9%) were found to have colon adenomas, 6 of whom had proximal adenomas only. Hemorrhoids were present in 135 patients (60.5%). Other findings included colitis, angiodysplasia, diverticulosis, anal fissures, and rectal ulcers. CONCLUSIONS: Colon neoplasms may be present even in younger adults with nonurgent rectal bleeding. Though most findings were benign and located in the distal colon, colonoscopy should be strongly considered for this patient group.

Adenoma↗

Morphological basis of multistep process in experimental colonic carcinogenesis.

Carcinogenesis has been shown to be a multistep process. However, the morphological basis of the multistep process in colonic carcinogenesis has not been adequately investigated. In the distal colon of adult female CF-1 mice given weekly injections of DMH, we are able to demonstrate that colonic adenocarcinomas develop and evolve in four distinct but continuous steps on morphological grounds. (1) A colonic neoplasm develops in a single crypt. A given crypt is first repopulated by atypical epithelial cells which have either originated at the cryptal base or occurred as an outpocketing pouch in the proliferative zone of the crypt. (2) In the atypical crypt thus repopulated by atypical cells, the epithelial lining becomes invaginated and/or evaginated in the upper half to form an earliest identifiable neoplastic glandular lesion there. (3) The neoplastic lesion thus formed keeps invaginating, evaginating and expanding in various directions by unceasing proliferation of neoplastic cells, giving rise to a polypoid or a discoid lesion. (4) As the neoplasm grows, its leading downward edge would eventually penetrate the muscularis mucosae, and the malignant behavior of the neoplasm becomes apparent with further invasion into the submucosa, muscularis externa and serosa. In the due process, we have also explored the mode of villous formation in some neoplasms and analyzed the possible regulatory mechanisms in the various steps of colonic carcinogenesis.

Animals↗

Tritiated-thymidine labeling of rectal epithelial cells in 'non-prep' biopsies of individuals at increased risk for colonic neoplasia.

Recent measurements have shown increased proliferation of colonic epithelial cells in individuals at heightened risk for cancer of the large intestine. This biomarker has facilitated measurements of the effects of nutritional intervention in studies that are attempting to inhibit tumor development in high-risk individuals. In this study, further measurements were made of the proliferation of rectal epithelial cells, when biopsies were removed from mucosa that had not previously been disturbed by any tapwater or other enema preparations. Progressive increases were found in the numbers of [3H]dThd-labeled epithelial cells in rectal crypts, and in labeling index profiles, in patients having previous sporadic adenomas or colon cancer, compared to individuals who had not developed colonic neoplasms. The most quiescent proliferative equilibrium was found in individuals without previous colonic disease. Findings indicated that 'non-prep' rectal biopsies obtained from the most accessible region of the large intestine, show modifications in the biomarker of cell proliferation paralleling colon cancer risk.

Aged↗

Prospective survey of investigations in outpatients referred with iron deficiency anaemia.

Recent evidence has suggested that colonic neoplasm may be missed in patients presenting with iron deficiency anaemia unless colonic investigations are performed on all patients even when an alternative cause has been found. This study prospectively surveyed 114 consecutive patients referred from family practitioners to an outpatient clinic for the investigation of iron deficiency anaemia to determine the diagnoses contributing to the anaemia, the usefulness of certain clinical features, and the role of colonic and other investigations in obtaining the diagnosis. Upper gastrointestinal lesions contributing to anaemia were identified in 45 patients while colonic lesions were found in 18. Twenty three patients had a non-gastrointestinal cause for anaemia and in 12 patients no cause was found. Only two patients were identified as having colonic neoplasia (a small adenomatous polyp in each case) coexisting with upper gastrointestinal lesions. Symptoms and signs had a sensitivity and specificity of upper gastrointestinal disease of 50% and 83% respectively, and 44% and 80% for colonic disease. Endoscopy had a high yield (42%) and duodenal biopsy identified coeliac disease in three patients (two were aged > 70 years) each of whom had normal folate values. Barium enema had a yield of 13%. All colonic carcinomas occurred in patients > 65 years. The coexistence of colonic cancer or large polyps with an upper gastrointestinal lesion identified at endoscopy was rare in outpatients referred from family practitioners. Clinical symptoms and signs were poor indicators of the investigations that will detect a cause for the anaemia. Endoscopy (with duodenal biopsy) should be performed on all patients. The yield from barium enema is so low in young patients that if an upper gastrointestinal cause is found and there are no clinical indicators it would seem unnecessary.

