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PubMed1996

Overview of natural history, pathology, molecular genetics and management of HNPCC (Lynch Syndrome).

Hereditary non-polyposis colorectal cancer (HNPCC) predisposes to cancers of the colon, endometrium and several other extra-colonic sites in the absence of premonitory physical stigmata (Muir-Torre syndrome excepted). Discovery of the several DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, hPMS2) holds the potential for determining the cancer destiny of patients, theoretically in utero. Pre-symptomatic DNA testing is now possible in patients from HNPCC families and will be clinically available once inexpensive and simple tests for these germ-line mutations have been effected. Genetic counseling will be mandatory, given the myriad socio-psychological, insurance, and potentially other personal issues which may impact this knowledge. New findings in the pathology of HNPCC, particularly an increased frequency of interval cancers and the likely accelerated rate of the adenoma to cancer sequence, indicate the need for more frequent colonoscopic surveillance with an option for prophylactic subtotal colectomy in germ-line-positive individuals.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1996

Familial risk and colon cancer.

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

Adult↗
PubMed1998

Fine-needle aspiration biopsy of colonic masses.

Between 1989 and 1996, fine-needle aspiration biopsy was performed in 22 patients with palpable colonic masses. In all of these patients colonoscopic examination was either not possible or could not be carried out successfully. The results of aspiration biopsy were confirmed by surgery and histopathological examination of the tissue. Aspiration biopsy correctly diagnosed all except one case. It identified all cases of colonic cancer. One patient with colonic tuberculosis was also diagnosed correctly. However, in another patient with colonic tuberculosis, aspiration biopsy showed only nonspecific changes in the form of inflammatory and epithelial cells. There were no false-positive results or complications from the procedure. It is concluded that fine-needle aspiration biopsy is a simple, rapid, and accurate method of diagnosing palpable colonic masses in patients in whom a colonoscopy is not possible or cannot be performed satisfactorily.

Adenocarcinoma↗
PubMed1975

Endoscopic polypectomy. Therapeutic and clinicopathologic aspects.

The problem of the malignant potential of neoplastic colonic polyps is being, in large measure, resolved by newly derived techniques. Now most polyps may be removed endoscopically using the fiberoptic colonoscope. The largest world experience is at the Beth Israel Medical Center in New York, where over 2000 polyps have been endoscopically removed without a single death and with but one complication requiring operative intervention. Laparotomy is now reserved for polyps not suitable for endoscopic resection or where a question of residual cancer exists. Experience with endoscopic resection has called for: 1) re-assessment of colonic polyps in terms of their malignant potential; and 2) clarification of the indications for laparotomy and bowel resection subsequent to or instead of endoscopic removal. Among all polypoid lesions 0.5 cm or greater in size in the Beth Israel series, a variety of pathologic types was encountered. If only the neoplastic polyps were considered, the incidence of "malignant change" was 10.5% for 855 polyps analyzed. There is, however, a need to clarify terminology and to differentiate between carcinoma in situ and invasive cancer whenever possible. Superficial cancers (carcinomas in situ) do not recur or metastasize and require no treatment other than polyp removal. When "invasive" cancer is present (4.5% of neoplastic polyps) or the lesion is a "polypoid carcinoma" each case must be individually evaluted. Criteria for diagnosis, gross morphological features suggesting cancerous change, and current management of "malignant" polyps are discussed. Colonoscopy is an important component of the followup program whether malignant polyps are resected endoscopically or by the transabdominal route.

Adenoma↗
PubMed1975

The control of large bowel cancers. Present status and it challenges.

The incidence of carcinoma of the large bowel in the United States is higher than for any other site. In Japan it is about one quarter as frequent, and the cause of this discrepancy appears to be more environmental than genetic on the basis of migrant studies. The incidence of carcinoma in familial polyposis approaches 100% and in villous adenoma the incidence of carcinoma is 40-50%. The relation of adenomatous polyps to carcinoma is not so strong, yet there is a notable association between the occurrence of polyps and carcinoma in the same bowel. With modern surgical techniques, the risk of removing polypoid lesions of the colon transabdominally appears much lower than the average risk of leaving such lesions alone unless and until they give signs and symptoms of carcinoma. The greater use of the colonoscope should, however, greatly reduce the need for laparotomy.

Adenoma↗
PubMed1976

Flexible colonoscopy.

