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3.  Serrated Colon Polyps as Precursors to Colorectal Cancer 
Identification of the serrated neoplasia pathway has improved our understanding of the pathogenesis of colorectal cancer (CRC). Insights have included an increased recognition of the malignant potential of different types of serrated polyps, such as sessile and traditional serrated adenomas. Sessile serrated adenomas share molecular features with colon tumors, such as microsatellite instability and a methylator phenotype, indicating that these lesions are precursors that progress via the serrated neoplasia pathway. There is evidence that the serrated pathway contributes to interval or missed cancers. These data have important implications for clinical practice and CRC prevention, since hyperplastic polyps were previously regarded as having no malignant potential. Endoscopic detection of serrated polyps is a challenge because they are often inconspicuous with indistinct margins, and are frequently covered by adherent mucus. It is important for gastroenterologists to recognize the subtle endoscopic features of serrated polyps, which would facilitate their detection and removal, to ensure a high-quality colonoscopy examination. Recognition of the role of serrated polyps in colon carcinogenesis has led to the inclusion of these lesions in post-polypectomy surveillance guidelines. However, an enhanced effort is needed to identify and completely remove serrated adenomas, with the goal of increasing the effectiveness of colonoscopy to reduce CRC incidence.
doi:10.1016/j.cgh.2012.12.004
PMCID: PMC3628288  PMID: 23267866
Serrated Polyps; Sessile Serrated Adenomas; Serrated Polyposis Syndrome; Colon Cancer
5.  Association Between Celiac Disease and Iron Deficiency in Caucasians, but not Non-Caucasians 
Background & Aims
Celiac disease is an increasingly recognized disorder in Caucasian populations of European origin. Little is known about its prevalence in non-Caucasians. Although it is thought to be a cause of iron deficiency anemia, little is known about the extent to which celiac disease contributes to iron deficiency in Caucasians, and especially non-Caucasians. We analyzed samples collected from participants in the Hemochromatosis and Iron Overload Screening (HEIRS) study to identify individuals with iron deficiency and assess the frequency of celiac disease.
METHODS
We analyzed serum samples from white men (25 y old or older) and women (50 y old or older) who participated the HEIRS study; cases were defined as individuals with iron deficiency (serum level of ferritin ≤12 mg/L) and controls were those without (serum level of ferritin >100 mg/L in men and >50 mg/L in women). All samples were also analyzed for human recombinant tissue transglutaminase immunoglobulin A; positive results were confirmed by an assay for endomysial antibodies. Patients with positive results from both celiac disease tests were presumed to have untreated celiac disease, and those with a positive result from only 1 test were excluded from analysis. We analyzed HLA genotypes and frequencies of celiac disease between Caucasians and non-Caucasians with iron deficiency.
RESULTS
Celiac disease occurred in 14 of 567 of cases (2.5%) and in only 1 of 1136 controls (0.1%; Fisher’s exact test, P=1.92 × 10−6). Celiac disease was more common in Caucasian cases (14/363, 4%) than non-Caucasian cases (0/204; P=.003). Only 1 Caucasian control and no non-Caucasian controls had celiac disease. The odds of celiac disease in individuals with iron deficiency was 28-fold (95% confidence interval, 3.7–212.8) that of controls; 13/14 cases with celiac disease carried the DQ2.5 variant of the HLA genotype.
CONCLUSIONS
Celiac disease is associated with iron deficiency of Caucasians. Celiac disease is rare among non-Caucasians—even among individuals with features of celiac disease, such as iron deficiency. Celiac disease is also rare among individuals without iron deficiency. Men and post-menopausal women with iron deficiency should be tested for celiac disease.
doi:10.1016/j.cgh.2013.02.009
PMCID: PMC3843318  PMID: 23416278
SNP; risk factor; gluten allergy; intestine; absorption
7.  Factors Associated with Outcomes and Response to Therapy in Patients with Infiltrative Hepatocellular Carcinoma 
Background & Aims
Infiltrative hepatocellular carcinoma (iHCC) is characterized by its indistinct borders and lack of a typical pattern of contrast enhancement. There are few published data on iHCC. We assessed outcomes, effects of treatment, and prognostic factors in a large cohort of patients with iHCC.
Methods
We analyzed data from 155 patients (median age 60 years; 79% male; median level of α-fetoprotein [AFP] 347 ng/mL; median model for end-stage liver disease score [MELD] 13) with iHCC, based on contrast-enhanced computed tomography or magnetic resonance imaging, from 2002 to 2010 at the University of California, San Francisco Medical Center. All imaging study results were independently reviewed by 2 investigators.
Results
Most of the patients had tumors of Barcelona Clinic Liver Cancer stage C (70%) or D (22%). The median maximum tumor diameter was 11.3 cm; 41% of lesions were hypovascular, 82% had macrovascular invasion, and 52% had extra-hepatic metastases. Median survival was 4.0 months, and rates of survival at 6 and 12 months were 30% and 10%, respectively. On multivariate analysis, predictors of 6-month mortality were Child-Pugh class B or C cirrhosis; lack of tumor-directed therapy with chemoembolization (TACE), radiofrequency ablation, or sorafenib; AFP level >1000 ng/mL; female sex; MELD score; and maximum tumor diameter. The percentages of patients surviving 6 and 12 months were 17% and 2% for those that received no therapy (n=109), 73% and 36% for those that received sorafenib (n=11), and 45% and 17% for those that that received TACE (n=18) (all P values <.01).
Conclusions
iHCC is a radiographically distinct and advanced form of HCC with a poor prognosis. Therapy with TACE or sorafenib appears to prolong survival and requires further investigation.
doi:10.1016/j.cgh.2012.12.030
PMCID: PMC4052891  PMID: 23333661
RFA; liver cancer; prognosis; predictors of outcome
8.  Mutant TP53 in Duodenal Samples of Pancreatic Juice from Patients with Pancreatic Cancer or High-Grade Dysplasia 
Background & Aims
Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated wither mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer.
Methods
We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls.
Results
TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2/22), 17.8% of PanIN-2 (8/45), 38.1% of high-grade IPMNs (8/21), 47.6% of PanIN-3(10/21), and 75% of invasive pancreatic adenocarcinomas (15/20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29/43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52−0.80) and 4/8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions.
Conclusion
We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dyplasia.
clinicaltrials.gov (NCT00438906, NCT00714701)
doi:10.1016/j.cgh.2012.11.016
PMCID: PMC3600161  PMID: 23200980
Pancreatic cancer; pancreatic intraepithelial neoplasm; intraductal papillary mucinous neoplasm; pancreatic juice; TP53; mutation; secretin; tumor; biomarker; diagnostic; early detection
9.  Cost-Effectiveness of Universal Serological Screening to Prevent Non-Traumatic Hip and Vertebral Fractures in Patients with Celiac Disease 
Background & Aims
Patients with asymptomatic or poorly managed celiac disease can experience bone loss, placing them at risk for hip and vertebral fractures. We analyzed the cost-effectiveness of universal serologic screening (USS) vs symptomatic at-risk screening (SAS) strategies for celiac disease, given the risk of non-traumatic hip and vertebral fractures if untreated or undiagnosed.
Method
We developed a lifetime Markov model of the screening strategies, each with male or female cohorts of 1000 patients, 12 years old when screening began. We screened serum samples for levels of immunoglobulin A (IgA), compared with tissue transglutaminase and total IgA, and findings were confirmed by mucosal biopsy. Transition probabilities and quality of life estimates were obtained from the literature. We used generalizable cost estimates and Medicare reimbursement rates, and ran deterministic and probabilistic sensitivity analyses.
Result
For men, the average life-time costs were $8532 and $8472 for USS and SAS strategies, respectively, corresponding to average quality adjusted life years (QALY) gains of 25.511 and 25.515. Similarly, for women, costs were $11,383 and $11,328 for USS and SAS strategies, corresponding to QALY gains of 25.74 and 25.75. Compared to the current standard of care (SAS), USS produced higher average lifetime costs and lower quality of life for each sex. Deterministic and probabilistic sensitivity analyses showed that the model was robust to realistic changes in all the variables, making USS cost ineffective, based on these outcomes.
