Ganesh R. Veerappan

Meta-analysis : Computed tomographic colonography

Colorectal cancer is the second most frequent cause of cancer-related death in the United States. Nearly 150000 new cases and 60000 deaths occur each year from this disease (1). Because colorectal cancer develops insidiously over time as genetic mutations accumulate in clinically silent adenomatous polyps, it is most commonly diagnosed at an advanced stage (2-4). If the condition is diagnosed at an early stage, the prognosis is favorable, with 5-year survival rates exceeding 90% (5, 6). Colorectal cancer, unlike many other types of cancer, can be prevented by removal of precancerous lesions. The long preclinical phase, early detectability, and improved prognosis of colorectal cancer have established the need for an accurate screening method. Various screening tests in current use reduce the incidence and rate of death from colorectal cancer (7, 8). Despite the proven efficacy of these tests, however, patient adherence to screening guidelines is low: Only 30% to 45% of persons eligible for screening undergo such tests. Low adherence rates are believed to be due to poor public awareness and poor public acceptance of current screening techniques (9-13). An increasingly popular screening test for colorectal cancer is computed tomographic (CT) colonography, also known as CT colography or virtual colonoscopy. Computed tomographic colonography was first described in 1994 as a radiographic technique in which thin-section images of pneumocolon could be reconstructed by sophisticated software into high-resolution 2- and 3-dimensional images (14). Over time, improvements in hardware and software have allowed faster scanning, reduced exposure to radiation, and better imaging. Newer modes of imaging (called fly-through) can produce results that resemble endoscopic images and permit sophisticated characterization of detected lesions (15-17). Early studies primarily used the spiral CT scanner, which has limitations in spatial resolution that can make small polyps more difficult to detect (17). The multidetector CT scanner has permitted rapid acquisition of finer images, obtained during a single breath-hold, that can greatly improve image quality and spatial resolution (17, 18). Many aspects of this technology are under study, including software that assists in detection of lesions, refinements in image reconstruction, and stool tagging (19-21). The latter development relies on ingestion of contrast material over several days or hours, after which software digitally subtracts residual solid and fluid fecal material from the acquired images, creating a virtually clean mucosal surface (22, 23). This technique may improve sensitivity and may someday obviate the need for bowel cleansing before examination. Although it is touted as a less invasive screening method than flexible sigmoidoscopy or colonoscopy, CT colonography typically requires full bowel cleansing and insufflation of air through the rectum (24). Studies have suggested that CT colonography may be similar, and in some cases preferable, to colonoscopy in terms of comfort and acceptability, but no convincing difference between these 2 approaches has been demonstrated (25-31). If virtual colonoscopy is found to have equivalent test characteristics, improve patient adherence, and be safer or less expensive than colonoscopy, it may be more cost-effective and become the screening method of choice (32, 33). Studies of the test characteristics of CT colonography have had mixed results. Pickhardt and colleagues used CT colonography in 1233 patients and found a sensitivity of 93.9% for adenomatous polyps larger than 8 mm (25). Other studies have had less favorable results, with sensitivities as low as 55% for polyps larger than 10 mm, raising concerns about the overall test performance of CT colonography when used in a broader range of settings (34). Various reasons for these discrepant results have been offered, but the source of this heterogeneity has not been fully explored (16, 35, 36). Such assessment is needed because patients and providers look to this technology in the hope of improving screening rates (29). We systematically reviewed the literature to assess the test performance of CT colonography compared with colonoscopy or surgery, to define characteristics of these studies, and to attempt to explain the sources of conflicting results. Methods Study Identification and Selection We searched the PubMed, EMBASE, and MEDLINE databases and the Cochrane Controlled Trials Register for all relevant articles published in the English language between 1975 and February 2005 by using the Medical Subject Headings or text words virtual colonoscopy, CT colonography, CT colography, or CT pneumocolon. The title and abstract of potentially relevant studies and review articles were screened for appropriateness before retrieval of the full articles. Two reviewers independently searched the literature. Inclusion criteria were a prospective, blinded