News & Views in 2017

At the squamocolumnar junction of mice and humans,a new study has identified a unique population of transitional basal cells that express molecular markers of both oesophageal stratified squamous epithelium and gastrointestinal columnar epithelium. These transitional basal cells are an attractive candidate for the cell of origin for Barrett oesophagus.

Oncolytic viruses have made headlines owing to increasing numbers of reports of clinical success. Compelling data now indicate that small anticancer molecules can serve as potent sensitizers of tumour cells in hepatocellular carcinoma to enhance the oncolytic potential of systemically applied viruses.

Although Helicobacter pylori is associated with gastric cancer, bacterial communities that reside in the stomach are mostly unacknowledged. A new study shows that some gastric bacterial communities have emigrated from our mouth, prefer certain neighbours and prefer certain environments. By understanding the interactions of these bacteria, we hope to understand the environment most conducive to gastric cancer carcinogenesis.

Ileocaecal resection has traditionally been reserved for the treatment of biologic-refractory inflammatory, fibrostenotic or fistulizing Crohn's disease of the terminal ileum. Now, for the first time, this surgical approach has been investigated as an initial treatment for steroid or immunomodulator-refractory Crohn's ileitis, in comparison with anti-TNF therapy.

Childhood malnutrition is a global health issue influenced by poorly understood microbial interactions. A new model of co-infection in mice now sheds light on the complex interplay between pathogens, the host and the resident gut microbiota during malnutrition.

The presence of lymph node metastases (LNM) is considered one of the most important features of colorectal cancer (CRC) staging, indicating the need for additional surgery after local excision and adjuvant chemotherapy after surgery. Now, a new study challenges the role of LNM in the progression of CRC.

Non-anatomical resection of colorectal liver metastases is the current preferred approach to maximize sparing of the hepatic parenchyma. A new study raises the question of whether resection in patients with KRAS-mutated colorectal liver metastases should be performed along segmental, anatomical lines to reduce the risk of local liver recurrence.

Various mechanisms eliciting symptoms in GERD and its most common phenotypic presentation, nonerosive reflux disease (NERD), have been suspected and investigated. One study now suggests that superficial nerves in the oesophageal epithelium might have a key role in the pathogenesis of NERD and could represent a potential target for topical therapies.

KRAS oncogene mutations are commonly encountered in pancreatic ductal adenocarcinoma, driving tumour initiation, proliferation, progression and metastasis. Human exosomes engineered to deliver small interfering RNA silencing KRAS^G12D are highly efficient at specifically targeting pancreatic cancer cells to dramatically reduce RAS activation, cancer cell proliferation and metastatic processes.

A large-scale comprehensive analysis of hepatocellular carcinoma (HCC) based on the integration of six distinct data platforms has pinpointed novel oncogenic processes and prognostic subgroups. These findings confirm previously identified molecular subclasses and fuel the need for a clear strategy of precision medicine in HCC.

In a new report, adolescents with genotype 2 or 3 HCV infection who were given sofosbuvir and ribavirin showed a near 100% sustained virologic response. This study is the beginning of a new wave of treatments for paediatric HCV infection, forming part of a global strategy to eradicate viral hepatitis.

A new study reveals an involvement of SLC22A3 in the development of familial oesophageal squamous cell carcinoma (ESCC). Reduced expression of SLC22A3 is detected not only in ESCC tumours but also in non-tumour tissues of patients with familial ESCC. Interestingly, adenosine-to-inosine editing of SLC22A3 mRNA is proposed to drive early tumour invasion and metastasis, by inhibiting SLC22A3 expression.

Biosimilar monoclonal antibodies are now being accepted in clinical practice by IBD specialists. However, switching patients already undergoing originator biologic treatment to biosimilars has been debated due to lack of controlled studies. The NOR-SWITCH study now provides novel clinical evidence in switching from originator to biosimilar in patients with IBD.

The stability of the neuronal circuits and cells of the enteric nervous system can no longer be taken for granted; new evidence suggests astounding rates of apoptosis and neurogenesis.

NAFLD, the hepatic manifestation of the metabolic syndrome, is a multifactorial condition — environmental factors influence an inherited genetic risk. Stender et al. now describe the additive effect of obesity and NAFLD-associated genetic polymorphisms on steatosis, elevated serum alanine aminotransferase levels and cirrhosis, remarkably illustrating the principle of gene–environment interactions.

A new study shows that the prebiotic inulin improves vascular function in an animal model of cardiovascular disease. A key mechanism for how dietary gut microbiota modulation regulates host physiology through the activities of host–microbiota co-metabolic signalling via bile acids and glucagon-like peptide 1 is also explained.

A new study identifies heterozygous loss-of-function mutations in three additional genes (ALG8, SEC61B and PKHD1) as causative for the development and progression of isolated polycystic liver diseases. Mutations in these genes, together with previously described mutations in other genes (PRKCSH, SEC63, LRP5 and GANAB), might now explain ∼50% of PLD cases.

There have been no major improvements in the prevention or treatment of necrotizing enterocolitis (NEC) over the past several decades, and therefore a 'magic bullet' is urgently needed. However, new data demonstrate that disialyllacto-N-tetraose levels in breast milk can predict the risk of NEC, and these findings might provide a strategy for successful intervention.

International guidelines recognize surgery as a standard treatment option for type 2 diabetes mellitus, including in mildly obese individuals who fail to respond to conventional therapies. A new report from the STAMPEDE trial now provides further evidence and emphasizes the need for health care regulators to introduce appropriate reimbursement policies for metabolic surgery.

Cell culture infection models help to develop antiviral agents, but animal models are required to understand complex virus–host interactions and the development of immune therapies. Although identification of the HBV uptake receptor enabled establishing cell lines that replicate HBV from its natural transcription template, animal models supporting the full HBV life cycle are still lacking.