Review Articles in 2012

Infantile hypertrophic pyloric stenosis (IHPS) is a common condition in neonates with a largely unknown aetiology. In this article, Babette Peeters and colleagues provide an overview of molecular and genetic studies in patients with isolated IHPS and categorize the various syndromes associated with IHPS. The authors hope this article will provide a basis for future studies in IHPS and stimulate researchers to use the results of extreme phenotype studies in evaluation of their results in isolated IHPS.

Anti-TNF antibodies have acquired a prominent place in the management of IBD. However, with increasing use of these agents, paradoxical adverse effects involving the skin, joints and lungs have been reported. The authors review the paradoxical inflammation induced by anti-TNF agents in patients with IBD, provide hypotheses for the occurrence of this paradoxical inflammation and give practical advice on how to manage these patients.

Pancreatic cancer is a highly lethal malignancy that presents multiple technical challenges for genomic studies. Next-generation sequencing and its applications have proven successful in other tumour types, and could be useful for studying pancreatic cancer. This Review outlines pancreatic cancer genomics to date, the genomic discovery applications enabled by next-generation sequencing technology and analysis, and a synthesis of the two areas that might be suggestive of a path forward.

Hepatopulmonary syndrome (HPS), characterized by dyspnoea and hypoxaemia, is a serious condition that commonly occurs in patients with cirrhosis and, as outlined in this Review, can influence survival and candidacy for liver transplantation. Here, Zhang and Fallon provide an update on the clinical features of HPS, describing the pathophysiology and pathogenesis, diagnosis and management of this condition.

Pancreatic surgery is challenging for both surgeon and patient. With the advent of minimally invasive surgical techniques, patient morbidity could be reduced. In this article, Josh Winer and colleagues review the techniques and outcomes of robotic-assisted pancreatic resections, focusing on robotic-assisted pancreaticoduodenectomy, robotic-assisted distal pancreatectomy and robotic-assisted central pancreatectomy.

Survival in patients with advanced pancreatic cancer is particularly poor, and improvements in diagnosis and treatment are urgently needed. Identification of new biomarkers and targets in pancreatic cancer could enable prediction of treatment response. In this Review, Costello and colleagues describe predictive pancreatic cancer biomarkers as well as novel treatment approaches and future treatment targets.

Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer and the third most common cause of cancer-related deaths, and the incidence of this cancer is increasing. A substantial portion of HCCs are thought to arise from hepatic stem cells. In this Review, Lopa Mishra and colleagues describe TGF-β signalling in liver stem cell niches, and examine the roles of this cytokine including those in tumour progression and suppression. Important translational studies that are needed to develop novel therapies are discussed.

Abundant fibrotic stroma is a typical feature of pancreatic ductal adenocarcinoma (PDAC) in humans. It is becoming clear that this stromal tissue is not just a bystander in PDAC, but has a crucial role in tumorigenesis, angiogenesis and resistance to therapy. Targeting the stroma for diagnostic and therapeutic purposes opens a new avenue of research in the management of PDAC.

Familial pancreatic cancer (FPC) is a rare, hereditary tumour syndrome. High morbidity and mortality is associated with development of pancreatic cancer in these high-risk individuals and, as outlined in this Review, screening of FPC families seems appropriate. Here, Bartsch and colleagues describe the current knowledge of FPC, including phenotype, underlying genetic causes and clinical management (including genetic counselling and screening).

Endoscopic submucosal dissection (ESD) enables en bloc complete resection of superficial gastrointestinal neoplasms regardless of the size and location of the lesions. Although a high level of skill is required, oesophageal and gastric ESD are recognized as established therapeutic procedures in Japan, and colorectal ESD is also becoming popular. With the development of suitable devices for improvement of techniques, ESD should become an established procedure in many other countries as well.

The role ofIL28B in chronic HCV infection has been studied extensively since a series of genome-wide association studies linked the IL28B locus to response to HCV therapy. In this Review, the authors provide a summary of the role of IL28B in HCV infection, describing how IL28Bgenetics affect viral dynamics, host immune response to the virus and response to therapy.

Hepatorenal syndrome (HRS) is a serious complication of advanced cirrhosis with ascites. Although rare, HRS used to be a fatal condition. Improvements in our understanding of its pathophysiology, and consequent new treatments, mean that this is no longer the case. In this Review, Florence Wong summarizes the latest advances in the definition, pathophysiology, diagnosis and treatment options for HRS.

Colonic gases are integral to digestion, with changes in the volume and composition of these gases linked to bowel disorders. In this Review, the authors provide a comprehensive discussion of the clinical importance of colonic gases in health and disease, describing the microbes involved in production and utilization of these gases and the types of gastrointestinal diseases linked to them.

Now in use for over a decade, video capsule endoscopy (VCE) has become an integral part of the management of gastrointestinal diseases. In this Review, Fisher and Hasler provide a timely update on the current status and progress of VCE, describing the devices currently in use, established indications and future developments for this technology.

NAFLD, cardiovascular disease (CVD) and chronic kidney disease (CKD) are thought to be linked. However, whether NAFLD is a marker of, or a causal risk factor for, CVD and CKD is unclear. In this Review, Enzo Bonora and Giovanni Targher discuss the key pitfalls and main certainties surrounding the associations between these diseases.

Vitamin B₁₂ functions as an essential coenzyme in humans. The absorption of this molecule and its subsequent distribution in the body is mediated by a complex set of carrier proteins, receptors and transporters. This Review describes basic and clinical features of this multistep pathway with emphasis on the gastrointestinal transport of vitamin B₁₂and its importance in clinical medicine.

Advances in understanding the biology of tumour progression and metastasis have clearly highlighted the importance of aberrant tumour metabolism. Although much progress has been made in understanding the somatic mutations and expression genomics behind these alterations in metabolism, the regulation of these processes by microRNAs (miRNAs) is only beginning to be appreciated. This Review presents a comprehensive summary of current knowledge of miRNA-mediated metabolic regulation in cancer, with a particular focus on pancreatic cancer.

Around 50% of patients with ulcerative colitis who undergo ileal pouch–anal anastomosis develop at least one episode of pouchitis. In this Review, Bo Shen describes the aetiology and pathogenesis of pouchitis, particularly the role of dysbiosis andClostridium difficileinfection. Risk factors, clinical features, disease courses and prognoses of pouchitis are discussed, as well as the diagnosis and management of patients with 'conventional' pouchitis and systemic immune-mediated disorders associated with pouchitis.

The migrating motor complex (MMC) is a cyclic, recurring motility pattern that occurs in the stomach and small bowel during fasting. The physiological role of the MMC is incompletely understood, and the regulation of the MMC is complex, involving different gut hor-mones and activation of the parasympathetic and enteric nervous system. In this Review, the authors summarize current knowledge of the MMC, especially its role in health and disease.

Increased knowledge of the gut microbiota will be key to understanding its role in health and disease. This Review presents the techniques currently used to characterize the gut microbiota. The authors explain the various methods—from culture through to microbiome shotgun sequencing—suggesting when they can be most appropriately applied to human studies, and also critically reviewing their advantages and limitations as a guide to clinicians.