Irritable Bowel Syndrome: The Role of Food in Pathogenesis and Management

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that affects approximately 10% to 20% of the general adult population in Europe and the Americas and is characterized by abdominal pain and altered bowel habits in the absence of reliable biomarkers. The pathophysiology of IBS is poorly understood and is currently thought to represent a complex interplay among the gut microbiota, low-grade inflammation, impaired mucosal barrier function, visceral hypersensitivity, gut motility, and alterations in the gut-brain axis. In any individual patient, 1 or more of these factors may interact to generate symptoms. Although up to 50% of patients report postprandial exacerbation of symptoms, few studies have critically assessed the role of diet in IBS. Furthermore, although many patients with IBS adopt any one of a host of dietary changes in an attempt to alleviate their symptoms, there has been, up until recently, little scientific basis for any dietary recommendation in IBS. This review discusses the contribution of diet to the pathophysiology and symptoms of IBS.

Frontiers in the Treatment of Hepatitis C Virus Infection

In the United States, chronic hepatitis C virus (HCV) infection is the leading cause of blood-borne, virus-associated death related to advanced liver disease and the leading indication for liver transplantation. Although the diagnostic test for HCV has been available for more than 20 years, the majority of persons with HCV infection still have not received a diagnosis. This has led to a recent change in screening recommendations by the Centers for Disease Control and Prevention. Moreover, new medications were approved in 2011 after nearly a decade of minimal progress in the development of treatments for HCV infection. This was followed by the highly anticipated approval of sofosbuvir and simeprevir in 2013. In the past 3 years, there has been an explosion of reports on medications from different classes, promising a dramatic expansion to an all-oral regimen for the treatment of HCV genotype 1 infection within the next few years. This article reviews the current screening recommendations and standard of care for treatment of HCV infection and highlights specific agents in the pipeline that should change the landscape of how HCV infection is treated in the near future.

Emerging Therapeutic Options for Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus that often occurs in atopic persons. Management strategies include pharmacotherapy, dietary modification, and endoscopic therapy, although patients will often have a relapsing and remitting course. Currently, the primary pharmacotherapy for EoE consists of corticosteroids. Immunomodulators, leukotriene antagonists, biologics, and monoclonal antibodies are currently under study for treatment of EoE. The role of immunoglobulin E–mediated allergic reactions has been well documented and may provide insight into the etiology and effective therapy of EoE.

Gastrointestinal Motility Disorders in Children

The most common and challenging gastrointestinal motility disorders in children include gastroesophageal reflux disease (GERD), esophageal achalasia, gastroparesis, chronic intestinal pseudo-obstruction, and constipation. GERD is the most common gastrointestinal motility disorder affecting children and is diagnosed clinically and treated primarily with acid secretion blockade. Esophageal achalasia, a less common disorder in the pediatric patient population, is characterized by dysphagia and treated with pneumatic balloon dilation and/or esophagomyotomy. Gastroparesis and chronic intestinal pseudo-obstruction are poorly characterized in children and are associated with significant morbidity. Constipation is among the most common complaints in children and is associated with significant morbidity as well as poor quality of life. Data on epidemiology and outcomes, clinical trials, and evaluation of new diagnostic techniques are needed to better diagnose and treat gastrointestinal motility disorders in children. We present a review of the conditions and challenges related to these common gastrointestinal motility disorders in children.

Patterns of Acetaminophen Use Exceeding 4 Grams Daily in a Hospitalized Population at a Tertiary Care Center