Adenoma↗

Modulation of symmetrical 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis by isoproterenol (IPR).

The modulatory effect of IPR on the initiation and promotion of DMH-induced colon carcinogenesis was investigated using CF-1 young adult female mice. IPR given soon after each of weekly DMH injections inhibited the initiation phase of colon carcinogenesis when the cumulative dose of DMH was small. However, such inhibition was not observed when the cumulative dose of DMH was doubled. Colon neoplasms that developed in spite of IPR treatments seemed to infiltrate the colon wall earlier as compared to those without IPR. On the other hand, IPR did not appear to affect the promotion phase of colon carcinogenesis.

1,2-Dimethylhydrazine↗

Colon and anorectal neoplasms in a tropical African population.

At the University College Hospital, Ibadan, Nigeria, over a 30-month period (January 1975 to June 1977) more than 29 cases were fully studied. Nine patients presented with acute large bowel obstruction. In five cases, colonic neoplasms were palpated abdominally before surgery, and four of the patients were initially being treated for "hemorrhoids". All the patients presented at late stages. There was neither socio-economic nor sexual bias in this affliction. Sixty-nine percent of all the tumors occurred in the anorectal area well within the reach of the index finger, and 27.5% occurred in the right colon. Differential diagnosis included ameboma, rectal schistosomiasis, rectal tubercolosis, anal fistula and adult chronic intermittent intussusception. The treatment administered depended on the nature, location and stage of the disease. There was a case of metastatic squamous cell carcinoma of the hepatic flexure causing obstruction. The metastasis was from carcinoma of the cervix which had been treated with cesium insertions about three years previously. It is now known that colon and anorectal neoplasms, once regarded as rare among Africans living in tropical Africa, is not that rare. With the Africans boycotting native "doctors" in favor of medical institutions, many of the diseases once thought to be rare in Africans will unfortunately become less rare.

Adenocarcinoma↗

Streptococcus bovis bacteremia and underlying gastrointestinal neoplasms.

Two patients are described in whom Streptococcus bovis bacteremia was the only clue to the presence of a colonic neoplasm. A third patient had the rare association of gastric carcinoma and Streptococcus bovis bacteremia that followed an operation for the carcinoma. The need for both complete gastrointestinal survey in patients with Streptococcus bovis bacteremia and administration of appropriate antibiotic prophylaxis during surgical manipulation is emphasized.

Aged↗

Human papillomavirus type 18 in colorectal cancer.

Human papillomaviruses (HPVs) have been recognized as the etiological agent of warts, and they may also be associated with many cancers. HPV-18 is very common both in genital papillomas and in large bowel cancer. The relation between HPV-18 infection and natural course of colorectal cancer has not been fully defined. In this study, normal mucosa and colorectal cancer tissue were evaluated for the presence of HPV gene to determine whether or not HPV was involved in the development of colon neoplasm. The DNA extracted from colon tissue was screened for HPV by polymerase chain reaction (PCR) to amplify the viral gene fragment. These PCR products were digested with restriction enzyme, and Southern blotting was then performed to confirm the existence of HPV-18. The nucleotide sequence related to HPV-18 DNA was detected in 53% (10/19) of the normal mucosa specimens and in 84% (16/19) of the colorectal cancer specimens. The correlation between cancer samples and positive rate of HPV-PCR was statistically significant by chi-square test (p < 0.01). These data indicate that HPV-18 can infect the normal mucosa of the colon, and that this infection may be a risk factor for the development of colorectal cancer. The presence of HPV-18 DNA in patients with colorectal cancer suggests that the pathogenesis of colorectal cancer includes viral involvement.

