Background The optimal endoscopic approach to the drainage of malignant hilar strictures remains controversial, especially with regard to the extent of desirable drainage and unilateral or bilateral ...stenting. Objective To identify useful criteria for predicting successful endoscopic drainage. Design and Setting Retrospective 2-center study in the greater Paris area in France. Patients A total of 107 patients who had undergone endoscopic stenting for hilar tumors Bismuth type II, III, or IV and a set of contemporaneous cross-sectional imaging data available. Interventions The relative volumetry of the 3 main hepatic sectors (left, right anterior, and right posterior) was assessed on CT scans. The liver volume drained was estimated and classified into 1 of 3 classes: less than 30%, 30% to 50%, and more than 50% of the total liver volume. Main Outcome Measurements The primary outcome was effective drainage, defined as a decrease in the bilirubin level of more than 50% at 30 days after drainage. Secondary outcomes were early cholangitis rate and survival. Results The main factor associated with drainage effectiveness was a liver volume drained of more than 50% (odds ratio 4.5, P = .001), especially in Bismuth III strictures. Intubating an atrophic sector (<30%) was useless and increased the risk of cholangitis (odds ratio 3.04, P = .01). A drainage > 50% was associated with a longer median survival (119 vs 59 days, P = .005). Limitations Heterogeneous population and volume assessment methodology to improve in further prospective studies. Conclusion Draining more than 50% of the liver volume, which frequently requires bilateral stent placement, seems to be an important predictor of drainage effectiveness in malignant, especially Bismuth III, hilar strictures. A pre-ERCP assessment of hepatic volume distribution on cross-sectional imaging may optimize endoscopic procedures.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background & Aims Mosaic G-protein alpha-subunit ( GNAS )-activating mutations are responsible for the McCune–Albright (MCA) syndrome. This oncogene that activates the adenylate cyclase is also ...mutated in various tumor types leading to the accumulation of cyclic-AMP. Identification of a hepatocellular adenoma (HCA) in two MCA patients led us to search for GNAS activation in benign and malignant hepatocellular carcinogenesis. Methods GNAS mutations were screened by sequencing 164 HCA, 245 hepatocellular carcinoma (HCC), and 17 fibrolamellar carcinomas. Tumors were characterized by quantitative RT-PCR, gene mutation screening and pathological reviewing. The consequences of wild type and mutant GNAS expression were analyzed in hepatocellular cell lines. Results A somatic GNAS -activating mutation was identified in 5 benign tumors and in 2 HCC. In benign tumors, GNAS mutations were exclusive from HNF1A , CTNNB1 , and IL6ST mutations whereas one HCC demonstrated both CTNNB1 and GNAS mutations. Quantitative RT-PCR showed an activation of the IL-6 and interferon pathways in GNAS -mutated tumor tissues. Accordingly, pathological reviewing identified in GNAS -mutated tumors an inflammatory phenotype characterized by fibrosis and STAT3 activation. We further demonstrated in HCC cell lines that GNAS mutant expression induced inflammatory response and STAT3 activation. Conclusions We identified for the first time the association between two rare diseases, MCA syndrome and HCA occurrence, but also that somatic GNAS -activating mutations in sporadic benign and malignant liver tumors are characterized by an inflammatory phenotype. These results showed a cross-talk between cyclic-AMP and JAK/STAT pathways in liver tumors and they reinforce the role of STAT3 activation in liver tumorigenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
AIM： To study predictive factors of thyroid dysfunction associated with interferon-alpha （IFNa） therapy in chronic hepatitis C （CHC） and to describe its long-term evolution in a large population ...without previous thyroid dysfunction. METHODS： We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNα from 1999 to 2004. RESULTS： Thyroid disorder developed in 30/301 （10%） patients with a mean delay of 6 ± 3.75 mo： 13 patients had hyperthyroidism, 11 had hypothyroidism, and 6 had biphasic evolution. During a mean follow-up of 41.59 ± 15.39 mo, 9 patients with hyperthyroidism, 3 with hypothyroidism, and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo. Recovery rate of dysthyroidism was not modified by treatment discontinuation, but was better for patients with negative thyroid antibodies before antiviral treatment （P = 0.02）. Women had significantly more dysthyroidism （P = 0.05）. Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism （P 〈 0.0003 and P = 0.0003, respectively）. In a multivariate model, low fibrosis was found to be a predictive factor of dysthyroidism （P = 0.039）.
