Douglas R. Morgan

Burden of Gastrointestinal Disease in the United States: 2012 Update

BACKGROUND & AIMS Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. METHODS We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiatives National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. RESULTS Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was

The burden of gastrointestinal and liver diseases, 2006.

32.4 billion. CONCLUSIONS GI diseases are a source of substantial morbidity, mortality, and cost in the United States.

Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori

BACKGROUND:Digestive and liver diseases are a source of significant morbidity, mortality, and health-care costs for the U.S. population. An annual report of the toll of these diseases could be helpful to clinicians, policymakers, and researchers.AIM:To describe the epidemiology of gastrointestinal and liver diseases in the United States using data from privately and publicly held databases.METHODS:We collected data from the National Center for Health Statistics, the National Ambulatory Medical Care Survey, the National Inpatient Sample, the Centers for Disease Control and Prevention, and the National Cancer Institute, as well as proprietary pharmaceutical databases to construct a report on the impact of gastrointestinal and liver diseases on the U.S. population. We compiled information on causes of death, hospitalization, clinic visits, cancer incidence, and mortality and infectious disease incidence from these databases, and extracted data specific to gastrointestinal diseases. Because of the high costs associated with medications used to treat gastrointestinal diseases, we also include in this years report a special section on pharmacoepidemiology and pharmacoeconomics.RESULTS:Colorectal cancer continues to be the leading cause of GI-related death, although the data indicate a downward trend in deaths. Abdominal pain, diarrhea, vomiting, and nausea are the most common GI symptoms precipitating a visit to the physician, and GERD is the most common GI-related diagnosis given in office visits. Chest pain not specified to be cardiac in origin is the most common cause of inpatient admission possibly related to GI disease, with cholelithiasis and pancreatitis following. Americans spend in excess of

14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial

10 billion/yr on proton pump inhibitors (PPIs), and two of the top five selling drugs in the United States are PPIs. Trends in PPI use demonstrate turbulent changes, likely reflecting both new drug entries into the field, as well as drug marketing. The number of PPI prescriptions/yr in the United States has doubled since 1999. Twenty-three drugs used for gastrointestinal diseases are among the top 200 generic drugs used in the United States.CONCLUSIONS:Gastrointestinal and liver diseases are significant contributors to the morbidity, mortality, and health-care expenditures of the U.S. population.

Agile patency system eliminates risk of capsule retention in patients with known intestinal strictures who undergo capsule endoscopy.

Non-motile variants of Helicobacter pylori (strain 26695) occurred with a frequency of 1.6 (SD 0.4) x 10(-4) variants/cell/division cycle, and reversion to the motile form occurred with a frequency of less than 10(-7) variants/cell/division cycle. The two forms remained greater than 90% pure for up to 50 cell divisions and differed only in the presence or absence of motility and flagella. Bacteria were recovered from nine of 10 gnotobiotic piglets inoculated orally with motile H. pylori, but from only two of eight inoculated with the non-motile variant. The motile form survived for 21 days in infected piglets, but the non-motile variant survived for only 6 days. Bacteria recovered from piglets inoculated with the non-motile variant were non-motile. These data support the hypothesis that motility is a colonisation factor for H. pylori.

A multicenter, U.S. experience of single-balloon, double-balloon, and rotational overtube–assisted enteroscopy ERCP in patients with surgically altered pancreaticobiliary anatomy (with video)

BACKGROUND Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy. METHODS Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, registration number NCT01061437. FINDINGS 1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. INTERPRETATION Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations. FUNDING Bill & Melinda Gates Foundation, US National Institutes of Health.

Iron deficiency accelerates Helicobacter pylori–induced carcinogenesis in rodents and humans

BACKGROUND Capsule endoscopy (CE) of the small bowel has become a standard diagnostic tool, but there have been concerns regarding the risk of capsule retention in certain high-risk groups. The Agile patency system, an ingestible and dissolvable capsule with an external scanner, was developed to allow physicians to perform CE with greater confidence that the capsule will be safely excreted in patients at risk for capsule retention. OBJECTIVE Our purpose was to assess the ability of the device to help physicians identify which patients with known strictures may safely undergo CE. DESIGN Patients with known strictures ingested the new patency capsule and underwent periodic scanning until it was excreted. The intestinal tract was considered to be sufficiently patent if the capsule was excreted intact or if the capsule was not detected by the scanner at 30 hours after ingestion. If patency was established, then standard CE was performed. SETTING International multicenter study. PATIENTS A total of 106 patients with known strictures. INTERVENTION Agile patency system. MAIN OUTCOME MEASUREMENTS Performance and safety of Agile patency system. RESULTS A total of 106 patients ingested the patency capsule. Fifty-nine (56%) excreted it intact and subsequently underwent CE. There were no cases of capsule retention. Significant findings on CE were found in 24 (41%). There were 3 severe adverse events. CONCLUSIONS These results suggest that the Agile patency system is a useful tool for physicians to use before CE in patients with strictures to avoid retention. This group of patients may have a high yield of clinically significant findings at CE. This capsule may determine whether patients who have a contraindication to CE may safely undergo CE and obtain useful diagnostic information.