Colonoscopy with fiberoptic instruments has opened new vistas in diagnosis and treatment of colonic disease. Such endoscopy requires skill, experience, and judgment to be accomplished readily and safely but permits visual examination of the entire colon and, frequently, the terminal ileum as well. Although in experienced hands colonoscopy may have greater diagnostic accuracy than the barium enema, particularly with respect to colorectal cancer and polyps, the two are complementary modalities and with their combined use an extremely high rate of detection and confirmed diagnosis can be expected. The Beth Israel group introduced the technique of snare-cautery removal of colonic polyps via the colonoscope and has now successfully resected over 2500 such polyps without a single death. This is the largest world experience. Selected polyps can be removed endoscopically as an ambulatory procedure, reducing costs and incapacitation time. Neoplastic polyps often harbor invasive cancer and their extirpation is expected to reduce the incidence of overt colorectal cancer. Colonoscopy and endoscopic polypectomy offers the opportunity to check the rising incidence, morbidity, and mortality related to colorectal cancer.

Adenoma↗
PubMed1981

The macroscopic appearance of colorectal polyps.

The macroscopic (10 to 30 times magnification) surface features of 187 colonic lesions are described. The lesions were studied using a dissecting microscope and a 1% trypan blue solution as a contrast agent. Using five criteria, lesions were evaluated for the presence or absence of adenoma, the type of adenoma present, the presence of dysplasia or carcinoma-in-situ, and the presence of invasive carcinoma. The technique has proven to be a rapid, sensitive, and relatively specific means of separating tumors in the adenoma--carcinoma sequence from nonadenomatous lesions (sensitivity, 99%, specificity 90%). The technique is accurate in differentiating tubular, tubulovillous, and villous lesions. It is suggested that areas of dysplasia (sensitivity 100%, specificity 93%), carcinoma-in-situ, and microinvasive carcinoma may also be differentiated, but need further investigation. The present study suggests that the macroscopic architecture of the various lesions in the adenoma--carcinoma sequence is unique and may be used diagnostically. These preliminary findings need to be confirmed in a prospective double-blind study, and to be adapted to use in colonoscopic and radiologic diagnosis.

Adenoma↗
PubMed1984

Breast cancer and polyps of the colon. A case-control study.

A case-control study was conducted involving 145 patients with breast cancer and 144 controls. A pansigmoidoscopy was performed in each case and control. There was no statistically significant difference in the length of the colon explored (cases, 50.3 cm; controls, 48.9). The odds ratio for adenomatous polyps was 2.65 (confidence limits, 1.56 and 3.74). As adenomas of the colon can be considered as precursors of colon cancer, this study demonstrates new evidence of the close relationship between breast and colon cancer. These results show the usefulness of performing a pansigmoidoscopy in all breast cancer patients and, if positive, the removal of all of the polyps through the colonoscope.

Adenoma↗
PubMed1985

Recurrence rates for colorectal polyps.

Of 276 patients who underwent an initial colonoscopic polypectomy for adenomatous polyps over a 45-month period, 118 subsequently had one or more repeat screening colonoscopies. The mean follow-up time was 26 months with an overall polyp recurrence rate of 30%. Analysis of these data retrospectively suggests that the bulk of the recurrences occurred within the first year. Increasing age was found to be a significant risk factor for polyp recurrence. Asymptomatic recurrence of adenomatous polyps detectable by colonoscopy is a common occurrence in postpolypectomy patients. Prospective studies utilizing colonoscopy as a screening tool are needed to establish a rational screening policy for this high-risk group.

Colonic Diseases↗
PubMed1987

Synchronous neoplasms in patients with diminutive colorectal adenomas.

The distribution of synchronous neoplasms was retrospectively analyzed in 220 patients undergoing initial colonoscopic evaluation for colorectal neoplasms. In 159 of the 220 patients, an index neoplasm was present in the rectosigmoid region. Of these 159 patients, 32 had an index rectosigmoid adenoma less than 5 mm in diameter (diminutive), 105 had an index rectosigmoid adenoma greater than or equal to 5 mm in diameter and 22 had an index rectosigmoid adenocarcinoma. Among these patients with different index neoplasms the frequency of synchronous neoplasms was 34%, 53%, and 73%, respectively. The synchronous neoplasm was an adenoma greater than or equal to 5 mm in diameter in 13%, 40%, and 64%, respectively. The synchronous neoplasm was a carcinoma in 0%, 7%, and 5%, respectively. Two or more synchronous neoplasms occurred in 9%, 34%, and 41% of the index neoplasm groups, respectively. Finally, symptoms providing an indication for colonoscopy were present in 31%, 75%, and 86%, respectively. It is concluded that patients with diminutive index adenomas had fewer and smaller synchronous neoplasms (P less than 0.025) than patients with larger adenomas or invasive carcinoma as the index lesion. Thus, total colonoscopy does not appear to be necessary in asymptomatic patients with only diminutive adenomas found at flexible sigmoidoscopy.

Adenoma↗
PubMed1987

The relative value of fecal occult blood tests and flexible sigmoidoscopy in screening for large bowel neoplasia.

