Yu-Xiao Yang

American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts

This article has an accompanying continuing medical education activity on page e12. Learning Objective: At the conclusion of this exercise, the learner will understand the approach to counseling patients regarding the optimal method and frequency of radiologic imaging, indications for invasive tests like endoscopic ultrasonography (EUS) and surgery, select patients for follow-up after surgery, decide the duration of such follow-up, and decide when to stop surveillance for those with and without surgery.

Proton-Pump Inhibitor Use and the Risk for Community-Acquired Pneumonia

Context Some studies suggest that proton-pump inhibitors (PPIs) may increase risk for community-acquired pneumonia (CAP). Contribution This large, nested casecontrol study involving adults in general practices in the United Kingdom found that current, long-term PPI use was not associated with increased risk for CAP. Recently started PPI therapy was associated with increased risk: Adjusted odds ratios for PPI use started within 2, 7, and 14 days of CAP diagnosis were 6.5, 3.8, and 3.2, respectively. Implication Long-term PPI use is not associated with increased risk for CAP. The association between recently started PPIs and CAP risk is not clear but is not necessarily causal. The Editors Proton-pump inhibitors (PPIs) are potent gastric acid suppressants. With its excellent efficacy for acid-related diseases and increasing availability of both over-the-counter and generic formulations, PPI use continues to escalate (1). Antiulcer drugs, primarily PPIs, ranked second in overall U.S. retail sales at

SCENIC International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease

10.8 billion in 2001 (2). Two studies recently suggested that PPI use may increase the risk for community-acquired pneumonia (CAP) (3, 4). A proposed mechanism is increased bacterial colonization in the upper gastrointestinal tract due to gastric acid suppression (3, 4). However, other noncausal mechanisms may also be responsible for the association between PPIs and CAP. Residual confounding may have contributed to the relatively modest increased risk seen in these studies. Furthermore, both studies found that the association was weakest among current recipients who had been taking PPIs for the longest duration, which is contrary to what one would expect if PPIs increase the risk for CAP. Community-acquired pneumonia leads to significant morbidity and mortality and dramatic costs to the health care system. In the United States, more than 1.1 million persons are hospitalized each year because of CAP (5). In the Medicare program alone, more than

