Reviews & Analysis

Pancreatic ductal adenocarcinoma (PDAC) is thought to develop through the stepwise accumulation of cancer gene mutations. A new study suggests that 16% of PDACs exhibit genetic rearrangements that simultaneously altered two or more cancer driver genes. These findings challenge the current models of PDAC development, but arguably remain compatible with a stepwise tumour progression.

Incidence of food allergy has increased considerably in the past two decades, especially in developed countries. Here, Nowak-Wegrzyn and colleagues discuss the epidemiology, pathophysiology, diagnosis and gastrointestinal manifestations of food allergy, and examine current and future treatment approaches.

Patients with ulcerative colitis in clinical remission are increasingly undergoing colonoscopies to determine endoscopic remission. However, the histological evaluation of biopsy samples provides additional criteria to predict which patients are most likely to undergo relapse, so what is the ideal therapeutic end point for patients with ulcerative colitis?

The liver regulates immune defence during sepsis, but is also a target for sepsis-related injury. Liver dysfunction can affect the prognosis of sepsis, particularly in patients with cirrhosis. In this Review, the importance of the liver in sepsis, the factors contributing to sepsis in patients with liver cirrhosis and new therapeutic strategies are discussed.

Chronic HCV infection is a global health problem. In this Review, the authors describe the global burden of hepatitis C and HCV-related disease, including hepatocellular carcinoma, cirrhosis and extrahepatic manifestations. How the new direct-acting antiviral agents might influence disease burden is also discussed.

Obesity affects 15–40% of patients with IBD. Here, Singh and colleagues discuss the evidence linking obesity to IBD pathogenesis, the effect of obesity on disease outcomes and treatment response, and obesity-related issues in abdominal imaging and IBD surgery.

Obesity is a major public health problem worldwide, and bariatric surgery offers an effective option for treatment of obesity and related comorbidities. Here, Nguyen and Varela discuss the indications, safety and outcomes of different bariatric operations in obesity and related metabolic disorders, such as type 2 diabetes mellitus, and examine emerging surgical treatment options.

Systemic vasculitides can involve the gastrointestinal tract, hepatic system and pancreas, causing a range of gastrointestinal manifestations. In this Review, the authors summarize the epidemiology, gastrointestinal manifestations and management of systemic vasculitides as well as single-organ vasculitides in the gastrointestinal tract.

Long-standing IBD is associated with an increased risk of neoplasia. Chromoendoscopy was proven to be the most sensitive modality for dysplasia detection in several clinical trials, but a new study has now shown it to be an effective screening strategy in a routine clinical setting, further warranting its implementation into real-world practice.

Evidence suggests that food composition affects colonic health and colon cancer risk via its effects on gut microbiota metabolism. In this Review, O'Keefe discusses the mechanisms behind microbial metabolite effects, which could be modified by diet to prevent colorectal cancer in western societies.

The intestinal epithelium acts as a barrier requiring a contiguous layer of cells and junctions that seal the paracellular space. This Review discusses the mechanisms of intestinal barrier loss and the role of epithelial barrier function in the pathogenesis of intestinal and systemic diseases.

In a new study, Younossi et al. poignantly depict the daunting and enormous prevalence of NAFLD and its associated clinical and economic burden in the USA and four countries in Europe. The astronomical health-care costs will increase as the prevalence of NAFLD increases. All stakeholders are called to action.

Zinc is essential for biological processes in both mammalian hosts and their microbial symbionts. Sequestration of zinc is a strategy used by mammals to protect against bacterial pathogens. A new study has demonstrated that zinc supplementation increased susceptibility and worsened disease in a mouse model of Clostridium difficile infection.

Effective diagnostic imaging can improve prognosis for patients with pancreatic diseases such as pancreatitis, pancreatic cancer and diabetes mellitus, which benefit from early treatment. Here, Kelly and colleagues review current and future technologies for imaging pancreatic disease, and discuss the development of new contrast agents and molecular imaging targets.

Endoscopy is vital for detection and treatment of early oesophageal cancer. Here, Ragunath and Mannath discuss current and emerging imaging technologies that might improve detection of oesophageal lesions. Endotherapy techniques, including ablation therapy, endoscopic resection and endoscopic submucosal dissection, are also explored.

Here, the authors comprehensively explore evidence that maternal obesity and/or obesogenic diet, mediated by factors such as altered maternal metabolism, microbiota colonization, macrophage programming and epigenetic changes, can programme NAFLD risk and disease progression in offspring. Current and potential clinical interventions are also discussed.

In this article, the authors review the evidence supporting preoperative optimization of patients undergoing surgery for Crohn's disease, including strategies that potentially improve surgical outcomes and reduce perioperative morbidity and mortality. Patient-related and operation-related factors are discussed.

Rhythmic electrical slow waves generate the contractions fundamental to gastrointestinal motility and certain disorders. In this Perspective, Sanders and colleagues discuss the application of slow-wave extracellular recording techniques to gastrointestinal organs and how mechanical artefacts might contaminate these recordings and confound interpretation.

The association between NAFLD and diabetes mellitus has garnered increasing attention in the past few years. In this Review, Tilg and colleagues explore in detail the molecular mechanisms linking NAFLD and diabetes mellitus, and discuss clinical aspects arising from the interaction of both diseases.

Biologic agents have revolutionized the management of IBD and biosimilars (copy versions of the originator agents) are emerging as an alternative. This Review outlines the concept of biosimilars and their adoption in gastroenterology, their current use and future challenges.