CONCLUSION： In this monocentric population of CHC, dysthyroidism, especially hyperthyroidism, developed in 10% of patients, Low fibrosis was found to be a predictive factor of dysthyroidism, Thyroid disorder recovered in 16/30 patients （53%） and recovery was better in the non-autoimrnune form,
Background
: Although metallic stents remain patent longer than plastic stents, the optimal palliation of inoperable malignant biliary strictures remains controversial because of the high cost of ...metallic stents and short patient survival.
Methods
: A total of 101 patients (mean age 72.5 ± 12.9 years) with malignant strictures of the common bile duct were included in this study, after three exclusions for technical failure (n = 3) and one for noncompliance with study design. The etiology of the strictures included pancreatic cancer (65), cholangiocarcinoma (21), ampullary tumor (3), and metastatic lymph nodes (12). Patients were randomized to receive either an 11.5F polyethylene stent to be exchanged in case of dysfunction (group 1, n = 33), an 11.5F stent to be exchanged every 3 months (group 2, n = 34), or a self-expanding metallic Wallstent (group 3, n = 34).
Results
: Endoscopic procedures were successful (including complete relief of jaundice) in 97.1% of cases. Procedure-related morbidity was 11.9%, and mortality was 2.9%. Bilirubinemia after 48 hours (37.2% ± 21.7% decrease from the preoperative level) did not differ between groups. Patients were followed for a mean of 166 days (median 143, range 0 to 596 days). Overall survivals were not different between groups, but complication-free survival for groups 2 and 3 was longer than that of group 1 (
p
< 0.05). Cumulated hospital days were 7.4 ± 1.5, 10.6 ± 1.7, and 5.5 ± 1.4 (groups 1, 2, and 3, respectively) (
p
< 0.05; analysis of variance). Cost analysis showed that metallic stents were advantageous in patients surviving more than 6 months, whereas a plastic stent was advantageous in patients surviving 6 months or less.
Conclusions
: Metallic stents and plastic stents exchanged every 3 months are valuable alternatives for increasing complication-free survival in patients with malignant strictures of the common bile duct. Metal stents are advantageous in patients with the longest life expectancy. (Gastrointest Endosc 1998;47:1-7.)
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: Pancreatitis is the most common complication of ERCP. Calcium channel inhibitors have been shown to prevent the development of experimental pancreatitis. The aim of this randomized, ...placebo-controlled trial was to determine whether the calcium channel blocker nifedipine prevents post-ERCP pancreatitis.
Methods: Patients referred for ERCP were enrolled. Those being treated with a calcium channel inhibitor and those with acute or chronic pancreatitis were excluded. Nifedipine or placebo was administered orally less than 3 hours before and within 6 hours after ERCP. The main outcome measure was the number of cases of post-ERCP pancreatitis; a secondary outcome was the rate of post-ERCP pain (without pancreatitis) that persisted for 12 or more hours.
Results: One hundred fifty-five patients (70 women, 85 men; mean SD age 65.8 18.2 years; range, 23-97 years) were enrolled and randomized to receive nifedipine (76 patients) or placebo (79 patients). The two groups were comparable. Procedures performed were retrograde diagnostic cholangiopancreatography alone (n = 33), biliary sphincterotomy (n = 31), stone extraction (n = 39), stent placement (n = 37), sphincteroplasty (n = 5), and other (n = 3). ERCP was unsuccessful in 5 patients. A single case of severe pancreatitis was observed (placebo group). The rate of post-ERCP pancreatitis was not different between groups (nifedipine, 10 patients, 13.2%; placebo, 14 patients, 17.7%;
p = 0.4). The frequency of post-ERCP pain was not different between the groups. The only independent predictor of post-ERCP pancreatitis was difficult cannulation in both groups (OR = 3.78: 95% CI 1.25, 11.45).
Conclusion: This study failed to demonstrate a significant effect of nifedipine in the prevention of post-ERCP pancreatitis. A multicenter trial with greater statistical power would be needed to demonstrate a benefit for this drug. (Gastrointest Endosc 2002;56:202-8.)
