Lisa M. Gangarosa

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.

Burden of Gastrointestinal, Liver, and Pancreatic Diseases in the United States

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

A Raf-independent Epidermal Growth Factor Receptor Autocrine Loop Is Necessary for Ras Transformation of Rat Intestinal Epithelial Cells*

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.

Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits.

BACKGROUND & AIMS Gastrointestinal (GI), liver, and pancreatic diseases are a source of substantial morbidity, mortality, and cost in the United States. Quantification and statistical analyses of the burden of these diseases are important for researchers, clinicians, policy makers, and public health professionals. We gathered data from national databases to estimate the burden and cost of GI and liver disease in the United States. METHODS We collected statistics on health care utilization in the ambulatory and inpatient setting along with data on cancers and mortality from 2007 through 2012. We included trends in utilization and charges. The most recent data were obtained from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the National Cancer Institute. RESULTS There were 7 million diagnoses of gastroesophageal reflux and almost 4 million diagnoses of hemorrhoids in the ambulatory setting in a year. Functional and motility disorders resulted in nearly 1 million emergency department visits in 2012; most of these visits were for constipation. GI hemorrhage was the most common diagnosis leading to hospitalization, with >500,000 discharges in 2012, at a cost of nearly

Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress.

5 billion dollars. Hospitalizations and associated charges for inflammatory bowel disease, Clostridium difficile infection, and chronic liver disease have increased during the last 20 years. In 2011, there were >1 million people in the United States living with colorectal cancer. The leading GI cause of death was colorectal cancer, followed by pancreatic and hepatobiliary neoplasms. CONCLUSIONS GI, liver and pancreatic diseases are a source of substantial burden and cost in the United States.

Methylene Blue Staining and Endoscopic Ultrasound Evaluation of Barrett's Esophagus with Low-Grade Dysplasia

We recently have shown that activated Ras, but not Raf, causes transformation of intestinal (RIE-1, IEC-6) epithelial cells, whereas both activated Ras and Raf transform NIH 3T3 fibroblasts (Oldham, S. M., Clark, G. J., Gangarosa, L. M., Coffey, R. J., and Der, C. J. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6924–6928). The observations that conditioned medium from Ras-, but not Raf-, transfected RIE-1 cells, as well as exogenous transforming growth factor α (TGFα), promoted morphological transformation of parental RIE-1 cells prompted us to identify epidermal growth factor (EGF) receptor (EGFR) ligands produced by Ras-transformed RIE-1 cells responsible for this autocrine effect. Since studies in fibroblasts have shown that v-Src is transforming, we also determined if v-Src could transform RIE-1 cells. H- or K-Ras-transformed cells secreted significant amounts of TGFα protein, and mRNA transcripts for TGFα, amphiregulin (AR), and heparin-binding EGF-like growth factor (HB-EGF) were induced. Like Ras, v-Src caused morphological and growth transformation of parental RIE-1 cells. However, TGFα protein was not secreted by RIE-1 cells stably expressing v-Src or activated Raf, and only minor increases in EGFR ligand mRNA expression were detected in these cells. A selective EGFR tyrosine kinase inhibitor PD153035 attenuated the Ras-, but not Src-, transformed phenotype. Taken together, these observations provide a mechanistic and biochemical basis for the ability of activated Ras, but not activated Raf, to cause transformation of RIE-1 cells. Finally, we suggest that an EGFR-dependent mechanism is necessary for Ras, but not Src, transformation of these intestinal epithelial cells.