Unintentional acetaminophen-induced hepatotoxicity has been increasingly recognized as a significant problem, prompting increased scrutiny and restrictions from the US Food and Drug Administration on products combining acetaminophen with narcotics. Patterns of acetaminophen use have not previously been reported in the hospitalized patient population, which may be especially vulnerable to liver injury. We aimed to quantify the frequency at which acetaminophen dosing exceeded the recommended maximum of 4 g/day in hospitalized patients. This was a retrospective, single-center, cohort study at a large tertiary care academic hospital. We queried our inpatient electronic medical record database to identify patients admitted between 2008 and 2010 who were receiving cumulative daily acetaminophen doses exceeding 4 g on at least 1 hospital day. Of 43,761 admissions involving acetaminophen administration, the recommended maximum cumulative daily dose of 4 g was exceeded in 1119 (2.6%) cases. Patients who were administered a larger number of acetaminophen-containing medications were more likely to receive doses in excess of the recommended maximum. Alanine aminotransferase (ALT) levels were checked within 14 days following acetaminophen exposure in excess of 4 g in 35 (3.1%) cases. Excessive acetaminophen dosing of hospitalized patients, who may be at increased risk for acetaminophen-induced hepatotoxicity, occurred in a minority of patients. The use of multiple acetaminophen-containing medication formulations contributed to excessive dosing. ALT level monitoring in this group was infrequent, precluding assessment of biochemical evidence of liver injury. This cohort of patients may represent an ideal population for further prospective study with more intensive and longer-term biochemical monitoring to assess for evidence of liver injury.

Ethical Considerations for Clinical Trials in Inflammatory Bowel Disease

Although advancements in the field of inflammatory bowel disease (IBD) include effective therapies for many patients with Crohn’s disease and ulcerative colitis, there remains a large unmet need, and there is a large number of investigational agents in the pipeline. Drug development through clinical trials is critical to understanding the safety and efficacy of new therapies in the affected human population, and the need for ethical trial design is of the utmost importance. This paper explores the ethical issues of clinical trials in IBD, focusing on placebo-controlled trials, vulnerable patients, exposure to monoclonal antibodies, globalization of trials, and surgical advances.

Dysphagia in the Elderly

Elderly patients are inherently predisposed to dysphagia predominately because of comorbid health conditions. With the aging of the population in the United States, along with the increased prevalence of obesity and gastroesophageal reflux disease, healthcare providers will increasingly encounter older patients with either oropharyngeal or esophageal disease and complaints of dysphagia. Useful tests to evaluate dysphagia include the videofluoroscopic swallowing study and the fiberoptic endoscopic evaluation of swallowing. Swallow rehabilitation is useful to help patients compensate for swallowing difficulty and ultimately help strengthen the neuromusculature involved in swallowing.

Environmental Influences on the Onset and Clinical Course of Crohn’s Disease—Part 2: Infections and Medication Use

The pathogenesis of Crohn’s disease (CD) involves host, genetic, and environmental factors. These factors result in disturbances in the innate and adaptive immune systems and composition of the intestinal microbiota. Epidemiologic and migration studies support an environmental component in the development of CD. Environmental risk factors include childhood hygiene, air pollution, breastfeeding, smoking, diet, stress, exercise, seasonal variation, appendectomy, medications, and infections. This 2-part series provides an overview of these external contributors to the development or exacerbation of CD. Part 1, which was published in a previous issue, focused on childhood factors, perinatal influences, and lifestyle choices. Part 2, presented here, details the effects of infections, antibiotics, nonsteroidal anti-inflammatory drugs, and oral contraceptives.

Environmental Influences on the Onset and Clinical Course of Crohn’s Disease—Part 1: An Overview of External Risk Factors

The pathogenesis of Crohn’s disease (CD) involves host, genetic, and environmental factors. These factors result in disturbances in the innate and adaptive immune systems and composition of the intestinal microbiota. Epidemiologic and migration studies support an environmental component in the development of CD. Environmental risk factors include childhood hygiene, air pollution, breastfeeding, smoking, diet, stress, exercise, seasonal variation, and appendectomy. This review, part 1 of a 2-part series, provides an overview of these external contributors to the development or exacerbation of CD. Part 2, which will be published in a subsequent issue, will discuss the influences of infections, vaccinations, and medications (including antibiotics, nonsteroidal anti-inflammatory agents, and oral contraceptives) on CD. Inflammatory bowel disease (IBD) is a chronic, relapsing, and remitting disease of the gastrointestinal tract manifesting as Crohn’s disease (CD) or ulcerative colitis (UC). The development of IBD involves a complex interplay between genetic predisposition and the environment. Genetic factors have been well documented as contributing to the pathogenesis of CD; however, twin studies have shown an important environmental influence on CD.1 Several epidemiologic studies have demonstrated a rising incidence of CD and geographic variation over the past several decades, suggesting an environmental impact on the pathogenesis of IBD.2,3 It has been speculated that environmental factors can influence intestinal permeability, alter the mucosal immune system, and disrupt the intestinal microbiota, thereby creating a predisposition to IBD.4 This review, part 1 of a 2-part series, will focus on these environmental risk factors, including childhood influences, lifestyle choices, seasonal variation, and appendectomy, on the development or exacerbation of CD. Part 2, which will be published in a subsequent issue, will focus on the microbiota and the influences of infections, immunizations, and medications on CD. The Table summarizes childhood, lifestyle, perinatal, and environmental factors.

