What Role Does Wheat Play in the Symptoms of Irritable Bowel Syndrome?

Recently, increasing attention has been paid to the pathologic role of food in irritable bowel syndrome (IBS). Nevertheless, healthcare providers often avoid addressing diet with their patients because of a lack of training, guideline consensus, and high-quality data. Recent literature supports the existence of a subgroup of IBS patients with undiagnosed nonceliac gluten sensitivity (NCGS), a term that is used to describe individuals who experience gastrointestinal and extraintestinal symptoms as a result of immunologic, morphologic, or symptomatic abnormalities that are precipitated by the ingestion of gluten. NCGS represents an important subgroup of patients with IBS who are highly treatable via dietary modification. Gluten may influence gastrointestinal symptoms through immune activation or alteration of intestinal permeability, but the true role of food in functional gastrointestinal symptomatology remains unclear. For example, gluten is just 1 component of the complex milieu of nutrients found in wheat and related grains, and NCGS likely represents only the tip of the iceberg as it pertains to the role of food in IBS.

The Potential Applications of Capsule Endoscopy in Pediatric Patients Compared with Adult Patients

Capsule endoscopy (CE) avoids the ionizing radiation, deep sedation, and general anesthesia required by other imaging modalities, making it particularly valuable in the evaluation of gastrointestinal disease in pediatric patients. In examining the use of CE in pediatric and adult patients through a review of the literature, it was observed that CE is most frequently indicated for the evaluation of Crohn’s disease (CD) in pediatric patients and most frequently indicated for obscure gastrointestinal bleeding (OGIB) in adults, although OGIB is a more frequent indication than CD in pediatric patients younger than 8 years of age. Diagnostic accuracy has been good and comparable to that of magnetic resonance enterography, and capsule retention rates as well as other adverse events appear to be low in pediatric patients. Research is needed to explore broader indications and applications of CE in the diagnosis and monitoring of gastrointestinal disease.

Crohn’s Disease: The Subsequent Visit

Abstract: The diagnosis and subsequent management of Crohn’s disease are challenging for both the patient and the gastroenterologist. After the initial assessment, subsequent visits should assess the patient’s readiness to begin therapy, monitor progress if therapy has been initiated, assess for complications of the disease or therapy, and ensure that all appropriate health maintenance measures are current. This article is intended to be a companion to our earlier paper “Crohn’s Disease: The First Visit,” which was published in Gastroenterology & Hepatology in March 2011. This article will offer a methodologic and sequential approach to subsequent office visits, as well as provide a checklist for the assessment of Crohn’s disease.

The Burden of Diverticular Disease on Patients and Healthcare Systems

Abstract: Diverticulitis is a debilitating complication of diverticular disease that affects approximately 2.5 million individuals in the United States. Compared to many other gastrointestinal conditions, diverticular disease is poorly understood in terms of its burden on patients and healthcare systems. This review examines the existing literature and discusses the current knowledge of the burden of diverticular disease. Literature confirmed that bothersome symptoms (such as abdominal pain and bloating) and potentially serious, disease-related complications (such as diverticulitis and diverticular bleeding) place a significant burden on patients. Broad-spectrum antibiotic therapy and surgery are the generally accepted mainstays of treatment for acute complications of diverticular disease. Despite these options, patients frequently experience substantially reduced quality of life (particularly in terms of social and emotional functioning) and increased mortality (predominantly due to disease-related complications) compared to healthy controls. Furthermore, diverticular disease accounted for 254,179 inpatient discharges and 1,493,865 outpatient clinic visits in the United States in 2002, at an estimated cost per hospitalization of $9,742–$11,729. Enhancing the quality of life of patients with diverticular disease and reducing disease exacerbations and complications will substantially benefit patients and healthcare systems. However, long-established treatment algorithms fall short of these therapeutic goals. Research into new treatment options for patients with diverticular disease should therefore be pursued.

