Oral contraceptives and Crohn's disease
Dear Sir, I read with interest the study by Khalili et al,1 which confirms the association between oral contraceptive use and increased risk for Crohn's disease in two impressively large cohorts. When we studied this some years ago, we found that oral contraceptive use associated much more strongly with isolated colonic Crohn's disease than with small intestinal disease.2 Further analysis of our cases and those previously published as case reports suggested that most of these had non–granulomatous colitis—the diagnosis of Crohn's being based mainly on marked rectal sparing, suggesting a possible ischaemic aetio...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Rhodes, J. M. Tags: PostScript Source Type: research

'High definition': not all it appears
We read with interest the article from Chung et al,1 which suggests limited benefits in adenoma detection with narrow band imaging or flexible spectral imaging compared with standard white light examination. After a short learning curve period, there was no difference in adenoma detection even for the less experienced endoscopist. These are important results as we are increasingly inundated with new technologies or adjuncts that are hypothesised to improve adenoma detection rate (ADR). Adopting these technologies often involves high capital expenditure and a learning curve often for unsubstantiated clinical benefits. Simil...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Lim, Y. C., Corbett, G., Parkes, M., Cameron, E. A. B. Tags: PostScript Source Type: research

The insulin-like growth factor 2 (IGF2) mRNA-binding protein p62/IGF2BP2-2 as a promoter of NAFLD and HCC?
Non-alcoholic fatty liver disease (NAFLD) represents the most common hepatic manifestation of chronic liver diseases in developed countries. Since non-alcoholic steatohepatitis (NASH) is responsible for a large proportion of cryptogenic cirrhosis and cirrhosis represents the main risk factor for hepatocellular carcinoma (HCC), HCC is a severe complication of end-stage NAFLD.1 Recent evidence published in this journal showed the therapeutic potential of an inhibition of the chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1) in NASH.2 The study by Baeck et al elegantly demonstrated that the phar...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Simon, Y., Kessler, S. M., Bohle, R. M., Haybaeck, J., Kiemer, A. K., Dilly, Guth Tags: Open access PostScript Source Type: research

Exonic variants affecting pre-mRNA splicing add to genetic burden in chronic pancreatitis
We read with great interest the recent paper by Rosendahl et al1 describing the incidence of variants in CFTR, SPINK1, CTRC and PRSS1 in a German cohort of chronic pancreatitis cases. The authors conclude that chronic pancreatitis is a complex genetic disease and the net effect of mutations in multiple susceptibility genes underlies increased disease risk. Indeed, in the studied cohort, at least one genetic risk factor was identified in 36.7% of patients. Surprisingly, however, only 6.5% of cases carried multiple risk factors, which seems to contradict the complex genetics theory of chronic pancreatitis. While it is likely...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Beer, S., Sahin-Toth, M. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceThe complexities of host-microbiota interaction  Faith JJ, Ahern PP, Ridaura VK, et al. Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice. Sci Trans Med 2014;6:220ra11. Identifying which members of the colonic microbiota actively participate in processes that affect physiology, metabolism, immunity and disease progression is challenging. Gut commensal bacteria and metabolites they produce, including short chain fatty acids, have been shown to regulate colonic regulatory T (Treg) cells in mice. These cells express the transcription factor Foxp3, secret...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

An unusual cause of weight loss in a young Caucasian man
Clinical presentation A 37-year-old Caucasian male presented to our institution for progressive weight loss and recurrent abdominal pain. An enteral CT performed in another centre showed a diffuse thickening of the duodenal walls suggestive of lymphoma or Crohn’s disease. Esophagogastroduodenoscopy showed a normal appearance of gastroesophageal mucosa while the duodenal and proximal jejunal mucosa appeared completely covered with pseudo-polypoid lesions with maximum size of 5 mm (figure 1A,B). At the ileocolonoscopy, the colorectal mucosa was diffusely micronodular (figure 1D), while the terminal ileum presented...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Cecinato, P., Fuccio, L., Sabattini, E., Laterza, L., Caponi, A., Azzaroli, F., Mazzella, G. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Hepatocellular carcinoma: clinical frontiers and perspectives
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for ea...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Bruix, J., Gores, G. J., Mazzaferro, V. Tags: GUT Recent advances in clinical practice, Editor's choice, Hepatic cancer Source Type: research