Colorectal Neoplasms↗

[Intestinal anastomosis with biodegradable ring].

The authors report their experience using biofragmentable anastomosis ring (BAR) in bowel anastomosis. Starting January 1993 to February 1994, 46 intestinal anastomoses were performed using BAR, and particularly 39 end-to-end colo-colostomies, 2 end-to-side colo-colostomies and 5 end-to-side ileo-colostomies. 35 patients were affected by colonic neoplasm, 5 patients by diverticular colonic complications- and 5 patients by several unusual bowel diseases. Four emergency operations were performed, while 42 patients had an accurate bowel preparation before surgery. In this series of patients one case of preoperative mortality is reported, due to massive pulmonary embolism. Instead several minor complications occurred in other patients, such as paroxysmal atrial fibrillation (one case), basal pleuritis (one case), hyperpyrexia (three cases), temporary subocclusion or delayed canalization (five cases). Only one patient suffered from intestinal occlusion induced by adhesions and a second laparotomy was required. Delayed canalization seems to be caused by the small size of the BAR employed (25 mm) or by inadequate intestinal preparation, that usually occurs in emergency operations. After surgery all patients were followed up and 18 of them were examined by coloscopy six months after surgery. No clinical problem connected with bowel anastomosis was reported and all anastomosis looked quite previous and resilient. No anastomotic stenosis was found. In our experience and from recent reviewed reports, BAR seems to be a rapid, effective and safe device for sutureless bowel anastomosis.

Adult↗

Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380.

BACKGROUND AND METHODS: The role of colonoscopy in screening for colorectal cancer is uncertain. At 13 Veterans Affairs Medical Centers, we performed colonoscopy to determine the prevalence and location of advanced colonic neoplasms and the risk of advanced proximal neoplasia in asymptomatic patients (age range, 50 to 75 years) with or without distal neoplasia. Advanced colonic neoplasia was defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. In patients with more than one neoplastic lesion, classification was based on the most advanced lesion. RESULTS: Of 17,732 patients screened for enrollment, 3196 were enrolled; 3121 of the enrolled patients (97.7 percent) underwent complete examination of the colon. The mean age of the patients was 62.9 years, and 96.8 percent were men. Colonoscopic examination showed one or more neoplastic lesions in 37.5 percent of the patients, an adenoma with a diameter of at least 10 mm or a villous adenoma in 7.9 percent, an adenoma with high-grade dysplasia in 1.6 percent, and invasive cancer in 1.0 percent. Of the 1765 patients with no polyps in the portion of the colon that was distal to the splenic flexure, 48 (2.7 percent) had advanced proximal neoplasms. Patients with large adenomas (> or = 10 mm) or small adenomas (< 10 mm) in the distal colon were more likely to have advanced proximal neoplasia than were patients with no distal adenomas (odds ratios, 3.4 [95 percent confidence interval, 1.8 to 6.5] and 2.6 (95 percent confidence interval, 1.7 to 4.1], respectively). However, 52 percent of the 128 patients with advanced proximal neoplasia had no distal adenomas. CONCLUSIONS: Colonoscopic screening can detect advanced colonic neoplasms in asymptomatic adults. Many of these neoplasms would not be detected with sigmoidoscopy.

Adenoma↗

Diagnosis of colorectal neoplasms at double-contrast barium enema examination.

