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PubMed1989

Colonoscopic screening of persons with suspected risk factors for colon cancer: II. Past history of colorectal neoplasms.

Colonoscopic screening has been recommended for all persons who have had a colorectal adenoma or carcinoma. Such persons have been assumed to be at increased risk of having additional, asymptomatic colorectal neoplasms, the removal of which would reduce morbidity and mortality from colorectal cancer. In this prospective study, initial colonoscopy was performed on 544 asymptomatic subjects with past histories of colorectal index lesions ranging from small tubular adenomas to invasive cancers. In 402 subjects whose worst index lesion was an adenoma, the prevalence of neoplasms detected at colonoscopy, above the reach of the rigid sigmoidoscope, increased with age, male sex, black race, and the number and size of their index adenomas. In 142 subjects whose worst index lesion was invasive cancer, colonoscopy findings were marginally related to age and white race. A subgroup of 133 subjects whose worst index lesion was a single, small (less than 10 mm) tubular adenoma and who had no first-degree relatives with colorectal cancer had only a 3% prevalence of advanced colonic neoplasms (tubular adenomas greater than or equal to 10 mm in diameter; tubulovillous, villous, or severely dysplastic adenomas; or invasive cancers) found on colonoscopy--no greater than would be expected in the general population. Subgroups of the remaining 411 subjects, who had advanced or multiple index lesions, had prevalences of advanced neoplasms ranging from 8% to 18%. These findings indicate that for persons whose only risk factor is a single small tubular adenoma, current screening guidelines could be modified to recommend techniques less costly and less invasive than colonoscopy.

Adenoma↗
PubMed2006

Colorectal neoplasm and acromegaly.

The risk for colorectal carcinoma in acromegaly remains controversial. In our earlier study, we have demonstrated that the risk of colorectal carcinoma in Asian Indians with acromegaly is not increased and after this report, routine colonoscopy in our patients with acromegaly was abandoned. Subsequently, two consecutive young men aged 30 and 35, one 6 years after and other at the time of diagnosis of acromegaly had colorectal carcinoma respectively. None of them had family history of colonic neoplasm. These two younger patients with no other predisposition for colorectal neoplasm suggests that colonoscopy should be done in all patients with acromegaly at diagnosis and they should remain under surveillance.

Acromegaly↗
PubMed2002

Colorectal neoplasms: prospective comparison of thin-section low-dose multi-detector row CT colonography and conventional colonoscopy for detection.

PURPOSE: To prospectively compare thin-section low-dose multi-detector row computed tomographic (CT) colonography with conventional colonoscopy for the detection of colorectal neoplasms. MATERIALS AND METHODS: One hundred five patients underwent CT colonography immediately before colonoscopy. Supine and prone CT colonographic acquisitions to image the region during a 30-second breath hold were performed. CT colonographic images were prospectively interpreted for the presence, location, size, and morphologic features of polyps. The time of image interpretation was noted. Sensitivity, specificity, and positive and negative predictive values of CT colonography were calculated, with 95% CIs, by using colonoscopic findings as the reference standard. The weighted CT dose index was calculated on the basis of measurements in a standard body phantom. Effective dose was calculated by using commercially available software. RESULTS: Median CT data interpretation time was 12 minutes. One hundred thirty-two polyps in 59 patients were identified at colonoscopy; no polyps were detected in 46 patients. Sensitivities for detection of polyps smaller than 5 mm, 6-9 mm, and larger than 10 mm in diameter were 12% (11 of 91 polyps), 70% (19 of 27 polyps), and 93% (13 of 14 polyps), respectively. Estimated overall specificity was 97.7% (515 of 527 imaging results). The total weighted CT dose index for combined supine and prone CT colonography was 11.4 mGy. The effective doses for combined CT colonography were 5.0 mSv and 7.8 mSv for men and women, respectively. CONCLUSION: Low-dose multi-detector row CT colonography has excellent sensitivity and specificity for detection of colorectal neoplasms 10 mm and larger.

Aged↗
PubMed2005

BRAF mutation associated with dysregulation of apoptosis in human colorectal neoplasms.