design (in which results of CT colonography were interpreted independently of findings on colonoscopy or during surgery); enrollment of adult patients who were to undergo CT colonography after a full bowel preparation, followed by complete colonoscopy or surgery; and use of at least a single-detector CT scanner, with colon insufflation by air or carbon dioxide, scan intervals no greater than 5 mm, and use of both 2-dimensional and 3-dimensional views during scan interpretation. Study Quality Two observers independently extracted data on test characteristics; study setting; patients; and components of methodologic quality that may be associated with bias in test accuracy studies, including disease severity, disease prevalence, prospective design, relevant clinical sample (as opposed to a diagnostic casecontrol study), enrollment of a series of consecutive patients, assurance that all patients underwent reference testing, performance and interpretation of the index test without knowledge of the results of the reference test, and performance and interpretation of the reference test without knowledge of the results of the index test (33). A piloted standardized data extraction sheet was used, and disagreements were resolved by consensus. Data Abstraction We abstracted characteristics of the study (design, country, year, reference standard, and type of contrast used), patients (demographic and risk for colorectal cancer), scanners (manufacturer, type of viewer, type of contrast, software, and hardware), and study quality. Sensitivity and specificity were calculated per patient, per polyp, and for polyps of 3 size categories: smaller than 6 mm, 6 to 9 mm, and larger than 9 mm. When data on test performance were reported for 2 or more separate CT colonography readers, we calculated an average value. When possible, we excluded data on double readings. If a study reported data related specifically to adenomas instead of polyps, in general, we abstracted only the data for adenomas. For studies that performed retrospective analysis (for example, fly-through imaging in the study by Cotton and associates [34]), we abstracted only data on CT colonography findings before colonoscopy. If data could not be extracted or calculated from the manuscript with confidence, none were entered. Two reviewers independently abstracted data, and disagreements were resolved by consensus. Statistical Analysis Pooled sensitivities and specificities on a per-patient basis were combined and weighted according to sample size. Confidence intervals for each study were calculated by using exact binomial methods in a random-effects model. We focused our analysis on per-patient data because this is the most important perspective for a screening test, whereas per-polyp data emphasize the ability of CT colonography to find colonic lesions. That is, the latter analysis assesses the performance of the technology rather than its utility as a screening tool. Heterogeneity was assessed by using the I2 statistic (37). The I2 statistic provides an estimate of the amount of variance due to heterogeneity rather than chance and is based on the traditional measure of variance, the Cochrane Q statistic. Potential threshold effects were assessed by using the Spearman statistic and by creating receiver-operating characteristic curves according to the method of Moses and coworkers (38). Heterogeneity was assessed by performing stratified analyses when the potential confounding variable was dichotomous or categorical, by plotting the weighted effect size against the potential confounding variable when that variable was continuous, and by applying meta-regression methods in either case (39). Subgroup analyses were done by year of publication, imaging technique (2-dimensional imaging with 3-dimensional confirmation only when a lesion was noted, 3-dimensional imaging with 2-dimensional confirmation, 2-dimensional imaging with concomitant 3-dimensional imaging, or fly-through technology), collimation width and reconstruction interval (in millimeters), type of scanner (single-detector, multidetector, or mixed), and use of a contrast agent (yes or no). When collimation or reconstruction thickness was given in half-millimeter increments, we rounded the values up to the next whole number. The meta-regression analysis used the restricted maximum likelihood method and was performed by using indicator variables to assess differences among the strata. All analyses were performed with Stata software, version 8.2 (Stata Corp., College Station, Texas). Data Synthesis Our final pool of eligible studies (Appendix Figure) included 33 prospective studies involving 6393 patients that compared CT colonography to the reference standard of colonoscopy or surgery (22, 25, 34, 40-69). Studies originated from 7 different countries, but most were done in the United States (64%). The average number of participants in a study was 248 (range, 20 to 1233). The mean age of participants was 61.9 years; 63.6% of participants were ma