A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma
Conclusions These findings highlight the fact that the differentially expressed ADARs in tumours, which are responsible for an A to I editing imbalance, has great prognostic value and diagnostic potential for HCC. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Chan, T. H. M., Lin, C. H., Qi, L., Fei, J., Li, Y., Yong, K. J., Liu, M., Song, Y., Chow, R. K. K., Ng, V. H. E., Yuan, Y.-F., Tenen, D. G., Guan, X.-Y., Chen, L. Tags: Cirrhosis, Open access, Hepatic cancer Hepatology Source Type: research

Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis
Conclusions Patients with AP often develop prediabetes and/or DM after discharge from hospital, and have a greater than twofold increased risk of DM over 5 years. Further studies are warranted to determine the optimal strategy for its detection and whether the risk of developing DM after AP can be reduced. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Das, S. L. M., Singh, P. P., Phillips, A. R. J., Murphy, R., Windsor, J. A., Petrov, M. S. Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo
Conclusions These data reveal a novel antisecretory role for the FXR in colonic epithelial cells and suggest that FXR agonists have excellent potential for development as a new class of antidiarrheal drugs. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Mroz, M. S., Keating, N., Ward, J. B., Sarker, R., Amu, S., Aviello, G., Donowitz, M., Fallon, P. G., Keely, S. J. Tags: Drugs: gastrointestinal system, Pancreas and biliary tract, Diarrhoea Colon Source Type: research

Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia
Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Cheng, I., Kocarnik, J. M., Dumitrescu, L., Lindor, N. M., Chang-Claude, J., Avery, C. L., Caberto, C. P., Love, S.-A., Slattery, M. L., Chan, A. T., Baron, J. A., Hindorff, L. A., Park, S. L., Schumacher, F. R., Hoffmeister, M., Kraft, P., Butler, A. M., Tags: Colon cancer Source Type: research

Investigation of the atypical FBXW7 mutation spectrum in human tumours by conditional expression of a heterozygous propellor tip missense allele in the mouse intestines
Conclusions Heterozygous Fbxw7 propellor tip (R482Q) mutations promote intestinal tumorigenesis on an Apc mutant background. Klf5 and Tgif1 are strong candidates for mediating this effect. Although heterozygous null Fbxw7 mutations also promote tumour growth, these have a weaker effect than R482Q. These findings explain the FBXW7 mutation spectrum found in human cancers, and emphasise the need for animal models faithfully to reflect human disease. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Davis, H., Lewis, A., Behrens, A., Tomlinson, I. Tags: Open access, Colon cancer Source Type: research

Comparison of detection and miss rates of narrow band imaging, flexible spectral imaging chromoendoscopy and white light at screening colonoscopy: a randomised controlled back-to-back study
Conclusions Neither NBI nor FICE improved adenoma detection or miss rates, with no difference in diagnostic efficacy between the two systems. Virtual CE had no additional benefits over WL for non-experts. Clinical trial registration number: KCT0000570. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Chung, S. J., Kim, D., Song, J. H., Kang, H. Y., Chung, G. E., Choi, J., Kim, Y. S., Park, M. J., Kim, J. S. Tags: Endoscopy, Colon cancer Source Type: research

Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease
Conclusions A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Ananthakrishnan, A. N., Khalili, H., Konijeti, G. G., Higuchi, L. M., de Silva, P., Fuchs, C. S., Willett, W. C., Richter, J. M., Chan, A. T. Tags: Crohn's disease, Ulcerative colitis Inflammatory bowel disease Source Type: research