Safety of Proton Pump Inhibitor Exposure

3.5 billion are spent on pneumonia-related admissions annually (5). Given the widespread use of PPIs, clarifying the potential association between PPI therapy and risk for CAP is of great importance to public health. A recent systematic review on management strategies for gastroesophageal reflux disease, commissioned by the U.S. Agency for Healthcare Research and Quality, called for further studies to elucidate the role of acid suppression on the development of CAP (6). Thus, we sought to more definitively examine the effect of current PPI exposure on CAP development in a large, population-based cohort. Methods Data Source We conducted a nested casecontrol study by using the General Practice Research Database (GPRD). The GPRD comprises prospectively collected, computerized medical records from a sample of general practices throughout the United Kingdom that represents the U.K. population in terms of age, sex, and geographic distribution (7). Under the National Health Service, a general practitioner coordinates the health care of 98% of U.K. residents. The GPRD differs fundamentally from claims databases because it comprises the actual medical record, which contains complete and comprehensive clinical data. The information collected in the database includes demographic characteristics, prescription use, clinical diagnoses, subspecialty consultation notes, and hospital discharge diagnoses. Prescriptions for most medications are written for 1 month in U.K. general practices. Details of every prescription issued include date, dosage, quantity dispensed, duration of therapy, and indication. The Read clinical classification and the Oxford Medical Information System codes are used to classify medical diagnoses (8, 9). The Read clinical classification was adopted in the United Kingdom in 1990 as an electronic medical coding system. These codes incorporate information on medical history, physical examination, procedures, symptoms, medication use, and social history. These codes are cross-referenced with other major systems of medical coding, including but not limited to the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10), and Current Procedural Terminology-4. The Oxford Medical Information System codes are related to the ICD-9 codes, with the first 3 numbers typically corresponding to the first 3 digits of the ICD-9 codes. The GPRD uses a practice-based quality marker known as up-to-standard to indicate when data recording by the practice adhered to specific quality measures according to GPRD Recording Guidelines, with respect to completeness, continuity, and plausibility (7). We used only data that were collected after the up-to-standard date in each practice to maximize the validity of the study. Previous validation studies have shown that the GPRD captures 90% to 95% of the diagnoses from specialty referral visits and greater than 90% of the principal hospital discharge diagnoses (1012). The institutional review board at the University of Pennsylvania and the GPRD Independent Scientific Advisory Committee approved this study. The University of Pennsylvanias institutional review board granted a waiver of informed consent because we used existing data that contained no patient identifiers. Study Cohort Study participants were drawn from a cohort of approximately 9 million patients who started follow-up in the GPRD from May 1987 to April 2002. The Figure shows the cohort selection process and the exclusion criteria. A substantial proportion of patients met several exclusion criteria. We excluded patients who received a diagnosis of CAP within the initial 6 months of GPRD follow-up to avoid misclassification of prevalent CAP cases as incident cases (13). We excluded patients receiving Helicobacter pylori eradication therapy because their antibiotics concurrent with PPI therapy could potentially mask the effect of PPI use on the risk for CAP. We excluded patients who received a diagnosis of aspiration pneumonia because it differs from CAP in terms of pathophysiology and risk factors. Only 1% of case patients were excluded solely on the basis of this criterion. Figure. Study flow diagram. GPRD = General Practice Research Database. * Some patients met multiple exclusion criteria. Case Patients Case patients consisted of all individuals in the eligible study cohort who received a diagnosis with their first episode of CAP within the GPRD follow-up period. The CAP diagnosis was determined on the basis of a list of relevant Read clinical classification or Oxford Medical Information System codes. The date of the first CAP diagnosis was designated as the index date for each case. To improve the specificity of our CAP case patient definition, we did a secondary analysis in which we restricted our case-patient group to those who had a first episode of CAP in the GPRD that resulted in a hospital admission. A case of CAP was considered to have required hospitalization if the recorded diagnosis was linked with a hospitalization outcome code. Control Participants By using incidence density sampling, we randomly selected up to 10 control participants for each case patient from the eligible study cohort. Incidence density sampling of control participants yields odds ratios (ORs) that are unbiased estimates of the incidence rate ratios (14). Control participants were selected 1 case at a time with replacement (that is, a patient can be a control participant for several cases). For each CAP case, we first identified all patients in the study cohort who remained at risk for CAP on the index date of the case. We then selected, among patients at risk, those who were followed at the same general practice site as the case. From those at-risk patients in the same practice site, we then selected patients who started GPRD follow-up on a date that is within 1 month before or after the GPRD start date of the case. Patients who fulfilled all criteria were eligible matched control participants and were assigned an index date that was the same as the case index date. By definition, all eligible control participants were matched to their respective case patients on index date, general practice site, and both calendar period and duration (1 month) of follow-up before the index date. In the event that 10 or fewer eligible matched control participants were available for a particular case, all control participants were included. If more than 10 eligible matched control participants were available for a case, we randomly selected 10 for our analysis. We then repeated the process for all case patients. We were able to identify 10 control participants for greater than 99% of the cases and at least 1 eligible matched control participant for all cases. The reason for choosing 10 control participants was based on considerations for statistical power and efficiency of analysis. Generally, significant statistical power can be gained by going from a 1-to-1 to a 1-to-10 casecontrol ratio. There would be little further gain in statistical power, yet the computational time would increase significantly by increasing the controlcase ratio above 10. Measure of Exposure The primary exposure of interest was current PPI therapy: use of any PPI (esomeprazole, omeprazole, rabeprazole, pantoprazole, or lansoprazole) within 30 days before the index date. Patients were considered to be exposed if they had a PPI prescription that would have lasted beyond 30 days before the index date. Among current PPI recipients, we examined the effect of daily dose (1.5 defined daily dose/d vs. >1.5 defined daily dose/d) (15) and duration of use before index date (that is, <30 days, 30 to 180 days, or >180 days) as a secondary analysis. We also did a sensitivity analysis by varying the current exposure window to 15, 60, 90, and 120 days. Past recipients were those who were exposed to PPI therapy that ended more than 30 days before the index date in the primary analysis. Statistical Analysis We used conditional logistic re