Chromoendoscopy and Advanced Imaging Technologies for Surveillance of Patients with IBD

Abstract: Inflammatory bowel disease patients with long-standing colitis have an increased risk of colorectal cancer. The high rate of interval colitis-associated cancers among patients who adhere to a nontargeted, random biopsy surveillance strategy underlies the need for improved methods of early dysplasia detection. Compelling evidence supports the efficacy of chromoendoscopy for increasing the detection rate of dysplasia; however, this technology is currently underutilized in the clinical setting. Other contrast-based technologies—including confocal laser endomicroscopy (Pentax), endocytoscopy, multiband imaging, i-scan (Pentax), and molecular-targeted techniques—show promise in the detection of dysplasia in patients with inflammatory bowel disease. The strategies currently available for identifying patients with dysplasia or colitis-associated cancers remain inadequate and need to demonstrate both cost and time efficiency before they can be adopted in community-based practices.

Tumor Factors Associated with Clinical Outcomes in Patients with Hepatitis B Virus Infection and Hepatocellular Carcinoma

Background and aims: Hepatitis B virus (HBV) infection is a common cause of hepatocellular carcinoma (HCC) in the United States. This study evaluated the impact of surveillance and treatment on HBV-infected HCC patients and identified factors associated with survival. Methods: From 1981 to 2010, 166 hepatitis B surface antigen (HBsAg)-positive HCC patients were evaluated. Fifty-eight patients had HCC detected by surveillance, while 108 patients presented with HCC. Results: Compared to patients detected by surveillance, those presenting with HCC had more symptoms (65.7% vs 41.4%; P=.002), were more frequently outside of Milan criteria (73.7% vs 29.6%; P<.001), more often presented with diffuse tumors (23.2% vs 1.9%; P<.001), and had a shortened median survival time (9.5 months vs 18.7 months; P=.003). Patients who presented with diffuse tumors were younger and more often male (P=.002–.007), had a higher alpha-fetoprotein (AFP) level (P=.023), and had a median survival time of only 1.68 months. By multivariate analysis, factors that were significantly associated with mortality included diffuse tumors (hazard ratio [HR], 6.30; 95% confidence interval [CI], 3.14–12.66; P<.001), being outside of Milan criteria (HR, 2.02; 95% CI, 1.26–3.23; P=.005), albumin level (HR per 1 standard deviation decrease, 1.4; 95% CI, 1.15–1.72; P=.001), AFP level (HR per 1 log standard deviation increase, 1.38; 95% CI, 1.13–1.67; P=.001), and receiving liver transplantation versus other treatments (HR, 0.08–0.38; 95% CI, 0.03–0.87; P<.001 to P=.022). Conclusion: In the United States, HBV-related HCC is a common malignancy, especially among Asian immigrants. Identification of HBsAg-positive subjects and routine HCC surveillance are essential for improving survival in these patients.

Direct-Acting Antiviral Agents in Patients with Hepatitis C Cirrhosis

Patients with cirrhosis who are infected with hepatitis C virus (HCV) are the most in need of antiviral treatment. Virologic cure improves fibrosis and quality of life while reducing liver-related morbidity and mortality. In mid-2011, the addition of direct-acting antiviral agents (DAAs)—the protease inhibitors boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex)—to pegylated interferon a-2a/b and ribavirin revolutionized the treatment of HCV infection by increasing cure rates across all fibrosis scores in patients with genotype 1 HCV infection. However, patients with advanced fibrosis or cirrhosis are the most difficult to treat, and the addition of DAAs increases treatment side effects as well as potency. Five phase III DAA trials have been published to date, but they contain limited data on patients with cirrhosis. This review will examine the available data and will describe the evolution of HCV therapy in patients with cirrhosis from the standard-of-care therapy of the past decade into the new era of DAAs

Low-FODMAP Diet for Treatment of Irritable Bowel Syndrome

Functional bowel disorders, including irritable bowel syndrome (IBS), are common disorders that have a significant impact on patients’ quality of life. These disorders present major challenges to healthcare providers, as few effective medical therapies are currently available. Recently, there has been increasing interest in dietary therapies for IBS, particularly a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Since ingestion of FODMAPs increases the delivery of readily fermentable substrates and water to the distal small intestine and colon—which results in luminal distention and gas—the reduction of FODMAPs in a patient’s diet may improve functional gastrointestinal symptoms. This paper will review the pathophysiology of IBS and the role of FODMAPs for the treatment of this condition.