Mortality and causes of death in Crohn's disease: results from 20 years of follow-up in the IBSEN study
Conclusions In our population-based inception cohort followed for 20 years, there was no increased mortality or more deaths from cancer compared with the general population. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Hovde, O., Kempski-Monstad, I., Smastuen, M. C., Solberg, I. C., Henriksen, M., Jahnsen, J., Stray, N., Moum, B. A., Hoie, Sauar, Huppertz-Hauss, Bernklev, Bengtson, Vatn, Opheim, Aadland, Flaaten, Kjellevold, Roseth, Strom, Palm, Lygren, Lie Hoivik Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer
Conclusions IBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Prorok-Hamon, M., Friswell, M. K., Alswied, A., Roberts, C. L., Song, F., Flanagan, P. K., Knight, P., Codling, C., Marchesi, J. R., Winstanley, C., Hall, N., Rhodes, J. M., Campbell, B. J. Tags: Crohn's disease, Ulcerative colitis, Irritable bowel syndrome, Open access, Colon cancer Inflammatory bowel disease Source Type: research

Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit
Conclusions The most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. ClinicalTrials.gov NCT00745004. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Tooth, D., Garsed, K., Singh, G., Marciani, L., Lam, C., Fordham, I., Fields, A., Banwait, R., Lingaya, M., Layfield, R., Hastings, M., Whorwell, P., Spiller, R. Tags: Drugs: gastrointestinal system, Pancreas and biliary tract, Diarrhoea, Irritable bowel syndrome, Open access Neurogastroenterology Source Type: research

Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation
Objective To determine the role of colonic barrier defects and low-grade inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent inflammatory bowel disease (IBD). Design Caecal biopsies were collected from 51 IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC)) patients and 27 controls. IBS was assessed using the Rome III criteria and the IBS severity score. Epithelial barrier integrity was evaluated by determining the paracellular permeability of biopsies mounted in Ussing chambers and the mRNA expression of tight junction proteins (ZO-1, α-catenin and occludin). Low-grad...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Vivinus-Nebot, M., Frin-Mathy, G., Bzioueche, H., Dainese, R., Bernard, G., Anty, R., Filippi, J., Saint-Paul, M. C., Tulic, M. K., Verhasselt, V., Hebuterne, X., Piche, T. Tags: Crohn's disease, Ulcerative colitis, Irritable bowel syndrome Neurogastroenterology Source Type: research

Shanghai fever: a distinct Pseudomonas aeruginosa enteric disease
Background Shanghai fever, a community-acquired enteric illness associated with sepsis caused by Pseudomonas aeruginosa, was first described in 1918. The understanding of Shanghai fever is incomplete. Objective To delineate the clinical features and to examine the host and microbial factors associated with Shanghai fever. Methods We prospectively enrolled 27 consecutive previously healthy children with community-acquired P aeruginosa enteritis and sepsis between July 2003 and June 2012. An immunological investigation, including measurement of serum immunoglobulin levels and lymphocyte subpopulations, was performed. The c...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Chuang, C.-H., Wang, Y.-H., Chang, H.-J., Chen, H.-L., Huang, Y.-C., Lin, T.-Y., Ozer, E. A., Allen, J. P., Hauser, A. R., Chiu, C.-H. Tags: Diarrhoea, Open access Enteric infections Source Type: research

An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice
Background Recent evidence indicates that the composition of the gut microbiota contributes to the development of metabolic disorders by affecting the physiology and metabolism of the host. Metformin is one of the most widely prescribed type 2 diabetes (T2D) therapeutic agents. Objective To determine whether the antidiabetic effect of metformin is related to alterations of intestinal microbial composition. Design C57BL/6 mice, fed either a normal-chow diet or a high-fat diet (HFD), were treated with metformin for 6 weeks. The effect of metformin on the composition of the gut microbiota was assessed by analysing 16S ...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Shin, N.-R., Lee, J.-C., Lee, H.-Y., Kim, M.-S., Whon, T. W., Lee, M.-S., Bae, J.-W. Tags: Gut microbiota Source Type: research

Impact of regurgitation on health-related quality of life in gastro-oesophageal reflux disease before and after short-term potent acid suppression therapy
Objective Limited data exist on the impact of regurgitation on health-related quality of life (HRQOL) in gastro-oesophageal reflux disease (GORD). We assessed the relationship between regurgitation frequency and HRQOL before and after acid suppression therapy in GORD. Method We used data from two randomised trials of AZD0865 25–75 mg/day versus esomeprazole 20 or 40 mg/day in non-erosive reflux disease (NERD) (n=1415) or reflux oesophagitis (RO) (n=1460). The Reflux Disease Questionnaire was used to select patients with frequent and intense heartburn for inclusion and to assess treatment response. The Qual...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Kahrilas, P. J., Jonsson, A., Denison, H., Wernersson, B., Hughes, N., Howden, C. W. Tags: Dyspepsia, Gastro-oesophageal reflux Oesophagus Source Type: research

Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium
Conclusions Nrf2 deficiency impairs oesophageal barrier function through disrupting energy-dependent tight junction. (Source: Gut)
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Chen, H., Hu, Y., Fang, Y., Djukic, Z., Yamamoto, M., Shaheen, N. J., Orlando, R. C., Chen, X. Tags: Gastro-oesophageal reflux Oesophagus Source Type: research

Editing liver tumours
There is an urgent need for new therapeutic options for hepatocellular carcinoma (HCC), which is currently the third cause of cancer-related death worldwide.1 HCC develops most frequently in the setting of cirrhosis. This premalignant condition occurs as a consequence of chronic liver disease, mainly as a result of hepatitis B and C viral infection, alcohol abuse and obesity. The poor efficacy of many antiproliferative agents against HCC is due in part to the inefficient drug delivery and metabolism in cirrhotic livers, leading to unbearable drug toxicity. Novel therapies for HCC could be developed after the identification...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Colnot, S., Fortes, P. Tags: Commentary Source Type: research

Fbxw7 hotspot mutations and human colon cancer: mechanistic insights from new mouse models
The recent explosion in cancer genomics provides an unprecedented view of the genetic changes present in solid tumours. The characterisation of colorectal cancer samples via DNA sequencing has confirmed the importance of established oncogene and tumour suppressor pathways (including the ‘mountains’ of Apc, Tp53 and Ras) but has also identified novel cancer genes that are mutated in a small percentage of patient samples (hills).1 2 Furthermore, these studies give a new appreciation of the spectrum of gene mutations present in cancers, especially in candidate tumour suppressor genes (TSGs). While classic genetics...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Grim, J. E. Tags: Commentary Source Type: research

The antidiabetic gutsy role of metformin uncovered?
Why are grams of metformin recommended to lower hyperglycaemia in type 2 diabetic patients whereas the dose ranges from micrograms to milligrams for all other antidiabetic agents? Why is that 50% of the patients should discontinue or reduce the daily therapeutic doses to avoid diarrhoea? Why has the previously established mode of action of metformin been continuously disputed and re-evaluated by the scientific community? To these questions, Shin et al1 shifted again the paradigm related to numerous modes of action of metformin described so far to show that the drug lowers glycaemia by targeting gut microbiota. The gutsy ro...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Burcelin, R. Tags: Commentary Source Type: research

Oesophageal mucosal barrier: a key factor in the pathophysiology of non-erosive reflux disease (NERD) and a potential target for treatment
The stratified squamous epithelium of the oesophageal mucosa usually forms a tight protective barrier against noxious components of gastro-oesophageal reflux (such as acid and bile acids), a necessary function since the distal oesophageal mucosa is exposed to physiological reflux events, even in health. If there is a disruption to the effectiveness of this epithelial barrier (a so-called impairment of the mucosal integrity), its protective function is likely to be compromised, resulting in reflux-induced symptoms. Non-erosive reflux disease (NERD) is the phenotype of gastro-oesophageal reflux disease most frequently encoun...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: Woodland, P., Sifrim, D. Tags: Commentary Source Type: research

Highlights from this issue
LuminalShanghai fever—a Pseudomonas aeruginosa enteric disease Shanghai fever, first documented in 1918, is a syndrome comprising fever, diarrhoea and sepsis, and is caused by enteric Pseudomonas aeruginosa infection. Community-acquired cases were subsequently reported in children without pre-existing conditions, primarily from Taiwan, Hong Kong and China. The disease usually leads to serious complications and is associated with high mortality. Sadly our understanding of this disease is still incomplete and its pathogenesis remains unknown. In this issue of Gut, Chuang et al present the most comprehensive study to da...
Source: Gut - April 7, 2014 Category: Gastroenterology Authors: El-Omar, E., Gerbes, A., Grady, W., Rosch, T. Tags: Digest Source Type: research