Corticosteroids in Crohn’s disease

Patients with ulcerative colitis or Crohn’s colitis have an increased risk of colorectal cancer (CRC). Most cases are believed to arise from dysplasia, and surveillance colonoscopy therefore is recommended to detect dysplasia. Detection of dysplasia traditionally has relied on both examination of the mucosa with targeted biopsies of visible lesions and extensive random biopsies to identify invisible dysplasia. Current U.S. guidelines recommend obtaining at least 32 random biopsy specimens from all segments of the colon as the foundation of endoscopic surveillance. However, much of the evidence that provides a basis for these recommendations is from older literature, when most dysplasia was diagnosed on random biopsies of colon mucosa. With the advent of video endoscopy and newer endoscopic technologies, investigators now report that most dysplasia discovered in patients with inflammatory bowel disease (IBD) is visible. Such a paradigm shift may have important implications for the surveillance and management of dysplasia. The evolving evidence regarding newer endoscopic methods to detect dysplasia has resulted in variation among guideline recommendations from organizations around the world. We therefore sought to develop unifying consensus recommendations addressing 2 issues: (1) How should surveillance colonoscopy for detection of dysplasia be performed? (2) How should dysplasia identified at colonoscopy be managed?

Detection of Circulating Pancreas Epithelial Cells in Patients With Pancreatic Cystic Lesions

Proton pump (H(+)/K(+)-adenosine triphosphatase) inhibitors (PPIs) are widely used to treat patients with acid-related disorders because they are generally perceived to be safe and effective. However, as with any pharmacologic agent, they have the potential for side effects. Many studies have examined the side effects of long-term or short-term PPI exposure. We review the mechanism of action of PPIs, focusing on recently released products that might have greater risks of adverse effects than older products because of increased potency and/or duration of action. We summarize the data available on the putative adverse effects of PPI therapy and propose guidelines for clinicians who prescribe these agents to limit the potential for adverse outcomes in users of these effective therapeutic agents.

Type 2 Diabetes Mellitus and the Risk of Colorectal Cancer

Crohns disease is a lifelong illness characterized by chronic recurrent flares. The precise etiology of Crohns disease is unknown. However, it appears to involve an enhanced systemic immune response and intensified local intestinal mucosal inflammatory activity, mediated through various inflammatory cells and an array of proinflammatory cytokines. Corticosteroids have been the mainstay of treatment of Crohns disease. The controlled trials of the National Cooperative Crohns Disease Study and the European Cooperative Crohns Disease Study established that corticosteroids were effective for the induction of remission in Crohns disease for the duration of the studies (6–17 wk). However, corticosteroids have not been shown to have an impact on the maintenance of long term remission in patients with Crohns disease. In addition, they are associated with a high potential for dependence and serious toxic side effects. Alternative classes of medical therapy for Crohns disease, including modified corticosteroids and a group of new biological therapies, have proven to be efficacious in the management of active and/or quiescent Crohns disease.

Risk of hip fracture associated with hepatitis c virus infection and hepatitis C/human immunodeficiency virus coinfection

Hematogenous dissemination is thought to be a late event in cancer progression. We recently showed in a genetic model of pancreatic ductal adenocarcinoma that pancreas cells can be detected in the bloodstream before tumor formation. To confirm these findings in humans, we used microfluidic geometrically enhanced differential immunocapture to detect circulating pancreas epithelial cells in patient blood samples. We captured more than 3 circulating pancreas epithelial cells/mL in 7 of 21 (33%) patients with cystic lesions and no clinical diagnosis of cancer (Sendai criteria negative), 8 of 11 (73%) with pancreatic ductal adenocarcinoma, and in 0 of 19 patients without cysts or cancer (controls). These findings indicate that cancer cells are present in the circulation of patients before tumors are detected, which might be used in risk assessment.

