Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

Bioimpedance analysis predicts the etiology of cirrhosis in a prospective cohort study.

BACKGROUND: Obesity is associated with an increased risk of developing cirrhosis. However, body mass index (BMI) and waist-to-hip ratio (WHR) may not be indicative of body composition parameters that predispose to cirrhosis. Bioimpedance analysis (BIA) is a noninvasive cost-efficient method for more detailed estimation of body composition. METHODS: We examined patients with cirrhosis who underwent BIA as part of enrollment into a prospective cohort study. We examined the correlation between BIA variables, BMI, and WHR. We performed sex-adjusted and race-adjusted and race-specific multivariable logistic regression analyses to examine the association between anthropometric variables and risk factors [NAFLD, alcohol-associated liver disease (ALD), and HCV]. RESULTS: We analyzed data from 348 cirrhosis patients; 23.3% were women; 48.3% were non-Hispanic White; 19.3% were Hispanic; and 30.7% were African American. The cirrhosis etiology was 21.8% NAFLD, 56.9% HCV mostly cured, and 11.5% ALD. Several BIA variables correlated well with BMI, and others showed modest correlations, but none correlated well with WHR. Higher body fat mass and basal metabolic rate were positively associated, while higher lean body mass, dry lean mass, total body water, or skeletal muscle mass were negatively associated with NAFLD. Associations between these BIA parameters and ALD-related cirrhosis were in the opposite direction. These associations of BIA variables were seen only in Hispanic and non-Hispanic White patients but not non-Hispanic Blacks. BIA variables were more predictive of cirrhosis etiology than BMI or WHR. CONCLUSIONS: Among patients with cirrhosis, several BIA-derived measurements indicative of body fat and muscle are associated with NAFLD and ALD etiology. BIA variables show stronger associations, as well as race/ethnicity-specific associations, with cirrhosis etiology than those of BMI or WHR.

The Performance of AFP, AFP-3, DCP as Biomarkers for Detection of Hepatocellular Carcinoma (HCC): A Phase 3 Biomarker Study in the United States.

BACKGROUND & AIMS: α-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations. METHODS: We conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded fashion. True positive rate (TPR) and false positive rate (FPR) for any or early HCC were calculated within 6, 12, and 24 months of HCC diagnosis based on published thresholds for biomarkers individually, in combination and in GALAD and Hepatocellular Carcinoma Early Detection Screening (HES) scores. We calculated the area under the receiver operating curve and estimated TPR based on an optimal threshold at a fixed FPR of 10%. RESULTS: The analysis was conducted in a cohort of 534 patients; 50 developed HCC (68% early) and 484 controls with negative imaging. GALAD had the highest TPR (63.6%, 73.8%, and 71.4% for all HCC, and 53.8%, 63.3%, and 61.8 % for early HCC within 6, 12, and 24 months, respectively) but an FPR of 21.5% to 22.9%. However, there were no differences in the area under the receiver operating curve among GALAD, HES, AFP-L3, or DCP. At a fixed 10% FPR, TPR for GALAD dropped (42.4%, 45.2%, and 46.9%) and was not different from HES (36.4%, 40.5%, and 40.8%) or AFP-L3 alone (39.4%, 45.2%, and 44.9%). CONCLUSIONS: In a prospective cohort phase III biomarker study, GALAD was associated with a considerable improvement in sensitivity for HCC detection but an increase in false-positive results. GALAD performance was modest and not different from AFP-L3 alone or HES.

Antibiotic Resistance of Helicobacter pylori Among Male United States Veterans.

