Andrew J. Gawron

Blood leukocyte DNA hypomethylation and gastric cancer risk in a high‐risk Polish population

Global hypomethylation has been shown to increase genome instability potentially leading to increased cancer risk. We determined whether global methylation in blood leukocyte DNA was associated with gastric cancer in a population‐based study on 302 gastric cancer cases and 421 age‐ and sex‐matched controls in Warsaw, Poland, between 1994 and 1996. Using PCR‐pyrosequencing, we analyzed methylation levels of Alu and LINE‐1, 2 CG‐rich repetitive elements, to measure global methylation levels. Gastric cancer risk was highest among those with lowest level of methylation in either Alu (OR = 1.3, 95% CI = 0.9–1.9) or LINE‐1 (OR = 1.4, 95% CI = 0.9–2.0) relative to those with the highest levels, although the trends were not statistically significant. For Alu, the association was stronger among those aged 70 or older (OR = 2.6, 95% CI = 1.3–5.5, p for interaction = 0.02). We did not observe meaningful differences in the associations by other risk factors and polymorphisms examined. For LINE‐1, the association tended to be stronger among individuals with a family history of cancer (OR = 3.1, 95% CI = 1.4–7.0, p for interaction = 0.01), current alcohol drinkers (OR = 1.9, 95% CI = 1.0–3.6, p for interaction = 0.05), current smokers (OR = 2.3, 95% CI = 1.1–4.6, p for interaction = 0.02), those who rarely or never consumed fruit (OR = 3.1, 95% CI = 1.2–8.1, p for interaction = 0.03), CC carriers for the MTRR Ex5+123C>T polymorphism (OR = 2.3, 95% CI = 1.2–4.4, p for interaction = 0.01) and TT carriers for the MTRR Ex15+572T>C polymorphism (OR = 1.7, 95% CI = 1.0–2.8, p for interaction = 0.06). The association was not different by sex, Helicobacter pylori infection, intake of folate, vitamin B6 and total protein and the remaining polymorphisms examined. Our results indicate that interactions between blood leukocyte DNA hypomethylation and host characteristics may determine gastric cancer risk.

Surrogate tissue telomere length and cancer risk: shorter or longer?

Telomeres play a critical role in chromosome stability. Telomere length (TL) shortening is a risk factor for cancers. Measuring TL in surrogate tissues that can be easily collected may provide a potential tool for early detection of cancers. A number of studies on surrogate tissue TL and cancer risks have been conducted and results are inconsistent, including positive, negative, or null associations. In this article, we reviewed the published data on surrogate tissue TL in relation to cancer risks, discussed the possible reasons for the differences in the results and future directions and challenges for this line of research.

Assessing Bolus Retention in Achalasia Using High-Resolution Manometry With Impedance: A Comparator Study With Timed Barium Esophagram

OBJECTIVES:The aim of this study was to assess whether high-resolution impedance manometry (HRIM) could be used to assess bolus retention similar to the timed barium esophagram (TBE).METHODS:Twenty achalasia patients (10 males, aged 21–79 years) were prospectively evaluated with HRIM and TBE to determine the correlation between barium column height and the impedance bolus height (IBH). The TBE protocol used a 200-ml barium challenge and the HRIM protocol used a 200-ml saline challenge protocol. Both protocols were performed in an upright position and the heights of the barium and impedance columns were measured at 1 and 5 min. Analysis of IBH was performed with a topographic technique and a spatial impedance variation plot.RESULTS:There was no significant difference between the median IBH and barium column at 1 min (IBH: 12.0 cm (interquartile range (IQR), 8.0–18.0); TBE: 12.0 cm (IQR, 7.0–19.0); P=0.90) or at 5 min (IBH: 11.0 cm (IQR, 1.0–17.0); TBE: 9.0 cm (IQR, 4.0–12.0); P=0.47). In addition, the correlation between the two measurements at 1 and 5 min was 0.60 and 0.86, respectively. Using a barium column or impedance height of >5.0 as a definition of bolus retention was associated with 75% concordance at 1 min and 95% concordance at 5 min.CONCLUSIONS:There was excellent agreement between TBE and high-resolution impedance manometry (HRIM) for assessing bolus retention at 5 min. Thus, HRM with impedance may be used as a single test to assess bolus retention and motor function in the management of achalasia.

