Foreword

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Revising consensus in portal hypertension

Portal hypertension is associated with the most severe complications of cirrhosis, including ascites, hepatic encephalopathy, and bleeding from gastro-esophageal varices. Despite the progress achieved over the last decades, the 6-week mortality associated with variceal bleeding is still in the order of 10–20%. Awareness of the difficulty inherent to the evaluation of diagnostic tools and the design and conduct of good clinical trials for the treatment of portalhypertensionhas led to theorganization, since1986,of a series of consensus meetings. The first one was organized by Andrew Burroughs in Groningen, The Netherlands [1]. After Groningen, other meetings followed, in Baveno in 1990 (Baveno I) [2] and in 1995 (Baveno II) [3,4], in Milan in 1992 [5], in Reston, USA, in 1996 [6], in Stresa in 2000 (Baveno III) [7,8], again in Baveno in 2005 (Baveno IV) [9,10], and in Atlanta in 2007 [11]. The aims of these meetings were to develop definitions of key events in portal hypertension and variceal bleeding, to review the existing evidence on the natural history, the diagnosis and the therapeutic modalities of portal hypertension, and to issue evidence-based recommendations for the conduct of clinical trials and the management of patients. All these meetings were successful and produced consensus statements on some important points, although some issues remained unsettled. To continue the work of the previous meetings, a Baveno V workshop was held on May 21–22, 2010. The workshop was attended by many of the experts responsible for most of the major achievements of the last years in this field. Many of them had attended the previous meetings as well. The main fields of discussion of the Baveno V workshop were the same as in Baveno I–IV, i.e. the definitions of key events concerning the bleeding episode and the therapeutic options in patients with portal hypertension. For each of these topics, a series of consensus statements were discussed and agreed upon. As in Baveno IV, whenever applicable, the level of existing evidence was evaluated and the recommendations were ranked according to the Oxford System [12] (i.e.: level of evidence from 1 = highes

Rôle actuel de la capsule endoscopique dans la détection des tumeurs néoplasiques de l’intestin grêle

Although small-bowel tumors are a small proportion of gastrointestinal neoplasms recent studies suggest that the incidence of these diseases is increasing. In fact, using new diagnostic modalities, their frequency has been shown to be slightly superior than previously thought. Until recently, diagnosis and management of these tumors were delayed by the difficult of access to the small bowel and the poor diagnostic capabilities of the available diagnostic techniques. An array of new methods has recently been developed, increasing the possibility of detecting these tumors at an earlier stage. In this particular subset of patients capsule endoscopy, despite its possible limitations, may provide crucial information changing the subsequent patient management and possibly influencing the long-term clinical outcome.Bien que les tumeurs de l’intestin grêle ne représentent qu’une faible proportion des lésions néoplasiques du tractus digestif, de récentes études ont mis en évidence une légère augmentation de leur incidence. En fait, grâce aux nouvelles modalités diagnostiques, leur fréquence s’est avérée légèrement supérieure à ce qui était précédemment rapporté. Jusqu’à très récemment, le diagnostic et la prise en charge de ces tumeurs étaient retardés en raison d’un accès difficile à l’intestin grêle et aux faibles capacités diagnostiques des moyens techniques disponibles. Tout un éventail de nouvelles méthodes ont récemment été mises au point, améliorant la possibilité de détecter ces lésions à un stade plus précoce. Pour cette catégorie spécifique de patients avec lésions de l’intestin grêle, la capsule endoscopique, en dépit de ses limites, peut fournir une information cruciale influant par conséquent sur la prise en charge du patient et sur les résultats cliniques au long cours

Thrombin regulates the ability of Schwann cells to support neuritogenesis and to maintain the integrity of the nodes of Ranvier

Schwann cells (SC) are characterized by a remarkable plasticity that enables them to promptly respond to nerve injury promoting axonal regeneration. In peripheral nerves after damage SC convert to a repair-promoting phenotype activating a sequence of supportive functions that drive myelin clearance, prevent neuronal death, and help axon growth and guidance. Regeneration of peripheral nerves after damage correlates inversely with thrombin levels. Thrombin is not only the key regulator of the coagulation cascade but also a protease with hormone-like activities that affects various cells of the central and peripheral nervous system mainly through the protease-activated receptor 1 (PAR1). Aim of the present study was to investigate if and how thrombin could affect the axon supportive functions of SC. In particular, our results show that the activation of PAR1 in rat SC cultures with low levels of thrombin or PAR1 agonist peptides induces the release of molecules, which favor neuronal survival and neurite elongation. Conversely, the stimulation of SC with high levels of thrombin or PAR1 agonist peptides drives an opposite effect inducing SC to release factors that inhibit the extension of neurites. Moreover, high levels of thrombin administered to sciatic nerve ex vivo explants induce a dramatic change in SC morphology causing disappearance of the Cajal bands, enlargement of the Schmidt-Lanterman incisures and calcium-mediated demyelination of the paranodes. Our results indicate thrombin as a novel modulator of SC plasticity potentially able to favor or inhibit SC pro-regenerative properties according to its level at the site of lesion