Linaclotide: A Novel Therapy for Chronic Constipation and Constipation-Predominant Irritable Bowel Syndrome

Chronic constipation and irritable bowel syndrome (IBS) are functional gastrointestinal disorders that significantly affect patients’ quality of life. Chronic constipation and IBS are prevalent—12% of the US population meet the diagnostic criteria for IBS, and 15% meet the criteria for chronic constipation—and these conditions negatively impact the healthcare system from an economic perspective. Despite attempts at dietary modification, exercise, or use of over-the-counter medications, many patients have persistent symptoms. Alternative treatment options are limited. This article describes linaclotide (Linzess, Ironwood Pharmaceuticals/Forest Pharmaceuticals), a new, first-in-class medication for the treatment of chronic constipation and constipation-predominant IBS.

Noninvasive Diagnosis of NASH and Liver Fibrosis Within the Spectrum of NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in the United States, affecting an estimated 70 million Americans. The histologic spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually cirrhosis. Patients with NASH and significant fibrosis seen on liver biopsy have an increased risk for liver-related morbidity and mortality compared to patients with simple steatosis. Due to the high prevalence of NAFLD, there has been an urgent need to develop reliable noninvasive markers and tests that can accurately predict the presence of advanced disease without the need for liver biopsy. These tests can be divided into 2 groups: those that predict the presence of NASH (such as markers of hepatocyte apoptosis, oxidative stress, and inflammation, as well as predictive models based on clinical variables) and those that predict the presence of fibrosis (such as simple and complex predictive models). This paper provides an overview of various noninvasive methods for detecting NAFLD and suggests a diagnostic algorithm that can be used in clinical practice.

Emerging Therapeutic Options for Celiac Disease: Potential Alternatives to a Gluten-Free Diet

Celiac disease is an autoimmune disorder of the small intestine that is more common than was previously thought. This disease is caused by an inappropriate immune response to wheat gluten, barley, and rye. Three main pathways cause celiac disease: the environmental trigger (gluten), genetic susceptibility, and unusual gut permeability. The only treatment currently available is a strict gluten-free diet. Unfortunately, a majority of patients have difficulty complying with this diet, and the response to therapy is poor. Therefore, alternative treatments are being developed, and new insights into the pathophysiology of celiac disease have led to research into novel therapies. New treatments include engineering gluten-free grains, decreasing intestinal permeability by blockage of the epithelial zonulin receptor, inducing oral tolerance to gluten with a therapeutic vaccine, and degrading immunodominant gliadin peptides using probiotics with endopeptidases or transglutaminase inhibitors. These nondiet-based therapies provide hope for enhanced, lifelong celiac disease management with improved patient compliance and better quality of life.

New Developments in Extraesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) can present with a wide variety of extraesophageal symptoms that are usually difficult to diagnose because of the absence of typical GERD symptoms (ie, regurgitation or heartburn). The diagnostic process is further complicated by the lack of a definitive test for identifying GERD as the cause of extraesophageal reflux symptoms. Due to the low predictive value of upper endoscopy and pH testing—as well as the lack of reliability of the symptom index and symptom association probability—extraesophageal reflux disease is still an area of investigation. This paper discusses recent developments in this field, with special emphasis on new diagnostic modalities and treatment options.

Vaccination Issues in Patients with Inflammatory Bowel Disease Receiving Immunosuppression

Treatment regimens for Crohn’s disease and ulcerative colitis increase susceptibility to infections, many of which can be prevented by vaccinations. Increased awareness concerning vaccine-preventable diseases has led to several studies investigating the immunologic responses to vaccines in immunosuppressed patients with inflammatory bowel disease. This review provides an overview of the evidence-based rationale for currently accepted recommendations regarding the use of both inactivated and live vaccines in this unique population.