American Gastroenterological Association Institute Guideline on the Management of Acute Diverticulitis

BACKGROUND & AIMS Type 2 diabetes mellitus might increase the risk of colorectal cancer on the basis of chronic hyperinsulinemia and hyperglycemia. However, epidemiologic evidence for this association is inconclusive. We conducted a population-based study to clarify this association. METHODS We conducted a case-control study in the United Kingdom General Practice Research Database. Cases included all patients with incident colorectal cancer diagnoses (n = 10,447). Up to 10 control subjects were selected for each case, matching on year of birth, enrollment date, and duration of database follow-up. The exposure of interest was type 2 diabetes mellitus. Odds ratios (ORs) were calculated by using conditional logistic regression. RESULTS A prior diagnosis of type 2 diabetes mellitus was associated with a modestly increased risk of colorectal cancer (OR, 1.42; 95% confidence interval [CI], 1.25-1.62). The association between type 2 diabetes mellitus and colorectal cancer was observed in both men (OR, 1.36; 95% CI, 1.16-1.61) and women (OR, 1.38; 95% CI, 1.14-1.67). The risk increase was observed in both colon (OR, 1.45; 95% CI, 1.25-1.70) and rectal (OR, 1.34; 95% CI, 1.08-1.68) cancers. CONCLUSIONS Type 2 diabetes mellitus is associated with an increased risk of colorectal cancer. The risk increase is present in both sexes, as well as in both colonic and rectal cancers.

Fibrate/Statin Initiation in Warfarin Users and Gastrointestinal Bleeding Risk

Hepatitis C virus (HCV) infection has been associated with reduced bone mineral density, but its association with fracture rates is unknown, particularly in the setting of human immunodeficiency virus (HIV) coinfection. Our aims were to determine whether persons with HCV infection alone are at increased risk for hip fracture, compared to uninfected individuals, and to examine whether the risk of hip fracture is higher among HCV/HIV‐coinfected persons, compared to those with HCV alone, those with HIV alone, and those uninfected with either virus. We conducted a cohort study in 36,950 HCV/HIV‐coinfected, 276,901 HCV‐monoinfected, 95,827 HIV‐monoinfected, and 3,110,904 HCV/HIV‐uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999‐2005). Incidence rates of hip fracture were lowest among uninfected persons (1.29 events/1,000 person‐years), increased with the presence of either HIV infection (1.95 events/1,000 person‐years) or HCV infection (2.69 events/1,000 person‐years), and were highest among HCV/HIV‐coinfected individuals (3.06 events/1,000 person‐years). HCV/HIV coinfection was associated with an increased relative hazard (adjusted hazard ratio [HR] [95% confidence interval; CI]) of hip fracture, compared to HCV‐monoinfected (HR, 1.38; 95% CI: 1.25‐1.53), HIV‐monoinfected (females: HR, 1.76; 95% CI: 1.44‐2.16; males: HR, 1.36; 95% CI: 1.20‐1.55), and HCV/HIV‐uninfected persons (females: HR, 2.65; 95% CI: 2.21‐3.17; males: HR, 2.20; 95% CI: 1.97‐2.47). HCV monoinfection was associated with an increased risk of hip fracture, compared to uninfected individuals, and the relative increase was highest in the youngest age groups (females, 18‐39 years: HR, 3.56; 95% CI: 2.93‐4.32; males, 18‐39 years: HR, 2.40; 95% CI: 2.02‐2.84). Conclusion: Among Medicaid enrollees, HCV/HIV coinfection was associated with increased rates of hip fracture, compared to HCV‐monoinfected, HIV‐monoinfected, and HCV/HIV‐uninfected persons. HCV‐monoinfected patients had an increased risk of hip fracture, compared to uninfected individuals. (HEPATOLOGY 2012;56:1688–1698)