Bile acids and cancer of the large bowel.
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Inter-observer agreement rate in double readings of 246 Hemoccult-II tests was 0.88 (Kappa analysis). The slides were not rehydrated. The Hemoccult-II test was performed immediately before 748 total colonoscopies in asymptomatic patients after previous polypectomy or radical surgery for cancer to estimate the diagnostic value of the test in mass screening, accepting a higher prevalence of neoplasia in the study group but realizing that colonoscopy can only be performed in high-risk groups. Another purpose was to investigate the possibility of replacing colonoscopy with Hemoccult-II in surveillance after previous adenoma or cancer. The 79 colonoscopies after a positive test showed cancer in 3, adenomas in 13, and other intestinal pathology in 34 cases. The 669 colonoscopies after negative tests showed cancer in 1, adenomas in 67, and other pathology in 141 cases. In conclusion, the test cannot be used as a guideline for colonoscopy in follow-up programs for patients who have had adenomas, since it missed 84% of the new cases in the present series. The test does not exclude the presence of colorectal carcinoma, but the risk of cancer is probably several times less in patients with negative tests (1 of 669) than in patients with positive tests (3 of 79), which may justify the use of the Hemoccult-II test for mass screening in asymptomatic populations.
Because of the increasing and repeated application of colonoscopy and double-contrast barium enema with the Welin modification in connection with the checking of patients who have been treated for neoplastic polyps, we have found it valuable to examine the amount of radiation that the patients are exposed to in the two kinds of examinations. The radiation dose in the examination of the colon with the Welin modification (35 examinations) and at colonoscopy (114 examinations) was, on an average, 387 and 10 mSv, respectively. Since colonoscopy gives a possibility not only of diagnosis but also of treatment and also exposes the patients to 40 times less radiation than X-ray examination with the Welin modification, we recommend colonoscopy for diagnosis and treatment of neoplastic colonic polyps.
The frequency of synchronous colorectal cancers ranges from 1.7 to 9.3% according to the series. The incidence of these cancers has been appreciated in various ways, according to variable diagnostic criteria, especially because some authors have included in situ carcinomas developing on degenerated polyps. A retrospective study of the synchronous cancers operated in our department from January, 1980 to August, 1990 allowed us to assess their frequency and location and to discuss the therapeutic choices. Two hundred and forty-nine patients with cancers of the colon or of the rectum have been operated during that period. Twelve (4.8%) presented with more than one colorectal cancer, all discovered simultaneously. The average age of the patients operated for synchronous cancer was higher that that of those operated of isolate cancer (68.8 years versus 63.3). Two thirds of the synchronous cancers were located in the sigmoid loop or the colon and, in one third of all cases, on non-adjacent segments of the colon. The frequent association of colic adenomatous polyps and of synchronous cancers--in one half of the patients in our series--must raise a discussion on the merits of systematic subtotal, or even total, colectomy in the treatment of synchronous colorectal cancers. This is also true for tumoral sites in 2 different segments of the colon. Segmental colectomy may be advocated in the other cases: cancers located on one segment, polyps located only on the resected segment of the colon, or polyps that can be resected via endoscopy.
Recent research into an early detection of colorectal cancers shows a surprisingly great progress. In 1991, Mr. Hisamichi reports that a mass screening method for colorectal cancers through immunological fecal occult blood tests may result in fewer fatalities due to colorectal cancers. This paper describes the current situations and future prospects of UICC workshops in principle, as undermentioned in 1 through 6. 1. The target population should be clearly defined and selected in such a way that, given the likely sensitivity and specificity of the test, an acceptable predictive value will be achieved. 2. As far as possible, the target population should be limited to those at particular risk of the disease in order to give a reasonable prevalence of detection when such individuals at risk can be identified. 3. There should be a reasonable expectation of reaching the target population and of achieving reasonable compliance in response to invitations to attend. The expected level of compliance should be stated. 4. There should be a reasonable expectation that recommendations for further diagnostic evaluation will be complied with by individuals who have a positive test. 5. There should be an agreed-upon policy on the classification of borderline abnormalities and also on their management, as well as on recommendations for their follow-up. 6. There should be a reasonable expectation that recommendations for appropriate management of lesions discovered by a screening program will be complied with both by the individual with the lesion and by the physicians responsible for his health care.
Subtotal and total colectomy was the choice therapeutic solution for multiple colonic cancer, diffuse rectocolonic polyposis, multiple colonic polyposis, ulcerohaemorrhagic rectocolitis, and for two rare diseases; megacolon with extensive atrophy of lymph nodes, and acute ischaemia of the colon. A total of 35 cases are reported. Ileorectal anastomosis was the method used for this type of intervention. The opportunity of rectal conservation is discussed, in cases of rectocolonic polyposis and ulcerative haemorrhagic rectocolitis. The difficulty of making an optimal choice in complicated forms of ulcerohaemorrhagic rectocolitis is exemplified with the aid of clinical observations.
Hereditary large bowel cancer is roughly divided into the hereditary gastrointestinal polyposis (HGIP) that is including adenomatosis coli (AC), Peutz-Jeghers syndrome and juvenile polyposis, and non-polyposis familial large bowel cancer (NPF) which is including cancer family syndrome and its related conditions. In the HGIP, AC is most frequent and of highest risk of large bowel cancer, and epidemiological method of approach to patients has been well studied. NPF, however, has been insufficiently studied because of lacking of distinctive marker as seen in the polyposis in spite of that it may be actually present much more frequently than AC. In order to extract NPF from the general large bowel cancer group, the marker or criteria for it has been studied. The factors besides family history presently considered to be useful for detecting NPF are multiple cancers, proximal cancer, association of multiple adenoma and young (50 years or younger) onset of the disease.
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Diminished blood selenium levels have been associated with increased risk of gastrointestinal cancers in man, while dietary selenium supplementation reduces the incidence of experimental colon cancer in rats. However, no previously published data are available concerning selenium and the evolution of colon cancer from benign neoplastic colonic polyps through localized and metastatic cancer. To assess any influence of selenium on this polyp to cancer sequence, we measured plasma and erythrocyte selenium levels in colonoscopically and histologically evaluated patients with adenomatous polyps (group I), locally resectable colon cancer (group II), metastatic colon cancer (group III), and selected colonoscopy negative controls (group IV). We found no difference in selenium levels between groups IV versus groups I or II. Likewise, within group I, no difference in selenium was present for different polyp histologies or numbers of polyps. However, selenium levels did drop progressively (p = 0.028, ANOVA) from polyp (group I) to local cancer (group II, p = NS vs group I) to metastatic cancer (group III, p less than 0.05 vs group I or group II). Parallel changes were seen in both plasma and erythrocyte levels, suggesting that these selenium abnormalities are of long duration, reflecting tissue stores, and therefore capable of influencing cancer risk. We conclude that selenium stores may not be an important factor in the de novo formation of benign neoplastic colonic polyps. Although these data suggest that selenium does not affect the polyp-cancer sequence, it is possible that a subset of patients with polyps and the lowest selenium levels are at higher risk for malignant transformation. However, these human data do not support a significant role for selenium in colon carcinogenesis.
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In vitro clonal growth of tumour cells may reflect biological properties of cancer and thus have prognostic value. This study seeks to establish correlations between the clinical outcome in patients after surgery for colorectal cancer and clonal growth of their tumours. History, status and follow-up data are collected. Tumour samples taken at operation under sterile conditions are plated immediately in our methylcellulose clonal assay system. Out of 65 consecutive samples, 3 did not yield sufficient cells for culture. Thirty-four (55%) grew more than 0.3 colonies/10(5) cells seeded; cloning efficiency was greater than 10 colonies/10(5) cells in 19. The 28 (45%) failures included 3 benign polyps cultured; 7 samples had visible bacterial or fungal contamination. The other 18 negative cultures may be due to cytotoxicity of the antibiotics or heterogeneity of tumour cells. These preliminary results show that colorectal cancers grow well in vitro in the absence of restricting factors, but they do not confirm the hypothesis that proliferative potential and differentiation are opposing processes. Location of the tumour may play a role, since best growth was seen in tumours of the caecum and terminal colon.
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Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. In addition to its hypercalcemic action, PTHrP has been implicated as an autocrine modulator of growth and differentiation, as well as an early response gene in some tissues. Several different types of tumors have been evaluated for the presence of PTHrP immunoreactivity. In the present study, we evaluated the expression of PTHrP by immunohistochemical staining in tissue samples from normal colorectal mucosa, polyps, and colorectal carcinoma removed from the same patients (n = 10 each). We have used a commercially available monoclonal antibody directed against epitopes between amino acids [53-64] which share no homology to parathyroid hormone (PTH). In normal colon, 94.3 per cent of the tissue samples were negative for PTHrP immunoreactivity. In polyps of the colon, only 22.6 per cent of the cells showed positive immunostaining, whereas 91.5 per cent of the samples from colon cancer stained positive for PTHrP. In the case of polyps, the intensity of staining was 1-3+; however, all of the samples from adenocarcinoma stained with 4+ intensity. In the positive samples, the immunoreactivity was present throughout the cytoplasm of the glandular epithelium. Omission of primary antibody, as well as substitution of the primary antibody by a negative control monoclonal antibody or non-immune rabbit serum, resulted in a negative reaction. All analyses were performed in duplicate, and the data have been presented as mean +/- SEM. Differences in normal polyps, carcinoma of the colon, and PTHrP expression were tested for statistical significance by student's t test. Our results show the expression of PTHrP is enhanced in colon cancer tissue as compared to normal colorectal mucosa and polyps. In addition, the expression appears to be greater in polyp than in normal colon. The role of PTHrP in the pathogenesis of colon cancer deserves further study.