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
: Aims: Steatosis may increase oxidative stress, which is counteracted by cellular enzymatic (cytosolic and mitochondrial superoxide dismutases (Cu/Zn‐SOD and Mn‐SOD), glutathione peroxidase (GPx), ...catalase) and non‐enzymatic antioxidant systems. We aimed to determine, in patients with non‐alcoholic fatty liver disease (NAFLD), the level of antioxidant defenses (1) in liver biopsies, to demonstrate the existence of oxidative stress; (2) in erythrocytes and plasma, to determine whether their antioxidant defenses reflect liver oxidative stress.
Methods: Erythrocyte and plasma antioxidant defenses were prospectively studied in two groups of 16 patients: patients with NAFLD and controls. Liver biopsies were performed in eight NAFLD patients; liver antioxidant enzyme activities were measured and compared with those in 12 control livers used for transplantation.
Results: Cu/Zn‐SOD, GPx and catalase activities were significantly higher in NAFLD livers than in controls whereas no significant differences were observed in Mn‐SOD activity, and thiobarbituric acid‐reactive substance (TBARS) concentration. No differences were observed in erythrocyte antioxidant enzyme activities (GPx, catalase, Cu/Zn‐SOD), erythrocyte TBARS concentration, and plasma α‐tocopherol concentration.
Conclusions: Liver antioxidant enzyme activities were high in patients with NAFLD, reflecting an oxidative stress possibly involved in inflammation and fibrogenesis. However, erythrocyte and plasma antioxidant defenses did not reflect intrahepatic peroxidation.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
7.
Not Available Buffet, Catherine
Bulletin de l'Académie nationale de médecine,
02/2016, Volume:
200, Issue:
2
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
8.
Présentation Buffet, Catherine
Bulletin de l'Académie nationale de médecine,
02/2016, Volume:
200, Issue:
2
Journal Article
Peer reviewed
Full text
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background & Aims: The impact of interferon (IFN) treatment on the occurrence of complications related to hepatitis C virus (HCV)-related cirrhosis is debated because the majority of studies are ...retrospective. We designed a randomized controlled trial comparing the efficacy of prolonged IFN alfa-2a treatment vs nontreatment on complication-free survival in patients with compensated HCV cirrhosis. Methods: A total of 102 patients (mean age, 60.5 ± 9.5 y; male/female ratio, .82) with biopsy examination–proven HCV cirrhosis, Child–Pugh score A, who were hepatocellular carcinoma (HCC) free, and had at least 1 risk factor of complications were randomized to receive IFN or no therapy for 24 months. Results: During the follow-up evaluation, the complication rate was 24.5%: HCC occurred in 12 and decompensation unrelated to HCC occurred in 13 patients. The number of HCC patients was similar in both groups. The probability of complication-free survival was not significantly different between treated and untreated patients (98% and 72.3% vs 90% and 70.7% at 12 and 24 mo, respectively, P = .59). The median time until complication occurrence was 17.1 months in the treated group vs 13.6 months in the untreated group ( P = .2). Conclusions: This randomized controlled trial showed that a 2-year course of IFN has little or no impact on complication-free survival in patients with high-risk compensated HCV cirrhosis.
Non alcoholic fatty liver diseases (NAFLD) is a clinicopathological entity that encompasses simple steatosis, necroinflammation known as non alcoholic steatohepatitis (NASH) with or without fibrosis. ...It is strongly associated with the metabolic syndrome. NAFLD is by far the most common cause of liver disease. Key issues in the diagnosis of patients with NAFLD are the differentiation of NASH from simple steatosis and the degree of liver fibrosis. Patients with NASH are at greatest risk of developing complications of chronic liver disease, such as hepatocellular carcinoma even in the absence of cirrhosis. Liver biopsy, which is the gold standard diagnostic method, cannot be proposedfor all patients, given the risk of this procedure and the prevalence of NAFLD. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. Knowledge about the interaction between the intestinal microbiota in obesity has rapidly increased in the past few years. Several lines of evidence suggest a role for the gut microbiota in the pathogenesis of NAFLD. Dysbiosis, i.e. imbalance of the intestinal microbiome, may have a role in the progression of NAFLD. At the present time, there are limited treatment options wich include lifestyle modification to lose weight, treatment of the disorders included in the metabolic syndrome and different therapeutic agents. However results are disappointing concerning liver inflammation and fibrosis. Manipulating the gut microbiota may represent a new strategy for patients with NAFLD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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