Review Articles in 2010

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.

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.

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.

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.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis is associated withHelicobacter pyloriinfection and genetic aberrations involving the nuclear factor κB signaling pathway. In this Review, gastric MALT lymphoma is presented an outstanding example of the close pathogenetic link between chronic inflammation and tumor development.

Pancreatic cancer has a poor prognosis and it is often diagnosed at an advanced stage, which makes it difficult to treat. Various natural and synthetic compounds have shown efficacy as chemopreventive agents in cellular andin vivoanimal models of pancreatic cancer. Few clinical trials of pancreatic cancer chemopreventive agents have been completed and some are in early stages. This Review discusses the current state of the field of pancreatic cancer chemo-prevention and highlights the challenges ahead.

Hepatocyte transplantation has shown potential as an additional treatment modality for certain diseases of the liver, particularly liver-based metabolic disorders. The authors of this Review outline the current bench-to-beside experience with hepatocyte transplantation, and discuss the limitations that need to be overcome for its wider application.

Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide, and is associated with the metabolic syndrome. This Review discusses the mechanisms involved in hepatic steatosis and inflammation—the two steps of liver injury in NAFLD. The authors also discuss the role of fructose in the development of both NAFLD and the metabolic syndrome.

The signaling pathways that are involved in the regulation of hypoxia in the intestinal epithelial barrier during active inflammatory diseases, such as IBD, are discussed by Sean Colgan and Cormac Taylor in this Review. The activation of hypoxia-inducible factor (HIF) promotes the resolution of inflammation in mouse models of disease and ways of stabilizing HIF to treat IBD are being sought.

Occult gastrointestinal bleeding is common and can be caused by virtually any lesion in the gastrointestinal tract. It includes fecal occult blood and/or iron-deficiency anemia. Obscure gastrointestinal bleeding is recurrent and is often caused by bleeding from the small intestine. In this Review, Don Rockey discusses the causes, diagnostic evaluation and treatment of patients with these types of bleeding, as well as the impact that capsule endoscopy and deep enteroscopy have had on patient management.

Celiac disease is an enteropathy associated with gluten sensitivity that affects people of all ages and is a major healthcare problem worldwide. Tack and colleagues discuss the epidemiology and risk factors of celiac disease, draw attention to the broad spectrum of its presenting features and highlight its potential complications. Diagnosis and treatment strategies for uncomplicated and complicated celiac disease are also presented.

Endoscopy is the primary diagnostic and therapeutic tool for upper gastrointestinal bleeding. Faced with the clinical mandate of performing therapeutic endoscopy, the gastroenterologist encounters a myriad of available techniques, including various forms of injection, ablation, and mechanical therapy. This Review article comprehensively analyzes the principles, indications, instrumentation, techniques, and efficacy of endoscopic hemostasis, and describes important, practical, details to improve the safety and efficacy of these procedures.

The diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) ultimately depend on histopathologic evaluation. Elizabeth Brunt discusses the histologic features that are diagnostic for NAFLD and discriminate between steatosis and steatohepatitis. The histologic differences between adult and pediatric NAFLD are also considered, along with the value and potential drawbacks of liver biopsy. Current pathophysiologic concepts relevant to histologic findings are put into context.

Although the prevalence rates of celiac disease tend to be very similar in different Western populations, mortality rates for this disease vary widely. This Review focuses on the mortality rates for the different forms of celiac disease and potential protective factors, such as adherence to a gluten-free diet, early diagnosis and severity of clinical presentation. The authors also propose a hypothesis that links mortality rates to the amount of gluten consumed not only after but also before the diagnosis of celiac disease.

Eosinophils are potent innate immune cells that are numerous in the gastrointestinal tract in health and disease. This Review discusses the role of eosinophils in the pathogenesis of numerous disorders of the gastrointestinal tract, including primary eosinophilic gastrointestinal disorders, common functional conditions (such as dyspepsia), and gastrointestinal disorders in patients with allergic disease.

Chronic alcohol use has been linked to pancreatitis for over a century, but its role in the disease has only been recently elucidated. This Review focuses on what is known from animal models and association studies conducted in humans about the relationship between alcohol consumption, smoking, and chronic pancreatitis. The authors discuss the incidence, pathogenesis and etiology of pancreatitis as well as mechanisms of disease.

Despite the widespread use of biologic therapy for IBD, safety concerns still exist. To realize the full potential of these therapies it is important to select appropriate patients for therapy and to optimize the delivery of these agents, thus maximizing their effectiveness. At the same time it is important to adopt strategies before and during treatment that minimize the occurrence of adverse effects. This Review outlines the adverse events associated with biologic therapies, and gives recommendations on how to reduce the risk of these events.