The secondary prevention of colorectal cancer is based on the early detection of noninvasive cancer and removal of adenomatous polyps. The two commonly used screening tests are flexible sigmoidoscopy and guaiac fecal occult blood testing. Both were performed simultaneously and independently on 1176 asymptomatic volunteers followed by colonoscopic examination if either occult blood or a neoplasm was detected. Neoplasia (adenomatous polyps or cancer) were found in 48 screenees. Only ten had positive stool occult blood while 45 were detected by sigmoidoscopy. Analysis of sensitivity for neoplasia was 93.8% for sigmoidoscopy but only 20.8% for the occult blood tests, while the positive predictive values for neoplasia were 100% and 23.8% respectively. The fecal occult blood test detected only 18% of screenees with adenomas and 60% with invasive cancer. Flexible sigmoidoscopy detected 95% and 80% respectively. Analysis (kappa statistic) demonstrated little agreement between the two tests (P greater than 0.05), indicating that they are diagnosing different neoplasia. Evaluation of expected gain in diagnosing neoplasia, by combining both tests, gave 18% for the fecal blood test and 94% for the endoscopic test. These results confirm the complementary value of performing both tests, but especially the high sensitivity and predictive value positive of flexible sigmoidoscopy for adenomas, including those with severe dysplasia, and the converse for the fecal occult blood test. This latter test must be recommended and used within a screening program with caution and full understanding of its limitations.

Adult↗
PubMed1988

Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents.

Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man.

Animals↗
PubMed1991

Imaging techniques in the diagnosis of carcinoma of the colon.

The variability in the published results for colonoscopy and barium enema examinations is confusing. With both, optimum results are dependent on meticulous preparation, technical excellence, and operator proficiency. It is a mistake to place colonoscopy and the barium enema in competitive positions; the two methods ideally complement one another in the evaluation of high risk individuals, including those with positive Hemoccult tests. The exclusion of significant pathology by the double-contrast enema can be relied on and is less costly to the patient. Detection of abnormalities by a barium enema should, when necessary, be followed by colonoscopic verification and/or biopsy. When used in this sequence, the procedures provide a cost-effective approach to the early detection and control of cancer; it is estimated that observance of the ACS guidelines can reduce mortality rates by 30%.

Barium Sulfate↗
PubMed1992

Primary colorectal lymphoma in Taiwan.

BACKGROUND: Sixteen patients with primary lymphoma of the colon and rectum were studied. METHODS: The median age of these patients was 34 years, and 13 were men. These patients often experienced abdominal pain, diarrhea, a palpable abdominal mass, weight loss, bloody stools, and tumor of the cecum. Intermediate or high-grade lymphomas occurred in 14 patients, and 5 patients had T-cell lesions. The diagnoses were established by using laparotomy in 14 patients and colonoscopic biopsy in 2 patients. Fourteen patients had surgical resections followed by chemotherapy: cyclophosphamide, doxorubicin, vincristine, and prednisolone in 10; cyclophosphamide, vincristine, and prednisolone (COP) in 2; and cyclophosphamide, vincristine, methotrexate, and prednisolone in 1 patient. Two patients underwent biopsy alone followed by chemotherapy with COP in one and chemotherapy with prednisolone in the other. RESULTS: The median follow-up time was 38 months (range, 2-82 months). Eight patients are alive with no evidence of disease (range, 10-82+ months). Six patients died of disease from 2 to 44 months after diagnosis. One patient who had no evidence of lymphoma died of esophageal carcinoma at 61 months. The median survival time was 59 months. CONCLUSIONS: The authors' experience with colorectal lymphoma in Taiwan is different from that reported from Japan and other countries. The patients of this study were significantly younger and many had T-cell lesions. Despite the frequently poor histologic types, surgical resection and adjuvant chemotherapy can result in long-term, disease-free survival in many patients with primary colorectal lymphoma.

Adolescent↗
PubMed1992

The role of the barium enema in the detection of colonic neoplasms.

The variability in the published results for colonoscopy and barium enema examinations is confusing. With both, optimum studies depend on meticulous preparation, technical excellence, and operator proficiency. The equivalency of results and the lower cost of the radiologic study indicate that the double-contrast barium enema is the technique of choice for the examination of asymptomatic patients or symptomatic individuals without known antecedent disease. The relatively small difference between the cost of the double-contrast enema examination and sigmoidoscopy ($193 versus $135) suggests that it should replace the latter on the 3-5-year screening schedule because, on average, 50% more of the colon is examined by the barium study. It is a mistake to place colonoscopy and barium enema in competitive positions; the two methods ideally complement one another. The exclusion of significant pathologic findings by the double-contrast enema can be accepted, but the detection of abnormalities should be followed, when necessary, by colonoscopic verification and/or biopsy. The number of times both will be required are few. Radiologically demonstrated colon carcinomas seldom require biopsy verification, and 90% of all polyps are smaller than 5 mm in diameter with a negligible incidence of malignant transformation. When the examinations are used in the proper sequence, they provide a cost-effective approach to the early detection and control of cancer of the large bowel.