Sleep and Inflammatory Bowel Disease: Exploring the Relationship Between Sleep Disturbances and Inflammation

Sleep disturbances are associated with a greater risk of serious adverse health events, economic consequences, and, most
importantly, increased all-cause mortality. Several studies support the associations among sleep, immune function, and inflammation. The relationship between sleep disturbances and inflammatory conditions is complex and not completely understood. Sleep deprivation can lead to increased levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and C-reactive protein, which can lead to further activation of the inflammatory cascade. The relevance of sleep in inflammatory bowel disease (IBD), a chronic immune-mediated inflammatory disease of the gastrointestinal tract, has recently received more attention. Several studies have shown that patients with both inactive and active IBD have self-reported sleep disturbances. Here, we present a concise review of sleep and its association with the immune system and the process of inflammation. We discuss the studies that have evaluated sleep in patients with IBD as well as possible treatment options for those patients with sleep disturbances. An algorithm for evaluating sleep disturbances in the IBD population is also proposed. Further research is still needed to better characterize sleep disturbances in the IBD population as well as to assess the effects of various therapeutic interventions to improve sleep quality. It is possible that the diagnosis and treatment of sleep disturbances in this population may provide an opportunity to alter disease outcomes.

The Impact of the Affordable Care Act on the Future of Endoscopy Practice

The Impact of the Affordable Care Act on the Future of Endoscopy Practice Klaus Mergener, MD, PhD, MBA Partner, Digestive Health Specialists, Clinical Medical Director, Gastroenterology, MultiCare Health System, Tacoma, […]

Liver Disease in Women: Influence of Gender on Epidemiology, Natural History, and Patient Outcomes

Women more commonly present with acute liver failure, autoimmune hepatitis, benign liver lesions, primary biliary cirrhosis, and toxin-mediated hepatotoxicity. Women less commonly have malignant liver tumors, primary sclerosing cholangitis and viral hepatitis. There is a decreased rate of decompensated cirrhosis in women with hepatitis C virus, no survival difference in alcohol-related liver disease, and improved survival from hepatocellular carcinoma. In general, men are 2-fold more likely to die from chronic liver disease and cirrhosis than are women. Liver transplant occurs less commonly in women compared with men, with variable disease outcomes based on etiology. In this review we highlight the epidemiology, natural history, treatment outcomes, and pathophysiology of common liver diseases in women. We discuss how gender influences disease incidence, presentation, progression, and outcomes and explore the pathophysiology. Pregnancy related-liver disease is not covered in this review.

Gastric Polyps: A Review on Clinical, Endoscopic, Histopathologic Features and Management Decisions

The increasing use of endoscopy has led to more discernable abnormalities in the stomach, including polyps. Gastric polyps encompass a spectrum of pathologic conditions that can vary in histology, neoplastic potential, and management. Despite their high prevalance, there is a paucity of literature to support managment and treatment decisions for endoscopists. The goal of this review is to summarize clinical, endoscopic and histopathologic features among various polyps, review syndromes associated with such polyps, and provide management recommendations.

