Reviews & Analysis

The modern colonoscopist faces two problems: identifying all relevant lesions and then making an appropriate risk assessment of the detected lesions. The latter is crucial for determining patient outcome. A feasibility study suggests that a new endomicroscopy technology could greatly improve the detection and assessment of neoplastic colorectal lesions.

The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases; however, the specific immune and physiological effects of probiotics in health and disease have not been fully elucidated. This Review considers recent advances in clinical trials of probiotics for intestinal disorders. An overview ofin vitro and in vivoresearch related to potential mechanisms of action of various probiotic formulations is also considered.

Chronic infection with HCV is a major cause of liver-related death worldwide and can be treated with interferon α therapy. This Review focuses on pegylated interferons and will discuss the mechanisms of action, structure, and pharmacokinetics of two different pegylated interferons—PEG-IFN-α2a and PEG-IFN-α2b. Alessio Aghemo and colleagues analyze all available data on these two pegylated interferons and discuss and directly compare the efficacy and safety of these drugs.

A 72-year-old man was evaluated for dysgeusia, diarrhea and ano-rexia. 3 months earlier he began to experience taste changes, a de-cline in appetite and 3–7 loose, non-bloody stools per day, followed by nausea, lower abdominal cramping and weight loss of 22.68 kg. Cronkhite–Canada syndrome was diagnosed and treatment started with prednisone, a histamine-2-receptor blocker and oral micronutrient supplementation. All visible polyps were removed and subtotal colectomy with end-to-side ileorectostomy per-formed.

Hepatocellular carcinoma is a global health problem, although developing countries are disproportionally affected. About three-quarters of hepatocellular carcinomas are attributed to chronic HBV and HCV infections. This Review provides an overview of the global variation in hepatocellular carcinoma incidence and etiology, as well as the prevention, screening, diagnosis and treatment of this cancer.

The prognosis for locally advanced pancreatic carcinoma remains dismal despite advances in chemotherapy and radiotherapy over the past few decades. The use of radiotherapy for pancreatic carcinoma is often disputed because of the hypothesis that patients with pancreatic cancer die from distant metastases. This Review discusses the data from prospective and retrospective studies evaluating radiotherapy and other treatment options for locally advanced pancreatic carcinoma.

Confocal laser endomicroscopy (CLE) is an emerging technology with important applications in gastrointestinal imaging. Fluorescein, the contrast agent most commonly employed in CLE, has not yet been approved by the FDA for intravenous use with this technique in the gastrointestinal setting. A cross-sectional study suggests that fluorescein is generally safe and usually has none or only mild adverse effects in patients undergoing CLE.

Chronic sacral nerve stimulation has an important role in the treatment of fecal incontinence. Newly reported findings indicate that this technique is an effective treatment for fecal incontinence resulting from unrepaired morphological defects of the anal sphincters, and suggest that the indications for this treatment can be expanded to include intractable constipation.

Few effective treatments for the common disorder of chronic constipation are currently available. Linaclotide, a guanylate cyclase C receptor agonist, has shown promising efficacy as a treatment for chronic constipation in a phase IIb, double-blinded, placebo-controlled, dose-ranging trial. This new therapy could potentially improve symptoms, such as bloating and discomfort, as well as bowel habits for patients with chronic constipation.

Food allergy seems to result from inadequate or abrogated mucosally induced tolerance to dietary antigens caused by inappropriate interactions between genes and the environment. Any event causing defects in the epithelial barrier may underlie sensitization against food proteins, not only in the gut but elsewhere in the body, including the skin and airways. In this comprehensive Review, Brandtzaeg dissects the immunoregulatory network and identifies variables that lead to food allergy. He also outlines the scientific basis for future food allergy prevention.

The field of hepatic fibrosis enjoys remarkable vitality. As a result, we now have a comprehensive and nuanced portrait of fibrosis progression and regression. In this Review, Scott Friedman provides an update on recent advances in our understanding of the pathways of hepatic fibrosis before considering the key challenges that lie ahead when translating these discoveries into new treatments.

The pathophysiology of IBS is poorly understood. Epidemiological studies point to risk factors such as familial clustering, sexual abuse and other forms of childhood trauma, low birth weight and gastrointestinal infection. Epigenetics focuses on the interaction between DNA sequence, DNA modifications and environmental factors to produce a phenotype. In this Perspective, Dinan and colleagues present an epigenetic model of IBS. Applying epigenetic methodology to IBS may help unravel its pathophysiology and lead to more effective treatments.

Autoimmune pancreatitis (AIP) is a unique form of pancreatitis that is suspected to involve autoimmune mechanisms. Given that AIP responds dramatically to steroid therapy, it is important to distinguish it from pancreatic cancer. AIP may be one manifestation of IgG4-related sclerosing disease, which is a systemic disease in which IgG4-positive plasma cells and T lymphocytes extensively infiltrate various organs. Kamisawa and colleagues describe the clinical and pathophysiological features of AIP and IgG4-related sclerosing disease.

Venous thromboembolism is an important cause of morbidity and mortality in patients with IBD. A large population-based study now suggests that patients with active disease, whether they are hospitalized or ambulatory, are at increased risk of developing thromboembolic complications. The value of thromboprophylaxis in patients with active IBD should now be evaluated.

One of the major challenges in IBD therapy is targeting delivery of the drug to the specific site of inflammation. A recent approach to combat this problem is the use of nanoparticulate drug delivery systems that selectively accumulate a given drug at the site of affected tissue. As the drug load is delivered locally, drug dose and adverse effects are reduced.

Aldosterone antagonists are the first-line diuretic therapy for moderate ascites in patients with cirrhosis. In patients who do not respond to aldosterone antagonists alone, the addition of a loop diuretic is recommended; however, for patients with recurrent ascites, receiving a combination of agents from the start might be preferable to such 'sequential' therapy.

Biliary drainage before surgery for cancer of the head of the pancreas can relieve obstructive jaundice and potentially improve surgical outcomes. However, van der Gaag et al. found that preoperative biliary drainage increases the rate of serious complications in these patients. Should this procedure be routinely performed in patients undergoing surgery for pancreatic cancer?

The field of Barrett esophagus is evolving. New definitions of the disorder have had an immediate impact on cancer risk and screening. New hypotheses elucidating progression to intestinal metaplasia have been proposed. Advances in imaging techniques have facilitated the diagnosis of Barrett esophagus and ablative techniques are becoming increasingly accepted treatments. This Review provides a timely update on the advances in understanding of the pathogenesis, diagnosis and treatment of this disorder.

This Review provides an overview of the symptoms, complications, nutritional deficiencies and medical disorders associated with Roux-en-Y gastric bypass—the most frequently performed bariatric procedure in the USA and Canada. Although some symptoms are expected and predictable, some complications may require active medical or surgical intervention. Physicians should be able to predict and manage most postoperative medical and nutritional disorders and should be prepared to assess patients for potential referral for surgical intervention or revision.

Fatigue is a common symptom of primary biliary cirrhosis (PBC) yet little is understood about the pathogenesis of this condition and there is no specific treatment. In this Review article, Abbas and colleagues discuss the natural history and measurement of fatigue in patients with PBC. The central and the peripheral mechanisms that have been suggested for the pathogenesis of fatigue in PBC are also described and treatment options are outlined.