Lubiprostone does not Influence Visceral Pain Thresholds in Patients with Irritable Bowel Syndrome

OBJECTIVES:Irritable bowel syndrome (IBS) patients show pain hypersensitivity and hypercontractility in response to colonic or rectal distention. Aims were to determine whether predominant bowel habits and IBS symptom severity are related to pain sensitivity, colon motility, or smooth muscle tone.METHODS:One hundred twenty-nine patients classified as IBS with diarrhea (IBS-D, N = 44), IBS with constipation (IBS-C, N = 29), mixed IBS (IBS-M, N = 45), and unspecified IBS (IBS-U, N = 11) based on stool consistency, and 30 healthy controls (HC) were studied. A manometric catheter containing a 600-mL capacity plastic bag was positioned in the descending colon. Pain threshold was assessed using a barostat. Motility was assessed for 10 min with the bag minimally inflated (individual operating pressure [IOP]), 10 min at 20 mmHg above the IOP, and for 15-min recovery following bag inflation. Motility was also recorded for 30 min following an 810-kcal meal.RESULTS:Compared with HC, IBS patients had lower pain thresholds (medians 30 vs 40 mmHg, P < 0.01), but IBS subtypes were not different. IBS symptom severity was correlated with pain thresholds (rho =− 0.36, P < 0.001). During distention, the motility index (MI) was significantly higher in IBS compared with HC (909 ± 73 vs 563 ± 78, P < 0.01). Average barostat bag volume at baseline was higher (muscle tone lower) in HC compared with IBS-D and IBS-M but not compared with IBS-C. The baseline MI and bag volume differed between IBS-D and IBS-C and correlated with symptoms of abdominal distention and dissatisfaction with bowel movements. Pain thresholds and MI during distention were uncorrelated.CONCLUSIONS:Pain sensitivity and colon motility are independent factors contributing to IBS symptoms. Treatment may need to address both, and to be specific to predominant bowel habit.

Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt

Abstract  Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of irritable bowel syndrome (IBS), although the issue is still under debate. The aim of this study was to determine the prevalence of SIBO in those with IBS and its association with colonic motility, bowel symptoms and psychological distress. Sucrose hydrogen and methane breath tests were performed in 158 IBS patients and 34 healthy controls (HC). Thresholds for pain and urgency were tested by barostat in the descending colon. The motility index (MI) was calculated as the average area under the curve for all phasic contractions. Questionnaires assessed psychological distress, IBS symptom severity (IBS‐SS), IBS quality of life (IBS‐QOL) and self‐reported bowel symptoms. Fifty‐two of 158 (32.9%) IBS patients had abnormal breath tests compared with six of 34 (17.9%) HC (χ2 = 0.079). SIBO (SIBO+) and non‐SIBO (SIBO−) patients did not differ in the prevalence of IBS subtypes, IBS‐SS, IBS‐QOL and psychological distress variables. IBS patients had a greater post‐distension increase in MI than HC, but there was no difference between SIBO+ and SIBO− patients. Predominant methane producers had higher urge thresholds (28.4 vs 18.3, P < 0.05) and higher baseline MI (461 vs 301.45, P < 0.05) than SIBO− IBS patients, and they reported more ‘hard or lumpy stools’ when compared with predominant hydrogen producers (P < 0.05) and SIBO− IBS patients (P < 0.05). SIBO is unlikely to contribute significantly to the pathogenesis of IBS. Methane production is associated with constipation.

A randomized, controlled, double-blind trial of air insufflation versus carbon dioxide insufflation during ERCP

This study was performed to determine if either methylene blue staining or endoscopic ultrasound helped direct biopsies in patients with a history of Barretts esophagus with low-grade dysplasia. Patients underwent radial endoscopic ultrasound scanning to measure esophageal wall thickness, followed by endoscopy with methylene blue staining and biopsies. Mean esophageal wall thickness for squamous mucosa (2.3 ± 0.2 mm), nondysplastic Barretts (2.6 ± 0.2 mm), and Barretts with dysplasia (2.9 ± 0.3 mm) were similar. With staining, Barretts mucosa stained blue more often than gastric epithelium (68% vs 15%, respectively; P < 0.001). The sensitivity and specificity for strong staining detecting Barretts were 68% and 85%, respectively. Barretts with low-grade dysplasia stained blue less frequently (52%) than nondysplastic Barretts (74%; P < 0.05), but the positive predictive value for poor staining indicating dysplasia was 41%. Endoscopic ultrasound was not helpful in directing biopsies in these patients. The utility of methylene blue for detecting dysplasia needs further investigation.