To understand the role of BRAF dysfunction in the carcinogenesis and progression/development of colorectal tumors, the authors investigated genetic alterations in the BRAF gene in human colorectal neoplasms as well as the effects of an RAS inhibitor in BRAF-mutant cells. Seven colon cancer cell lines and 116 colorectal tumors (34 adenomas and 82 adenocarcinomas) were analyzed. Genetic alterations in the BRAF and K-ras genes were examined using polymerase chain reaction-single strand conformation polymorphism and direct sequencing analyses. The growth-inhibitory and apoptosis-inducing effects of the FTI-277 RAS inhibitor in colon cancer cell lines were analyzed as well. An immunohistochemical study was also performed to investigate the correlations between the clinicopathologic parameters involved in the Ki-67 labeling index and the number of apoptotic bodies in tumor cells. FTI-277 did not suppress the proliferation of BRAF-mutant cells (WiDr and TCO), but remarkably inhibited the growth of K-ras mutant cells (LoVo). Interestingly, LoVo cells underwent apoptosis by FTI-277 in a dose-dependent manner, whereas WiDr cells were resistant to this agent. In tumor samples, BRAF mutations were found in 1 (3.0%) of 33 adenomas and 6 (7.2%) of 83 adenocarcinomas. No tumor exhibited mutations in both the BRAF and K-ras genes. Neither BRAF nor K-ras mutations correlated with the Ki-67 labeling index immunohistochemically. However, the number of apoptotic bodies was significantly decreased in the BRAF-mutant tumors. Mutation in the BRAF gene may contribute to colorectal carcinogenesis by upregulating the antiapoptotic role of the RAS/RAF/MEK/ERK pathway.

Adenocarcinoma↗
PubMed2003

Predictors of metachronous colorectal neoplasms in sporadic adenoma patients.

Our objective was to assess the overall risk of subsequent colorectal neoplasms (cancer or adenoma) in relation with the various characteristics of the index lesion in a cohort of patients who underwent endoscopic polypectomies of colorectal adenomas. A total of 1086 patients with adenomas of the large bowel were reported between 1979 and 1999 at the National Cancer Institute of Milan during a screening program for colorectal carcinoma. Data on patients who had colonoscopic examinations and treatments were collected prospectively. The relation between colorectal cancer (CRC) and adenoma features was assessed by computing the hazard ratio (HR) values and corresponding confidence intervals (95% CI) according to Cox proportional hazard models. Of the 1086 eligible patients (487 females, 579 males), 736 had single adenomas (67.7%) and 350 had multiple adenomas (32.3%). Histologic examination revealed 772 cases of tubular adenoma (73%), 205 cases of tubulovillous adenoma and 80 cases of villous adenoma (7.5%). Severe dysplasia was found in 3.3% of the cases. During the 11393 person-years of follow-up, with an average time of surveillance of 10.5 years, colorectal carcinomas developed in 10 patients (0.8%) and a new adenoma in 323 patients (29%). Multivariate analysis showed that male gender (HR 1.6; 95% CI 1.3-2.0), multiple polyps (HR 1.6; 95% CI 1.3-2.0), polyps larger than 2 cm (HR 1.5; 95% CI 1.1-2.1), tubulovillous and villous histology (HR 1.3; 95% CI 1.0-1.6 and HR 1.8; 95% CI 1.2-2.6, respectively) at index polypectomy were statistically significant risk factors for developing metachronous adenomatous polyps. The standardized incidence rates (SIR) for CRC was 0.52 (95% CI 0.25-0.95). The SIR was increased in subjects with severe dysplasia (2.8; 95% CI 0.34-1.02). Some features of large bowel adenomas are strongly correlated with an increased risk of metachronous adenomas and colorectal cancer. However, the endoscopic polypectomy is able to reduce by 50% the incidence of CRC in patients with large bowel adenomas.

Adenoma↗
PubMed1994

An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms.

Immunohistochemical detection of intranuclear p53 gene product may indicate mutation of the p53 suppressor gene on chromosome 17p. We used six commercially available antibodies for p53 immunohistochemistry on 19 archival colorectal neoplasms and compared the results with the mutation status of the p53 gene and 17p allelic deletion status. By Friedman's ranking analysis, use of mouse monoclonal antibody DO7 with Target Unmasking Fluid (TUF) for antigen retrieval was the most sensitive and specific procedure (P < 0.0001). Six of 7 cases with high expression (p53 Labeling Index > 30 per cent using a CAS 200 image analyser) had p53 mutation. Of seven tumours without expression (LI < 1 per cent), six had no mutation and one had a truncating mutation which prohibited nuclear localization of gene product. The low expression group (1 per cent < LI < 30 per cent, n = 5) consisted of three tumours without and two tumours with mutation. The sensitivity of high expression with the DO7-TUF method for p53 gene mutation was 67 per cent with specificity of 90 per cent, predictive value of a positive of 86 per cent, predictive value of a negative of 75 per cent, and efficiency of 79 per cent. This study suggests that immunohistochemistry is valuable for assessing p53 gene mutations in colorectal neoplasms, but further study is needed to elucidate the precise link between immunohistochemistry and molecular genetic alterations.

