Review Articles, News & Views, Perspectives, Hypotheses, Analyses and Review in 2005

Pyoderma gangrenosum is a rare condition of unknown etiology that was described as an extraintestinal manifestation of inflammatory bowel disease in 1930. At present, there are few well-designed published studies that help determine the optimal therapeutic strategy to use for the management of pyoderma gangrenosum. This article reviews the published treatment strategies in current use and aims to guide effective management.

This Review discusses the use of C-reactive protein as an inflammatory marker in gastrointestinal diseases. Inflammation does not produce a good C-reactive protein response in all diseases, however, and until there are more data, the use of C-reactive protein and other biomarkers should be seen only as an aid to clinical observation and physical examination and not as a replacement.

Gastroesophageal reflux disease is associated with laryngopharyngeal reflux, but the cause and effect relationship between these two clinical entities is far from established. This Review considers studies of the pathogenesis of laryngopharyngeal reflux, the value of diagnostic testing either on or off therapy, and treatment options and duration, that have increased our our understanding of this field.

Although there are many similarities among pediatric and adult Crohn's disease patients, some unique features of the pediatric population influence the therapeutic approach adopted; pediatric Crohn's disease can have a significant impact on the patient's quality of life, growth, bone health, and development. This Review focuses on the latest advances in the treatment of complicated pediatric Crohn's disease, including the use of biologic therapies such as infliximab.

The demonstration that endoscopic band ligation has a greater efficacy and fewer side effects than endoscopic injection sclerotherapy has renewed interest in endoscopic treatments for esophageal varices in patients with cirrhosis. This Review focuses on the role of endoscopic band ligation in the primary and secondary prevention of variceal bleeding as well as in the treatment of acute bleeding episodes.

Smoking can have a detrimental and beneficial effect on gastrointestinal disease—it has such a 'polarizing effect' in patients with Crohn's disease and ulcerative colitis. Studies in tobacco smokers have made it difficult to identify which agents are responsible for these effects, but work on the action of nicotine alone might help to explain some of the positive and negative links between smoking and gastrointestinal disease.

Fecal incontinence is a common symptom that is generally caused by conditions associated with anorectal sensorimotor dysfunction or diarrhea. Clinical assessment and diagnostic testing should be tailored to the patient's age and symptom severity. Management options, including modulation of disordered bowel habits, biofeedback and surgery, must be tailored to the clinical manifestations, and include treatment of underlying diseases.

The availability of new, less-invasive diagnostic tools means that pathological diagnoses are increasingly required to be made from smaller biopsy specimens. The author of this Review addresses the diagnostic terminology used in the reporting of nongynecologic aspiration cytology results, makes recommendations of how clinicians should interpret these results and discusses additional tests that are required for certain diagnostic categories.

This Review considers the optimal approach to assessing the common medical problem of noncardiac chest pain, for which the appropriate application of investigations is controversial. In addition to musculoskeletal and psychiatric investigations, gastroesophageal investigations include esophagogastroduodenoscopy, radiological assessment, ambulatory esophageal pH monitoring, esophageal manometry, provocative tests, and a proton pump inhibitor test.

The authors of this Review discuss the common causes and pathophysiology of gastroparesis—delayed gastric emptying in the absence of mechanical obstruction. The diagnostic approach to gastroparesis is also considered, along with evidence to support medical and surgical therapies, including currently available prokinetic drugs, novel medical therapies, and the promising technique of gastric electrical stimulation.

The authors consider the use of prognostic and diagnostic markers as an addition to initial clinical assessment for the identification of patients who are likely to develop severe acute pancreatitis. They also discuss antibiotic prophylaxis, fluid resuscitation and rehydration, enteral versus parenteral nutrition, pain management and the timing of surgical or interventional necrosectomy.

This article reviews an area of translational research that is currently receiving a great deal of attention—the role of the intestinal epithelial barrier in the pathogenesis of gastrointestinal disease. In particular, the authors consider the contribution of the intestinal epithelial barrier, with its intercellular tight junctions, to the development of autoimmunity.

Several liver support systems have been described for use as a bridge to orthotopic liver transplantation in patients with fulminant hepatic failure, but no system has gained FDA approval or widespread clinical acceptance. The authors of this Review present an overview of published experience with liver support systems since the 1960s.

This Review provides an update on the molecular pathogenesis of gallbladder stones, one of the most prevalent and expensive gastroenterological diseases. The authors discuss evidence supporting the hypothesis that genetic factors are key predisposing elements, and the progress that is being made in human genetic studies of cholesterol gallstones.

In the gastrointestinal tract, defensins—endogenous antibiotics with microbicidal activity—help regulate the composition and number of colonizing microbes, and protect against food-borne and water-borne pathogens. Inspired by recent studies of defensins in human disease and animal models, this Review discusses emerging evidence for the importance of defensins in gastrointestinal infections and inflammatory diseases.

The indications for self-expandable metallic stents (SEMS) now include relief of luminal obstruction of the upper gastrointestinal tract, colon or rectum, in which case they are referred to as enteral SEMS. The authors of this Review discuss data on the efficacy, complications, and cost effectiveness of enteral SEMS, and consider future directions for enteral stenting technology.

Almost 30% of patients with pancreatic cancer present with large, locally advanced tumors in the absence of distant metastases. Because surgical resection is often contraindicated by vascular invasion, this disease has a dismal prognosis. This Review summarizes the status of aggressive surgical resection and neoadjuvant chemoradiation for locally advanced pancreatic cancer and suggests a treatment algorithm based on published clinical evidence.

This Review considers the endoscopic ablative techniques now available for use in the esophagus—photodynamic therapy, laser therapy, multi-polar electro-coagulation, argon plasma coagulation, endoscopic mucosal resection, radiofrequency ablation and cryotherapy. At present, photodynamic therapy is the only FDA-approved ablative modality for high-grade dysplasia in Barrett's esophagus, but, at this stage, it is not clear which technique will emerge as superior for the treatment of esophageal adencocarcinoma precursors.

Intraductal papillary mucinous neoplasia (IPMN)—a spectrum of neoplastic changes in the epithelial lining of the pancreatic duct—is being increasingly recognized. There is controversy surrounding the natural history, evaluation, surgical management and surveillance of IPMN. The authors of this Review present pooled surgical data and future directions, and propose an algorithm for the management of patients with IPMN.

Until recently, the active form of vitamin D was thought to function primarily as a regulator of calcium and phosphate metabolism; discovery of the vitamin D receptor in tissues not involved in calcium and phosphate homeostasis has challenged this view. The authors of this Review discuss the immunomodulatory role of vitamin D and evidence for its involvement in the pathogenesis of inflammatory bowel disease.