Inverse Association of Esophageal Eosinophilia With Helicobacter pylori Based on Analysis of a US Pathology Database

BACKGROUND Data on overtube-assisted enteroscopy to facilitate ERCP in patients with surgically altered pancreaticobiliary anatomy, or long-limb surgical bypass, is limited. OBJECTIVE To evaluate and compare ERCP success by using single-balloon (SBE), double-balloon (DBE), or rotational overtube enteroscopy. DESIGN Consecutive patients identified retrospectively. SETTING Eight U.S. referral centers. PATIENTS Long-limb surgical bypass patients with suspected pancreaticobiliary diseases. INTERVENTION Overtube-assisted enteroscopy ERCP. MAIN OUTCOME MEASUREMENTS Enteroscopy success: visualizing the pancreaticobiliary-enteric anastomosis or papilla. ERCP success: completing the intended pancreaticobiliary intervention. Clinical success: greater than 50% reduction in abdominal pain or level of hepatic enzyme elevations or resolution of jaundice. RESULTS From January 2008 through October 2009, 129 patients had 180 enteroscopy-ERCPs. Anatomy was Roux-en-Y: gastric bypass (n = 63), hepaticojejunostomy (n = 45), postgastrectomy (n = 6), Whipple procedure (n = 10), and other (n = 5). ERCP success was 81 of 129 (63%). Enteroscopy success: 92 of 129 (71%), of whom 81 of 92 (88%) achieved ERCP success. Reasons for ERCP failure (n = 48): afferent limb entered but pancreaticobiliary anastomosis and/or papilla not reached (n = 23), cannulation failure (n = 11), afferent limb angulation (n = 8), and jejunojejunostomy not identified (n = 6). Select interventions: anastomotic stricturoplasty (cautery ± dilation, n = 16), stone removal (n = 21), stent (n = 25), and direct cholangioscopy (n = 11). ERCP success rates were similar between Roux-en-Y gastric bypass and other long-limb surgical bypass and among SBE, DBE, and rotational overtube enteroscopy. Complications were 16 of 129, 12.4%. LIMITATIONS Retrospective study. CONCLUSION (1) ERCP is successful in nearly two-thirds of long-limb surgical bypass patients and in 88% when the papilla or pancreaticobiliary-enteric anastomosis is reached. (2) Enteroscopy success in long-limb surgical bypass is similar among SBE, DBE, and rotational overtube enteroscopy methods. (3) Referral of long-limb surgical bypass patients who require ERCP to high-volume institutions may be considered before more invasive percutaneous or surgical alternatives.

Sex Hormones, Hormonal Interventions, and Gastric Cancer Risk: A Meta-Analysis

Gastric adenocarcinoma is strongly associated with Helicobacter pylori infection; however, most infected persons never develop this malignancy. H. pylori strains harboring the cag pathogenicity island (cag+), which encodes CagA and a type IV secretion system (T4SS), induce more severe disease outcomes. H. pylori infection is also associated with iron deficiency, which similarly augments gastric cancer risk. To define the influence of iron deficiency on microbial virulence in gastric carcinogenesis, Mongolian gerbils were maintained on iron-depleted diets and infected with an oncogenic H. pylori cag+ strain. Iron depletion accelerated the development of H. pylori-induced premalignant and malignant lesions in a cagA-dependent manner. H. pylori strains harvested from iron-depleted gerbils or grown under iron-limiting conditions exhibited enhanced virulence and induction of inflammatory factors. Further, in a human population at high risk for gastric cancer, H. pylori strains isolated from patients with the lowest ferritin levels induced more robust proinflammatory responses compared with strains isolated from patients with the highest ferritin levels, irrespective of histologic status. These data demonstrate that iron deficiency enhances H. pylori virulence and represents a measurable biomarker to identify populations of infected persons at high risk for gastric cancer.

Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study.

BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is of increasing prevalence and believed to result from allergic processes. Helicobacter pylori has been inversely associated with allergic diseases, but there is no known relationship between H pylori, EoE, and esophageal eosinophilia. We investigated the association between esophageal eosinophilia and H pylori infection. METHODS We performed a cross-sectional study of data, collected from a US pathology database, on 165,017 patients in the United States who underwent esophageal and gastric biopsies from 2008 through 2010. Patients with and without H pylori on gastric biopsy were compared, and odds of esophageal eosinophilia were determined. RESULTS From the data analyzed, 56,301 (34.1%) had normal esophageal biopsy specimens, 5767 (3.5%) had esophageal eosinophilia, and 11,170 (6.8%) had H pylori infection. Esophageal eosinophilia was inversely associated with H pylori (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.69-0.87). Compared with patients with normal esophageal biopsy specimens, odds of H pylori were reduced among patients with ≥ 15 eosinophils per high-power field (eos/hpf) (OR, 0.79; 95% CI, 0.70-0.88), ≥ 45 eos/hpf (OR, 0.75; 95% CI, 0.61-0.93), ≥ 75 eos/hpf (OR, 0.72; 95% CI, 0.50-1.03), and ≥ 90 eos/hpf (OR, 0.52; 95% CI, 0.31-0.87) (P for trend <.001). A similar dose-response trend was observed for increasing clinical suspicion for EoE and decreasing prevalence of H pylori. Additionally, severity of histologic effects of H pylori was inversely associated with esophageal eosinophilia. All trends held in multivariate analysis. CONCLUSIONS In a large cross-sectional analysis, H pylori infection was inversely associated with esophageal eosinophilia. This relationship could have implications for the pathogenesis and epidemiology of EoE.