Conclusion
USS and SAS are similar in lifetime costs and quality of life, although the current SAS strategy was overall more cost effective in preventing bone loss and fractures among patients with undiagnosed or subclinical disease. Based on best available supportive evidence, it is more cost effective to maintain the standard celiac screening practices, although future robust population-based evidence in other health outcomes could be leveraged to re-evaluate current screening guidelines.
doi:10.1016/j.cgh.2012.12.037
PMCID: PMC3655158  PMID: 23357490
tTG IgA; cost-benefit; cost-utility; bone health; detection; diagnosis
10.  Safety and Efficacy of Endoscopic Mucosal Therapy with Radiofrequency Ablation for Patients with Neoplastic Barrett’s Esophagus 
Background& Aims
The goal of radiofrequency ablation (RFA) for patients with Barrett’s esophagus (BE) is to eliminate dysplasia and metaplasia. The efficacy and safety of RFA for patients with BE and neoplasia are incompletely characterized.
Methods
We performed a retrospective study of 244 patients treated with RFA for BE with dysplasia or intramucosal carcinoma. Efficacy outcomes were complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia (CED), total treatments, and RFA sessions. Safety outcomes included death, perforation, stricture, bleeding, and hospitalization. We identified factors associated with incomplete EIM and stricture formation.
Results
CEIM was achieved in 80% of the patients, and CED in 87%; disease progressed in 4 patients. A higher percentage of patients with incomplete EIM were female (40%) than those with CEIM (20%, P=.045); patients with incomplete EIM also had a longer segment of BE (5.5 vs 4.0 cm, P=.03), incomplete healing between treatment sessions (45% vs 15%, P=0.004), and underwent more treatment sessions (4 vs 3, P=.007). Incomplete healing was independently associated with incomplete EIM. Twenty-three patients (9.4%) had a treatment-related complication during 777 treatment sessions (3.0%), including strictures (8.2%), post-procedural hemorrhages (1.6%), and hospitalizations (1.6%). Patients that developed strictures were more likely to use non-steroidal anti-inflammatory drugs (NSAID) than those without strictures (70% vs 45%, P=.04), have undergone antireflux surgery (15% vs 3%, P=.04), or had erosive esophagitis (35% vs 12%, P=.01).
Conclusions
RFA is highly effective and safe for treatment of BE with dysplasia or early-stage cancer. Strictures were the most common complications. Incomplete healing between treatment sessions was associated with incomplete EIM. NSAID use, prior anti-reflux surgery, and a history of erosive esophagitis predicted stricture formation.
doi:10.1016/j.cgh.2012.10.028
PMCID: PMC3660497  PMID: 23103824
Barrett’s esophagus; radiofrequency ablation; esophageal cancer; epidemiology
11.  Statins Are Associated with Reduced Risk of Esophageal Cancer, Particularly in Patients with Barrett’s Esophagus: A Systematic Review and Meta-Analysis 
Background & Aims
Esophageal cancer is increasing in incidence in US, especially among patients with Barrett’s esophagus (BE). Statins might prevent this cancer. We performed a systematic review with meta-analysis of studies that evaluated the effect of statins on the risk of esophageal cancer.
Methods
We conducted a systematic search of Medline, Embase, and Web of Science through August 2012. Studies were included if they evaluated exposure to statins, reported the development of esophageal cancer, and reported relative risks or odds ratios (ORs), or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random-effects model. The analysis included 13 studies (including a post-hoc analysis of 22 randomized controlled trials) reporting 9285 cases of esophageal cancer among 1,132,969 patients.
Results
Meta-analysis of the studies showed a significant (28%) reduction in incidence of esophageal cancer among patients who took statins (adjusted OR, 0.72; 95% CI, 0.60–0.86), though there was considerable heterogeneity among studies. In analyzing a subset of patients known to have BE (5 studies, 312 esophageal adenocarcinomas [EAC] developed in 2125 patients), statins were associated with a significant (41%) decrease in the risk of EAC, after adjusting for potential confounders (adjusted OR, 0.59; 95% CI, 0.45–0.78) with consistent results among all studies. The number needed to treat with statins to prevent 1 case of EAC in patients with BE was 389.