Variation in referral practice and differential cancer outcome: a strong reason to reflect on whether current guidelines are fit for purpose or implemented effectively in primary care
We thank the authors for their interest in our research1 which has attracted both professional and public media interest.2–4 Certainly, we accept that epidemiological studies can be at risk of ‘ecological fallacy’ and cannot adjust for all possible confounders. We make no claim that association proves causality. However, in offering a generic note of caution, Ford et al provide no specific hypothesis or insight to explain why the associations illustrated in our particular study could be explained by unacknowledged bias or an artefact of data aggregation. Taking the logic from their example, the counter hy...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Bodger, K., Shawihdi,, M. Tags: PostScript Source Type: research

Rates of upper gastrointestinal endoscopy and gastro-oesophageal malignancy outcomes
We read the excellent paper by Shawihdi et al with interest.1 The authors demonstrated in a retrospective study, using hospital episode statistics, that outcomes from gastro-oesophageal malignancy were worse among patients from practices with a low referral rate for upper gastrointestinal (GI) endoscopy. While the authors address some weaknesses in their data, we believe they have not highlighted all problems with their approach. As with all observational data, there is the problem of confounding, which often cannot be completely corrected in analyses. However, the major concern is that they looked at aggregate data, not i...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Ford, A. C., Glenn, L. F., Moayyedi, P. Tags: PostScript Source Type: research

Correctness is mandatory in science: response to 'correct determination of Critical Flicker Frequency is mandatory when comparisons to other tests are made'
Kircheis and coauthors suggest ‘inadequate handling of the test’ as reason for the worse sensitivity of the Critical Flicker Frequency (CFF) for diagnosing hepatic encephalopathy (HE) compared with other methods evaluated in our study.1 2 Their main criticism aims at our finding of CFF above 50 Hz in healthy controls. They argue that flicker frequencies above 50 Hz ‘cannot be sensed and therefore are invisible for the naked eye ...’ referring to a review by Shady et al3 In fact, Shady et al do not give a clear cut-off at 50 Hz but indicate that ‘... the temporal resolution of a ...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Tryc, A. B., Weissenborn, K. Tags: PostScript Source Type: research

Correct determination of critical flicker frequency is mandatory when comparisons to other tests are made
Dear Sirs, There are many situations in daily life where we are exposed to flickering light. This is normally not appreciated because the flicker is so rapid that it is perceived as continuous light. The ability of the human visual system to identify flicker is dependent on the luminance and the chroma of the used stimulating light. The temporal resolution of the human photoreceptors in the central retina, where spatial resolution is optimal, is limited to critical flicker frequencies (CFF) below 50 Hz. Higher CFF values cannot be sensed and therefore are invisible to the naked eye due to the inertia of the human phot...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Kircheis, G., Hilger, N., Haussinger, D. Tags: PostScript Source Type: research