Adult↗
PubMed1992

Estimates of costs and effects of screening for colorectal cancer in the United States.

BACKGROUND: In many ways, colorectal cancer might be an excellent candidate for mass screening because of the following: (1) it is the second leading cause of cancer mortality in the United States; (2) it develops slowly from a precursor lesion; and (3) methods of early detection are available. Barriers to screening include unproven efficacy of the procedure and high costs. METHODS: Cost analyses are derived from two mathematic models that estimate screening costs and effects based on expert opinion and data from uncontrolled screening studies. RESULTS: One screening option that follows the guidelines of the American Cancer Society and the National Cancer Institute (annual testing for occult fecal blood and sigmoidoscopy every 5 years) could result in a 40% decrease in colon cancer mortality for American adults between the ages of 50 and 75 years if they comply with screening. This model, developed by David Eddy, projects an average of 44 days of extra life per person screened, at a net cost of $57 per day of life gained. Using assumptions much less favorable to screening, the Office of Technology Assessment modeled this same screening strategy for those aged 65 years and older. This model predicted a similar benefit of extra life per person at a cost of $118 per day of life gained. This doubling of the predicted cost was caused by the inclusion of subsequent colonoscopic surveillance costs for those found to have polyps. Direct costs of screening annually for fecal occult blood and every 5 years by sigmoidoscopy would cost an average of approximately $48 per person per year for screening and follow-up testing of all positive results. Fecal occult blood testing alone, although less effective, costs only $20 per person per year, including follow-up testing of all positive findings. CONCLUSIONS: The results from randomized trials of fecal occult blood screening will be known in the next 5 years, but trials of screening with sigmoidoscopy will not be complete for 10-15 years. Because mass screening programs will be difficult to fund without better data on their efficacy, colorectal cancer screening will continue to be a matter of individual decision making in the clinical setting for years to come. Clearer presentations of costs and benefits that can be understood by both patients and physicians are needed.

Adult↗
PubMed1992

Association of aneuploidy in index adenomas with metachronous colorectal adenoma development and a comparison.

BACKGROUND: Features of index adenomas in the colorectum may be important for the prediction of metachronous adenoma development. METHODS: Complete colonoscopic follow-up for a mean period of 10 years was achieved in 70 of 124 patients after endoscopic polypectomy of an adenoma from the colorectum. On the basis of the clinical outcome, the patients were divided into three groups: Group I, patients who had a colorectum free of adenomas and cancer; Group II, patients who had one or more metachronous adenomatous polyps; and Group III, patients who subsequently had a colorectal carcinoma. The clinical characteristics of the patients were collected, and the neoplastic specimens were re-examined with regard to pathologic parameters and flow cytometrically determined nuclear DNA content. RESULTS: Aneuploid stemlines were found in 35% of the index adenomas. Significantly more aneuploid adenomas were found in the index adenomas of Group I patients than in the adenomas of Group II patients (r = -0.20; P = 0.05). However, in the index adenomas of Group II patients, aneuploidy was associated with villous architecture (P < 0.05) and inversely related to cellular atypia (P < 0.05). Such relations were not found in the adenomas from Group I. In addition, in the Group II adenomas, aneuploidy was found frequently in the more proximally localized adenomas in the large intestine. Remarkably, all adenocarcinomas of the Group III patients were localized in the right colon. No significant differences were found in ploidy and mean DNA index between index adenomas and metachronous adenomas of the Group II patients. However, the ploidy class of the index adenomas was found not to be related to that of the metachronous adenomas in the individual patients. CONCLUSIONS: These results demonstrate that DNA cytometry in adenomas alone is not helpful in the prediction of the possibility of the development of a metachronous adenoma. However, aneuploidy in a villous adenoma located more proximally in the colon might indicate a higher risk for metachronous neoplasia development. Index and metachronous adenomas are similar in DNA content but show no relation with respect to ploidy class.

Adenoma↗
PubMed2000

MR virtual colonography using hyperpolarized (3)He as an endoluminal contrast agent: demonstration of feasibility.

Hyperpolarized gas MR virtual colonography was performed in plastic phantoms and in the dog colon. (3)He was laser polarized in a prototype commercial system. 2D and 3D gradient echo sequences were used to image the noble gas-filled structures. The hyperpolarized (3)He within the plastic tube and colon lumen produced high signal, providing excellent contrast from the surrounding structures. The virtual colonoscopic analysis of the canine dataset allowed visualization of the colonic features and the colonic wall from inside the colon. (3)He colonoscopy is a novel technique to visualize the colon with MRI with the application of an inert gaseous endoluminal contrast agent.

Animals↗