Conclusions
Meta-analysis of existing observational studies indicates that statins protect against esophageal cancer and reduce the risk of EAC in patients with BE.
doi:10.1016/j.cgh.2012.12.036
PMCID: PMC3660516  PMID: 23357487
Esophageal cancer risk; cholesterol-lowering drugs; HMG CoA reductase inhibitors; chemoprevention
12.  Chemoembolization and Radioembolization for Hepatocellular Carcinoma 
Hepatocellular carcinoma (HCC) continues to represent a major worldwide problem. While treatments such as resection, transplantation and ablation may provide a chance for cure, these options are often precluded because of advanced disease presentation. Palliative treatments include transarterial embolization and systemic therapies. This review will summarize the state of the science for embolic therapies in HCC (conventional and drug-eluting chemoembolization, radioembolization), as well as discuss related topics including HCC staging, assessment of response and ongoing clinical trials.
doi:10.1016/j.cgh.2012.12.039
PMCID: PMC3800021  PMID: 23357493
hepatocellular carcinoma; chemoembolization; radioembolization
14.  NATURAL LANGUAGE PROCESSING ACCURATELY CATEGORIZES FINDINGS FROM COLONOSCOPY AND PATHOLOGY REPORTS 
Background & Aims
Little is known about the ability of natural language processing (NLP) to extract meaningful information from free text gastroenterology reports for secondary use.
Methods
We randomly selected 500 linked colonoscopy and pathology reports from 10,798 non-surveillance colonoscopies to train and test the NLP system. Using annotation by gastroenterologists as the reference standard, we assessed the accuracy of an open-source NLP engine that processed and extracted clinically relevant concepts. The primary outcome was the highest level of pathology. Secondary outcomes were: location of the most advanced lesion, largest size of an adenoma removed, and number of adenomas removed.
Results
The NLP system identified the highest level of pathology with 98% accuracy, compared with triplicate annotation by gastroenterologists (the standard). Accuracy values for location, size, and number were 97%, 96%, and 84%, respectively.
Conclusions
The NLP can extract specific meaningful concepts with 98% accuracy. It might be developed as a method to further quantify specific quality metrics.
doi:10.1016/j.cgh.2012.11.035
PMCID: PMC4026927  PMID: 23313839
adenoma detection rate; colon cancer screening; software; computerized; natural language procession; colonoscopy; gastroenterology; adenoma detection rate; medical informatics
16.  Liver Injury From Tumor Necrosis Factor-α Antagonists: Analysis of Thirty-four Cases 
BACKGROUND & AIMS
Tumor necrosis factor (TNF)-α antagonists have been associated with drug-induced liver injury (DILI). We reviewed cases of DILI in the United States to identify those associated with use of TNF-α antagonists.
METHODS
We searched the U.S. DILI Network (DILIN) database, from 2003 to 2011, for cases associated with TNF-α antagonists. Mean Roussel-Uclaf Causality Assessment Method scores were calculated. A DILIN severity score was assigned according to a previously published scale, and we identified 6 subjects likely to have DILI associated with use of TNF-α antagonists. We also searched PubMed for articles that reported hepatotoxicity from TNF-α antagonists, identifying 28 additional cases suitable for analysis.
RESULTS
The drugs presumed to have caused DILI were infliximab (n = 26), etanercept (n = 4), and adalimumab (n = 4). The anti–TNF-α agent was the probable cause of 12 cases of DILI (35%), a very likely cause for 21 (62%), and a definite cause for 1 (3%). Median latency was 13 weeks (range, 2–104); however, 7 cases (20%) had latency periods longer than 24 weeks. Twenty-two of 33 subjects who underwent serologic analysis (67%) tested positive for anti-nuclear and/or smooth muscle antibodies. Of these 22, 17 underwent liver biopsy; 15 subjects had clear features of autoimmunity. The 22 subjects with autoimmune features had longer median latency (16 vs 10 weeks) and higher peak levels of alanine aminotransferase (784 vs 528 U/L) than the 12 without such features. There was 1 case of severe cholestasis. All but one subject improved after discontinuation of the implicated drug; 12 subjects received corticosteroid therapy. No deaths were attributed to liver injury, although one patient with preexistent cirrhosis required liver transplantation.
