Reviews & Analysis

A 33-year-old woman with a history of paroxysmal nocturnal hemoglobinuria (PNH) presented with abdominal pain, nausea and vomiting, accompanied by duodenal wall thickening seen on an abdominal CT scan and an ischemic-looking duodenal mucosa as visualized by endoscopy. She was diagnosed as having small bowel ischemia complicating PNH. Treatment with warfarin was started, but ischemic episodes recurred. Treatment with eculizumab was, therefore, proposed. This case highlights this rare gastrointestinal complication of PNH.

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.

The optimal treatment for classic Whipple disease has not yet been determined. A recent study reported encouraging results for initial treatment with intravenous ceftriaxone or meropenem followed by long-term treatment with oral trimethoprim–sulfamethoxazole. However, discrepancies in the failure and/or relapse rates associated with trimethoprim–sulfamethoxazole show that this regimen may not be optimal.

Insulin sensitizing agents, such as the thiazolidinediones pioglitazone and rosiglitazone, have been used in clinical trials for the treatment of nonalcoholic steatohepatitis, a common form of liver disease that is associated with insulin resistance. The results of these trials have been variable, suggesting that a deeper understanding of other contributing factors to the development of nonalcoholic steatohepatitis is needed to establish whether improving adipose insulin sensitivity might be important.

Although a great deal is known about the environmental and genetic causes of colorectal cancer, it is still one of the most common cancers in the world. A new German study including >17,500 patients focuses on differences between proximal and distal disease. Is there anything new from this study that could help us further understand the etiology of colorectal cancer and improve the screening and management of this disease?

The need for mass screening of the general population for colorectal cancer is well established. However, there is no consensus on the best screening test. A recent study brings new data to clinicians and health authorities regarding the optimal test for colorectal cancer screening.

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.

The best long-term treatment results for patients with idiopathic achalasia have been achieved with pneumatic dilation or surgical myotomy. A new study adds evidence that good or excellent symptomatic results can be achieved in the long term when pneumatic dilation is used as the primary treatment strategy. In cases of early treatment failure (<2 years), surgery was found to be the best rescue therapy.

Propofol sedation by nonanesthesiologists is still a highly controversial issue despite the fact that numerous studies have approved this sedation regimen for gastrointestinal endoscopy. A new position statement from a collaboration of four different American gastroenterology and hepatology societies outlines the latest recommendations for nonanesthesiologist administration of propofol.

Bleeding from gastric varices is relatively common and can be life threatening. The optimal treatment strategy for gastric variceal hemorrhage is controversial. Both interventional radiology and endoscopic therapies require a high level of clinical expertise. Which type of therapy is best? A recent study compared endoscopic cyanoacrylate glue injection with the insertion of a transjuglar intrahepatic portosystemic shunt.

The appropriate management of patients with Barrett esophagus in whom early carcinoma or high-grade intraepithelial neoplasia has been detected continues to be a subject of controversy. For many years radical esophageal resection has been regarded as the treatment of choice, but the high morbidity and mortality rates associated with this procedure have led to less radical treatment strategies being advocated by many groups.

A multicenter, randomized, controlled trial of 610 patients with chronic hepatitis C infected with HCV genotype 1 or 4 compared 48 weeks of standard of care therapy (PEG-IFN and ribavirin) with 12 weeks of induction therapy with high-dose PEG-IFN followed by 36 weeks of standard of care treatment. High-dose PEG-IFN induction therapy did not enhance early or sustained virologic response rates compared with standard of care therapy.

A 50-year-old man from Las Vegas with a history of complicated Crohn's disease and who had received adalimumab therapy presented with left lower quadrant abdominal pain, periorbital headache, blurry vision, tinnitus, polydipsia, right elbow pain and weight loss. He was diagnosed with having disseminated coccidioidomycosis. Despite antifungal treatment, surgical debridement and irrigation, and discontinuation of immunosuppressive therapy, the patient eventually died. This case highlights the risk of developing endemic mycoses while receiving biologic therapy.

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.