Antibodies↗
PubMed1998

Screening for colorectal neoplasms with a new immunological human faecal haemoglobin and albumin test.

In Germany, screening for colorectal cancer shows low efficiency, which is partly due to demographic changes with a rising mean age of the population, a low participation rate and an unsatisfactory sensitivity of guaiac tests for detecting faecal occult-blood. Therefore, a pilot screening study with a new immunological faecal haemoglobin and albumin test was performed in Ostringen, Germany to assess its compliance, performance characteristics and cost-effectiveness. Two thousand, seven hundred and eighty-five persons (1,498 women and 1,287 men) collected 1 ml samples from two different sites of one stool. The upper limit of normal was 10 micrograms/g stool for haemoglobin and 100 micrograms/g stool for albumin. The compliance was 82%; 224 persons (8%) had a positive test result. Of these, 184 underwent full colonoscopy. We detected 14 colorectal cancers, 10 of which were Dukes' stage A carcinomas removed by endoscopic polypectomy, 34 large adenomas and 43 small adenomas. The detection rate for colorectal neoplasms was above the rate described for other immunological haemoglobin tests and for Haemoccult tests. The specificity of the test--defined with false-positive results if a normal colon mucosa and no other reasons for upper or lower gastrointestinal bleeding were found--was 99.5%. The cost-effectiveness was assessed by comparing the diagnostic costs with the savings resulting from prevention of colorectal carcinomas by endoscopic polypectomy of malignant polyps (Dukes' stage A). The savings in our screening study exceeded the diagnostic costs by approximately 2.3 times. The combined immunological faecal haemoglobin and albumin test should substitute the Haemoccult test in colorectal cancer screening because of its higher sensitivity and specificity combined with cost-effectiveness and good patient compliance.

Adolescent↗
PubMedDate not supplied

Coenzyme Q10 and colorectal neoplasms in aged patients.

Coenzyme Q10 (CoQ10), a quinone located in cellular membranes, is a compound with mitochondrial bioenergetic functions whose antioxidant activity has recently been defined. CoQ10 content in colorectal neoplasms is significantly higher than in normal colorectal mucosa. While older patients (aged over 70 years) have also a significantly higher CoQ10 content, not observed in younger patients (aged under 70 years), the normal mucosa, instead; shows constant CoQ10 levels in both groups. For the same local stage (T), an increase in lymph node involvement (N) was observed in older patients as compared to younger ones, but not in distant metastases (M) with the same 5-year survival. These results justify the same therapeutic approach for patients older or younger than 70 years.

Adenocarcinoma↗
PubMed1994

[Macroscopic classification and kinetic alternations in the superficial lesion of colorectal neoplasms].

To clarify relation between macroscopic appearance and the mode of tumor growth in the superficial lesion of colorectal neoplasms, we compared their colonoscopic findings with histological architecture of tumor cells. Macroscopic type was classified into the superficial elevated lesion (II a, n = 42, mean 5.14mm) and the superficial depressed lesion (n = 42, mean 3.84mm). The latter was further divided into 3 subtypes; subtype A, an irregular depression with high marginal elevation (Dep (A), n = 20); subtype B, an irregular depression with irregular marginal elevation (Dep (B), n = 7); subtype C, a clear and wide depression without marginal elevation (Dep (C), n = 15). Histological architecture was evaluated by the transmucosal growth index (TGI) of tumor cells, which is a ratio of tumor width contacting with the muscularis mucosae against that of tumor surface, and by the distribution of proliferating cells detected by Ki-67 antibody (MIB-1). In adenomas TGI increased with a degree of central depression (IIa < Dep(A) < Dep(C)). In carcinomas TGI was high irrespective of their macroscopic forms. Ki-67 labeling indices tended to increase with histological atypia. Adenomas with severe atypia showed a high labeling consistent with carcinomas. In both adenomas and carcinomas, Ki-67 positive cells were mainly noted in upper third of neoplastic glands in II a, Dep (A) and Dep (B) neoplasms. By contrast, Dep (C) neoplasms lost a preferential distribution of proliferating cells, which reached the whole neoplastic glands. These results suggest that Dep (C) adenomas and carcinomas have a unique histopathological architecture in terms of a high TGI and an enlarged distribution of proliferating cells, implying a high malignant potential.

Cell Cycle↗
PubMed1998

Colorectal neoplasm detection using virtual colonoscopy: a feasibility study.

BACKGROUND: Virtual colonoscopy is a potentially powerful tool for non-invasive colorectal evaluation. In vitro studies have established its accuracy in simulated polyp detection but little data exist regarding its use in clinical practice. AIMS: To evaluate the ability of virtual colonoscopy to detect colorectal cancers and polyps in patients with endoscopically proven colorectal neoplasms and to correlate the findings of virtual colonoscopy with those of conventional colonoscopy, surgery, and histopathology. PATIENTS: Thirty eight patients with endoscopic findings suggestive of colorectal carcinoma. METHODS: Virtual colonoscopy was performed using thin section helical computed tomography (CT) of the abdomen and pelvis after rectal insufflation of room air. Commercially available software was used to generate endoscopic "fly through" examinations of the colon from the CT data. Results were correlated with the findings of conventional colonoscopy and with the surgical and histopathological outcome in each case. RESULTS: Thirty eight pathologically proven colorectal cancers and 23 adenomatous polyps were present. On virtual colonoscopy, all cancers and all polyps measuring greater than 6 mm in size were identified; there were two false positive reports of polyps. On conventional colonoscopy, there was one false positive report of a malignant sigmoid stricture; four subcentimetre polyps were overlooked. Virtual colonoscopy enabled visualisation of the entire colon in 35 patients; conventional colonoscopy was incomplete in 14 patients. Virtual colonoscopy correctly localised all 38 cancers, compared with 32 using conventional colonoscopy. CONCLUSION: Virtual colonoscopy is a feasible method for evaluating the colon; it may have role in diagnosis of colorectal cancer and polyps.

Adult↗
PubMed1997

Diagnostic value of immunochemical fecal occult blood test for small colorectal neoplasms.

This study was designed to assess the diagnostic value of an immunochemical fecal occult blood test for small colorectal adenomas. In a screening program based comparative study, 60 colorectal adenomas under 1 cm (small polyp group), 60 colorectal adenomas 1 cm or larger (large polyp group) and 60 colorectal cancers (cancer group) detected by occult blood screening, and 120 healthy controls (control group), served as subjects. Moreover, 50 small adenomas, 50 large adenomas and 50 cancers detected in out-patient clinics, and 100 controls, served as subjects of a hospital based comparative study. Each of these subjects was tested by an immunochemical occult blood with 3 consecutive days, after removal of these colorectal neoplasms in a screening program based study and before as well as after removal in a hospital based study, and the positivity rate of this test was evaluated among these four groups in the two comparative studies. The positivity rate in a screening program based study was 23% for small polyp group, 8% for large polyp group, 5% for cancer group and 6% for control group, respectively. Significant difference was noted between small polyp and cancer as well as control groups (p <0.01), and between small polyp and large polyp groups (p <0.05). In a hospital based study, however, there was no significant difference in the positivity rate among four groups. These results suggest that high proportion of small polyps detected by fecal occult blood test screening may not be associated with bleeding from adenomas but probably from another gastrointestinal pathology.

Adenoma↗
PubMed2000

[Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal neoplasm].

OBJECTIVES: To explore the relationship of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) to the oncogenesis and development of colorectal neoplasm. METHODS: RT-PCR was used to assay the level of MMP-2, MT1-MMP, MMP-7, TIMP-2, TIMP-3 mRNA in 28 cases of colorectal cancer, including tumor tissue and surrounding normal tissue. RESULTS: MMP-2, MT1-MMP, TIMP-2 and TIMP-3 were over-expressed in tumor and normal tissues, and MMP-7 was strong-expressed in tumor tissue but was weak-expressed only in one case of normal tissue. The expression of MMP-7 in tumor tissue was correlated to Dukes stage (P < 0.01). The expression of TIMP-2 in tumor tissue with positive-node was much higher than that with negative-node (P < 0.01). The expression of TIMP-3 was decreased with the Dukes stage and the depth of invasion (P < 0.01). There were no correlations between MMPs and TIMPs (P > 0.1). CONCLUSIONS: The expression of MMP-7 mRNA has a high specificity in colorectal cancer. MMP-7 may become a sensitive tumor marker. Inducing TIMP-2, TIMP-3 or suppressing MMP-2, MT1-MMP, MMP-7 mRNA's expressions may inhibit the invasion and metastasis of cancer.

Adult↗
PubMedDate not supplied

Water enema computed tomography (WE-CT) in the local staging of low colorectal neoplasms: comparison with transrectal ultrasound.