Prevalence of Eosinophilic Esophagitis in an Adult Population Undergoing Upper Endoscopy: A Prospective Study

BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus. The purpose of this prospective study was to determine the prevalence and clinical predictors of EoE in patients undergoing elective upper endoscopy. METHODS We enrolled 400 consecutive adults (median age, 50 years; range, 19-92 years) who underwent routine upper endoscopy from March to September 2007 at a tertiary care military hospital. All patients completed a symptom questionnaire. All endoscopic findings were noted. Eight biopsies were obtained from proximal and distal esophagus and were reviewed by a blinded gastrointestinal pathologist. Patients had EoE if > or =20 eosinophils/high-power field were present. RESULTS The prevalence of EoE in this cohort was 6.5% (25/385; 95% confidence interval, 4.3%-9.4%). Compared with EoE negative patients, EoE positive patients were more likely to be male (80.0% vs 48.1%, P = .003), younger than 50 years (72.0% vs 48.9%, P = .037), and have asthma (32.0% vs 10.8%, P = .006), a food impaction (32.0% vs 8.9%, P = .002), dysphagia (64.0% vs 38.1%, P = .018), and classic endoscopic findings (rings, furrows, plaques, or strictures) of EoE (all P < .01). Logistic regression identified asthma (odds ratio [OR], 4.48), male gender (OR, 4.23), and esophageal rings (OR, 13.1) as independent predictors of EoE. The presence of classic endoscopic findings of EoE had a sensitivity of 72% (54%-88%), specificity of 89% (87%-90%), and negative predictive value of 98% (95.6%-99.1%). CONCLUSIONS The prevalence of EoE in an outpatient population undergoing upper endoscopy was 6.5%. The characteristic findings of EoE patients included male gender, history of asthma, and the presence of classic findings of EoE on endoscopy, which is the strongest predictor of this disease process.

Randomized Controlled Trial Comparing Aerosolized Swallowed Fluticasone to Esomeprazole for Esophageal Eosinophilia

OBJECTIVES:Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole.METHODS:This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15 eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gastroesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440 mcg twice daily or esomeprazole 40 mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, defined as <7 eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validated Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment.RESULTS:Forty-two patients (90% male, 81% white, mean age 38±10 years) were randomized into fluticasone (n=21) and esomeprazole (n=21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm (n=4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P=0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group (P=0.029). In GERD-negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P=1.00). The MDQ score significantly decreased after treatment with esomeprazole (19±21 vs. 1.4±4.5, P<0.001), but not with fluticasone (17±18 vs. 12±16, P=0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups.CONCLUSIONS:Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

Extracolonic Findings on CT Colonography Increases Yield of Colorectal Cancer Screening

OBJECTIVE The purpose of this study is to evaluate the impact of extracolonic findings when screening is undertaken by CT colonography (CTC). MATERIALS AND METHODS We performed a retrospective cohort study of patients completing a screening CTC from August 2003 to June 2006 at Walter Reed Army Medical Center. Extracolonic findings were categorized using a CTC reporting and data system that classifies findings as highly significant, likely significant, and insignificant. All final diagnoses, surgeries, malignancies, and costs of diagnostic radiology procedures were calculated for each category. RESULTS Of 2,277 patients (mean +/- SD age, 59 +/- 11 years; 60% white; 56% male) undergoing CTC, extracolonic findings were identified in 1,037 (46%) patients, with 787 (34.5%) insignificant and 240 (11.0%) significant findings. Evaluation of significant findings generated 280 radiology procedures and 19 surgeries over a mean follow-up time of 19 +/- 10 months. The total cost of the radiology studies was

Resident run journal club: A model based on the adult learning theory

113,179; the studies added approximately

Vaccination-induced autoimmune hepatitis

50 extra per patient. Seven high-risk lesions were identified (six extracolonic malignancies and one large aortic aneurysm) in patients with significant findings. CTC also identified six intracolonic malignancies and three adenomas with high-grade dysplasia. When considering extracolonic findings, CTC increased the odds of identifying high-risk lesions by 78% (nine intracolonic lesions vs 16 intracolonic plus extracolonic lesions; p = 0.0156). Of the 16 intracolonic and extracolonic high-risk lesions, 11 (69%) underwent curative resection, and 5 of 11 (44.4%) were extracolonic. CONCLUSION CTC increased the odds of identifying high-risk lesions by 78%. CTC should be considered as an alternative to optical colonoscopy for colorectal cancer screening or as a onetime procedure to identify significant treatable intracolonic and extracolonic lesions.