Potential Applications of Thromboelastography in Patients with Acute and Chronic Liver Disease

Patients with acute and chronic liver disease have long been assumed to have a bleeding tendency on the basis of abnormal results for standard tests of hemostasis. However, recent studies have suggested that hemostasis in patients with liver disease exists in a state of rebalance, in which defects in prohemostatic drivers are compensated for by commensurate changes in antihemostatic drivers. Standard assays of hemostasis cannot evaluate this potential state of rebalance because they only assess components of clot formation and, therefore, may provide misleading information regarding the risk of bleeding, possibly leading clinicians to administer unneeded or even harmful prohemostatic factors. Thromboelastography (TEG) is a commercially available, rapid, point-of-care assay that assesses clot formation in whole blood, including plasmatic and cellular components. Studies using TEG in patients with cirrhosis and acute liver failure have suggested that rebalanced hemostasis exists in many patients, even in the presence of thrombocytopenia and an elevated prothrombin time/international normalized ratio. TEG has also been used to study mechanisms of rebalanced hemostasis and the pathogenesis of specific complications of liver disease, such as variceal rebleeding and infection. Finally, TEG has become widely used to guide factor repletion and fibrinolytic therapy during liver transplantation. The present clinical review will summarize these potential applications of TEG in patients with liver disease.

A Comprehensive Review of Esophageal Stents

Esophageal stents are important tools for palliative treatment of inoperable esophageal malignancies. With the development of multiple self-expandable stents, there are now several therapeutic options for managing benign and malignant esophageal diseases. This paper discusses the various types of esophageal stents currently available, indications for their placement, challenges and complications that gastroenterologists face when placing these stents, and some of the innovations that will become available in the near future.

Hepatitis C Virus and Its Renal Manifestations: A Review and Update

Hepatitis C virus (HCV) causes chronic systemic infection, primarily affecting the liver. Although HCV mainly causes hepatitis, a significant portion of chronic HCV patients manifests with at least 1 extrahepatic involvement during the course of their illness. Chronic HCV infection can cause various types of renal diseases. The most common renal manifestations of HCV infection are essential mixed cryoglobulinemia leading to membranoproliferative glomerulonephritis (MPGN), MPGN without cryoglobulinemia, and membranous glomerulonephritis. On the other hand, patients with end-stage kidney disease are at an increased risk of acquiring HCV due to their frequent exposure to potentially contaminated devices in dialysis units and their long-term use of vascular access. Among dialysis patients or patients undergoing renal transplantation, the presence of HCV is associated with higher rates of mortality. The optimal antiviral therapy in patients with severe renal insufficiency is not yet well established and, in most cases, is associated with serious adverse effects. Randomized controlled trials looking at treatment options are lacking. This article reviews the pathophysiology of renal manifestations of chronic HCV infection, discusses recent insights into diagnostic and treatment options for HCV-induced glomerulopathies and HCV-infected dialysis patients, and describes the work-up of HCV-positive renal transplant candidates.

Therapeutic Endoscopic Ultrasound

Endoscopic ultrasound (EUS) is a viable and often preferred alternative to interventional and radiologic procedures, and the therapeutic applications of EUS continue to evolve. This evolution was catalyzed by the introduction of linear echoendoscopes that provide continuous imaging and observation of needles and by therapeutic devices that pass through large-caliber working channels. In this paper, we will discuss the spectrum of EUS-guided interventions that are currently available and in development.

Drug Interactions: A Primer for the Gastroenterologist

One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications.

Update on Natural Orifice Translumenal Endoscopic Surgery

Natural orifice translumenal endoscopic surgery (NOTES) has moved from the realm of laboratory experiments to the realm of human clinical trials. This paper reviews the spectrum of NOTES procedures currently available in the United States and worldwide. It also discusses the limitations and avenues for further development of these procedures, particularly those involving the transgastric approach.

Hepatitis C Virus Infection and Nonalcoholic Steatohepatitis

Nonalcoholic fatty-liver disease (NAFLD) is one of the most prevalent liver diseases in the Western hemisphere. The rising rates of obesity and diabetes mellitus correlate with the increasing incidence of NAFLD, which is the hepatic manifestation of metabolic syndrome. Hepatitis C virus infection is another common cause of liver disease worldwide. Up to 70% of patients with chronic hepatitis C (CHC) will have concomitant steatosis. The presence of NAFLD has been implicated as a cause of lower viral response rates in CHC patients who are treated with pegylated interferon and ribavirin. This review will focus on the factors that lead to NAFLD in the setting of hepatitis C virus infection, including viral and host factors—in particular, inflammatory mediators, cytokines, and lipid peroxidation. This paper will also discuss the implications of NAFLD and nonalcoholic steatohepatitis regarding fibrosis progression, risk of hepatocellular carcinoma, and limitations with antiviral therapy.