BACKGROUND & AIMS: The most recent information published on resistance of Helicobacter pylori to antibiotics in a large population in the United States is more than 10 years old. We assessed the susceptibility of H pylori to antibiotics among patients in a large metropolitan hospital, as well as demographic, clinical, and lifestyle factors associated with antimicrobial resistance. METHODS: We performed a cross-sectional study of a random sample of 656 patients (90.2% men) from a cohort of 1559 undergoing esophagogastroduodenoscopy with collection of gastric biopsies from 2009 through 2013 at the Houston Veterans Affairs Medical Center. We performed culture analyses of gastric tissues to detect H pylori. The minimum inhibitory concentrations of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were determined by the Epsilometer test. Logistic regression analysis was performed to estimate the association between risk factors and antimicrobial resistance. RESULTS: Biopsies from 135 subjects (20.6%) tested positive for H pylori; 128 of these were from men (94.8%). Only 65 strains were susceptible to all 5 antibiotics. The prevalence of resistance to levofloxacin was 31.3% (95% confidence interval [CI], 23.1%-39.4%), to metronidazole it was 20.3% (95% CI, 13.2%-27.4%), to clarithromycin it was 16.4% (95% CI, 9.9%-22.9%), and to tetracycline it was 0.8% (95% CI, 0.0%-2.3%). No isolate was resistant to amoxicillin. Clarithromycin resistance increased from 9.1% in 2009-2010 to 24.2% in 2011-2013. In multivariate analysis, prior treatment of H pylori infection and use of fluoroquinolones were significantly associated with clarithromycin and levofloxacin resistance, respectively. CONCLUSIONS: H pylori resistance to clarithromycin increased between 2009 and 2013; resistance to metronidazole remains high in infected men in the United States. The high frequency of resistance to levofloxacin is a new and concerning finding.

Esophageal COX-2 expression is increased in Barrett's esophagus, obesity, and smoking.

BACKGROUND: Increased esophageal cyclooxygenase-2 (COX-2) expression has been associated with Barrett's esophagus (BE); however, it is unknown whether COX-2 expression varies among patient groups with different clinical or socio-demographic factors. METHODS: We conducted a case-control study among eligible patients scheduled for elective esophagogastroduodenoscopy and patients eligible for screening colonoscopy recruited from primary clinics. We compared 39 BE tissue samples and 47 squamous tissue samples from BE cases and 240 squamous tissue samples from controls. Clinical and socio-demographic data were prospectively collected. Immunohistochemical staining for esophageal COX-2 was performed and scored. RESULTS: The median COX-2 score was significantly higher in BE tissue than squamous tissue from cases or controls (p < 0.001). Median COX-2 expression levels were higher in tissue samples from participants with a waist-to-hip ratio (WHR) in the 2nd tertile [unadjusted odds ratio (OR) 2.04; 95 % confidence interval (95 % CI) 1.17-3.57] and 3rd tertile (unadjusted OR 2.24; 95 % CI 1.20-4.16) compared with the 1st tertile and from current smokers compared with former or non-smokers (unadjusted OR 1.68; 95 % CI 1.03-2.75). In the multivariate analysis, WHRs in the 2nd tertile (OR 1.92; 95 % CI 1.07-3.45) and the 3rd tertile (OR 2.14; 95 % CI 1.10-4.16) were associated with high COX-2 compared with the 1st tertile, as was current smoking (OR 1.78; 95 % CI 1.06-2.97) compared with former and non-smoking. CONCLUSION: We found a significant association between elevated esophageal mucosa COX-2 levels and the presence of BE tissue, as well as between elevated COX-2 levels and high WHR and current tobacco smoking. This information may assist in identifying patients likely to benefit from chemoprevention with COX-2 inhibitors.

Association between Helicobacter pylori and Barrett's esophagus: a case-control study.

OBJECTIVES: The estimated association between Helicobacter pylori and Barrett's esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association. METHODS: We conducted a case-control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders. RESULTS: We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35-0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥ 1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63). CONCLUSIONS: The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week).

Fat mass by bioelectrical impedance analysis is not associated with increased risk of Barrett esophagus.

GOAL: To evaluate whether the association between obesity and Barrett esophagus (BE) is due to total body fatness, abdominal obesity, or both. BACKGROUND: BE risk seems to be more strongly related to central obesity than total obesity. However, no studies have investigated the association between total obesity and BE using direct measures of total body fatness. STUDY: We conducted a case-control study among patients scheduled for elective esophagogastroduodenoscopy, and a sample of patients eligible for screening colonoscopy recruited from primary care clinics. BE cases were patients with specialized intestinal metaplasia, whereas controls had no endoscopic or histopathologic BE. All patients underwent a study esophagogastroduodenoscopy and had body measurements taken. Fat mass and fat-free mass were estimated from bioelectrical impedance analysis (BIA). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression. RESULTS: There were 70 BE cases, 229 endoscopy controls, and 118 primary care controls. BMI and BIA-derived fat mass were highly correlated; however, we found no association between BMI, fat mass, and BE (vs. all controls: BMI, OR/1 SD=1.01; 95% CI, 0.76-1.34; fat mass, OR=1.02; 95% CI, 0.77-1.36). Waist-to-hip ratio was significantly associated with increased BE risk (vs. all controls: OR/1 SD=1.45; 95% CI, 1.03-2.04). We found similar results when we analyzed the control groups separately. CONCLUSION: Waist-to-hip ratio, but not fat mass or BMI, was associated with increased BE risk. This study provides strong evidence that BE is related to body size and composition through central adiposity and not through total body fatness.

Circulating inflammatory cytokines and adipokines are associated with increased risk of Barrett's esophagus: a case-control study.

BACKGROUND & AIMS: Obesity is associated with Barrett's esophagus (BE) and with changes in circulating levels of adipokines (leptin and adiponectin) and cytokines. Although studies have reported that adipokines and inflammatory cytokines are necessary for the development of BE, their role is controversial. METHODS: We performed a case-control study; cases (n = 141) were patients who underwent esophagogastroduodenoscopy and were found to have BE, which was based on endoscopy and histology, and controls (n = 139) were primary care patients eligible for screening colonoscopies who agreed to undergo esophagogastroduodenoscopy. We examined the association between BE and circulating levels of adipokines and cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, and IL-12p70; tumor necrosis factor-α; and interferon-γ). Cases and controls were compared by calculating odds ratios (ORs) and 95% confidence intervals (CIs) and using unadjusted and multiple logistic regression, adjusting for age, sex, race, waist-hip ratio, use of proton pump inhibitors and nonsteroidal anti-inflammatory drugs, and Helicobacter pylori infection. RESULTS: The adjusted ORs for BE were 2.62 (95% CI, 1.0-6.8), 5.18 (95% CI, 1.7-15.7), and 8.02 (95% CI, 2.79-23.07) for the highest quintile vs the lowest quintile of levels of IL-12p70, IL-8, and leptin, respectively, but the OR was not significant for IL-6 (2.39; 95% CI, 0.84-6.79). The adjusted OR for BE was 0.14 for highest quintile of IL-10 compared with lowest quintile (95% CI, 0.05-0.35) and 0.03 for IL-1ß ≥ median vs none detected (95% CI, 0.006-0.13). Higher levels of IL-8 and leptin and lower levels of IL-10 and IL-1ß were associated with the presence of long-segment (≥3 cm) and short-segment BE. There were no differences between cases and controls in levels of interferon-γ, tumor necrosis factor-α, adiponectin, or insulin. CONCLUSIONS: BE is associated with circulating inflammatory cytokines and leptin and low levels of anti-inflammatory cytokines. These findings could partly explain the effect of obesity on BE.

Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett's oesophagus: a case-control study.

OBJECTIVE: Abdominal obesity has been associated with increased risk of Barrett's oesophagus (BE) but the underlying mechanism is unclear. We examined the association between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the risk of BE. DESIGN: A case-control study among eligible patients scheduled for elective oesophagastroduodenoscopy (EGD) and in a sample of patients eligible for screening colonoscopy recruited at the primary care clinic. All cases with definitive BE and a random sample of controls without BE were invited to undergo standardised mid-abdomen non-contrast computerised axial tomography images, which were analysed by semiautomated image segmentation software. The effect of VAT and SAT surface areas and their ratio (VAT to SAT) on BE were analysed in logistic regression models. RESULTS: A total of 173 BE cases, 343 colonoscopy controls and 172 endoscopy controls underwent study EGD and CT scan. Participants with BE were more than twice as likely to be in the highest tertile of VAT to SAT ratio (OR: 2.42 (1.51 to 3.88) and adjusted OR 1.47 (0.88 to 2.45)) than colonoscopy controls, especially for those long (≥3 cm) segment BE (3.42 (1.67 to 7.01) and adjusted OR 1.93 (0.92 to 4.09)) and for white men (adjusted OR 2.12 (1.15 to 3.90)). Adjustment for gastroesophageal reflux disease (GERD) symptoms and proton pump inhibitors (PPI) use attenuated this association, but there was a significant increase in BE risk even in the absence of GERD or PPI use. CONCLUSIONS: Large amount of visceral abdominal fat relative to subcutaneous fat is associated with a significant increase in the risk of BE. GERD may mediate some but not all of this association.

Oral bisphosphonates and the risk of Barrett's esophagus: case-control analysis of US veterans.

OBJECTIVES: This study examined Barrett's esophagus (BE) risk factors in veterans to determine the association between risk of BE and use of oral bisphosphonates. METHODS: We conducted a case-control study among eligible patients scheduled for an elective esophagogastroduodenoscopy (EGD) and a sample of patients eligible for screening colonoscopy recruited from primary care clinics from a single VA Medical Center. Cases with definitive BE were compared with controls; all underwent study EGD. Use of oral bisphosphonates was ascertained by reviewing filled prescriptions in electronic pharmacy records. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs), using multivariate logistic regression modeling while adjusting for sex, age, race, proton-pump inhibitor use, hiatal hernia, waist-to-hip ratio, Helicobacter pylori infection, and gastroesophageal reflux disorder (GERD) symptoms. RESULTS: There were 285 BE cases, 1,122 endoscopy controls, and 496 primary care controls. Alendronate and risedronate were the only oral bisphosphonates prescribed. The proportion of BE cases with filled prescription of oral bisphosphonates (4.6%) was greater than in endoscopy controls (1.6%) or primary care controls (2.9%). In the adjusted analysis, oral bisphosphonate use was significantly associated with BE risk (OR=2.33; 95% CI: 1.11-4.88) compared with the combined control groups. This association remained significant when BE cases were compared with endoscopy controls only (OR=2.74; 95% CI: 1.28-5.87) but was attenuated when compared with primary care controls only (OR=2.60; 95% CI: 0.99-6.84). The association was observed in patients with GERD symptoms (OR=3.29; 95% CI: 1.36-7.97) but not in those without GERD symptoms. CONCLUSION: Oral bisphosphonate use may increase the risk for BE, especially among patients with GERD.

Hepatocellular carcinoma screening practices in the Department of Veterans Affairs: findings from a national facility survey.

BACKGROUND: Previous studies suggest low rates of hepatocellular carcinoma (HCC) screening in clinical practice. There is little information on the provider- and healthcare-facility-related factors that explain the use of HCC screening. AIMS: We used data from the 2007 Survey to Assess Hepatitis C Care in Veterans Health Administration that collected information regarding the care of patients with hepatitis C virus (HCV) from 138 of 140 Veterans Administration healthcare facilities nationwide. METHODS: All providers caring for veterans with HCV were invited to respond. In addition, each facility was asked to identify a lead HCV clinician to respond to facility-specific questions. Our outcome was a response concordant with HCC screening guidelines [HCC screening in patients with cirrhosis or in patients with chronic hepatitis B virus (HBV), and screening every 6 or 12 months]. RESULTS: A total of 268 providers responded (98 % facility participation rate). Of these, 190 respondents (70.9 %) reported recommending HCC screening with guideline-concordant risk groups and frequency. Providers reporting guideline-concordant HCC screening practices were significantly more likely to have expertise in liver disease (MD, gastroenterologists or hepatologists), routinely screen for varices, prescribe HCV treatment, and refer or manage patients with liver transplant. The availability of HCC-specific treatments on site was the main facility factor associated with guideline-concordant HCC screening. CONCLUSIONS: Self-reported rates of guideline-concordant HCC screening are considerably higher than those seen in routine VA practice. Provider expertise in liver disease and the perceived availability of HCC treatment including transplantation in the local facility are important factors driving self-reported HCC screening practices.

Dietary intake of vegetables, folate, and antioxidants and the risk of Barrett's esophagus.

PURPOSE: Diet is a potentially modifiable risk factor for Barrett's esophagus (BE). We investigated the associations between intakes of fruits and vegetables and risk of BE. METHODS: We identified study subjects from 1,859 participants who underwent the endoscopy in a single VA Medical Center in the US between 2008 and 2011. Dietary intake in the previous year was elicited using a self-administered Block food frequency questionnaire (FFQ). Logistic regression model was used to estimate odds ratio (OR) and its 95 % confidence interval (CI) for BE. RESULTS: A total of 151 cases with definite BE and 777 controls completed the FFQ. When highest tertile of intake was compared with the lowest, the OR (95 % CI) was 0.46 (0.26-0.81) for dark green vegetables, 0.52 (0.30-0.90) for legumes, 0.50 (0.28-0.90) for total fiber, 0.45 (0.25-0.81) for isoflavones, 0.52 (0.30-0.67) for total folate, and 0.45 (0.26-0.79) for lutein, adjusting for multiple confounding factors including use of aspirin or proton pump inhibitor, gastro-esophageal reflux symptoms, and physical activity. The association for dark green vegetables was attenuated after adjustment for lutein, total fiber, and total folate (OR = 0.82; 95 % CI 0.30-2.22). CONCLUSION: Higher intake of dark green vegetables was associated with a decreased risk of BE in a veteran population. Such an inverse association may be partially mediated by lutein, fiber, and folate. The novel findings on the association between intake of lutein, total folate, or isoflavones and risk of BE need further confirmation.

Waist-to-hip ratio, but not body mass index, is associated with an increased risk of Barrett's esophagus in white men.

BACKGROUND & AIMS: Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD) and also might contribute to the development of Barrett's esophagus (BE), although results are inconsistent. We examined the effects of waist-to-hip ratio (WHR) and body mass index (BMI) on the risk of BE and investigated whether race, GERD symptoms, or hiatus hernia were involved. METHODS: We conducted a case-control study using data from eligible patients who underwent elective esophagogastroduodenoscopy; 237 patients had BE and the other 1021 patients served as endoscopy controls. We also analyzed data and tissue samples from enrolled patients who were eligible for screening colonoscopies at a primary care clinic (colonoscopy controls, n = 479). All patients underwent esophagogastroduodenoscopy, completed a survey, and had anthropometric measurements taken. WHR was categorized as high if it was 0.9 or greater for men or 0.85 or greater for women. Data were analyzed with logistic regression. RESULTS: There was no association between BMI and BE. However, more patients with BE had a high WHR (92.4%) than endoscopy controls (79.5%) or colonoscopy controls (84.6%) (P < .001 and P = .008, respectively). In adjusted analysis, patients with BE were 2-fold more likely to have a high WHR than endoscopy controls (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.1-3.5), this association was stronger for patients with long-segment BE (OR, 2.81; 95% CI, 1.0-7.9). A high WHR was associated significantly with BE only in whites (OR, 2.5; 95% CI, 1.2-5.4), but not in blacks or Hispanics. GERD symptoms, hiatus hernia, or gastroesophageal valve flap grade could not account for the association. CONCLUSIONS: High WHR, but not BMI, is associated with a significant increase in the risk of BE, especially long-segment BE and in whites. The association is not caused by GERD symptoms or hiatus hernia.

Helicobacter pylori-negative gastritis: prevalence and risk factors.

OBJECTIVES: Recent studies using histology alone in select patients have suggested that Helicobacter pylori-negative gastritis may be common. The objective of this study was to investigate the prevalence of H. pylori among individuals with histologic gastritis. METHODS: Subjects between 40 and 80 years underwent elective esophagogastroduodenoscopy at a VA Medical Center. Gastric biopsies were mapped from seven prespecified sites (two antrum, four corpus, and one cardia) and graded by two gastrointestinal pathologists, using the Updated Sydney System. H. pylori-negative required four criteria: negative triple staining at all seven gastric sites, negative H. pylori culture, negative IgG H. pylori serology, and no previous treatment for H. pylori. Data regarding tobacco smoking, alcohol drinking, nonsteroidal anti-inflammatory drug, and proton pump inhibitor (PPI) use were obtained by questionnaire. RESULTS: Of the 491 individuals enrolled, 40.7% (200) had gastritis of at least grade 2 in at least one biopsy site or grade 1 in at least two sites. Forty-one (20.5%) had H. pylori-negative gastritis; most (30 or 73.2%) had chronic gastritis, five (12.2%) had active gastritis, and six (14.6%) had both. H. pylori-negative gastritis was approximately equally distributed in the antrum, corpus, and both antrum and corpus. Past and current PPI use was more frequent in H. pylori-negative vs. H. pylori-positive gastritis (68.2% and 53.8%; P=0.06). CONCLUSIONS: We used multiple methods to define non-H. pylori gastritis and found it in 21% of patients with histologic gastritis. While PPI use is a potential risk factor, the cause or implications of this entity are not known.