Patient Factors That Affect Quality of Colonoscopy Preparation

BACKGROUND & AIMS Optimal colonoscopy preparation requires patients to adhere to written instructions and be activated to complete the task. Among patients with chronic disease, health literacy and patient activation have been associated with outcome, but these factors have not been studied for colonoscopy. We examined the association between health literacy, patient activation, and quality of bowel preparation. METHODS We analyzed outpatient colonoscopy results from 462 adults, 55-74 years old (mean, 62 ± 6 years), who previously completed extensive neurocognitive assessments as part of a prospective study (Health Literacy and Cognitive Function in Older Adults). We collected information on cecal intubation, polyp detection, bowel preparation quality, and histopathology. RESULTS One-third of the patients (n = 134) had suboptimal quality of bowel preparation; 15% (n = 62) had fair quality, and 17% (n = 72) had poor quality. Limited health literacy was associated with a lower level of education (P < .001), diabetes (P < .001), and a higher number of chronic conditions (P < .001), but not quality of colonoscopy preparation. No baseline characteristics were associated with patient activation. In multivariable analysis, after adjusting for demographics and clinical characteristics, diabetes (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.14-5.25) and patient activation (OR, 2.12; 95% CI, 1.30-3.45) were independent predictors of suboptimal bowel preparation quality, but limited health literacy was not (OR, 0.76; 95% CI, 0.38-1.52). CONCLUSIONS We investigated the relationship between health literacy, patient activation, and colonoscopy preparation quality. Lower patient activation was an independent predictor of suboptimal bowel preparation quality. Interventions to improve colonoscopy preparation quality should consider the importance of patient activation within their design.

A Cost-efficacy Decision Analysis of Prophylactic Clip Placement After Endoscopic Removal of Large Polyps

BACKGROUND & AIMS Delayed bleeding after lower endoscopy and polypectomy can cause significant morbidity. One strategy to reduce bleeding is to place an endoscopic clip on the polypectomy site. We used decision analysis to investigate the cost-effectiveness of routine clip placement after colon polypectomy. METHODS Probabilities and plausible ranges were obtained from the literature, and a decision analysis was conducted by using TreeAge Pro 2011 Software. Our cost-effectiveness threshold was an incremental cost-effectiveness ratio of

Many patients continue using proton pump inhibitors after negative results from tests for reflux disease.

100,000 per quality-adjusted life year. The reference case was a 50-year-old patient who had a single 1.0- to 1.5-cm polyp removed during colonoscopy. We estimated postpolypectomy bleeding rates for patients receiving no medications, those with planned resumption of antiplatelet therapy (nonaspirin), or those receiving anticoagulation therapy after polypectomy. We performed several sensitivity analyses, varying the cost of a clip and hospitalization, number of clips placed, clip effectiveness in reducing postpolypectomy bleeding, reduction in patient utility days related to gastrointestinal bleeding, and probability of harm from clip placement. RESULTS On the basis of the reference case, when patients did not receive anticoagulation therapy, clip placement was not cost-effective. However, for patients who did receive anticoagulation and antiplatelet therapies, prophylactic clip placement was a cost-effective strategy. The cost-effectiveness of a prophylactic clip strategy was sensitive to the costs of clips and hospitalization, number of clips placed, and clip effectiveness. CONCLUSIONS Placement of a prophylactic endoscopic clip after polypectomy appears to be a cost-effective strategy for patients who receive antiplatelet or anticoagulation therapy. This approach should be studied in a controlled trial.

The four phases of esophageal bolus transit defined by high-resolution impedance manometry and fluoroscopy

BACKGROUND & AIMS Ambulatory reflux testing is used to evaluate symptoms of gastroesophageal reflux disease (GERD) refractory to protein pump inhibitors (PPIs). We investigated the prevalence of PPI use in patients with negative results from Bravo pH or multichannel intraluminal impedance-pH (MII-pH) tests and factors that might predict the use of PPIs. METHODS We analyzed data from patients who had undergone Bravo pH monitoring or MII-pH testing at Northwestern University, without evidence of reflux disease. Demographics, endoscopy findings, pathology results, and provider recommendations were obtained via chart review. Eligible patients (n = 90) were contacted by telephone, and a cross-sectional survey was administered with questions about symptom severity, demographics, medication use, and health behaviors. Patients were compared by current PPI use, and statistical analyses were performed by using SAS version 9.2 software. RESULTS Thirty-eight patients (42.2%) reported current PPI use despite a negative result from a pH study. Only 17 patients (18.9%) recalled being instructed to stop taking PPIs; chart review showed documented instructions to stop PPI therapy for 15 patients (16.7%). There were no significant differences in demographic or clinical characteristics among patients compared by current PPI use. Patients taking a PPI were more likely than those not taking a PPI to report troublesome symptoms that affected their daily life, as measured by a questionnaire for the diagnosis of GERD (the GerdQ). CONCLUSIONS More than 42% of patients with negative results from pH monitoring studies continue PPI therapy despite physiological data that they do not have GERD.

Anatomic and advanced adenoma detection rates as quality metrics determined via natural language processing.