Anti-TNF-{alpha}-induced psoriasiform lesions in IBD: an abnormal immune activation or a 'patchy cutaneous' immune suppression?
We read with interest the original article by Tillack et al who reported the characteristics of psoriasiform skin lesions induced by antitumour necrosis factor (anti-TNF)-α in patients with IBD.1 The authors show by immunohistochemical analysis that cutaneous lesions are characterised by interferon (IFN)α expression, infiltrates of interleukin (IL)-17A/IL-22-secreting T helper (Th)17 cells and IFN-secreting Th1 cells. They also demonstrate that therapy with ustekinumab, an anti-IL-12/IL-23 antibody, is highly effective in treating anti-TNF-α antibody-induced psoriasis and psoriasiform lesions. Our group i...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Scaldaferri, F., Petito, V., Papa, A., Cesarini, M., Arena, V., Lopetuso, L. R., Corbi, M., Perino, F., Caldarola, G., Carbone, A., Corazziari, E., Sgambato, A., Gasbarrini, A., De Simone, C. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, Boué and colleagues set out to investigate whether colitogenic CD4 T cells that accumulate in the inflamed colon also produce opioids and are able to counteract inflammation-induced visceral pain in mice. Colitis was induced via transfer of naïve CD4 T cells to immune-deficient... (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Recent advances in clinical practice challenges and opportunities in the management of obesity
Despite advances in understanding the roles of adiposity, food intake, GI and adipocyte-related hormones, inflammatory mediators, the gut–brain axis and the hypothalamic nervous system in the pathophysiology of obesity, the effects of different therapeutic interventions on those pathophysiological mechanisms are controversial. There are still no low-cost, safe, effective treatments for obesity and its complications. Currently, bariatric surgical approaches targeting the GI tract are more effective than non-surgical approaches in inducing weight reduction and resolving obesity-related comorbidities. However, current g...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Acosta, A., Abu Dayyeh, B. K., Port, J. D., Camilleri, M. Tags: GUT Recent advances in clinical practice, Editor's choice Source Type: research

Iron deficiency anaemia and cataracts in a patient with haemochromatosis
Clinical presentation A 55-year-old woman presented to our hepatology outpatient clinic with symptoms of anaemia. Her medical history included hereditary haemochromatosis type 1, psoriatic arthropathy and bilateral cataracts since early adulthood. There was a family history of early-onset cataracts. Haemochromatosis was treated by frequent phlebotomies (2–4 per month) since diagnosis 2.5 years earlier, limited by several episodes of severe symptomatic anaemia (minimal haemoglobin: 7.0 g/dL). Despite anaemia, she presented with constantly high levels of ferritin (>1000 ng/mL) throughout the period of...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Peiffer, K.-H., Niemeyer, M., Buslau, A., Kohnen, T., Muckenthaler, M. U., Zeuzem, S., Sarrazin, C. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Keratin 19: a key role player in the invasion of human hepatocellular carcinomas
Objective Keratin (K)19, a biliary/hepatic progenitor cell (HPC) marker, is expressed in a subset of hepatocellular carcinomas (HCC) with poor prognosis. The underlying mechanisms driving this phenotype of K19-positive HCC remain elusive. Design Clinicopathological value of K19 was compared with EpCAM, and α-fetoprotein, in a Caucasian cohort of 242 consecutive patients (167 surgical specimens, 75 needle biopsies) with different underlying aetiologies. Using microarrays and microRNA profiling the molecular phenotype of K19-positive HCCs was identified. Clinical primary HCC samples were submitted to in vitro invasion...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Govaere, O., Komuta, M., Berkers, J., Spee, B., Janssen, C., de Luca, F., Katoonizadeh, A., Wouters, J., van Kempen, L. C., Durnez, A., Verslype, C., De Kock, J., Rogiers, V., van Grunsven, L. A., Topal, B., Pirenne, J., Vankelecom, H., Nevens, F., van de Tags: Open access, Hepatic cancer Hepatology Source Type: research

Dysregulation of interferon regulatory factors impairs the expression of immunostimulatory molecules in hepatitis C virus genotype 1-infected hepatocytes
Conclusions HCV genotype 1 infection downregulates IRF2 in hepatocytes attenuating hepatocellular expression of IL-7 and IL-15Rα. Our data reveal a new mechanism by which HCV abrogates specific T-cell responses and point to a novel therapeutic approach to stimulate anti-HCV immunity. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Larrea, E., Riezu-Boj, J.-I., Aldabe, R., Guembe, L., Echeverria, I., Balasiddaiah, A., Gastaminza, P., Civeira, M. P., Sarobe, P., Prieto, J. Tags: Hepatitis C Hepatology Source Type: research

Nr5a2 maintains acinar cell differentiation and constrains oncogenic Kras-mediated pancreatic neoplastic initiation
Conclusions Nr5a2 is a key regulator of acinar plasticity. It is required for maintenance of acinar identity and re-establishing acinar fate during regeneration. Nr5a2 also constrains pancreatic neoplasia driven by oncogenic Kras, providing functional evidence supporting a potential role as a susceptibility gene for human PDA. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: von Figura, G., Morris, J. P., Wright, C. V. E., Hebrok, M. Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

Nr5a2 heterozygosity sensitises to, and cooperates with, inflammation in KRasG12V-driven pancreatic tumourigenesis
Conclusions A full Nr5a2 dose is required to restore pancreatic homeostasis upon damage and to suppress the KRasG12V-driven mouse pancreatic intraepithelial neoplasia progression, indicating that Nr5a2 is a novel pancreatic tumour suppressor. Nr5a2 could contribute to PDAC through a role in the recovery from pancreatitis-induced damage. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Flandez, M., Cendrowski, J., Canamero, M., Salas, A., del Pozo, N., Schoonjans, K., Real, F. X. Tags: Pancreas and biliary tract, Pancreatitis, Pancreatic cancer Source Type: research

Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto-oncogenes in human colorectal cancer metastasis
Objective Hypomethylation of LINE-1 elements has emerged as a distinguishing feature in human cancers. Limited evidence indicates that some LINE-1 elements encode an additional internal antisense promoter, and increased hypomethylation of this region may lead to inadvertent activation of evolutionarily methylation-silenced downstream genes. However, the significance of this fundamental epigenetic mechanism in colorectal cancer (CRC) has not been investigated previously. Design We analysed tissue specimens from 77 CRC patients with matched sets of normal colonic mucosa, primary CRC tissues (PC), and liver metastasis tissue...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Hur, K., Cejas, P., Feliu, J., Moreno-Rubio, J., Burgos, E., Boland, C. R., Goel, A. Tags: Colon cancer, Hepatic cancer Source Type: research

Claudin-1 regulates intestinal epithelial homeostasis through the modulation of Notch-signalling
Conclusions Claudin-1 helps regulate intestinal epithelial homeostasis through the regulation of Notch-signalling. An upregulated claudin-1 expression induces MMP-9 and p-ERK signalling to activate Notch-signalling, which in turn inhibits the goblet cell differentiation. Decreased goblet cell number decreases muc-2 expression and thus enhances susceptibility to mucosal inflammation. Claudin-1 expression also induces colonic epithelial proliferation in a Notch-dependent manner. Our findings may help understand the role of claudin-1 in the regulation of inflammatory bowel diseases and CRC. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Pope, J. L., Bhat, A. A., Sharma, A., Ahmad, R., Krishnan, M., Washington, M. K., Beauchamp, R. D., Singh, A. B., Dhawan, P. Tags: Colon cancer Source Type: research

Canonical Wnt signals combined with suppressed TGF{beta}/BMP pathways promote renewal of the native human colonic epithelium
Conclusions Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Reynolds, A., Wharton, N., Parris, A., Mitchell, E., Sobolewski, A., Kam, C., Bigwood, L., El Hadi, A., Munsterberg, A., Lewis, M., Speakman, C., Stebbings, W., Wharton, R., Sargen, K., Tighe, R., Jamieson, C., Hernon, J., Kapur, S., Oue, N., Yasui, W., W Tags: Open access Colon Source Type: research

Non-redundant properties of IL-1{alpha} and IL-1{beta} during acute colon inflammation in mice
Conclusions The role of IL-1α and IL-1β differs in DSS-induced colitis in that IL-1α, mainly of colon epithelial cells is inflammatory, whereas IL-1β, mainly of myeloid cell origin, promotes healing and repair. Given the dissimilar functions of each IL-1 agonistic molecule, an IL-1 receptor blockade would not be as therapeutically effective as specific neutralising of IL-1α, which leaves IL-1β function intact. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Bersudsky, M., Luski, L., Fishman, D., White, R. M., Ziv-Sokolovskaya, N., Dotan, S., Rider, P., Kaplanov, I., Aychek, T., Dinarello, C. A., Apte, R. N., Voronov, E. Tags: Intestinal inflammation Source Type: research

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort
Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Burisch, J., Pedersen, N., Cuković-Cavka, S., Brinar, M., Kaimakliotis, I., Duricova, D., Shonova, O., Vind, I., Avnstrom, S., Thorsgaard, N., Andersen, V., Krabbe, S., Dahlerup, J. F., Salupere, R., Nielsen, K. R., Olsen, J., Manninen, P., Collin, Tags: Endoscopy, Crohn's disease, Ulcerative colitis, Colon cancer Inflammatory bowel disease Source Type: research

Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease
Conclusions The proteolytic cascade that generates PGP from collagen, as well as the tripeptide itself, is present in the intestine of patients with IBD and mice with DSS-induced colitis. PGP neutralisation in DSS-treated mice showed the importance of PGP-guided neutrophilic infiltration in the intestine and indicates a vicious circle in neutrophilic inflammation in IBD. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Koelink, P. J., Overbeek, S. A., Braber, S., Morgan, M. E., Henricks, P. A. J., Roda, M. A., Verspaget, H. W., Wolfkamp, S. C., te Velde, A. A., Jones, C. W., Jackson, P. L., Blalock, J. E., Sparidans, R. W., Kruijtzer, J. A. W., Garssen, J., Folkerts, G. Tags: Open access Inflammatory bowel disease Source Type: research

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-{gamma}-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment
Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL-23 antibody therapy is a highly effective therapy for these lesions. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Tillack, C., Ehmann, L. M., Friedrich, M., Laubender, R. P., Papay, P., Vogelsang, H., Stallhofer, J., Beigel, F., Bedynek, A., Wetzke, M., Maier, H., Koburger, M., Wagner, J., Glas, J., Diegelmann, J., Koglin, S., Dombrowski, Y., Schauber, J., Wollenberg Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section
Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Jakobsson, H. E., Abrahamsson, T. R., Jenmalm, M. C., Harris, K., Quince, C., Jernberg, C., Bjorksten, B., Engstrand, L., Andersson, A. F. Tags: Gut microbiota Source Type: research

Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis
Conclusions Our study does not support the proposition of a pharmacological effect of gastric acid suppressors on the risk of HCAP. (Source: Gut)
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Filion, K. B., Chateau, D., Targownik, L. E., Gershon, A., Durand, M., Tamim, H., Teare, G. F., Ravani, P., Ernst, P., Dormuth, C. R., the CNODES Investigators, Suissa, Dormuth, Hemmelgarn, Teare, Martens, Caetano, Henry, Paterson, LeLorier, Levy, Ernst, Tags: Open access Stomach Source Type: research

Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma
Objective To investigate the potential tumour suppressor functions of glutathione peroxidase 7 (GPX7) and examine the interplay between epigenetic and genetic events in regulating its expression in oesophageal adenocarcinomas (OAC). Design In vitro and in vivo cell models were developed to investigate the biological and molecular functions of GPX7 in OAC. Results Reconstitution of GPX7 in OAC cell lines, OE33 and FLO-1, significantly suppressed growth as shown by the growth curve, colony formation and EdU proliferation assays. Meanwhile, GPX7-expressing cells displayed significant impairment in G1/S progression and an in...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Peng, D., Hu, T., Soutto, M., Belkhiri, A., Zaika, A., El-Rifai, W. Tags: Oesophageal cancer Oesophagus Source Type: research

5-Methylcytosine hydroxylation-mediated LINE-1 hypomethylation: a novel mechanism of proto-oncogenes activation in colorectal cancer?
Commentary The human genome comprises the most predominant long interspersed nuclear element-1 (LINE-1) sequences, which are non-long-terminal repeat retrotransposons. The majority of LINE-1 repeats are inactivated through truncation, inversion and mutation.1 Importantly, DNA methylation attenuates the transcriptional activation, amplification and recombination of LINE-1 sequences, thereby maintaining genome stability.2 Indeed, global DNA hypomethylation has been associated with increased genomic instability and tumourigenesis, suggesting a more important role for hypomethylation in human cancers than the hypermethylation-...
Source: Gut - February 27, 2014 Category: Gastroenterology Authors: Belkhiri, A., El-Rifai, W. Tags: Commentary Source Type: research