Race May Play a Role in the Clinical Presentation of Eosinophilic Esophagitis

Background: Multiple formats of journal club exist but data is lacking regarding which model is most effective. Many residents are dissatisfied with their current format, which was the case at our institution. Aim: This article discusses a resident run model, residents’ perceptions following its implementation, and recommendations for running a successful journal club. Practice points Journal club formats vary extensively without a clearly superior method. Defining goals is the first step to a successful journal club. Structured review instruments for articles enhance journal club. The presence of subspecialty staff may augment learning. Resident run models of journal club can be successfully implemented. Methods: A resident run model of journal club was developed based on Adult Learning Theory. A 30-question survey was created to assess residents’ attitudes and satisfaction with the new model. Results: All respondents preferred the new model compared to the old model. Residents reported the new model increased their medical knowledge (88%) and they were able to apply the methods learned in journal club to actual patients (82%). Conclusions: A resident run model of journal club may be a viable option for those attempting to start or improve their current club.

Small Bowel Is the Primary Source of Obscure Gastrointestinal Bleeding

Autoimmune hepatitis (AIH) is a chronic, progressive liver disease that occurs predominantly in genetically predisposed individuals. The condition is characterized by the presence of autoantibodies and is associated with elevated serum globulin levels. AIH generally responds to steroid therapy by suppressing the autoimmune response. Over the last decade, a scoring system has been developed that can assist in making the diagnosis. The AIH diagnostic scoring system considers a wide range of clinical and serologic variables that are impacted by the presence of other liver disorders, along with clinical, immunologic, and histological abnormalities that increase or decrease the likelihood of AIH (1). If left untreated, AIH generally progresses to cirrhosis. The pathophysiology and natural course of this disease have been studied extensively; however, the initiating process in AIH remains unclear. Experts believe certain patients are genetically predisposed to develop AIH, but the exposure or insult responsible for triggering the process is unknown (2). Hepatitis C, hepatitis B, hepatitis A, measles, and Epstein–Barr virus (EBV) have all been implicated as possible triggers for development of AIH, but no consistent agent has been defined. Our patient presents with AIH based on labs, clinical course, and histology following simultaneous exposure to multiple vaccinations. This is the first reported case of AIH occurring after serial immunizations.

The Tug Sign: An Endoscopic Feature of Eosinophilic Esophagitis

To the Editor: We read with interest the article by Sperry et al. (1) describing the influence of race and gender on the presentation of eosinophilic esophagitis (EoE). EoE is commonly thought of as a disease predominantly affecting white men (2). In their study of 208 EoE cases, some differences were noted in presentation based on race and gender. Specifically, Caucasian patients were significantly older than African Americans (27 vs. 19 years of age, P=0.05) and more likely to have concentric rings (41% vs. 12%, P=0.05). At our institution, we also reported some racial differences with regards to the clinical presentation in 198 EoE patients (3).

Squamous Cell Lung Cancer Presenting as a Malar Mass

Dear Sir: In the recent American Gastroenterological Association Institute Technical Review on Obscure Gastrointestinal Bleeding, the authors state that only 5% of cases of obscure bleeding arise from the small intestine.1 Based on the current literature on obscure gastrointestinal bleeding and our own institutional experience, we feel that the majority of obscure gastrointestinal bleeding actually originates from a small bowel source. The CURE Hemostasis Study Group studied 206 patients with obscure gastrointestinal bleeding undergoing reevaluation with upper endoscopy with push enteroscopy and colonoscopy. These patients were found to have a lesion confirmed in the small bowel in 40% of the cases and another 20% were presumed to be in the small intestines distal to the reach of the video enteroscope.2 Another study by Mylonaki et al3 compared the diagnostic yield of video capsule endoscopy with push enteroscopy in patients with obscure gastrointestinal bleeding and 68% of patients had a small bowel source with the most common cause being vascular ectasias. Our own institutional experience at Walter Reed Army Medical Center, Washington, DC, over the last 6 months has been similar to the reports in the literature, with 55% (15/27) of patients with obscure gastrointestinal bleed diagnosed with a small bowel source. We feel that the statement made in the technical review was referring to the idea that 5% of all gastrointestinal bleeding occurs in the small intestine, and not that 5% of obscure GI bleeding arises from the small intestine. This is an important distinction that impacts the way we approach obscure gastrointestinal bleeding. Obscure bleeding is often synonymous with suspected small bowel bleeding and we write to you to clarify this to your readership.