We aimed to model esophageal bolus transit based on esophageal pressure topography (EPT) landmarks, concurrent intrabolus pressure (IBP), and esophageal diameter as defined with fluoroscopy. Ten healthy subjects were studied with high-resolution impedance manometry and videofluoroscopy. Data from four 5-ml barium swallows (2 upright, 2 supine) in each subject were analyzed. EPT landmarks were utilized to divide bolus transit into four phases: phase I, upper esophageal sphincter (UES) opening; phase II, UES closure to the transition zone (TZ); phase III, TZ to contractile deceleration point (CDP); and phase IV, CDP to completion of bolus emptying. IBP and esophageal diameter were analyzed to define functional differences among phases. IBP exhibited distinct changes during the four phases of bolus transit. Phase I was associated with filling via passive dilatation of the esophagus and IBP reflective of intrathoracic pressure. Phase II was associated with auxotonic relaxation and compartmentalization of the bolus distal to the TZ. During phase III, IBP exhibited a slow increase with loss of volume related to peristalsis (auxotonic contraction) and passive dilatation in the distal esophagus. Phase IV was associated with the highest IBP and exhibited isometric contraction during periods of nonemptying and auxotonic contraction during emptying. IBP may be used as a marker of esophageal wall state during the four phases of esophageal bolus transit. Thus abnormalities in IBP may identify subtypes of esophageal disease attributable to abnormal distensibility or neuromuscular dysfunction.

The Impact of Hormonal Contraception on Disease-related Cyclical Symptoms in Women with Inflammatory Bowel Diseases.

OBJECTIVES:The objectives of this study were to use an open-source natural language-processing tool (NLP) to accurately assess total, anatomic (left and right colon), and advanced adenoma detection rates (ADRs) and to determine how these metrics differ between high- and low-performing endoscopists.METHODS:An NLP tool was developed using the Apache Unstructured Information Management Architecture and queried all procedure records for screening colonoscopies performed in patients aged 50–75 years at a single institution from April 1998 to December 2013. Validation was performed on 200 procedures and associated pathology reports. The total, left colon, right colon, and advanced ADRs were calculated and physicians were stratified by total ADR (<20% and ≥20%). Comparisons of colonoscopy characteristics and ADR comparisons (advanced, left, right, and right/left ratio) were determined by t-tests and Wilcoxon rank-sum tests.RESULTS:The total ADR for 34,998 screening colonoscopies from 1998 to 2013 was 20.3%, as determined via NLP. The institutional left and right colon ADRs were 10.1% and 12.5%, respectively. The overall advanced ADR was 4.4%. Endoscopists with total ADRs ≥20% had higher left (12.4%) and right colon (16.4%) ADRs than endoscopists with ADRs <20% (left ADR=5.6%, right ADR=5.8%). Endoscopists with ADRs ≥20% had higher individual right/left ADR ratios than those with low ADRs (1.4 (interquartile range (IQR) 0.4) vs. 1.0 (IQR 0.4), P=0.02). There was a moderate positive correlation between advanced ADR detection and both right (Spearmans rho=0.5, P=0.05) and left colon (Spearmans rho=0.4, P=0.03) ADRs.CONCLUSIONS:Institutions should consider the use of anatomic and advanced ADRs determined via natural language processing as a refined measure of colonoscopy quality. The ability to continuously monitor and provide feedback on colonoscopy quality metrics may encourage endoscopists to refine technique, resulting in overall improvements in adenoma detection.

Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population

Background:Women with inflammatory bowel diseases (IBD) commonly report an increase in their IBD symptoms related to their menstrual cycle. Hormonal contraceptives are safe for women with IBD and frequently used for reproductive planning, but data are lacking on their effect on IBD-related symptoms. Methods:We completed a cross-sectional phone survey of 129 women (31% response rate), aged 18 to 45 years, with IBD in an academic practice between March and November 2013. An electronic database query identified eligible women, and we sent an opt-out letter before contact. Questions included demographics, medical and reproductive history, and current/previous contraceptive use. Women were asked if/how their menses affected IBD-related symptoms and if/how their contraceptive affected symptoms. We calculated descriptive statistics and made comparisons by Crohns disease versus ulcerative colitis on Stata V11. Results:Participants were predominately white (85%) and college educated (97%), with a mean age of 34.2 (SD 6.2, range 19–45) years. Sixty percent had Crohns disease, and 30% had IBD-related surgery previously. Half of the participants were parous, and 57% desired future pregnancy. Of the participants, 88% reported current or past hormonal contraceptive use and 60% noted cyclical IBD symptoms. Symptomatic improvement in cyclical IBD symptoms was reported by 19% of estrogen-based contraceptive users and 47% of levonorgestrel intrauterine device users. Only 5% of all hormonal method users reported symptomatic worsening. Conclusions:In a subset of women with IBD, 20% of hormonal contraception users reported improved cyclical menstrual-related IBD symptoms. Health care providers should consider potential noncontraceptive benefits of hormonal contraception in women with cyclical IBD symptoms.