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    Likelihood of missed and recurrent adenomas in the proximal versus the distal colon

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    Authors
    Laiyemo, Adeyinka O.
    Doubeni, Chyke A.
    Sanderson, Andrew K. II
    Pinsky, Paul F.
    Badurdeen, Dilhana S.
    Doria-Rose, V. Paul
    Marcus, Pamela M.
    Schoen, Robert E.
    Lanza, Elaine
    Schatzkin, Arthur
    Cross, Amanda J.
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    UMass Chan Affiliations
    Meyers Primary Care Institute
    Department of Family Medicine and Community Health
    Document Type
    Journal Article
    Publication Date
    2011-08-01
    Keywords
    Adenoma
    Aged
    Colon, Ascending
    Colon, Descending
    Colon, Sigmoid
    Colon, Transverse
    Colonic Neoplasms
    Colonoscopy
    False Negative Reactions
    Female
    Humans
    Male
    Middle Aged
    Neoplasm Recurrence, Local
    Prospective Studies
    Regression Analysis
    Risk Factors
    Community Health and Preventive Medicine
    Preventive Medicine
    Primary Care
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    http://dx.doi.org/10.1016/j.gie.2011.02.023
    Abstract
    BACKGROUND: Colonoscopy may be less efficacious in reducing colorectal cancer mortality in the proximal compared with the distal colon. A greater likelihood for missed and recurrent adenomas in the proximal colon may contribute to this phenomenon. OBJECTIVE: To examine whether a proximal adenoma is associated with the risk and location of missed and recurrent adenomas. DESIGN: Prospective. SETTING: Polyp Prevention Trial. PARTICIPANTS: A total of 1864 patients with an adenoma at baseline underwent a follow-up colonoscopy 4 years later (adenoma recurrence). Of these, 1731 underwent a clearing colonoscopy 1 year after the baseline examination (missed adenoma). MAIN OUTCOME MEASUREMENTS: Association of baseline adenoma location with the risk and location of adenomas found at colonoscopy performed 1 year and 4 years later. RESULTS: At the year 1 colonoscopy, 598 patients (34.6%) had an adenoma (missed adenoma). Compared with those with a distal-only adenoma at baseline, patients with a proximal-only adenoma at baseline were more likely to have any missed adenomas (relative risk [RR] 1.28; 95% CI, 1.09-1.49) and a proximal-only missed adenoma (RR 2.05; 95% CI, 1.49-2.80). At the year 4 colonoscopy, 733 patients (39.3%) had adenoma recurrence. Patients with a baseline proximal-only adenoma were more likely to have any adenoma recurrence (RR 1.14; 95% CI, 1.00-1.31) and a proximal-only adenoma recurrence (RR 1.52; 95% CI, 1.15-2.02). Sensitivity analyses involving missed adenomas did not materially affect the risk or location of recurrent adenomas at year 4 colonoscopy. LIMITATION: Lesions may still be missed on repeated colonoscopies. CONCLUSIONS: Missed and recurrent adenomas are more likely to be in the proximal colon. Published by Mosby, Inc. All rights reserved.
    Source
    Gastrointest Endosc. 2011 Aug;74(2):253-61. Epub 2011 May 6. Link to article on publisher's site
    DOI
    10.1016/j.gie.2011.02.023
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/30842
    PubMed ID
    21549375
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    ae974a485f413a2113503eed53cd6c53
    10.1016/j.gie.2011.02.023
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      Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma

      Lotz, Margaret M.; Andrews, Charles W. Jr.; Korzelius, Cynthia A.; Lee, Edward C.; Steele, Glenn D. Jr.; Clarke, Astrid; Mercurio, Arthur M. (1993-04-15)
      The Mac-2 lectin (carbohydrate binding protein 35) is a soluble, 32- to 35-kDa phosphoprotein that binds galactose-containing glycoconjugates. We report here that the colonic epithelium is a major site of Mac-2 expression in vivo based on immunohistochemistry of human tissue specimens. In this epithelium, proliferating cells at the base of the crypts do not express Mac-2 but its expression increases with differentiation along the crypt-to-surface axis. Mac-2 expression is concentrated in the nuclei of these differentiated epithelial cells. The progression from normal mucosa to adenoma to carcinoma is associated with significant changes in Mac-2 nuclear localization and expression. In all adenomas (9/9) and carcinomas (13/13) examined, Mac-2 was not present in the nucleus but was localized in the cytoplasm. Sequencing of Mac-2 cDNAs from normal mucosa and carcinoma revealed no specific mutations that could account for this loss of nuclear localization. We also observed a 5- to 10-fold decrease in Mac-2 mRNA levels in cancer compared to normal mucosa as well as a significant reduction in the amount of Mac-2 protein expressed. These observations suggest that Mac-2 exclusion from the nucleus and its decreased expression may be related to the neoplastic progression of colon cancer.
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      Identification of a high affinity TAG-72 binding peptide by phage display selection

      Xiao, Nan; Cheng, Dengfeng; Wang, Yi; Chen, Ling; Liu, Xinrong; Dou, Shuping; Liu, Guozheng; Liang, Min Min; Hnatowich, Donald J.; Rusckowski, Mary (2011-01-01)
      PURPOSE: Phage display was used to select novel peptides that specifically bind the TAG-72 antigen and with properties suitable for imaging TAG-72 positive cancers. RESULTS: After three rounds of selection against TAG-72 and using two different elution conditions including a long elution, the consensus sequences FRERCDKHPQKCTKFL and DPRHCQKRVLPCPAWL were expressed on phages G3-15 and T3-15 respectively. ELISA, fluorescence-activated cell sorting analysis and fluorescence microscopy provided evidence that both phages specifically bound TAG-72 in vitro. Both peptides are stable in 37oC serum. By a cell binding competition assay, the IC50 for T3-15 was measured as 0.29 nM and therefore 36-fold higher affinity than G3-15 at 10.32 nM. The biodistribution in mice carrying LS-174T tumors in one thigh were similar for both 99mTc-peptides at 30 min, but at 90 min the 99mTc-T3-15 peptide accumulated almost three times higher in the tumor. The SPECT/CT images were consistent with the biodistribution results. PROCEDURES: The f88-4/Cys6 phage library and two different elution conditions were used to identify two new higher affinity binding peptides for the TAG-72 antigen. One, was a single brief elution with pH 2.2 glycine buffer, and the second began with the glycine elution but was followed with a longer elution with Tris buffered saline (TBS) at pH 7.4. The phages that bound TAG-72 were evaluated by fluorescence-activated cell sorting analysis using TAG-72 positive LS-174T cells and confirmed by immunofluorescence imaging. The consensus peptides displayed on the selected phages were synthesized and conjugated with NHS-MAG3 for radiolabeling with 99mTc. The IC50 for TAG-72 binding was evaluated by cell binding competition in vitro while binding affinity was evaluated in vivo by necropsy and SPECT/CT imaging in a tumor mouse model. CONCLUSION: We have identified a peptide with a sub nanomolar inhibition constant for the TAG-72 antigen that may have application in cancer imaging.
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      Sucrase-isomaltase is an independent prognostic marker for colorectal carcinoma

      Jessup, J. Milburn; Lavin, Phillip T.; Andrews, Charles W. Jr.; Loda, Massimo; Mercurio, Arthur M.; Minsky, B. D.; Mies, C.; Cukor, B.; Bleday, R.; Steele, Glenn D. Jr. (1995-12-01)
      PURPOSE: Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC). METHODS: SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months. RESULTS: Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold. DISCUSSION: These results indicate that SI is a prognostic marker for CRC that is independent of stage-related variables in patients who have undergone potentially curative resections.
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