Gut Bacteria in Health and Disease

A new era in medical science has dawned with the realization of the critical role of the “forgotten organ,” the gut microbiota, in health and disease. Central to this beneficial interaction between the microbiota and host is the manner in which bacteria and most likely other microorganisms contained within the gut communicate with the host’s immune system and participate in a variety of metabolic processes of mutual benefit to the host and the microbe. The advent of high-throughput methodologies and the elaboration of sophisticated analytic systems have facilitated the detailed description of the composition of the microbial constituents of the human gut, as never before, and are now enabling comparisons to be made between health and various disease states. Although the latter approach is still in its infancy, some important insights have already been gained about how the microbiota might influence a number of disease processes both within and distant from the gut. These discoveries also lay the groundwork for the development of therapeutic strategies that might modify the microbiota (eg, through the use of probiotics). Although this area holds much promise, more high-quality trials of probiotics, prebiotics, and other microbiota-modifying approaches in digestive disorders are needed, as well as laboratory investigations of their mechanisms of action.

Colonoscopic Perforation in Inflammatory Bowel Disease

Colonoscopy has become the diagnostic and therapeutic modality of choice in patients with inflammatory bowel disease (IBD) by allowing for the assessment of disease extent and activity; the distinction between ulcerative colitis, Crohn’s disease, and other differential diagnoses; the surveillance of dysplasia; and the delivery of treatment (eg, stricture dilation). Colonoscopy-associated perforation is a dreaded complication associated with significant mortality and morbidity. Understanding and mitigating the risks of perforation in patients with IBD has become an important issue with the increasing use of immunomodulators and biologic agents. Studies have shown that patients with IBD are at a higher risk for perforation from diagnostic or therapeutic endoscopy than individuals in the general population. Reported risk factors associated with colonoscopic perforation include female sex, advanced age, severe colitis, use of corticosteroids, presence of multiple comorbidities, and stricture dilation. Disease-, technique-, and endoscopist-associated risk factors for perforation can be stratified and modified. This review, based on current available literature and the authors’ expertise, should shed some light on the proper management of this challenging disease phenotype.

Complications of Endoscopic Retrograde Cholangiopancreatography: How to Avoid and Manage Them

Endoscopic retrograde cholangiopancreatography (ERCP) is a therapeutic procedure used to treat problems associated with biliary and pancreatic diseases. The benefits of ERCP over surgical treatment are well documented; however, complications including infection, pancreatitis, hemorrhage, and perforation can occur even in expert hands. Several factors, such as patient selection, skill of the operator, and the complexity of the procedure, can add to the intrinsic risks of ERCP. This review outlines the current knowledge regarding ERCP complications and solutions for improved outcomes.

Evaluation of Peripapillary Lymphocytosis and Lymphocytic Esophagitis in Adult Inflammatory Bowel Disease

Lymphocytic esophagitis (LE) is a newly described entity characterized histopathologically by peripapillary lymph-ocytosis (PL) without significant granulocytes (neutrophils and eosinophils). In an initial study, a significant portion of patients with LE had Crohn’s disease (CD). A subsequent study revealed LE in one quarter of children with CD. The aim of this study was to test the hypothesis that LE is associated with adult inflammatory bowel disease (IBD) and assess the disease variables that link LE and IBD. Random esophageal biopsies from consecutive adults with CD, ulcerative colitis (UC), or indeterminate colitis (IC) were evaluated. The numbers of lymphocytes, eosinophils, and neutrophils were counted from 3 high-power fields (HPF) in each specimen. Four of 47 patients (8.5%; 3/30 CD, 1/15 UC, and 0/2 IC) had PL (esophageal biopsies with ≥50 lymphocytes/HPF; mean, 100.5±31.1/HPF). A significant number of granulocytes were seen in biopsies from 3 of the 4 patients with PL, leaving 1 who met criteria for LE (PL without significant granulocytes). PL was associated with a higher erythrocyte sedimentation rate (90.3±17.6 mm/hr vs 24.5±3.6 mm/hr; P<.001) and C-reactive protein level (5.5±2.2 mg/dL vs 1.0±0.2 mg/dL; P<.001), with risk ratios of 2.06 (95% confidence interval [CI], 1.45–2.93; P=.031) and 3.56 (95% CI, 2.04–6.19; P=.033), respectively, for elevated values. All patients with PL had a relapsing CD course. The mean Harvey-Bradshaw index (HBI) was higher in these patients (8.5±0.6 vs 4.3±0.7; P=.026), with a risk ratio of 4.78 for moderate-to-severe disease (95% CI, 2.67–8.54; P=.004). We found a less frequent association between IBD and LE than was previously reported. This may be due to differences between pediatric and adult IBD. Alternatively, it may be methodologic because, unlike in previous reports, we evaluated consecutive patients with IBD. PL was associated with elevated inflammatory markers and HBI. These observations suggest that PL may be a marker of disease activity in IBD.

Office-Based Management of Fecal Incontinence

Fecal incontinence (FI) is a devastating disorder that is more prevalent than previously realized. FI is the involuntary loss of stool. Many factors contribute to the pathophysiology of FI, including advanced age, bowel irregularity, parity, and obesity. A detailed history and focused rectal examination are important to making the diagnosis and determining contributing causes. Although multiple diagnostic studies are available to assess the cause of FI, specific guidelines that delineate when testing should be done do not exist. Clinicians must weigh the risk, benefit, and burden of testing against the need for empiric treatment. All types of FI are initially managed in the same way, which includes lifestyle modification to reduce bowel derangements, improved access to toileting, and initiation of a bulking regimen to improve stool consistency. If initial conservative management fails, pharmacologic agents, biofeedback, or surgery may be indicated.

The Effect of Liver Transplantation for Primary Sclerosing Cholangitis on Disease Activity in Patients with Inflammatory Bowel Disease

Immunosuppressive therapies are indicated following liver transplantation (LT) to prevent graft loss through rejection, and these same agents also may have a role in the management of inflammatory bowel disease (IBD). The aims of this study were to examine the effects of immunosuppression following LT on IBD activity and to identify markers of IBD control post-LT in patients with IBD who underwent LT for primary sclerosing cholangitis (PSC). A retrospective analysis of all adult patients with a pre-LT diagnosis of IBD who underwent LT for PSC over a 15-year period was performed. The primary outcome was IBD activity based on symptomatology and endoscopic assessment. Secondary outcomes included recipient mortality and post-LT development of colorectal cancer or small bowel lymphoma. A total of 105 patients underwent LT for PSC, and IBD was diagnosed in 27 (26%) pre-LT. Patients were followed for a mean of 88.5 months. Fourteen (52%) patients had stable IBD, 6 (22%) had worsening disease, and 7 (26%) had clinical improvement after LT. Colorectal cancer developed in 2 (7%) patients, and small bowel lymphoma developed in 1 (4%) patient. The absence of additional maintenance therapy for IBD was found to be associated with good outcome for IBD control. The use of either infliximab (Remicade, Janssen Biotech) or corticosteroids to control IBD post-LT was associated with poor outcome. Most patients with PSC and IBD had a stable course of IBD post-LT. The need for infliximab or additional or prolonged corticosteroids after LT appears to be a surrogate marker of aggressive disease.

Environmental Risk Factors for Inflammatory Bowel Disease

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases that often have a relapsing-remitting course in young persons. Genetic-risk polymorphisms explain less than one third of the heritability of disease. Epidemiologic and laboratory data suggest that environmental factors play a significant role in influencing the risk and natural history of disease. Smoking is the most widely and consistently described risk factor. It, however, increases the risk of CD while conferring protection against UC. The gut microbiome is a key component in the development of inflammatory bowel disease (IBD). Several external factors potentially exert an effect by influencing the composition of the gut microbiome or disrupting the intestinal barrier. These external influences include the use of antibiotics or nonsteroidal anti-inflammatory drugs and the presence of enteric infections. Data on diet have been inconsistent, but high fiber intake, particularly of soluble fiber, appears to protect against CD, whereas protein intake may increase disease risk. Vitamin D may also play an important protective role, particularly in patients with CD. Neurobehavioral factors, such as stress and depression, also influence the risk of IBD. Systematic and rigorous studies of environmental exposures in the management of IBD are needed. In particular, studies of whether environmental factors can be modified to reduce the likelihood of relapse or improve patient outcomes would be valuable.