Pascal Bourlier

Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation

BACKGROUND & AIMSnHepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.nnnMETHODSnWe analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation.nnnRESULTSnSymptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with β-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively.nnnCONCLUSIONSnUsing sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients risk factors for HCA,xa0disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients withxa0HCA.

Épreuve de lecture critique d'article scientifique des épreuves classantes nationales : pertinence de la correction

INTRODUCTIONnIn 2008 the national ranking examination (NRE) will include a test on critical reading of scientific articles. This decision has provoked controversy about whether reproducible correction is possible. The aim of our study was to assess the consistency of grading between this two-part test (critical analysis and summarizing, analyzed separately), and the more classic tests.nnnMETHODSnEight graders, all instructors at the Tours Medical School, corrected papers for each of the 3 tests. Papers for the critical reading test came from medical school final examinations and for the standard test from a practice examination. The instructors worked in pairs: each pair read 30 papers for each test, and both members separately graded each paper. The final grade was the mean of the two grades. The consistency of grading between the 4 pairs was estimated by Kendalls coefficient of concordance.nnnRESULTSnKendalls coefficients of concordance were estimated at 0.94 (95% CI=[0.86; 0.97]) for the standard test, at 0.92 (95% CI=[0.81;0.97]) for the critical analysis test, and at 0.75 (95% CI=[0.62; 0.84]) for the summaries. Pairwise comparisons estimated the difference in concordance between the standard test and the summary at 0.18 (95% CI=[0.08; 0.32]) and that between the standard and critical reading test at 0.01 (95% CI= [-0.07; 0.12]). Finally the difference in concordance between the 2 new tests - summary and critical reading - was estimated at -0.17 (95% CI=[-0.32; -0.04]).nnnCONCLUSIONnThe focus should be on the difficulty of reproducible correction of the summaries, to set up methods for appropriate correction and adequate grading. The elaboration of detailed scoring templates, including numerous items and specifying in which part of the summary each item must be placed, should help to improve the reproducibility of this tests correction.

Article originalÉpreuve de lecture critique d'article scientifique des épreuves classantes nationales : pertinence de la correctionCorrecting the critical reading test of the national ranking examination

INTRODUCTIONnIn 2008 the national ranking examination (NRE) will include a test on critical reading of scientific articles. This decision has provoked controversy about whether reproducible correction is possible. The aim of our study was to assess the consistency of grading between this two-part test (critical analysis and summarizing, analyzed separately), and the more classic tests.nnnMETHODSnEight graders, all instructors at the Tours Medical School, corrected papers for each of the 3 tests. Papers for the critical reading test came from medical school final examinations and for the standard test from a practice examination. The instructors worked in pairs: each pair read 30 papers for each test, and both members separately graded each paper. The final grade was the mean of the two grades. The consistency of grading between the 4 pairs was estimated by Kendalls coefficient of concordance.nnnRESULTSnKendalls coefficients of concordance were estimated at 0.94 (95% CI=[0.86; 0.97]) for the standard test, at 0.92 (95% CI=[0.81;0.97]) for the critical analysis test, and at 0.75 (95% CI=[0.62; 0.84]) for the summaries. Pairwise comparisons estimated the difference in concordance between the standard test and the summary at 0.18 (95% CI=[0.08; 0.32]) and that between the standard and critical reading test at 0.01 (95% CI= [-0.07; 0.12]). Finally the difference in concordance between the 2 new tests - summary and critical reading - was estimated at -0.17 (95% CI=[-0.32; -0.04]).nnnCONCLUSIONnThe focus should be on the difficulty of reproducible correction of the summaries, to set up methods for appropriate correction and adequate grading. The elaboration of detailed scoring templates, including numerous items and specifying in which part of the summary each item must be placed, should help to improve the reproducibility of this tests correction.

Interest of variations in miR-152 and miR-122 in a series of hepatocellular carcinomas related to HCV infection

Hepatocellular carcinoma (HCC) is a common outcome of chronic hepatitis C virus (HCV) infection and constitutes the main burden of this disease. The molecular mechanisms underlying the development of HCC are multiple and might involve certain microRNA (miR). As discordant results have been reported concerning the detection of expression of miR‐152 and miR‐122 in HCC, our aim was to measure the levels of both miRs in serum and liver samples.

Only Surgical Treatment to Be Considered for Adhesive Small Bowel Obstruction: A New Paradigm

Background Adhesive small bowel obstruction (SBO) represents a heavy burden in healthcare systems worldwide and is associated with significant morbidity and mortality. Although conservative treatment alone can lead to SBO resolution in most cases, its optimal duration is still a matter of debate. The aim of this study was to analyze different SBO evolution patterns in order to further determine when to switch to surgical treatment. Study Design All patients who were admitted for adhesive SBO between 2011 and 2016 were reviewed. Patients who had immediate surgery (IS), a successful medical treatment (SMT), and a failed medical treatment (FMT) were compared in terms of overall morbidity, mortality, and SBO recurrence. Results Overall 154 patients were identified, including 23 (14.9%) in IS, 27 (17.5%) in FMT, and 104 (67.6%) in SMT groups. In terms of comorbidities, patients were similar in all groups. Overall morbidity rates were highest in IS and FMT groups (30% and 33%, respectively, vs. 4% in the SMT group, p < 0.001) whereas mortality rate was highest in the FMT group (22% vs. 0% and 0% in IS and SMT groups, respectively, p < 0.001). SBO recurrence rate was highest in the SMT group (22% vs. 4% and 7% in IS and FMT groups, respectively, p = 0.042). Conclusion FMT seems to be associated with similar overall morbidity compared with IS but with increased postoperative mortality. Patient frailty seems to be worsened by prolonged inefficient medical treatment.