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    LEPTIN INCREASES THE RISK OF BARRETT’S OESOPHAGUS IN MEN

    Obesity is associated with increased risk for several cancers. Based on this, it has been speculated that this association might be due to factors secreted by adipose tissue. Leptin and adiponectin are adipokines that have been found to be associated with several malignancies but the relationship with Barrett’s oesophagus, the precursor of the majority of oesophageal adenocarcinomas, is unknown. In this Australian study, this relationship was investigated. There was a significant, three-fold increased risk of Barrett’s oesophagus among men in the highest quartile of serum leptin (see table) and this persisted after adjustment for reflux symptoms. On the contrary, a tendency towards decreased risk for Barrett’s oesophagus among women with increasing leptin levels was observed. No association with adiponectin was seen. Kendall et al conclude that there is an association between leptin and the presence of Barrett’s oesophagus in men—but not in women—and that this association is not explained by reflux or body mass index. Future studies are needed to determine mechanisms involved in this association.

    See pages 10.1136/gut.2007.131243

    View this table:
    Odds ratios and 95% CI for risk of Barrett’s oesophagus (BO) associated with serum leptin concentration

    NORMAL GROWTH RATES DESPITE FAT MALABSORPTION IN CHILDREN AFTER INTESTINAL TRANSPLANTATION

    Managing intestinal failure with total parenteral nutrition (TPN) in young children is demanding and intestinal transplantation is an initially attractive alternative. However, development has been slow and many patients are not completely weaned from TPN. This report from Paris of 31 children who survived at least 2 years free of TPN is, therefore, valuable. The median follow up was 7 years (2–18); 12 children received small bowel transplantation and 19 received liver plus small bowel transplantation. The underlying condition was small bowel disease in the majority of children (12), microvillus atrophy in 10 and dysmotility in 9. Growth and energy balance were regularly documented and surprisingly only a minority of children had severe growth failure (as shown by Z scores for height <2). Growth velocity was normal in 25 of the 31 children up to puberty. Energy intake was above normal, compensating for the reduced energy absorption of <90%, largely due to impaired fat absorption (61–90%). Endoscopic mucosal biopsies (see fig) showed normal villi in 25 children who remained TPN-free. Five children lost their graft due to chronic rejection, although most of these losses occurred early. Lacaille et al conclude that with careful supervision and early treatment of rejection a successful intestinal transplant should support normal growth and, even though puberty may be delayed, final adult height should be normal, an encouraging message for children facing this daunting prospect.

    Figure 1
    Figure 1 Ileal biopsy 10 years after liver plus small bowel transplantation. Villi are normal and there is no inflammation.

    See pages 10.1136/gut.2007.133389

    TH1/TH2 BALANCE ALTERS RESPONSE OF SEROTONIN CONTAINING ENTEROCHROMAFFIN CELLS TO INFECTION

    Enterochromaffin cells (EC) are sensory transducers in the mucosa, responding to luminal stimuli by releasing serotonin (5-hydroxytryptamine (5-HT)), which in turn stimulates the enteric nerves, driving motility and secretion throughout the gut. Parasitic infections increase EC numbers, an effect mediated by T lymphocytes. The study by Motomura et al examines the response to Trichuris muris infection, comparing BALB/c mice, who mount an effective T helper (Th) 2 response and expel the worm promptly, with AKR mice, who mount a Th1 response associated with impaired worm expulsion. The BALB/c mice showed increased EC numbers and 5-HT content at the peak of inflammatory reaction on day 14 compared with AKR mice. The response to inflammatory cytokines is mediated through signal transducer and activation of transcription (STAT) proteins. Mice lacking STAT6, which is key to the Th2 response, fail to expel the worms while those lacking STAT4 (key for the Th1 response) showed no impairment. This study shows the importance of the Th2 response in worm expulsion and EC cell hyperplasia and indicates that a differing Th1/Th2 balance may account for differing EC responses in various inflammatory diseases.

    See pages 10.1136/gut.2007.129296

    Figure 2
    Figure 2 BALB/c mice with a strong T helper 2 response showed greater enterochromaffin cell numbers compared with AKR mice.

    STREPTOCOCCUS PYOGENES INFECTION AS A TREATMENT FOR PANCREATIC CANCER?

