The efficacy of polypectomy in preventing colorectal cancer (CRC) has never been demonstrated in ... more The efficacy of polypectomy in preventing colorectal cancer (CRC) has never been demonstrated in a controlled, prospective study. This must be done by randomization within a population with a high prevalence of colorectal polyps, and the feasibility and safety of endoscopic screening examination is a prerequisite for this type of study. The present study is a randomized, controlled study of the feasibility and safety of flexible sigmoidoscopic screening of a normal population sample of 799 men and women aged 50-59 years, findings at 2 and 6 years' colonoscopic follow-up, and the appearance of clinical colorectal cancer (CRC) after 10 years. The attendance rate was high, and there were no complications. After 10 years 1 of 400 in the screening group had developed CRC (in the group of 76 (19%) not attending for screening examination). Four of 399 controls developed CRC. Poor yield of polyps at follow-up, slow growth of in situ polyps, and no clinical CRC among screenees after 10 years provides support to infrequent or no colonoscopic follow-up after initial polypectomy in individuals with otherwise average risk of CRC.
The clinical significance of methanogenic bacteria in large-bowel carcinogenesis has not been est... more The clinical significance of methanogenic bacteria in large-bowel carcinogenesis has not been established so far. As part of a screening study of a randomized population sample of 200 men and 200 women aged 50-59 years, the present breath methane study was designed to gain further information on methane excretion in relation to premalignant colorectal lesions, familial cancer disposition, and dietary fat and fiber. Testing for breath methane excretion did not contribute towards the identification of individuals with premalignant colorectal lesions and therefore should probably not be considered a screening tool.
Poster: "ECR 2016 / B-0008 / MR cholangiography screening in longstanding IBD: prevalence of... more Poster: "ECR 2016 / B-0008 / MR cholangiography screening in longstanding IBD: prevalence of bile duct pathology indicative of sclerosing cholangitis in a population based cohort" by: "A. K. Lunder1, J. R. Hov2, A. Borthne1, E. Viktil2, G. W. Johannesen3, K. Tveit4, J. Gleditsch5, M. Vatn1, A. Negard1; 1Lorenskog/NO, 2Oslo/NO, 3Skien/NO, 4Kristiansand/NO, 5Fredrikstad/NO"
Cancer Epidemiology and Prevention Biomarkers, Dec 1, 2006
Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B... more Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B128 We have studied promoter methylation in normal colon mucosa samples from healthy individuals (n = 21) and from cancer patients (n = 19), and compared the pattern with the ones in adenomas (n = 63), carcinomas (n = 53), and colon cancer cell lines (n = 20). To our knowledge, only one previous study has examined promoter methylation in normal mucosa from both healthy individuals and cancer patients. We examined the following eleven genes: ADAMTS1, APC, CDKN2A, CRABP1, HOXA9, MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1. In total, 38% "normal-normals", 84% "cancer-normals", 73% adenomas, 89% carcinomas, and 100% cell lines were methylated in one or more of the 11 genes analyzed with an average of 0.7, 2.1, 1.7, 3.4, and 5.3 methylated genes in the five respective tumor groups. The normal samples derived from cancer patients showed significantly more methylation compared with samples from non-cancerous individuals. This was apparent both for the widespread methylation (comparing mean number of methylated genes) (P = 0.002), as well as at the individual gene level (ADAMTS1, P = 0.040; APC, P = 0.009; MGMT, P = 0.051). With few exceptions gene methylation frequencies typically increased with tumor aggressiveness. The most frequently methylated genes in the primary carcinomas were ADAMTS1, CRABP1, and MGMT. To the best of our knowledge three genes, HOXA9, RUNX3, and SCGB3A1 are for the first time reported to be methylated in benign lesions of the large bowel. Three genes, HOXA9, MGMT, and APC showed comparable methylation frequencies in adenomas and carcinomas, suggesting that the inactivation of these occur early in colorectal tumorigenesis. Indeed, these genes were also the three most frequently methylated in normal samples. We confirmed that methylation is most common in carcinomas with MSI and proximal location. For some of the genes methylation status were associated to gender, age, and polyp size. In general, methylation frequencies were higher in cell lines than in primary tumors and statistically significant for CRABP1, CDKN2A, and SCGB3A1. However, the comparable overall methylation profiles between the two groups, suggests that colon cancer cell lines can be considered representative epigenetic models for large bowel carcinomas.
The colon and rectum were removed from 445 consecutive autopsies and examined for the presence of... more The colon and rectum were removed from 445 consecutive autopsies and examined for the presence of polypoid lesions under an illuminating magnifying lens. There were seven clinically undiagnosed carcinomas, 329 adenomas, 174 hyperplastic polyps, 59 mucosal tags, 34 other polypoid lesions, and 54 polyps in which no histologic diagnosis could be made. Adenomas were present in 34% of the men and 32% of the women. The adenoma prevalence rate increased smoothly with age in men, whereas the rate in women showed a biphasic variation with a peak at 50-59 years followed by a second increase after 70 years of age. The distribution of adenomas within the bowel showed a marked change with age, from a moderate left-sided predominance before 60 years of age to a marked right-sided predominance in patients over 80 years of age, particularly in men. Hyperplastic polyps were present in 27% of the men and 18% of the women. In men, their frequency and distribution within the bowel showed similar changes with age as were seen for the adenomas. In women, no such age-dependency was observed for hyperplastic polyps. Multiplicity of polyps increased with age and was more pronounced in men than in women. Adenomas in women tended to be larger, more atypical, and more villous than in men. A comparison with a similar study from Northern Norway showed no difference in the prevalence of adenomas in spite of a 70% higher incidence rate for colorectal cancer in Oslo. Cancer 49:819-825. 1982. REVIOUS studies have emphasized the significance P of adenomas as precursors of carcinomas of the large intestine,'-' but many aspects of the polyp-cancer sequence need further study. The incidence of adenomas and carcinomas of the colon is high in western Europe and the United state^,^ in contrast to the low incidence of both among populations of Afro-Asian Within Norway, the incidence of colorectal cancer is about 70% higher in Oslo than in Northern Norway.' In the present investigation we have studied the prevalence and distribution of colorectal polyps in patients coming to autopsy at Ulleval Hospital, the largest general hospital in Oslo. A similar study from Northern Norway has been published previo~sly.~
European Journal of Gastroenterology & Hepatology, Sep 1, 1998
BACKGROUND Crohn's disease is often treated with glucocorticoids or mesalamine. We compared t... more BACKGROUND Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both. METHODS In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02). CONCLUSIONS In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.
The efficacy of polypectomy in preventing colorectal cancer (CRC) has never been demonstrated in ... more The efficacy of polypectomy in preventing colorectal cancer (CRC) has never been demonstrated in a controlled, prospective study. This must be done by randomization within a population with a high prevalence of colorectal polyps, and the feasibility and safety of endoscopic screening examination is a prerequisite for this type of study. The present study is a randomized, controlled study of the feasibility and safety of flexible sigmoidoscopic screening of a normal population sample of 799 men and women aged 50-59 years, findings at 2 and 6 years&amp;amp;#39; colonoscopic follow-up, and the appearance of clinical colorectal cancer (CRC) after 10 years. The attendance rate was high, and there were no complications. After 10 years 1 of 400 in the screening group had developed CRC (in the group of 76 (19%) not attending for screening examination). Four of 399 controls developed CRC. Poor yield of polyps at follow-up, slow growth of in situ polyps, and no clinical CRC among screenees after 10 years provides support to infrequent or no colonoscopic follow-up after initial polypectomy in individuals with otherwise average risk of CRC.
The clinical significance of methanogenic bacteria in large-bowel carcinogenesis has not been est... more The clinical significance of methanogenic bacteria in large-bowel carcinogenesis has not been established so far. As part of a screening study of a randomized population sample of 200 men and 200 women aged 50-59 years, the present breath methane study was designed to gain further information on methane excretion in relation to premalignant colorectal lesions, familial cancer disposition, and dietary fat and fiber. Testing for breath methane excretion did not contribute towards the identification of individuals with premalignant colorectal lesions and therefore should probably not be considered a screening tool.
Poster: "ECR 2016 / B-0008 / MR cholangiography screening in longstanding IBD: prevalence of... more Poster: "ECR 2016 / B-0008 / MR cholangiography screening in longstanding IBD: prevalence of bile duct pathology indicative of sclerosing cholangitis in a population based cohort" by: "A. K. Lunder1, J. R. Hov2, A. Borthne1, E. Viktil2, G. W. Johannesen3, K. Tveit4, J. Gleditsch5, M. Vatn1, A. Negard1; 1Lorenskog/NO, 2Oslo/NO, 3Skien/NO, 4Kristiansand/NO, 5Fredrikstad/NO"
Cancer Epidemiology and Prevention Biomarkers, Dec 1, 2006
Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B... more Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 B128 We have studied promoter methylation in normal colon mucosa samples from healthy individuals (n = 21) and from cancer patients (n = 19), and compared the pattern with the ones in adenomas (n = 63), carcinomas (n = 53), and colon cancer cell lines (n = 20). To our knowledge, only one previous study has examined promoter methylation in normal mucosa from both healthy individuals and cancer patients. We examined the following eleven genes: ADAMTS1, APC, CDKN2A, CRABP1, HOXA9, MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1. In total, 38% "normal-normals", 84% "cancer-normals", 73% adenomas, 89% carcinomas, and 100% cell lines were methylated in one or more of the 11 genes analyzed with an average of 0.7, 2.1, 1.7, 3.4, and 5.3 methylated genes in the five respective tumor groups. The normal samples derived from cancer patients showed significantly more methylation compared with samples from non-cancerous individuals. This was apparent both for the widespread methylation (comparing mean number of methylated genes) (P = 0.002), as well as at the individual gene level (ADAMTS1, P = 0.040; APC, P = 0.009; MGMT, P = 0.051). With few exceptions gene methylation frequencies typically increased with tumor aggressiveness. The most frequently methylated genes in the primary carcinomas were ADAMTS1, CRABP1, and MGMT. To the best of our knowledge three genes, HOXA9, RUNX3, and SCGB3A1 are for the first time reported to be methylated in benign lesions of the large bowel. Three genes, HOXA9, MGMT, and APC showed comparable methylation frequencies in adenomas and carcinomas, suggesting that the inactivation of these occur early in colorectal tumorigenesis. Indeed, these genes were also the three most frequently methylated in normal samples. We confirmed that methylation is most common in carcinomas with MSI and proximal location. For some of the genes methylation status were associated to gender, age, and polyp size. In general, methylation frequencies were higher in cell lines than in primary tumors and statistically significant for CRABP1, CDKN2A, and SCGB3A1. However, the comparable overall methylation profiles between the two groups, suggests that colon cancer cell lines can be considered representative epigenetic models for large bowel carcinomas.
The colon and rectum were removed from 445 consecutive autopsies and examined for the presence of... more The colon and rectum were removed from 445 consecutive autopsies and examined for the presence of polypoid lesions under an illuminating magnifying lens. There were seven clinically undiagnosed carcinomas, 329 adenomas, 174 hyperplastic polyps, 59 mucosal tags, 34 other polypoid lesions, and 54 polyps in which no histologic diagnosis could be made. Adenomas were present in 34% of the men and 32% of the women. The adenoma prevalence rate increased smoothly with age in men, whereas the rate in women showed a biphasic variation with a peak at 50-59 years followed by a second increase after 70 years of age. The distribution of adenomas within the bowel showed a marked change with age, from a moderate left-sided predominance before 60 years of age to a marked right-sided predominance in patients over 80 years of age, particularly in men. Hyperplastic polyps were present in 27% of the men and 18% of the women. In men, their frequency and distribution within the bowel showed similar changes with age as were seen for the adenomas. In women, no such age-dependency was observed for hyperplastic polyps. Multiplicity of polyps increased with age and was more pronounced in men than in women. Adenomas in women tended to be larger, more atypical, and more villous than in men. A comparison with a similar study from Northern Norway showed no difference in the prevalence of adenomas in spite of a 70% higher incidence rate for colorectal cancer in Oslo. Cancer 49:819-825. 1982. REVIOUS studies have emphasized the significance P of adenomas as precursors of carcinomas of the large intestine,'-' but many aspects of the polyp-cancer sequence need further study. The incidence of adenomas and carcinomas of the colon is high in western Europe and the United state^,^ in contrast to the low incidence of both among populations of Afro-Asian Within Norway, the incidence of colorectal cancer is about 70% higher in Oslo than in Northern Norway.' In the present investigation we have studied the prevalence and distribution of colorectal polyps in patients coming to autopsy at Ulleval Hospital, the largest general hospital in Oslo. A similar study from Northern Norway has been published previo~sly.~
European Journal of Gastroenterology & Hepatology, Sep 1, 1998
BACKGROUND Crohn's disease is often treated with glucocorticoids or mesalamine. We compared t... more BACKGROUND Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both. METHODS In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02). CONCLUSIONS In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.
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