Quality performance measures for small capsule endoscopy: Are the ESGE quality standards met?

Background and study aims The European Society of Gastrointestinal Endoscopy (ESGE) recently issued a quality performance measures document for small bowel capsule endoscopy (SBCE). The aim of this nationwide survey was to explore SBCE practice with ESGE quality measures as a benchmark. Patients and methods A dedicated per-center semiquantitative questionnaire based on ESGE performance measures for SBCE was created by a group of SBCE experts. One-hundred-eighty-one centers were invited to participate and were asked to calculate performance measures for SBCE performed in 2018. Data were compared with 10 ESGE quality standards for both key and minor performance measures. Results Ninety-one centers (50.3 %) participated in the data collection. Overall in the last 5 years (2014–2018), 26,615 SBCEs were performed, 5917 of which were done in 2018. Eighty percent or more of the participating centers reached the minimum standard established by the ESGE Small Bowel Working Group (ESBWG) for four performance measures (indications for SBCE, complete small bowel evaluation, diagnostic yield and retention rate). Conversely, compliance with six minimum standards established by ESBWG concerning adequate bowel preparation, patient selection, timing of SBCE in overt bleeding, appropriate reporting, reading protocols and referral to device-assisted enteroscopy was met by only 15.5%, 10.9%, 31.1%, 67.7%, 53.4%, and 32.2% of centers, respectively. Conclusions The present survey shows significant variability across SBCE centers; only four (4/10: 40 %) SBCE procedural minimum standards were met by a relevant proportion of the centers ( ≥ 80 %). Our data should help in identifying target areas for quality improvement programs in SBCE

Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins

<p>Abstract</p> <p>Background</p> <p>Portal hypertension leads to the formation of portosystemic collateral veins in liver cirrhosis. The resulting shunting is responsible for the development of portosystemic encephalopathy. Although ammonia plays a certain role in determining portosystemic encephalopathy, the venous ammonia level has not been found to correlate with the presence or severity of this entity. So, it has become partially obsolete. Realizing the need for non-invasive markers mirroring the presence of esophageal varices in order to reduce the number of endoscopy screening, we came back to determine whether there was a correlation between blood ammonia concentrations and the detection of portosystemic collateral veins, also evaluating splenomegaly, hypersplenism (thrombocytopenia) and the severity of liver cirrhosis.</p> <p>Methods</p> <p>One hundred and fifty three consecutive patients with hepatic cirrhosis of various etiologies were recruited to participate in endoscopic and ultrasonography screening for the presence of portosystemic collaterals mostly esophageal varices, but also portal hypertensive gastropathy and large spontaneous shunts.</p> <p>Results</p> <p>Based on Child-Pugh classification, the median level of blood ammonia was 45 mcM/L in 64 patients belonging to class A, 66 mcM/L in 66 patients of class B and 108 mcM/L in 23 patients of class C respectively (p < 0.001).</p> <p>The grade of esophageal varices was concordant with venous ammonia levels (rho 0.43, p < 0.001). The best area under the curve was given by ammonia concentrations, i, e., 0.78, when comparing areas of ammonia levels, platelet count and spleen longitudinal diameter at ultrasonography. Ammonia levels predicted hepatic decompensation and ascites presence (Odds Ratio 1.018, p < 0.001).</p> <p>Conclusion</p> <p>Identifying cirrhotic patients with high blood ammonia concentrations could be clinically useful, as high levels would lead to suspicion of being in presence of collaterals, in clinical practice of esophageal varices, and pinpoint those patients requiring closer follow-up and endoscopic screening.</p

What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis?

<p>Abstract</p> <p>Background</p> <p>Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications.</p> <p>Methods</p> <p>Design: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography.</p> <p>Results</p> <p>The prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pugh's classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66).</p> <p>Conclusion</p> <p>Taking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence.</p

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation