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.

Optimizing Diagnostic Yield for EUS-Guided Sampling of Solid Pancreatic Lesions: A Technical Review

Endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) has a higher diagnostic accuracy for pancreatic cancer than other techniques. This article will review the current advances and considerations for optimizing diagnostic yield for EUS-guided sampling of solid pancreatic lesions. Preprocedural considerations include patient history, confirmation of appropriate indication, review of imaging, method of sedation, experience required by the endoscopist, and access to rapid on-site cytologic evaluation. New EUS imaging techniques that may assist with differential diagnoses include contrast-enhanced harmonic EUS, EUS elastography, and EUS spectrum analysis. FNA techniques vary, and multiple FNA needles are now commercially available; however, neither techniques nor available FNA needles have been definitively compared. The need for suction depends on the lesion, and the need for a stylet is equivocal. No definitive endosonographic finding can predict the optimal number of passes for diagnostic yield. Preparation of good smears and communication with the cytopathologist are essential to optimize yield.

Quality Improvement in Inflammatory Bowel Disease

Chronic illnesses such as inflammatory bowel disease (IBD) present a unique opportunity to define and improve the quality of care. Processes of care can be complex, and outcomes of care may vary across different healthcare delivery settings. Patients with IBD are managed over long periods of time and often by the same physician within a single care delivery system. Both patients with Crohn’s disease and ulcerative colitis have variable courses of disease progression that require changes in therapy over time. These factors necessitate multiple areas of potential assessment and improvement of processes and outcomes of care. A current initiative is the development of quality measures. The American Gastroenterological Association has developed accountability measures for the Physician Quality Reporting System, and the Crohn’s and Colitis Foundation of America has developed a set of top 10 recommended processes and outcomes of measurement for high-quality care of patients with IBD. In addition, the pediatric ImproveCareNow collaborative network has collected improvement data from dozens of pediatric centers over the past 5 years and has demonstrated improvement in overall disease activity in their cohort through iterative quality improvement processes. Future directions for quality indicators for adults with IBD will involve implementation of quality-measure reporting, both for purposes of reimbursement as well as improvement of care. These strategies will need to be closely monitored to evaluate the effect of improvement programs on outcomes.

Screening for Hepatitis B Virus and Hepatitis C Virus at a Community Fair: A Single-Center Experience

Despite recommendations for screening for hepatitis B virus (HBV) and hepatitis C virus (HCV), most individuals are still unaware of their infection status. The disparities in screening for HBV and HCV can be attributed to lack of awareness, language barriers, and difficulty in accessing healthcare. To address these issues, an exhibit booth was set up at an annual cultural festival to promote awareness about HBV and HCV and also provide free screening for a local Floridian community. Recruitment was conducted in various languages by physicians and nurses who specialize in hepatology. All materials associated with the screening process were sponsored by the Schiff Center for Liver Diseases, which is located at the University of Miami Miller School of Medicine in Florida. In the first year of the screening initiative, 173 of 11,000 fair attendees were screened for HBV. Twenty-nine (17%) of those screened tested positive for antibodies to hepatitis B core antigen (anti-HBc), and only 1 individual tested positive for chronic HBV, with positive hepatitis B surface antigen (HBsAg). Screening for HCV and an extended patient questionnaire were added to the screening program in the second year of the initiative. A total 231 of 9,000 fair attendees volunteered to be screened for both HBV and HCV. Twenty-nine (13%) of these people tested positive for anti-HBc, and 3 tested positive for HBsAg. Only 1 person tested positive for anti-HCV, but this individual had undetectable HCV RNA levels. Our single-center experience illustrates that, despite efforts to improve access to screening, only 2–3% of attendees at a cultural fair embraced the screening efforts. Other strategies will be required to enhance participation in screening programs for viral hepatitis.

Quality Metrics in Endoscopy

Endoscopy has evolved in the past 4 decades to become an important tool in the diagnosis and management of many digestive diseases. Greater focus on endoscopic quality has highlighted the need to ensure competency among endoscopists. A joint task force of the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy has proposed several quality metrics to establish competence and help define areas of continuous quality improvement. These metrics represent quality in endoscopy pertinent to pre-, intra-, and postprocedural periods. Quality in endoscopy is a dynamic and multidimensional process that requires continuous monitoring of several indicators and benchmarking with local and national standards. Institutions and practices should have a process in place for credentialing endoscopists and for the assessment of competence regarding individual endoscopic procedures.

Sodium Benzoate for Treatment of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction.

Postinfectious Functional Gastrointestinal Disorders: A Focus on Epidemiology and Research Agendas

Epidemiologic research is fundamental and complementary to our understanding of disease and development of primary, secondary, and tertiary interventions. To put the current evidence into context and identify gaps and research priorities in the areas of disease attribution, burden of disease, clinical characterization, and management of postinfectious functional gastrointestinal disorders (PI-FGDs), we took a multidisciplinary approach from the domains of infectious disease, gastroenterology, epidemiology, and public health. Our review of data from these disciplines found that, despite a complete understanding of pathoetiology, studies continue to accumulate and point toward evidence of a causal association for FGD. For some FGDs, Bradford Hill’s criteria for causality yield more certainty than other criteria. In addition, the growing recognition of the impact of acute foodborne illness on economics and society is leading to exploration of the potential long-term health effects and disease burden of PI-FGDs, although a paucity of data exist in terms of pathogen-specific risk, disability duration, and relevant disability weights. Lastly, the understanding of PI-FGDs
is changing the way research is approached and suggests a need for a more expansive exploration of biologic mechanisms and how FGDs are categorized. Areas of research priorities are catalogued in this paper and will hopefully provide inspiration for future studies and contributions to the field of gastroenterology.

Computed Tomography Colonography for Colorectal Cancer Screening

Colorectal cancer screening has been shown to help prevent cancer-related death. Concerns about suboptimal adherence to conventional colonoscopy has led to the search for alternative screening modalities. Computed tomography colono-graphy (CTC) is a highly sensitive and minimally invasive alternative modality. The American College of Radiology has established a standardized reporting system for CTC. The advantages of CTC include complete colonic examination and extraluminal imaging in a single breath hold time. Lack of sensitivity in the evaluation of flat lesions and radiation exposure are the main concerns with this modality. Although the usefulness of CTC has been demonstrated in academic centers, larger studies in community settings are needed to facilitate its adoption by healthcare services.