Reid M. Ness

Efficacy of Esophageal Impedance/pH Monitoring in Patients With Refractory Gastroesophageal Reflux Disease, on and off Therapy

BACKGROUND & AIMS Intraluminal impedance monitoring has given new dimensions to the diagnosis of reflux disease. However, there is no defined algorithm for evaluating refractory reflux symptoms. We studied whether combined impedance/pH monitoring in patients on therapy can predict acid reflux in patients off therapy and whether testing should be carried out when patients are on or off therapy. METHODS Thirty-nine adults (mean age, 50 years; 24 female) with refractory reflux symptoms were evaluated by impedance/pH monitoring while on therapy, followed by wireless pH monitoring while off therapy. Non-acid reflux events in patients on therapy were correlated with acid reflux parameters studied off therapy. In addition, the likelihood of test abnormalities on and off therapy was determined. RESULTS In 25 of 39 patients (64%) on therapy, impedance testing was normal, with a median of 69 events (interquartile, 63.0-78.0). The percentage of time at pH <4 was within the normal range for all patients who were on therapy. The pH test results were abnormal in 28 of 39 patients (72%) when studied off therapy. Ninety-three of patients with abnormal impedance on therapy also had abnormal acid reflux off therapy. When both groups were off therapy, the patients with abnormal impedance parameters on therapy had significantly higher median (interquartile) 2-day baseline levels of esophageal acid exposure (8.7%, 6.9%-12.5%), compared with those of patients with normal impedance parameters while on therapy (6.0%, 2.8%-9.4%; P = .026). CONCLUSIONS Abnormal impedance in patients on therapy predicts acid reflux in patients off therapy. In patients with refractory reflux, combined impedance/pH monitoring might provide the single best strategy for evaluation of reflux symptoms.

Alcohol Drinking, Cigarette Smoking, and Risk of Colorectal Adenomatous and Hyperplastic Polyps

The authors evaluated alcohol drinking and cigarette smoking in relation to risk of colorectal polyps in a Nashville, Tennessee, colonoscopy-based case-control study. In 2003-2005, cases with adenomatous polyps only (n = 639), hyperplastic polyps only (n = 294), and both types of polyps (n = 235) were compared with 1,773 polyp-free controls. Unordered polytomous logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals. Consumption of at least five alcoholic drinks per week was not strongly associated with development of polyps. Odds ratios for all polyp types were increased for dose, duration, and pack-years of cigarette smoking and were stronger for hyperplastic polyps than for adenoma. Compared with never smoking, dose-response relations were particularly strong for current smoking and duration; for > or =35 years of smoking, odds ratios were 1.9 (95% confidence interval (CI): 1.4, 2.5) for adenomatous polyps only, 5.0 (95% CI: 3.3, 7.3) for hyperplastic polyps only, and 6.9 (95% CI: 4.4, 11.1) for both types of polyps. Compared with current smoking, time since cessation was associated with substantially reduced odds; for > or =20 years since quitting, odds ratios were 0.4 (95% CI: 0.3, 0.6) for adenoma only, 0.2 (95% CI: 0.1, 0.3) for hyperplastic polyps only, and 0.2 (95% CI: 0.2, 0.4) for both polyp types. These findings support the adverse role of cigarette smoking in colorectal tumorigenesis and suggest that quitting smoking may substantially reduce the risk of colorectal polyps.

Colorectal Cancer Screening

During the past decade we have seen dramatic advances in colon cancer screening. Reduction in mortality in average risk screening for colorectal cancer has now been shown in multiple trials. Efforts to increase public awareness and compliance with evidence-based screening guidelines are underway. Recent guidelines have incorporated family history, as it has been identified as a common risk factor. The genes responsible for the inherited syndromes of colon cancer have been identified and genetic testing is available. Currently, screening the average risk population over the age of 50 would reduce mortality from colon cancer by 50%. Future advances will likely include improved screening tests, and the development of familial genetic testing.

Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: the Tennessee Colorectal Polyp Study.

Although meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy‐based case‐control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp‐free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (ptrend = 0.076) or red meat (ptrend = 0.060), with an approximate 50–60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2‐amino‐I‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and 2‐amino‐3,4,8‐trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (ptrend = 0.036 and 0.038, respectively). With a possible exception of the intake of total well‐done meats (ptrend = 0.055) or well‐done red meats (ptrend = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps.

Meat Intake, Heterocyclic Amine Exposure, and Metabolizing Enzyme Polymorphisms in Relation to Colorectal Polyp Risk