The double-contrast barium enema examination has been recognized as an option for colorectal cancer screening in Americans with average risk who are greater than 50 years of age. The purpose of this article is to review the principles for diagnosing colorectal neoplasms on double-contrast images and the spectrum of findings associated with these lesions. Colonic polyps can be sessile or pedunculated; their appearance depends on whether they are located on the dependent or nondependent wall of the bowel. Villous tumors may be flat, lobulated lesions, also known as "carpet" lesions, that are characterized by a finely nodular or reticular surface pattern, without a discrete mass. Colonic carcinomas may manifest as plaquelike, polypoid, semiannular ("saddle") or annular lesions. Colonic neoplasms sometimes are more difficult to detect in the region of the ileocecal valve or the distal rectum or in patients with severe diverticulosis. Careful double-contrast technique and meticulous scrutiny of the images therefore are required to optimize detection of these lesions.

Barium Sulfate↗

Expression pattern of the neu (NGL) gene-encoded growth factor receptor protein (p185neu) in normal and transformed epithelial tissues of the digestive tract.

The neu gene (also called NGL, erbB-2, and HER-2) encodes a 185-190 kDa transmembrane glycoprotein, p185neu, which has tyrosine-specific kinase activity and is homologous to but distinct from the epidermal growth factor receptor. The normal expression of neu mRNA and protein has been demonstrated in epithelial tissues of adult animals. Also, activation of the neu oncogene has been implicated in a variety of human adenocarcinomas. In the present study, we examined the expression of the p185neu protein in normal and transformed digestive tract tissues and in a panel of digestive tract-derived cell lines. By immunohistochemistry, strong reactivity was observed in the mucosal epithelium of the stomach, small intestine, and colon of both rodents and humans. In the small intestine, there was prominent p185neu expression by mucosal epithelium of the villus, with little or no staining in the crypts. Prominent expression was observed in the liver parenchyma, the endocrine and exocrine portions of the pancreas, and in the salivary gland. Immunoreactive p185neu was also demonstrated in fetal human intestinal epithelium. Tissue sections of selected benign and malignant colonic neoplasms were also examined. Immunoreactivity was consistently greater in adenomatous polyps than in adjacent normal colonic epithelium or areas showing malignant degeneration. By radioimmunoprecipitation, there was decreased expression in cell lines derived from more anaplastic colonic tumors. The p185neu protein is expressed widely in normal and transformed epithelial tissues of the digestive tract of the adult rat and human. This finding suggests that p185neu, a putative growth factor receptor, may play a role in the regulation of normal growth and function or in the malignant transformation of these cells.

Animals↗

Flat and depressed neoplasms of the colon in Western populations.

Flat and depressed neoplasms of the colon are defined endoscopically as visible non-exophytic, flat and/or depressed mucosal lesions with a height less than half the diameter of the lesion. These neoplasms are typically smaller than their polypoid counterparts, and might be associated with a more aggressive biological behavior. While these lesions have been described in cohorts of Japanese patients for over two decades, their existence in Western populations has been less well described. This review focuses on the epidemiology and biological behavior of flat and depressed neoplasms in Western populations as well as the strategies for their identification, endoscopic staging, and therapy.

Adult↗

Role of dietary fiber in colon cancer: an overview.

Studies have demonstrated a reduced risk of colon cancer when populations with diets high in total fat switched to a diet high in total fiber and certain whole-grain foods. Case-control studies have shown convincingly the relationship between dietary fiber and colon cancer. Studies in animal models have demonstrated that the inhibitory effects of dietary fiber on the development of colonic neoplasms depend on the nature and source of the fiber; that wheat bran appears to inhibit colon tumor development more consistently than do other dietary sources of fiber, such as oat and corn bran; and that dietary administration of phytic acid, high levels of which are present in wheat bran, inhibits colon carcinogenesis. Human dietary intervention studies have also indicated that the modifying effect of dietary fiber on bacterial enzymes involved in the production of putative colon tumor promoters depends on the type of fiber consumed. Dietary wheat bran, but not oat or corn bran, significantly decreased the levels of several tumor promoters in the colon, independent of stool bulk.

Animals↗

A retrospective study of histopathological findings in 894 cases of megacolon: what is the relationship between megacolon and colonic cancer?

