Patrick E. Young

The Prevalence of Celiac Disease Among Patients With Nonconstipated Irritable Bowel Syndrome Is Similar to Controls

BACKGROUND & AIMS Guidelines recommend that patients with symptoms of nonconstipated irritable bowel syndrome (NC-IBS) undergo testing for celiac disease (CD). We evaluated the prevalence of CD antibodies, and biopsy confirmed CD among patients with NC-IBS in a large US population. METHODS In a study conducted at 4 sites, from 2003 to 2008, we compared data from 492 patients with symptoms of NC-IBS to 458 asymptomatic individuals who underwent colonoscopy examinations for cancer screening or polyp surveillance (controls). All participants provided blood samples for specific and nonspecific CD-associated antibodies. Additionally, patients with IBS were analyzed for complete blood cell counts, metabolic factors, erythrocyte sedimentation rates, and levels of C-reactive protein and thyroid-stimulating hormone. Any subjects found to have CD-associated antibodies were offered esophagogastroduodenoscopy and duodenal biopsy analysis. RESULTS Of patients with NC-IBS, 7.3% had abnormal results for CD-associated antibodies, compared with 4.8% of controls (adjusted odds ratio, 1.49; 95% confidence interval: 0.76-2.90; P=.25). Within the NC-IBS group, 6.51% had antibodies against gliadin, 1.22% against tissue transglutaminase, and 0.61% against endomysium (P>.05 vs controls for all antibodies tested). CD was confirmed in 0.41% of patients in the NC-IBS group and 0.44% of controls (P>.99). CONCLUSIONS Although CD-associated antibodies are relatively common, the prevalence of CD among patients with NC-IBS is similar to that among controls in a large US population. These findings challenge recommendations to routinely screen patients with NC-IBS for CD. More than 7% of patients with NC-IBS had CD-associated antibodies, suggesting that gluten sensitivity might mediate IBS symptoms; further studies are needed.

Endoscopic Ultrasound Does Not Accurately Stage Early Adenocarcinoma or High-Grade Dysplasia of the Esophagus

BACKGROUND & AIMS Patients with esophageal high-grade dysplasia or mucosal esophageal cancer can be successfully treated by endoscopy. We performed a systematic review of the literature to determine whether endoscopic ultrasound (EUS) correctly predicts the T-stage of early esophageal cancers, compared with pathology specimens obtained by using endoscopic mucosal resection (EMR) or surgery. METHODS Standard systematic review methods were used to perform reference searches, determine eligibility, abstract data, and analyze data. When possible, individual patient-level data were abstracted, in addition to publication-level aggregate data. RESULTS Twelve studies had sufficient information to abstract and review for quality; 8 had individual patient-level data (n = 132). Compared with surgical or EMR pathology staging, EUS had T-stage concordance of 65%, including all studies (n = 12), but only 56% concordance when limited to individual patient-level data. Factors such as initial biopsy pathology (high-grade dysplasia vs early-stage cancer) did not appear to affect the concordance of staging between EUS and EMR/surgical staging. CONCLUSIONS EUS is not sufficiently accurate in determining the T-stage of high-grade dysplasias or superficial adenocarcinomas; other means of staging, such as EMR, should be used.

Early Detection of Colorectal Cancer Recurrence in Patients Undergoing Surgery with Curative Intent: Current Status and Challenges

Despite advances in neoadjuvant and adjuvant therapy, attention to proper surgical technique, and improved pathological staging for both the primary and metastatic lesions, almost half of all colorectal cancer patients will develop recurrent disease. More concerning, this includes ~25% of patients with theoretically curable node-negative, non-metastatic Stage I and II disease. Given the annual incidence of colorectal cancer, approximately 150,000 new patients are candidates each year for follow-up surveillance. When combined with the greater population already enrolled in a surveillance protocol, this translates to a tremendous number of patients at risk for recurrence. It is therefore imperative that strategies aim for detection of recurrence as early as possible to allow initiation of treatment that may still result in cure. Yet, controversy exists regarding the optimal surveillance strategy (high-intensity vs. traditional), ideal testing regimen, and overall effectiveness. While benefits may involve earlier detection of recurrence, psychological welfare improvement, and greater overall survival, this must be weighed against the potential disadvantages including more invasive tests, higher rates of reoperation, and increased costs. In this review, we will examine the current options available and challenges surrounding colorectal cancer surveillance and early detection of recurrence.

Colonoscopy for Colorectal Cancer Screening

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Many, if not most, cases arise from premalignant lesions (adenomas) which may be identified and removed prior to becoming frankly malignant. For over a decade, colonoscopy has been the preferred modality for both CRC screening and prevention in the US. Early reports suggested that colonoscopic screening imparted a 90% risk reduction for colorectal cancer. Subsequent studies showed that estimate to be overly optimistic. While still an outstanding CRC screening and detection tool, colonoscopy has several important limitations. Some of these limitations relate to the mechanics of the procedure such as the risk of colonic perforation, bleeding, adverse consequences of sedation, and the inability to detect all colonic polyps. Other limitations reflect issues with patient perception regarding colonoscopy which, at least in part, drive patient non-adherence to recommended testing. This review examines the literature to address several important issues. First, we analyze the effect of colonoscopy on CRC incidence and mortality. Second, we consider the patient-based, periprocedural, and intraprocedural factors which may limit colonoscopy as a screening modality. Third, we explore new techniques and technologies which may enhance the efficacy of colonoscopy for adenoma detection. Finally, we discuss the short and long-term future of colonoscopy for CRC screening and the factors which may affect this future.

Influence of provider discussion and specific recommendation on colorectal cancer screening uptake among U.S. adults

OBJECTIVES It is unclear if provider recommendations regarding colorectal cancer (CRC) screening modalities affect patient compliance. We evaluated provider-patient communications about CRC screening with and without a specific screening modality recommendation on patient compliance with screening guidelines. METHODS We used the 2007 Health Information National Trends Survey (HINTS) and identified 4283 respondents who were at least 50 years of age and answered questions about their communication with their care providers and CRC screening uptake. We defined being compliant with CRC screening as the use of fecal occult blood testing (FOBT) within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We used survey weights in all analyses. RESULTS CRC screening discussions occurred with 3320 (76.2%) respondents. Approximately 95% of these discussions were with physicians. Overall, 2793 (62.6%) respondents were current with CRC screening regardless of the screening modality. Discussion about screening (odds ratio (OR)=8.83; 95% confidence interval (CI): 7.20-10.84) and providers making a specific recommendation about screening modality rather than leaving it to the patient to decide (OR=2.04; 95% CI: 1.54-2.68) were associated with patient compliance with CRC screening guidelines. CONCLUSION Compliance with CRC screening guidelines is improved when providers discuss options and make specific screening test recommendations.

Association Between Circulating Levels of Sex Steroid Hormones and Barrett’s Esophagus in Men: A Case–Control Analysis

BACKGROUND & AIMS Esophageal adenocarcinoma is believed to result from the progression of gastroesophageal reflux disease to erosive esophagitis and re-epithelialization of the esophagus with a columnar cell population termed Barretts esophagus (BE). Men develop BE and esophageal adenocarcinoma more frequently than women, yet little is known about the mechanisms of this difference. We assessed whether sex steroid hormones were associated with BE in a male population. METHODS We analyzed data from the Barretts Esophagus Early Detection Case Control Study, based at the Walter Reed National Military Medical Center. Blood samples were collected from 174 men with BE and 213 men without BE (controls, based on endoscopic analysis); 13 sex steroid hormones were measured by mass spectrometry and sex hormone binding globulin was measured by enzyme-linked immunosorbent assay. We also calculated free estradiol, free testosterone, and free dihydrotestosterone (DHT). We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, race, smoking status, alcohol consumption, body mass index, heartburn, regurgitation, and gastroesophageal symptom score (excluding heartburn and regurgitation). RESULTS Levels of free testosterone and free DHT were associated positively with BE risk; patients in the highest quartile for these hormones were most likely to have BE (free testosterone: OR, 5.36; 95% CI, 2.21-13.03; P = .0002; free DHT: OR, 4.25; 95% CI, 1.87-9.66; P = .001). Level of estrone sulfate was associated inversely with BE risk (P for trend = .02). No other hormone was associated with BE risk. Relationships were not modified by age or BMI. CONCLUSIONS In an analysis of men, levels of free testosterone and free DHT were significantly associated with BE.

Global changes in gene expression of Barrett's esophagus compared to normal squamous esophagus and gastric cardia tissues.

Background Barretts esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. Design We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barretts metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 40 BE patients. Results Using a cut off of 2-fold and P<1.12E-06 (0.05 with Bonferroni correction), we identified 1324 differentially-expressed genes comparing BE vs NE and 649 differentially-expressed genes comparing BE vs NC. Except for individual genes such as the SOXs and PROM1 that were dysregulated only in BE vs NE, we found a subset of genes (n = 205) whose expression was significantly altered in both BE vs NE and BE vs NC. These genes were overrepresented in different pathways, including TGF-β and Notch. Conclusion Our findings provide additional data on the global transcriptome in BE tissues compared to matched NE and NC tissues which should promote further understanding of the functions and regulatory mechanisms of genes involved in BE development, as well as insight into novel genes that may be useful as potential biomarkers for the diagnosis of BE in the future.

