The management of inflammatory bowel disease (IBD) poses a particular challenge during pregnancy because the health of both the mother and the fetus must be considered.

The advent of biologic agents for the treatment of inflammatory bowel disease (IBD) was accompanied in parallel with emerging understanding of persisting underlying inflammation and ensuing bowel damage that can occur even in patients with seeming clinical remission. This lead to the concepts of mucosal healing and deep remission gaining acceptance as the more desired goals for therapy within an ambitious disease-control therapeutic approach, namely, treat-to-target strategy. However, how to practically monitor IBD patients, which objective measures to follow, at what time-points and whether to act upon results in asymptomatic patients are all questions that remain disputed.

The circadian clock is an endogenous biological timekeeping system that synchronizes physiology and behavior to day/night cycles. A wide variety of processes throughout the entire gastrointestinal tract and notably the liver appear to be under circadian control. These include various metabolic functions such as nutrient uptake, processing, and detoxification, which align organ function to cycle with nutrient supply and demand. Remarkably, genetic or environmental disruption of the circadian clock can cause metabolic diseases or exacerbate pathological states. In addition, modern lifestyles force more and more people worldwide into asynchrony between the external time and their circadian clock, resulting in a constant state of social jetlag. Recent evidence indicates that interactions between altered energy metabolism and disruptions in the circadian clock create a downward spiral that can lead to diabetes and other metabolic diseases. In this review, we provide an overview of rhythmic processes in the liver and highlight the functions of circadian clock genes under physiological and pathological conditions; we focus on their roles in regulation of hepatic glucose as well as lipid and bile acid metabolism and detoxification and their potential effects on the development of fatty liver and nonalcoholic steatohepatitis.

A proportion of patients with Barrett's esophagus (BE) are diagnosed with esophageal adenocarcinoma (EAC) within 1 year of an endoscopic examination that produced negative findings. These cases of missed cancers have not been well studied, despite current surveillance strategies for BE. We performed a systematic review and meta-analysis to determine the magnitude of missed EAC in cohorts of patients with BE.

Leukocyte trafficking to the small and large intestines is tightly controlled to maintain intestinal immune homeostasis, mediate immune responses, and regulate inflammation. A wide array of chemoattractants, chemoattractant receptors, and adhesion molecules expressed by leukocytes, mucosal endothelium, epithelium, and stromal cells controls leukocyte recruitment and microenvironmental localization in intestine and in the gut-associated lymphoid tissues (GALTs). Naive lymphocytes traffic to the gut-draining mesenteric lymph nodes where they undergo antigen-induced activation and priming; these processes determine their memory/effector phenotypes and imprint them with the capacity to migrate via the lymph and blood to the intestines. Mechanisms of T-cell recruitment to GALT and of T cells and plasmablasts to the small intestine are well described. Recent advances include the discovery of an unexpected role for lectin CD22 as a B-cell homing receptor GALT, and identification of the orphan G-protein-coupled receptor 15 (GPR15) as a T-cell chemoattractant/trafficking receptor for the colon. GPR15 decorates distinct subsets of T cells in mice and humans, a difference in species that could affect translation of the results of mouse colitis models to humans. Clinical studies with antibodies to integrin α4β7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 are proving the value of lymphocyte trafficking mechanisms as therapeutic targets for inflammatory bowel diseases. In contrast to lymphocytes, cells of the innate immune system express adhesion and chemoattractant receptors that allow them to migrate directly to effector tissue sites during inflammation. We review the mechanisms for innate and adaptive leukocyte localization to the intestinal tract and GALT, and discuss their relevance to human intestinal homeostasis and inflammation.

The malignant form of atrophic papulosis (Köhlmeier-Degos disease) is a rare thrombo-occlusive vasculopathy that can affect multiple organ systems. Patients typically present with distinctive skin lesions reflective of vascular drop out. The small bowel is the most common internal organ involved, resulting in considerable morbidity and mortality attributable to ischemic microperforations. Determination of the presence of gastrointestinal lesions is critical in distinguishing systemic from the benign, cutaneous only disease and in identifying candidates for treatment.