BACKGROUND: To determine the accuracy of computed tomography performed with a water enema application (WE-CT) in the local staging of low colorectal neoplasms and to compare the results with those of transrectal ultrasonography (TRUS). METHODS: Forty patients with low colorectal tumors were evaluated prospectively by CT with the simultaneous administration of a lukewarm rectal enema (0.5-1.5 L). Thin slices (5 mm) and intravenous application of iodinated contrast media were routinely used. TRUS was performed in 18 patients. Tumor size, location, and staging according to the TNM classification of the UICC were registered. Tumors were classified as < T3 (T1 or T2) or as T3 or T4. For staging peritumoral lymph node metastases on WE-CT, two criteria of positivity were tested: N+ if at least one peritumoral node > or 5 mm in diameter was seen (reading A); N+ if at least one peritumoral node > or = 5 mm or three peritumoral nodes < 5 mm were identified (reading B). RESULTS: For the tumor staging, WE-CT showed a sensitivity of 90%, a specificity of 73%, a positive predictive value (PPV) of 90%, a negative predictive value (NPV) of 73%, and an accuracy of 85%. For TRUS, the results were sensitivity of 73%, specificity of 29%, PPV of 62%, NPV of 40%, and an accuracy of 39%. Concerning nodal staging with WE-CT, results were superior when reading A was used: sensitivity = 84%, specificity = 83%, PPV = 73%, NPV = 91%, and accuracy = 84%. TRUS showed a sensitivity of 29%, specificity of 100%, PPV of 100%, NPV of 67%, and an accuracy of 71%. CONCLUSION: WE-CT is a reliable technique for the local staging of low colorectal tumors that can be superior to TRUS. For diagnosis of peritumoral metastatic lymph nodes on WE-CT, the 5-mm diameter cutoff value is the most appropriate size criterion.

Adenocarcinoma↗
PubMed1994

Follow-up after screening for colorectal neoplasms with fecal occult blood testing in a controlled trial.

PURPOSE: The aim of this study was to investigate the number of new colorectal neoplasms during the first seven years after the end of rescreening in a prospective randomized screening study. METHODS: 27,700 inhabitants of Göteborg born between 1918 and 1922 (60-64 years old) who were randomly allocated to a control or a test group in 1982 were followed up. All people in the latter group were offered six fecal occult blood tests and rescreening 16 to 22 months later. RESULTS: One hundred one carcinomas were diagnosed in the screened group and 128 in the control group during the seven years of follow-up. The number of carcinomas in the test group was half that in the control group during the first two years of follow-up, but equal during the rest of the follow-up period. The distribution of carcinomas according to Dukes classification was significantly better among the participants compared with the refusers (P < 0.02) but there was no difference in the Dukes distribution when the test and control groups as a whole were compared. The number of adenomas in the two groups during seven years of follow-up was the same. CONCLUSION: The results indicate that screening and rescreening of a population has little influence upon the stage of the carcinomas in the test group compared with a control group during the first seven years of follow-up. The number of carcinomas was higher in the control than in the test group during the follow-up, probably because of a lead time effect during the screening.

Adenoma↗
PubMed1996

A twenty-year review of malignant colorectal neoplasms at University College Hospital, Ibadan, Nigeria.

PURPOSE: Colorectal malignancies are less common in developing than developed nations because of lower per capita income and higher dietary fiber consumption. This clinicopathologic study attempts to determine changes in the pattern of these neoplasms in Ibadan, Nigeria, during the last two decades. METHODS: The present study is based on the clinical Cancer Registry records and gross and morphologic surgical pathology findings of 526 patients with histologically verified malignant colorectal neoplasms received in the Department of Pathology, University College Hospital, Ibadan, between 1971 and 1990. RESULTS: Colonic malignancies increased by 81 percent, whereas rectal malignancies decreased 16.1 percent in frequency (P < 0.05). The modal ages were 55 to 60 years and 45 to 50 years for colonic and rectal neoplasms, respectively, in contrast to reported peak occurrence in the seventh decade among Caucasians. Colonic neoplasms were predominantly right-sided (34.3 percent cecal), abdominal mass and pain being major clinical manifestations. This differs from the pattern in American Negroes, among whom colonic carcinomas are predominantly left-sided, dyschezia being an important presentation. As in most other studies, adenocarcinomas were the predominant neoplasms. CONCLUSIONS: Further work is required to determine prognostically significant features of colorectal cancer in our environment.

Adenocarcinoma↗