Most colorectal cancers arise from adenomatous polyps or certain hyperplastic polyps. Only a few studies have investigated potential genetic modifiers of the associations between meat intake and polyp risk, and results are inconsistent. Using data from the Tennessee Colorectal Polyp Study, a large colonoscopy-based study, including 1,002 polyp cases (557 adenoma only, 250 hyperplastic polyp only, 195 both polyps) and 1,493 polyp-free patients, we evaluated the association of colorectal polyp risk with carcinogen exposure from meat and genetic polymorphisms in enzymes involved in heterocyclic amine (HCA) metabolism, including N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2), cytochrome P450 1A2 (CYP1A2), and aryl hydrocarbon receptor (AhR). Data on intake levels of meats by preparation methods, doneness preferences, and other lifestyle factors were obtained. Fourteen single nucleotide polymorphisms in the AhR, CYP1A2, NAT1, and NAT2 genes were evaluated. No clear association was found for any polymorphisms with polyp risk. However, apparent interactions were found for intake of meat and HCAs with AhR, NAT1, and NAT2 genotypes, and the interactions were statistically significant for the group with both adenomatous and hyperplastic polyps. Dose-response relationships with meat or HCA intake were found only among those with the AhR GA/AA (rs2066853) genotype, NAT1 rapid, or NAT2 rapid/intermediate acetylators but not among those with other genotypes of these genes. This dose-response relationship was more evident among those with both AhR GA/AA and the NAT1 rapid acetylator than those without this genotype combination. These results provide strong evidence for a modifying effect of metabolizing genes on the association of meat intake and HCA exposure with colorectal polyp risk. (Cancer Epidemiol Biomarkers Prev 2008;17(2):320–9)

Lifestyle Factors and Their Combined Impact on the Risk of Colorectal Polyps

Understanding patterns of shared and type-specific etiologies for colorectal polyps may provide insights into colorectal carcinogenesis. The authors present the first systematic comparison of risk factors by colorectal polyp type in a large colonoscopy-based case-control study of 3,764 polyp-free controls and 2,543 polyp patients, including 1,444 cases with adenomas only, 662 cases with hyperplastic polyps (HPPs) only, and 437 cases with synchronous HPPs and adenomas. Surveys were completed to obtain information on usual dietary intake and other lifestyle factors. Six lifestyle factors, including cigarette smoking, obesity, no regular use of nonsteroidal anti-inflammatory drugs, high intake of red meat, low intake of fiber, and low intake of calcium, were found to be independently associated with the risk of polyps. The risk of polyps increased progressively with an increasing number of adverse lifestyle factors. Compared with participants with no or only 1 risk factor, odds ratios for those with 5 to 6 risk factors were 2.72 (95% confidence interval: 1.94, 3.79) for adenoma only, 4.12 (95% confidence interval: 2.78, 6.09) for HPPs only, and 9.03 (95% confidence interval: 5.69, 14.34) for synchronous HPPs and adenomas. This study provides strong evidence that lifestyle modification is important for the prevention of colorectal polyps, especially advanced and multiple adenomas, which are established precursors of colorectal cancer.

Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III

BackgroundMagnesium plays an essential role in the synthesis and metabolism of vitamin D and magnesium supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. We hypothesized that dietary magnesium alone, particularly its interaction with vitamin D intake, contributes to serum 25-hydroxyvitamin D (25(OH)D) levels, and the associations between serum 25(OH)D and risk of mortality may be modified by magnesium intake level.MethodsWe tested these novel hypotheses utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2006, a population-based cross-sectional study, and the NHANES III cohort, a population-based cohort study. Serum 25(OH)D was used to define vitamin D status. Mortality outcomes in the NHANES III cohort were determined by using probabilistic linkage with the National Death Index (NDI).ResultsHigh intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency. Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin D insufficiency. Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median.ConclusionsOur preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium. Future studies, including cohort studies and clinical trials, are necessary to confirm the findings.

Urinary Prostaglandin E2 Metabolite and Risk for Colorectal Adenoma

COX-2 is upregulated in most colorectal cancers. Most of the COX-2 tumor–inducing effects are believed to be mediated through overproduction of prostaglandin E2 (PGE2), which can be measured using a urinary metabolite of PGE2, PGE-M. Urinary PGE-M was assessed in a case–control study of colorectal adenoma. Included in the analysis were 224 cases with at least one advanced adenoma, 152 cases with multiple small tubular adenomas, 300 cases with only a single small tubular adenoma, and 364 polyp-free controls. There were no statistical differences in PGE-M levels between controls and cases with a single small tubular adenoma. However, cases with either an advanced adenoma or multiple small tubular adenomas had more than 25% higher levels of PGE-M than controls. Participants with the highest quartile level of PGE-M were approximately 2.5-fold more likely to have advanced or multiple small tubular adenoma in comparison with those with the lowest level of PGE-M [OR = 2.53; 95% confidence interval (CI), 1.54–4.14; Ptrend < 0.001]. The association was strongest among women. PGE-M level was associated with increased risk for multiple or advanced adenoma but not single small adenoma. Our study suggests that PGE-M may be a useful risk marker for assessing the risk of harboring clinically more important versus less important colorectal neoplasia. Cancer Prev Res; 5(2); 336–42. ©2011 AACR.

A Cost Analysis of Colonoscopy using Microcosting and Time-and-motion Techniques

BackgroundThe cost of an individual colonoscopy is an important determinant of the overall cost and cost-effectiveness of colorectal cancer screening. Published cost estimates vary widely and typically report institutional costs derived from gross-costing methods.ObjectivePerform a cost analysis of colonoscopy using micro-costing and time-and-motion techniques to determine the total societal cost of colonoscopy, which includes direct health care costs as well as direct non-health care costs and costs related to patients’ time. The design is prospective cohort. The participants were 276 contacted, eligible patients who underwent colonoscopy between July 2001 and June 2002, at either a Veterans’ Affairs Medical Center or a University Hospital in the Southeastern United States.Major resultsThe median direct health care cost for colonoscopy was

Fruit and Vegetable Intakes Are Associated with Lower Risk of Colorectal Adenomas

379 (25%, 75%;