Opinion

Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world, yet consensus is lacking on whether to treat patients with resection or transplantation. In this Perspectives, Sheung Tat Fan discusses the treatment outcome of HCC by transplantation or resection and the future development of surgical treatment of HCC.

The changing composition of the human microbiota is linked with alterations in human behaviour and the rising prevalence of immunoallergic and metabolic disorders. In this article, Fergus Shanahan discusses the clinical implications of advances in human microbial ecology; the lessons learned extend beyond the gut and are germane to all clinical specialities.

Whole-organ tissue engineering could help address the shortage of donor livers by using damaged organs that would otherwise be rejected for transplantation. In this Perspectives article, Uygun and colleagues outline progress in the decellularization and recellularization of damaged livers and describe the next steps needed for whole-organ tissue engineering to be applied in a clinical setting.

Personalized medicine is a new framework for medical care that involves modelling and simulation of a disease on the basis of underlying mechanisms. In this article, David Whitcomb uses chronic pancreatitis and an example to outline the limitations of the 20^thcentury framework for medical care and examines the advantages of personalized medicine.

Liver transplantation is often used to treat patients with end-stage liver disease as a result of infection with HCV. However, the optimal choice of immunosuppressants in these patients is still undecided. In this article Luc van der Laan and colleagues explore the effect of different immunosuppressants on the complex cellular events involved in HCV infection and interferon signalling.

Gluten sensitivity is an emerging entity that is becoming increasingly common; however, little is known about its pathogenesis. Here, Umberto Volta and Roberto De Giorgio discuss the current knowledge of gluten sensitivity and define its pathogenetic, clinical and diagnostic criteria. They aim to provide a practical appraisal of gluten sensitivity that is useful for doctors and researchers in the diagnosis and appropriate management of patients with gluten sensitivity.

This Perspectives describes the characteristics of stem and progenitor cells in the liver, biliary tree and pancreas. A hypothetical model of maturational cell lineages is presented, highlighting the common embryological origin of these organs. The potential of these stem and progenitor cells in regenerative medicine is discussed, along with their role in the pathophysiology and oncogenesis of midgut organs.

Pelvic floor dysfunction encompasses a range of symptoms that are presented to specialists across multiple disciplines. In this Perspectives Hans Peter Dietz provides an interdisciplinary overview of imaging pelvic floor dysfunction. Modern pelvic floor imaging techniques, including MRI, defecation proctography and ultrasound are discussed as well as their potential application to improving management of pelvic floor disorders.

Mucins have an important role in protecting the esophagus from the effects of acids, pepsins and other noxious materials. Mucins are altered in patients with GERD, which could be key to the development of new therapeutics. This Perspectives will cover studies about mucin secretion in the esophagus in health and disease states, and its potential role as a protective substance.

Chemoprevention of colorectal cancer (CRC) has been the focus of intensive research for more than two decades. Here, Ricciardiello, Bazzoli and Fogliano discuss the association between fruit and vegetable intake and CRC risk, and the chemopreventive activities of dietary phytochemicals. They argue that a single-agent 'magic' pill for CRC chemoprevention doesn't exist and that consuming a complex mixture of phytochemicals may be the answer.

In this Perspectives, the authors contemplate the identity of the cell of origin for pancreatic ductal adenocarcinoma. They hypothesize that a subset of cells that renew the adult organ physiologically or regenerate it upon severe tissue damage would be more susceptible to oncogenic transformation than mature, differentiated cells. They contend that such a cellular compartment could consist of putative pancreatic stem cells, progenitor cells, facultative stem cells or transdifferentiated bone marrow cells.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively new, clinically distinct entity, which is being increasingly diagnosed. The publication of international consensus guidelines for the management of IPMN helped to increase the awareness and improve the management of patients with this disease; however, a number of issues still need to be addressed. This Perspectives discusses several of these issues, including the classification of mixed-type IPMNs, criteria for the resection of branch duct IPMNs and surveillance.

The pathophysiology of IBS is poorly understood. Epidemiological studies point to risk factors such as familial clustering, sexual abuse and other forms of childhood trauma, low birth weight and gastrointestinal infection. Epigenetics focuses on the interaction between DNA sequence, DNA modifications and environmental factors to produce a phenotype. In this Perspective, Dinan and colleagues present an epigenetic model of IBS. Applying epigenetic methodology to IBS may help unravel its pathophysiology and lead to more effective treatments.

A range of treatments for hepatic fibrosis are currently in the development process. However, the single greatest limitation in bringing these therapies to the clinical setting is a lack of sufficient methodology for assessing their pharmacological effects. This Perspectives article highlights the potential for novel and existing biomarkers to act as treatment end points in clinical trials of new drugs for hepatic fibrosis.

The use of CT has been increasing exponentially over the past decade. Unfortunately, there is little cognizance among health-care providers (or their patients) about the relative latent cancer risks associated with repetitive exposure to ionizing radiation. Given the exposure of a relatively high proportion of the population to these tests, it is incumbent on health-care providers to have an improved understanding of these risks and discuss them accordingly with their patients.

The incidence ofClostridium difficile infection has dramatically risen, in concert with the increasing use of PPIs for gastric acid suppression. This Perspective focuses on the role that PPI use may have in C. difficileinfection, and weighs up the pros and cons of PPI therapy.