Plasma soluble receptor for advanced glycation end-products and risk of colorectal adenoma.

Receptor for advanced glycation end products (RAGE) plays an important role in promoting chronic inflammation with activation of NF-κB. Soluble form of RAGE (sRAGE) represents a naturally occurring competitive inhibitor of RAGE-mediated events. In a colonoscopy-based case-control study, we examined the associations of plasma levels of sRAGE, sTNF-αRI, sTNF-αRII, sIL-6R, EGF, IFNα2, G-CSF, MCP1, TNFß, and VEGF with risk of colorectal adenoma. We prospectively identified 158 cases with colorectal adenoma and 203 polyp-free controls who were frequency-matched according to age, sex, race, and time of blood draw. Exposure information was collected using a questionnaire and fasting plasma samples were obtained before the colonoscopy. We used Luminex bead-based multiplex assays to determine level of biomarkers. Multivariate logistic regression model was used to estimate odds ratio (OR) and its 95% confidence interval (CI). Cases had insignificant lower levels of sRAGE, and higher levels of EGF and VEGF than controls. When the highest compared with the lowest category, the OR (95% CI) of colorectal adenoma was 0.55 (0.31-0.96) (P trend = 0.03) for sRAGE and 1.75 (1.05-2.93) (P trend =0.04) for VEGF, adjusting for age, smoking status, hypertension and type 2 diabetes. The inverse association between sRAGE and colorectal adenoma was seen only among those without hypertension (P interaction = 0.02). An inverse association between sRAGE and colorectal adenoma was in line with an inverse association between sRAGE and colorectal cancer previously reported. This study supported the involvement of RAGE-NF-kB related inflammatory mechanism in the formation of colorectal adenoma.

Prevalence of colorectal polyps in pediatric colonoscopy.

BACKGROUND: The available data regarding the prevalence, types, and clinical determinants of colonic polyps in children is limited. AIMS: We aimed to estimate the prevalence of colorectal polyps in a large cohort of children. METHODS: We conducted a cross-sectional study to determine the presence, number, and location of colorectal polyps reported in all children (0-20 years) who underwent colonoscopy at 14 pediatric facilities between January 2000 and December 2007 recorded in Pediatric Endoscopy Database System Clinical Outcomes Research Initiative (PEDS-CORI). We compared procedures with and without polyps with respect to procedure indication, age, sex, and race. We also reviewed a sample of histopathologic reports from one participating center. RESULTS: We analyzed 13,115 colonoscopy procedures performed in 11,637 patients. Colorectal polyps were reported in 810 procedures (6.1%; 95% CI: 5.7-6.5%) performed in 705 patients, and in 12% of patients with lower GI bleeding. Children with colorectal polyps were significantly younger (8.9 years vs. 11.9 years; p < 0.0001), male (58.3% vs. 49.0%; p < 0.001), non-white race (27.5% vs. 21.9%; p < 0.001), and had lower GI bleeding (54.4% vs. 26.6%; p < 0.001) as compared to children without polyps. In a sample of 122 patients with polyps from a single center, the histological types were solitary juvenile in 91 (70.5%), multiple juvenile in 20 (15.5%), adenoma in 14 (10.9%) and hyperplastic polyps in four patients (3.1%). CONCLUSIONS: Colorectal polyps are detected in 6.1% overall and in 12.0% among those with lower gastrointestinal bleeding during pediatric colonoscopy. Approximately 26% are multiple juvenile or adenoma.