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Gut. 2007 June; 56(6): 876.
PMCID: PMC1954851


Measure for small measures

[filled triangle] Prasad S, Dhiman RK, Duseja A, et al. Lactulose improves cognitive functions and health‐related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology 2007;45:549–59.

Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy and the diagnostic criteria for MHE were formally standardised in 2002 (Hepatology 2002;35:716–21). Although patients with MHE may not have overt symptoms and signs, MHE impairs health‐related quality of life (HRQoL), activities of daily life (including ability to drive) and predicts development of overt encephalopathy.

Prasad et al measured psychometric performance by number and finger connection tests, picture completion and block design tests in 90 patients with cirrhosis to identify 61 (68%) patients with MHE. These 61 patients were randomised in a non‐blinded study design to receive lactulose (30–60 ml in two to three doses so that patients passed two to three semisolid stools per day) for 3 months (n = 31) or no treatment (n = 30). Mean number of abnormal neuropsychological tests decreased significantly from 2.74 (95% CI 2.4 to 3.1) at baseline to 0.75 (95% CI 0.4 to1.2) in the treated group (p = 0.001). HRQoL as measured by Sickness Impact Profile improved among treated patients from a mean baseline score of 10.39 (95% CI 9.4 to11.4) to 3.77 (95% CI 2.5 to 5.0) after 3 months (p = 0.002). Improvement in HRQoL was related to the improvement in psychometry. The mean number of abnormal neuropsychological tests or HRQoL did not change in the untreated group during the 3‐month period.

Despite its common use, lactulose hasn't been shown consistently to be of benefit to patients with hepatic encephalopathy. The findings of this study suggest that the effect of lactulose on hepatic encephalopathy is small and may only be measurable in the setting of MHE and only by subtle neuropsychological tests. The study confirms that MHE reduces the quality of life in patients with cirrhosis. It strengthens the argument that these apparently small improvements seen with lactulose treatment may yet be significant for an individual patient.

CARD15/NOD2 in Crohn's: only part of the story

[filled triangle] Hugot J‐P, Zaccaria I, Cavanaugh J, et al. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am J Gastroenterol 2007;102:1–9.

Three mutations of the CARD15/NOD2 susceptibility gene account for the majority of mutated chromosomes in Crohn's disease in Caucasians. The risk of developing Crohn's disease differs for the three disease‐susceptibility alleles, with odds ratios ranging from 2 to 4. For mutated homozygotes or compound heterozygotes the risk is 10‐ to 40‐fold greater than wild‐type controls. The effect of these mutations is generally thought to be loss of response to bacteria in gut mucosa, which should be more pronounced in homozygotes or compound heterozygotes. In a complex genetic disorder such as Crohn's, the odds ratio for at‐risk genotypes is generally thought to be no more than a few‐fold increased compared with the wild‐type genotype. Does the very high odds ratio seen with double‐dose CARD15/NOD2 mutations imply that there is a subgroup of Crohn's with Mendelian‐type inheritance? (This is known to occur in other diseases, such as diabetes, where maturity‐onset diabetes of the young is a distinct subgroup.) If this was true, and there was Mendelian inheritance with near complete penetrance, then very few individuals with the most at‐risk genotype would be disease‐free.

In order to answer this question, 15 groups worldwide pooled their data on healthy Caucasian controls (3575 in all). The allele frequencies for the R702W, G908R and 1007fs mutations were 4.3% (95% CI 3.6 to 4.9), 1.2% (95% CI 0.8 to 1.6) and 2.3% (95% CI 1.8 to 2.8), respectively. There were large geographic fluctuations in the frequencies of these alleles, with no simple relationship with disease incidences in these populations. There was no significant deficit of double‐dose mutation carriers among these healthy controls without Crohn's disease.

In conclusion, these results confirm that the majority of individuals with two CARD15/NOD2 mutations are healthy and the disease penetrance is therefore limited, consistent with a complex genetic disorder. The findings tally with the incomplete concordance of disease in monozygotic twins carrying these mutations. There is no subgroup with Mendelian inheritance and there must be other significant environmental and/or genetic factors that are required to produce the disease.

Don't look back in anger … I heard you say!

[filled triangle] Triadafilopoulos G, Watts HD, Higgins J, et al. A novel retrograde‐viewing auxiliary imaging device (third eye retroscope) improves the detection of simulated polyps in anatomic models of the colon. Gastrointest Endosc 2007;65:139–44.

I've always been a fan of “What's the story morning glory”. Looking back through my old CD collection revealed the battered and well played disk ... curry and beer stains on the cover confirmed the last days of bachelorhood. A quick dust‐off with a spare alcohol‐based rub from the endoscopy unit meant it played as good as new … I was up the ileum by the last verse. Then something got me thinking ... Liam's droning voice accompanied by that great guitar riff of Noel's said “Don't look back in anger … I heard you say.” Strange then that I started thinking about the colon … how about looking backwards in the colon? The Stanford group has recently published their experience of a third eye retroscope developed given the concerns regarding significant lesion miss rates at forward viewing colonoscopy.

The auxiliary device extends beyond the colonoscope's tip and provides a continuous retrograde video image. Using three colonic anatomical models with simulated polyps, six endoscopists examined each model using either a standard video colonoscope (method A) or the retrograde‐viewing device positioned within the auxiliary port (method B). When assessing the principle outcome measure of “virtual” polyp detection, of the 162 polyps placed on proximal aspects of folds, 20 (12%) and 131 (81%) were detected by methods A and B, respectively (p<0.001).

The device now needs human trials; but I just like the concept. To close with more lyrics – “And so, Sally can wait, she knows it's too late as we're walking on by…”, perhaps an interval cancer springs to mind!

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