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Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. β-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.

Background: Surgical site infection is a key hospital-level patient safety indicator. All risk factors for surgical site infection are not always taken into account and adjusted for., Objective: This study aimed to measure the impact of IBD in comparison with diverticulitis and colorectal cancer on the national rates of surgical site infection., Design: The American College of Surgeons National Surgical Quality Improvement Project database was queried for all patients undergoing elective colectomy for colon cancer, diverticulitis, and IBD from 2008 through 2012., Outcome Measures: The association between surgical site infection and IBD patients was assessed. Patient demographics, rates of surgical site infection, wound class, return to operating room, and various patient characteristics were analyzed. Logistic regression was performed to determine the association with surgical site infection., Results: The query yielded 71,845 patients undergoing elective colectomy. Of these patients, 42,132 had colon cancer, 22,143 had diverticulitis, and 7570 had IBD. The rate of surgical site infection was 12.0% for colon cancer, 12.8% for diverticulitis, and 18.0% for IBD. Return to operating room within 30 days was 7.3% for IBD patients, 4.4% for patients with diverticulitis, and 4.9% for patients with colorectal cancer. Return to operating room within 30 days had the highest correlation to surgical site infection in both univariate and multivariable analysis. Other associative factors for surgical site infection common to both analyses included diabetes mellitus, smoking, open procedures, and obesity., Limitations: This study was limited by the data collection errors inherent to large databases, exclusion of emergent operations, and the inability to identify patients taking immunosuppressive agents., Conclusions: Patients with IBD undergoing elective colectomy have significantly increased rates of surgical site infection, specifically deep and organ/space infections. Given this information, risk adjustment models for surgical site infection may need to include IBD in their calculation.

We have previously reported reduced overall and disease-free survival in black patients from a 10-year retrospective review of 668 patients from tumor registry data. This study of 213 patients reports the analysis of available archived tissue from a city hospital (n=44 patients, 53% black) and from a university medical center (n=169, 10.6% black). Two senior pathologists independently reviewed slides for predetermined histologic criteria reported to correlate with survival: tumor type, stage at diagnosis, character of invasion, vascular or perineural invasion, the presence of residual adenoma, the presence of a Crohn's-like reaction and number of nodes resected. Differences in discrete variables were compared using the Chi-squared test. Differences in continuous variables were analyzed using independent t tests. No statistically significant differences were identified in tumor stage or type by institution or race. In patients treated at the city hospital, there was a higher incidence of infiltrating tumors (85% vs. 61%, p<0.001), vascular invasion (70% vs. 36%, p<0.05) and residual adenoma (84% vs. 39%, p<0.05); however, no differences by race were identified. Blacks at both hospitals had significantly more perineural invasion (81% vs. 30%, p<0.05) and Crohn's-like reaction (64% vs. 30%, p<0.05) when compared to white patients, although there was no difference between hospitals. The total number of lymph nodes resected was higher at the university hospital (17.0 vs. 8.9, p<0.001). There were no differences in number of nodes resected at either institution by race. Histopathologic findings did not explain the apparent disparity in survival. The differences in number of nodes harvested may suggest inadequate resection or insufficient recovery of nodes by the pathologist.

Background: Blacks are more likely to be diagnosed at a later stage of colorectal cancer (CRC), and have poorer survival than Whites. Colorectal cancer (CRC) is usually curable when diagnosed at an early stage., Objectives: We compare the use of CRC tests for screening between Whites and Blacks and compare the use of CRC tests for either screening or diagnosis and further check the test results for a diagnosis of CRC., Data: The data we use are from physician claims files provided by the Centers for Medicare and Medicaid Services (CMS) (1996-2000) for a closed cohort of all Tennesseans eligible for Medicare in 1996, age > or = 6., Results: Half as many Blacks as Whites were screened with fecal occult blood testing (FOBT), sigmoidoscopy, and colonoscopy. Significantly fewer Blacks had any colorectal procedures, sigmoidoscopy, colonoscopy, and/ or barium enema, for screening or diagnosis; however, the test results show that more Blacks were diagnosed with CRC than Whites. The use of CRC tests is low regardless of race. Only 24% of beneficiaries used at least one of the four procedures during the five years. During the five years, FOBT and barium enema use decreased significantly for both Blacks and Whites, while colonoscopy use increased significantly. Sigmoidoscopy use was highest in 1998, which corresponds to the change of Medicare coverage policy in 1998., Conclusions: Removal of financial barriers to screening alone has failed to substantially improve the use of colorectal procedures. Lack of vigilance and lack of access to good quality of care contribute to the fact that Blacks are more likely to be diagnosed at a late stage of CRC than Whites.

Background: Studies exploring CRC testing prevalence and correlates within US populations have provided limited and sometimes conflicting information. The most recent national-level reports have described US usage of CRC tests but none have considered only those tests done specifically for screening reasons as an outcome variable., Methods: Using the NHIS 2000 sample of >or=50 year-old, we assessed screening behavior using an outcome variable accounting for (1) any combination of recommended tests (2) done within their respective time guidelines, and (3) specifically for screening purposes., Results: Only 25.8% (95% CI: 24.9-26.7%) of the population reported getting a test done for screening purposes within the recommended time. Most (>85%) of the FOBTs and only about 60% of endoscopies were done for screening. Among those who had an endoscopy within the recommended time, Blacks were more likely than Whites to report screening as the purpose of the test. Hispanics had the lowest test usage irrespective of test time, reason or type. Hispanics were 50% (p<0.001) less likely to be adherent, and Blacks approximately 22% (p<0.01) less likely to be adherent, than Whites. After multivariate adjustment, differences between Whites and Blacks disappeared; Hispanics remained less likely. Increasing education predicted higher adherence among Whites but only undergraduate completion did so among Blacks. Male gender predicted adherence only among Blacks and insurance only among Hispanics., Conclusions: Preventive screening for CRC is lower than estimates from previous studies. Future studies should consider accounting for test purpose. Our findings need confirmation through studies based on objective data.

Background: Increasing evidence suggests significant disparity in colorectal cancer outcomes between black and white patients. Contributing factors may include advanced tumor stage at diagnosis, differences in treatment, more aggressive tumor biology, access to care, and patient comorbidity., Hypothesis: Disparities in colorectal cancer outcomes exist despite similar objective measures of treatment., Design and Setting: Ten-year retrospective review of all patients with colorectal cancer using tumor registries at a city hospital (n = 83) and a university medical center (n = 585) in the same city. We assessed stage at diagnosis; curative surgical resection; use of adjuvant treatment; overall, disease-free, and stage-specific survival; and socioeconomic status. Patients with nonwhite, nonblack ethnicity (4% overall) were excluded. Differences in stage and treatments were compared using the chi(2) test, and median survival rates were compared using log-rank tests., Results: Significantly more black patients were treated at the city hospital (53.0%) vs the university medical center (10.6%) (P<.001). No differences were identified in stage distribution or treatments received between hospitals or between black and white patients. Significantly worse survival was noted among patients treated at the city hospital (2.1 vs 5.3 years; P<.001) and among black patients treated at both institutions (city hospital: 1.4 vs 2.1 years, and university hospital: 3.2 vs 5.7 years; P<.001 for both). Disease-free survival rates showed similar significant reductions for black patients at both institutions. There was no association between survival and socioeconomic status at either institution., Conclusion: The marked reductions in overall and disease-free survival for black patients with colorectal cancer do not seem to be related to variation in treatment but may be due to biologic factors or non-cancer-related health conditions.