    Several bacterial strains have been demonstrated to stimulate the host immune response to cancer. This study by Maletzki et al examines the possible role of Streptococcus pyogenes infection in treating a tumour induced by injecting a murine pancreatic cancer cell line Panc02 into the flank of mice. A S pyogenes strain M49, shown to be effective in activating apoptosis of Panc02 cells, was injected into the tumour after 9–12 days growth and compared with saline control. As the figure shows, M49, when injected into the tumour, dramatically reduced tumour growth with near complete regression at 4 weeks. A lesser effect was seen again when the mice were rechallenged with tumour. This effect was associated with massive splenomegaly and infiltration of the tumour with lymphocytes, mainly granulocytes and T cells. Analysis of splenocytes showed an increase in macrophages and monocytes and increased release of interferon when exposed to the Panc02 cells, suggesting some specificity of the immune response. The complete regression seen in this model marks this study out from others and suggests that this may be a most promising treatment advance.

    See pages 10.1136/gut.2007.125419

    Figure 3
    Figure 3 Tumour growth was markedly reduced by M49 injection. Rechallenge with repeated injection of Panc02 cells was associated with reduced growth compared with control naive animals given tumour for the first time (M49-C).

    PEGYLATED INTERFERON α-2A IS EFFECTIVE AND SAFE IN PATIENTS UNDERGOING DIALYSIS WITH CHRONIC HEPATITIS C

    Chronic hepatitis C virus (HCV) infection is common in patients undergoing dialysis. Standard interferon (IFN) α-2a is the current standard treatment for these patients; pegylated IFN together with ribavirin is the standard treatment for other patients with HCV infection but to date only small non-randomised studies on the use of pegylated IFNα-2a in patients undergoing dialysis exist. Liu et al performed a randomised–controlled study in 50 patients with HCV infection undergoing dialysis, comparing pegylated α-2a once per week with standard IFNα-2a three times per week for 24 weeks. Patients receiving pegylated IFNα-2a tended to have a higher sustained virological response (48% vs 20%; p  =  0.07) (see table). By using multivariate analysis, treatment with pegylated IFN α-2a and a lower pre-treatment HCV RNA level (<800 000 IU/ml) were independent predictors of a sustained virological response. Moreover, fewer patients withdrew during treatment with pegylated IFNα-2a compared with standard IFN (0% vs 20%; p  =  0.04). Based on these data, it is fair to say that pegylated IFNα-2a seems to be more effective and safer than the current standard treatment in patients with chronic hepatitis C undergoing dialysis.

    See pages 10.1136/gut.2007.133884

    View this table:
    Virological response (rapid (RVR), early (EVR), end of treatment (ETVR), sustained (SVR)) to pegylated and standard interferon in treatment-naive patients with chronic HCV infection undergoing dialysis

    CITALOPRAM IS EFFECTIVE IN TREATING INTERFERON-INDUCED DEPRESSION IN PATIENTS WITH CHRONIC HEPATITIS C

    Depression is a known side-effect during treatment with pegylated interferon (IFN) plus ribavirin for chronic hepatitis C virus (HCV) infection. This may cause non-compliance or even discontinuation of the IFN treatment, thereby jeopardising the excellent treatment results with this regimen. So far, only open label studies with selective serotonin reuptake inhibitors such as citalopram have been performed. Kraus et al performed a randomised, double-blind, placebo–controlled study, comparing the effect of citalopram 20 mg/day with placebo in patients with clinically relevant IFN-induced depression. During the IFN treatment, 28% of the subjects developed depression and these were included in this study (n = 28). Depression scores, using the Hospital Anxiety and Depression Scale (HADS), declined significantly in the citalopram group but not during placebo treatment (see fig) and the difference between the treatment groups was statistically significant. All patients treated with citalopram were able to complete the IFN treatment as planned. Citalopram can be initiated after the onset of clinically relevant depression in HCV patients treated with IFN and general selective serotonin reuptake inhibitor prophylaxis seems unnecessary.

    See pages 10.1136/gut.2007.131607

    Figure 4
    Figure 4 Hospital Anxiety and Depression Scale (HADS) scores for the treatment groups.

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