CONCLUSIONS
Acute liver injury caused by TNF-α antagonists may be a class effect because multiple agents in this category have been implicated. The most common presentation is an autoimmune phenotype with marked hepatocellular injury, but a mixed non-autoimmune pattern or predominant cholestasis also occurs. The prognosis is usually good after drug discontinuation, although some patients may benefit from a course of corticosteroids. ClinicalTrials.gov: Number, NCT00345930
doi:10.1016/j.cgh.2012.12.025
PMCID: PMC3865702  PMID: 23333219
Drug-Induced Liver Injury; Tumor Necrosis Factor; TNF-α Antagonists; Hepatotoxicity; Autoimmunity
17.  Rural vs Urban Residence Affects Risk-Appropriate Colorectal Cancer Screening 
Background & Aims
Little is known about the effects of geographic factors, such as rural vs urban residence and travel time to colonoscopy providers, on risk-appropriate use of colorectal cancer (CRC) screening in the general population. We evaluated the effects of geographic factors on adherence to CRC screening and differences in screening use among familial risk groups.
Methods
We analyzed data from the 2010 Utah Behavior Risk Factor Surveillance System, which included state-added questions on familial CRC. Using multiple logistic regression models, we assessed the effects of rural vs urban residence, travel time to the nearest colonoscopy provider, and spatial accessibility of providers on adherence to risk-appropriate screening guidelines. Study participants (n=4260) were respondents 50–75 years old.
Results
Sixty-six percent of the sample adhered to risk-appropriate CRC screening guidelines, with significant differences between urban and rural residents (68% vs 57%, respectively; P<.001) across all familial risk groups. Rural residents were less likely than urban dwellers to be up-to-date with screening guidelines (multivariate odds ratio=0.65; 95% confidence interval [CI], 0.53–0.79). In the unadjusted analysis, rural vs urban residence (P<.001), travel time to the nearest colonoscopy provider (P=.003), and spatial accessibility of providers (P=.012) were significantly associated with adherence to screening guidelines. However, rural vs urban residence (P<.001) was the only geographic variable independently associated with screening adherence in the adjusted analyses.
Conclusion
There are marked disparities in use of risk-appropriate CRC screening between rural and urban residents in Utah. Differences in travel time to the nearest colonoscopy provider and spatial accessibility of providers did not account for the geographic variations observed in screening adherence.
doi:10.1016/j.cgh.2012.11.025
PMCID: PMC3615111  PMID: 23220166
travel time; health disparities; geography
19.  A point-of-care paper-based fingerstick transaminase test: towards low-cost “lab-on-a-chip” technology for the developing world 
There is currently great need for high-quality, low-cost, point-of-care diagnostics that can benefit patients in resource-limited settings, and correspondingly growing interest in the diagnostic utility of microfluidic platforms based on paper. We describe the development, early clinical testing, and potential clinical impact of a novel paper-based, multiplexed microfluidic assay designed for rapid, semi-quantitative measurement of AST and ALT in a fingerstick specimen. This device ultimately holds promise for providing universal access to affordable point-of-care screening for drug-induced liver injury in resource-limited settings, and opens the door to development of similar point-of-care clinical assays for other important analytes.
doi:10.1016/j.cgh.2013.02.022
PMCID: PMC3646590  PMID: 23466712
20.  The Stool DNA Test is More Accurate than the Plasma Septin 9 Test in Detecting Colorectal Neoplasia 
Background & Aims
Several noninvasive tests have been developed for colorectal cancer (CRC) screening. We compared the sensitivities of a multi-marker test for stool DNA (sDNA) and a plasma test for methylated Septin 9 (SEPT9) in identifying patients with large adenomas or CRC.
Methods
We analyzed paired stool and plasma samples from 30 patients with CRC and 22 with large adenomas from Mayo Clinic archives. Stool (n=46) and plasma (n=49) samples from age- and sex-matched patients with normal colonoscopy results were used as controls. The sDNA test is an assay for methylated BMP3, NDRG4, vimentin, and TFPI2; mutant KRAS; the β-actin gene, and quantity of hemoglobin (by the porphyrin method). It was performed blindly at Exact Sciences (Madison WI); the test for SEPT9 was performed at ARUP Laboratories (Salt Lake City UT). Results were considered positive based on the manufacturer's specificity cutoff values of 90% and 89%, respectively.
Results
The sDNA test detected adenomas (median 2 cm, range 1–5 cm) with 82% sensitivity (95% confidence interval [CI], 60%–95%); SEPT9 had 14% sensitivity (95% CI, 3%–35%; P=.0001). The sDNA test identified patients with CRC with 87% sensitivity (95% CI, 69%–96%); SEPT9 had 60% sensitivity (95% CI, 41%–77%; P=.046). The sDNA test identified patients with stage I–III CRC with 91% sensitivity (95% CI, 71%–99%); SEPT9 had 50% sensitivity (95% CI, 28%–72%; P=.013); for stage IV CRC, sensitivity values were 75% (95% CI, 35%–97%) and 88% (95% CI, 47%–100%), respectively (P=.56). False-positive rates were 7% for the sDNA test and 27% for SEPT9.
Conclusions
Based on analyses of paired samples, the sDNA test detects non-metastatic CRC and large adenomas with significantly greater levels of sensitivity than the SEPT9 test. These findings might be used to modify approaches for CRC prevention and early detection.
doi:10.1016/j.cgh.2011.10.008
PMCID: PMC3980432  PMID: 22019796
colon cancer; early detection; marker; genetics; Plasma Septin 9; Stool DNA; colorectal cancer; adenoma detection
21.  Association between Sex Hormones and Colorectal Cancer Risk in Men and Women 
Background & Aims
There is observational and clinical evidence that indicate that sex hormones affect development of colorectal cancer (CRC) in men and women. However, the relationship between endogenous sex hormone levels and CRC is unclear.
Methods
We collected data on lifestyle, medical history, and diet etc. (through 2008), along with blood samples, from the Nurses’ Health Study, the Women’s Health Study, the Health Professional Follow-Up Study, and the Physicians’ Health Study II. We measured plasma levels of estrone, estradiol, testosterone, sex hormone binding globulin (SHBG), and c-peptide among 730 women (293 cases of CRC and 437 healthy individuals, as controls) and 1158 men (439 CRC cases and 719 controls), and used unconditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were 2-sided.
Results
Total testosterone, SHBG, and the ratio of estradiol to testosterone were associated with CRC in men after adjustments for matching and risk factors for CRC, including BMI and plasma levels of C-peptide. The RRs in the highest relative to the lowest quartile were 0.62 for testosterone (95% CI, 0.40–0.96), 0.65 for SHBG (95% CI, 0.42−0.99), and 2.63 for the ratio (95% CI, 1.58–4.36) (P-values for trend ≤0.02). However, in women, only the ratio of estradiol to testosterone was (inversely) associated with CRC after adjustments for all factors (RR, 0.43; 95% CI, 0.22−0.84; P-value for trend, .03).
Conclusions
Based on combined data from 4 population studies, there appears to be an association between levels of sex hormones and CRC risk in men. There also appears to be an inverse association between the ratio of estradiol to testosterone and CRC in postmenopausal women.
doi:10.1016/j.cgh.2012.11.012
PMCID: PMC3594467  PMID: 23200979
estrogen; incidence; colorectal cancer; testosterone
22.  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 might also contribute to 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 (EGD); 237 had BE and the other 1021 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 EGD, completed a survey, and had anthropometric measurements taken. WHR was categorized as high if was ≥0.9 for men and ≥0.85 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 significantly associated with BE only in Whites (OR=2.5; 95% CI, 1.2–5.4)—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 due to GERD symptoms or hiatus hernia.
doi:10.1016/j.cgh.2012.11.028
PMCID: PMC3606681  PMID: 23220167
visceral obesity; epidemiological study; Veterans Affairs; risk factorss
23.  Hepatitis C and Non-Hodgkin Lymphoma Among 4784 Cases and 6269 Controls From the International Lymphoma Epidemiology Consortium 
Background & Aims
Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin’s lymphoma (NHL) subtypes after HCV infection.
Methods
The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded.
Results
HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40–2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44–4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68–2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14–5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65–1.60).
Conclusions
These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).
doi:10.1016/j.cgh.2008.02.011
PMCID: PMC3962672  PMID: 18387498
24.  Variation of Adenoma Prevalence by Age, Sex, Race, and Colon Location in a Large Population: Implications for Screening and Quality Programs 
Background & Aims
Reliable community-based colorectal adenoma prevalence estimates are needed to inform colonoscopy quality standards and to estimate patient colorectal cancer risks; however, minimal data exist from populations with large numbers of diverse patients and examiners.
Methods
We evaluated the prevalence of adenomas detected by sex, age, race/ethnicity, and colon location among 20,792 Kaiser Permanente Northern California members ≥50 years of age who received a screening colonoscopy exam (102 gastroenterologists, years 2006-2008).
Results
Prevalence of detected adenomas increased more rapidly with age in the proximal colon (adjusted odds ratio [OR] = 2.39; 95% confidence interval [CI]: 2.05-2.80; 70-74 vs. 50-54 years) than in the distal colon (OR=1.89; 95% CI: 1.63-2.19). Prevalence was higher among men vs. women at all ages (OR=1.77; 95% CI: 1.66-1.89), increasing in men from 25% to 39% at ≥70 years and in women from 15% at 50-54 years to 26 % (P<0.001). Proximal adenoma prevalence was higher among blacks than whites (OR=1.26; CI: 1.04-1.54); although total prevalence was similar, including for persons <60 years old (OR=1.17; 95% CI: 0.91-1.50).
Conclusions
Prevalence of detected adenomas increases substantially with age and is much higher in men; proximal adenomas are more common among blacks than whites, although the total prevalence and the prevalence for ages <60 years were similar by race. These demographic differences are such that current adenoma detection guidelines may not be valid, without adjustment, for comparing providers serving different populations. The variation in prevalence and location may also have implications for the effectiveness of screening methods in different demographic groups.
doi:10.1016/j.cgh.2012.09.010
PMCID: PMC3954741  PMID: 22985608
adenoma/diagnosis; colonic neoplasms/diagnosis; polyps/diagnosis; colonoscopy/methods; colonoscopy/standards
25.  Cirrhosis is Present in Most Patients with Hepatitis B and Hepatocellular Carcinoma 
Background& Aims
There is not much data available about the prevalence or effects of cirrhosis in patients with hepatocellular carcinoma (HCC) from viral hepatitis. We compared patients with HCC and hepatitis B virus (HBV) or hepatitis C virus (HCV) infections to determine the proportions of cirrhosis in each group, virologic and tumor characteristics, and overall survival.
Methods
This analysis includes patients with HBV (n=64) or HCV (n=118) infection who were diagnosed with HCC at the Mayo Clinic in Rochester MN from 1994 to 2008; groups were matched for age and sex. The diagnosis of cirrhosis was based on histology and, if histologic information was insufficient or unavailable, clinical indicators that included ascites or varices, thrombocytopenia or splenomegaly, and radiographic configuration of cirrhosis. Virologic characteristics, tumor stage, and patient survival were also assessed.
Results
The prevalence of histologic cirrhosis was 88% among patients with HBV infection and 93% among those with HCV infection (P=0.46). When the most inclusive criteria for cirrhosis were applied, cirrhosis was present in 94% of patients with HBV and 97% with HCV (P=0.24). Among HCV patients, 5.2% were negative for HCV RNA following antiviral treatment; 63.4% of HBV patients had HBV DNA < 2000 u/ml with or without treatment. Patients with HBV tended to have less surveillance and more advanced stages of HCC, without differences in survival from those with HCV infection (P=0.75).
Conclusion
Most patients with HCC and chronic viral hepatitis had evidence of cirrhosis, including those with HBV infection and those without active viral replication.
doi:10.1016/j.cgh.2010.08.019
PMCID: PMC3951426  PMID: 20831903
Liver cancer; liver disease; virology; survival

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