Psychogenic Coma following Upper Endoscopy: A Case Report and Review of the Literature

BACKGROUND Failure to regain consciousness after general anesthesia has a multitude of life-threatening causes, including neurological injury, metabolic derangements, or drug effects. Failure to promptly recognize the cause of unconsciousness after anesthesia can result in significant patient morbidity or mortality, costly laboratory and radiographic evaluation, and physician anxiety. Rarely, patients fail to awaken after anesthesia due to a psychiatric cause. The early recognition of psychogenic coma can result in reduced iatrogenic complications, hospital cost, and physician anxiety. CASE We present a case of a 28-year-old female who became unresponsive after general anesthesia for an upper endoscopy. Physical, laboratory, and radiographic examination after the procedure revealed no apparent organic cause for her failure to awaken. The patient spontaneously awoke after 16 hours without neurological deficit. DISCUSSION We reviewed the literature and identified 10 previously reported cases of postanesthesia psychogenic coma. We have compared and contrasted our case with the 10 previous reports and propose bedside clues to assist the physician with diagnosing this unusual condition.

M1104 Predicting High-Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients With Non-Dysplastic Barrett's Esophagus (BE): Results From a Large, Multicenter Cohort Study

Predicting High-Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients With Non-Dysplastic Barretts Esophagus (BE): Results From a Large, Multicenter Cohort Study Srinivas Gaddam, Patrick E. Young, Amy Wang, Ajay Bansal, Neil Gupta, Sachin B. Wani, Mandeep Singh, Vikas Singh, Keng-Yu Chuang, Vikram Boolchand, Hemanth Gavini, Priti Sud, John Kuczynski, April D. Higbee, Amit Rastogi, Sharad C. Mathur, Brooks D. Cash, Gary W. Falk, Richard E. Sampliner, Prateek Sharma

475c Low Risk of Developing Dysplasia and Esophageal Adenocarcinoma (EAC) in Patients With Non-Dysplastic Barrett's Esophagus (BE): Results From a Large, Multicenter, Cohort Study

Background: Pregnancy-related gastroesophageal reflux (GERD) is a common condition, afflicting 40-85% of all expectant women. Thus, PPI have been prescribed to an increasing number of pregnant women for GERD1. However, the safety of PPI therapy in pregnancy is unclear; while previous observational studies failed to find a significant association between maternal PPI use and birth defects, all were under-powered or uncontrolled. Nevertheless, the proportion of cardiac defects observed in PPI-exposed pregnancies was unusually high in the two largest studies2,3. Hence, we conducted a large population-based study to determine if PPI exposure in utero is associated with increased risk for cardiac birth defects in newborns. Methods: Data from the The Health Improvement Network (THIN) database, a UK general practitioner (GP) electronic medical record system (2000-2008), were used to identify 208,951 pregnancies in which babies could be clearly linked to mothers who were followed by a GP for at least 1y prior to delivery. Within this source cohort, we then performed a nested case-control analysis in which all babies with a coded diagnosis for cardiac birth defect were identified. Up to 10 controls were identified per case matching for maternal age, GP location, delivery site, date of birth, and sex. Odds ratios (OR) for cardiac birth defects were calculated based on PPI exposure during the pregnancy. Conditional logistic regression was performed to adjust for potential confounders including BMI, cardiac malformation in the mother, smoking status, number of pregnancy GP visits, alcohol use, and use of medications associated with cardiac defects in published reports. To confirm the specificity of our analysis, case-control analyses were performed to determine if PPI exposure were associatedwith defects in other organ systems.Results: 2,445 cases of cardiac malformations and 19,530 matched controls were identified. Maternal PPI use during pregnancy was associated with a significant increase in cardiac birth defects (OR=2.08 (95% CI: 1.33, 3.25; p<0.001); adjusted OR=2.14 (1.37, 3.35; p<0.001)). Further, PPI use was not associated with birth defects in other organ systems. Conclusions: In this large population-based cohort, PPI exposure in utero was associated with a significant increase in the risk for cardiac birth defects. Thus, these findings, if confirmed, may have direct clinical implications in the treatment of millions of women worldwide. 1. Richter, JE. Aliment Pharmacol Ther 2005;22:749-57 2. Nielsen GL, et al. Aliment Pharmacol Ther 1999;13:10859 3. Kallen B. Br J Obstet Gynaecol 1998;105:87781