To determine the utility of pre-operative abdominal computerized tomography (CT) scanning in patients with colorectal cancer, a prospective analysis was undertaken of all patients referred to a colorectal clinic for the primary treatment of colorectal cancer in a 5-year period. A clinical decision regarding the type of surgery to be performed was made prior to CT scanning, and this was then compared with the final surgery performed for each patient. The reason for any change in management was noted. Definitive management differed from proposed management in 14 of 116 patients studied. Surgery was avoided in one patient found to have multiple liver metastases on the CT scan. Operative findings changed the management in the remaining 13 patients. Seven patients had less aggressive surgery than proposed, one patient's surgery was abandoned because of extensive disease, and five patients had more radical surgery. Routine pre-operative CT scanning of the abdomen in patients with colorectal cancer does not seem to be justified from the results of this study.
OBJECTIVES: Chicken skin mucosa is a newly described endoscopic finding associated with colonic neoplasms in adults. Chicken skin mucosa was sought in children with juvenile polyps to determine the prevalence, endoscopic features, and location. An alternative theory is proposed for the pathogenic mechanism of this finding. METHODS: Children having colonoscopy and polypectomy were prospectively evaluated for the presence of chicken skin mucosa. The location of the polyps was determined at colonoscopy; the size of removed polyps was measured during processing of samples in pathology. Biopsies from colonic chicken skin mucosa were stained with hematoxylin and eosin and mucicarmine. RESULTS: Over a 1-yr period, 27 juvenile polyps were removed from 15 children at colonoscopy. Eleven of 15 children (73%) were found to have polyps with chicken skin mucosa; overall, 43% of the polyps had associated chicken skin mucosa. Chicken skin mucosa-positive polyps were larger than chicken skin mucosa-negative polyps and were only found in the rectosigmoid colon. Lipid-laden macrophages were found in all samples of chicken skin mucosa tested. CONCLUSIONS: Chicken skin mucosa is a common finding in children with juvenile polyps. It probably is the result of local mucosal trauma, rather than a preneoplastic lesion.
A randomized, controlled trial was performed to compare the diagnostic yields and cost-effectiveness of two strategies for the evaluation of nonemergent lower gastrointestinal bleeding. Three hundred eighty patients aged greater than or equal to 40 yr were randomized to undergo initial flexible sigmoidoscopy plus air contrast barium enema or colonoscopy; 332 completed the initial studies. Initial colonoscopy detected more cases of polyps less than 9 mm in size, adenomas, and arteriovenous malformations but fewer cases of diverticulosis. No significant difference was found between strategies in the number of patients detected with cancers or polyps greater than or equal to 9 mm in size. In both strategies, cancers were more common in subjects aged greater than or equal to 55 yr (8% overall) than in those aged less than 55 yr (1%). Among patients aged less than 55 yr with suspected lower gastrointestinal bleeding, initial flexible sigmoidoscopy plus air contrast barium enema is a more cost-effective strategy for the detection of colonic neoplasms than initial colonoscopy. However, initial colonoscopy is more cost effective for those aged greater than or equal to 55 yr.
Radiologic examinations preceding the diagnosis of colorectal carcinomas were retrospectively scrutinized in 708 patients with 731 carcinomas that were radiographically investigated 741 times. Sixty-four lesions were missed 74 times, giving a 90% sensitivity of the radiographic methods used. Of the errors, 82% were perceptive, and 3% were interpretative. Eleven examinations in nine patients revealed no lesions, although the examinations were done within 2 years of the diagnosis of a carcinoma. Missed lesions were more common than expected in the cecum and the ascending colon (P less than 0.001), and 18% of the patients had multiple tumors (expected incidence 3.6%, P less than 0.001). The median delay in diagnosis was 20 months, and patients whose diagnosis was delayed for a long time tended to have more advanced carcinomas at diagnosis. As a lesion was identified either at the initial examination or retrospectively 730 of 741 times, the potential sensitivity of the radiographic methods used was 99%. It is concluded that barium enema is still an excellent method for the detection of colorectal carcinoma provided that perceptive errors can be minimized.