Patients with megaesophagus (ME) have increased prevalence of cancer of the esophagus. In contrast, a higher incidence of colorectal cancer is not observed in patients with megacolon (MC). MC is very common in some regions of Brazil, where it is mainly associated with Chagas disease. We reviewed the pathology records of surgical specimens of all patients submitted for surgical resection of MC in the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto (HC-FMRP), from the University of São Paulo. We found that 894 patients were operated from 1952 until 2001 for MC resection. Mucosal ulcers, hyperplasia and chronic inflammation were frequently found, while polyps were uncommon. No patients with MC presented any type of colonic neoplasm. This observation reinforces the hypothesis that MC has a negative association with cancer of the colon. This seems to contradict the traditional concept of carcinogenesis in the colon, since patients with MC presents important chronic constipation that is thought to cause an increase in risk for colon cancer. MC is also associated with other risk factors for cancer of colon, such as hyperplasia, mucosal ulcers and chronic inflammation. In ME these factors lead to a remarkable increase in cancer risk. The study of mucosal cell proliferation in MC may provide new insights and useful information about the role of constipation in colonic carcinogenesis.

Adolescent↗

Necrotic carcinoma of the colon.

The radiological appearances of necrotic colonic neoplasms have been described previously and their bad prognosis has been stressed. Four cases of carcinoma of the colon which exhibited characteristic radiological features are described. Survival following surgery in these cases was extremely variable.

Adenocarcinoma↗

Early development of cancer chemoprevention clinical trials: studies of dietary calcium as a chemopreventive agent for human subjects.

Early cancer chemoprevention clinical trials in human subjects had to be carried out with large numbers of subjects studied for long durations, measuring cancer as an end point. However new findings on abnormal epithelial cell growth and development during the multistage evolution of colonic tumors made it possible to carry out chemoprevention clinical trials in several stages, with fewer subjects studied for shorter durations, thus enabling investigators to analyze increasing numbers of chemopreventive agents and nutritional regimens in clinical trials. Supplemental dietary calcium was the first candidate chemopreventive agent studied in this multistage approach in human subjects, as a putative agent for colon cancer prevention. Early- and late-stage intermediate biomarker studies in humans have strongly suggested utility for supplemental dietary calcium to inhibit the development of benign and subsequent malignant colonic neoplasms. Preclinical experimental studies have further demonstrated the ability of increased dietary calcium to inhibit the evolution of colonic tumors when they were induced by targeted mutations, dietary factors, and particularly when given over a long duration of lifespan.

Anticarcinogenic Agents↗

Advanced proximal colon cancer.

BACKGROUND: Two recent studies have documented that sigmoidoscopy as a screening tool for colorectal cancers may miss advanced proximal colonic neoplasms. The purpose of this study was to assess the prevalence of distal synchronous lesions in patients with proximal colon cancer. We sought to determine if screening sigmoidoscopy would have missed these proximal colon cancers. METHODS: Data were collected on all patients (n = 305) diagnosed with colorectal cancer over a 6-year period. Patients were stratified by age, sex, tumor location, presenting complaint, AJCC stage, and TNM classification. The colonoscopy results of patients diagnosed with proximal colon cancer were analyzed to determine the incidence of synchronous distal colon lesions. RESULTS: Proximal colon cancer was diagnosed in 88 patients (29%). Of those studied, 45 (54%) did not have synchronous distal lesions detected by colonoscopy. The patients with proximal colon cancer were elderly (mean age 67), had advanced tumor size [59 patients (67%) T3/T4], and had advanced AJCC stages [37 patients (42%) stage III/IV]. Nearly all patients [84 (95%)] with proximal colon cancer were symptomatic. CONCLUSION: In this study, the majority of patients with proximal colon cancer did not have a synchronous lesion in the distal colon. Current screening methods for colon cancer based on sigmoidoscopy would not have identified these proximal lesions. These findings support the incorporation of screening colonoscopy in protocols designed to identify early colon cancer.

Aged↗