Syndecan-1 plays a vital role in the suppression, transformation, and migration of several cancer types, including colorectal cancer (CRC). However, the prognostic and clinical significance of syndecan-1 in CRC remains conflicting. Therefore, we performed a meta-analysis to clarify this relationship.

Pyoderma Gangrenosum (PG) is a cutaneous condition, its diagnosis suggested by the presence of a painful cutaneous ulcer showing rapid progression. Pyoderma gangrenosum is associated with a concomitant systemic disease in 50 to 70 % of cases, including inflammatory bowel disease (IBD), rheumatoid arthritis, and lymphoproliferative disorders. Although PG has also been reported with viral hepatitis, it is rarely associated with autoimmune hepatitis.

Trans-anal irrigation (TAI) is used widely to treat bowel dysfunction, although evidence for its use in adult chronic functional constipation remains unclear. Long-term outcome data are lacking, and the effectiveness of therapy in this patient group is not definitively known.

The choice of infant formula is thought to play an important role on gastric emptying (GE) in a variety of gastrointestinal disorders. It is known that many ingredients impact on GE, including the type of protein and level of hydrolysis. In clinical practice, feeds are often recommended due to putative improved GE related to the type of protein and level of hydrolysis, however whether this is scientifically justified still needs to be established. A systematic review comparing the impact of protein type and hydrolysis on GE in children was therefore performed.

Emphysematous cholecystitis is a severe variant of acute cholecystitis caused by anaerobic bacteria. Although intraperitoneal air as a complication has been described in association with emphysematous cholecystitis, pneumoretroperitoneum arising from emphysematous cholecystitis is extremely rare. Herein, we describe a rare case of pneumoretroperitoneum arising from emphysematous cholecystitis that was successfully treated with emergency surgery.

Intracellular components must be recycled for cells to maintain energy and ensure quality control of proteins and organelles. Autophagy is a highly conserved recycling process that involves degradation of cellular constituents in lysosomes. Although autophagy regulates a number of cell functions, it was first found to maintain energy balance in liver cells. As our understanding of autophagy has increased, we have found its connections to energy regulation in liver cells to be tight and complex. We review 3 mechanisms by which hepatic autophagy monitors and regulates cellular metabolism. Autophagy provides essential components (amino acids, lipids, and carbohydrates) required to meet the cell's energy needs, and it also regulates energy supply by controlling the number, quality, and dynamics of the mitochondria. Finally, autophagy also modulates levels of enzymes in metabolic pathways. In light of the multiple ways in which autophagy participates to control liver metabolism, it is no surprise that dysregulation of autophagy has been associated with metabolic diseases such as obesity, diabetes, or metabolic syndrome, as well as liver-specific disorders such as fatty liver, nonalcoholic steatohepatitis, and hepatocellular carcinoma. We discuss some of these connections and how hepatic autophagy might serve as a therapeutic target in common metabolic disorders.

There have been many studies of the effects of hepatitis C virus (HCV) infection on cardiovascular risk, but these have produced ambiguous results. We performed a meta-analysis of these studies to systematically assess the risk of HCV infection on cardiovascular disease (CVD)-related morbidity and mortality.

Patients with pancreatic ductal adenocarcinoma (PDA) have a poor prognosis despite new treatments; approximately 7% survive for 5 years. Although there have been advances in systemic, primarily cytotoxic, therapies, it has been a challenge to treat patients with PDA using targeted therapies. Sequence analyses have provided a wealth of information about the genetic features of PDA and have identified potential therapeutic targets. Preclinical and early-phase clinical studies have found specific pathways could be rationally targeted; it might also be possible to take advantage of the genetic diversity of PDAs to develop therapeutic agents. The genetic diversity and instability of PDA cells have long been thought of as obstacles to treatment, but are now considered exploitable features. We review the latest findings in pancreatic cancer genetics and the promise of targeted approaches in PDA therapy.

Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness show the sophisticated relationship between H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori's activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism.