The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

BACKGROUND: Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. METHODS: We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. RESULTS: For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. CONCLUSION: The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to confirm this observation

Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study

In HCC, tumor microenvironment, heavily influenced by the underlying chronic liver disease, etiology and stage of the tissue damage, affects tumor progression and determines the high heterogeneity of the tumor. Aim of this study was to identify the circulating and tissue components of the microenvironment immune-mediated response affecting the aggressiveness and the ensuing clinical outcome. We analyzed the baseline paired HCC and the surrounding tissue biopsies from a prospective cohort of 132 patients at the first diagnosis of HCC for immunolocalization of PD-1/PD-L1, FoxP3, E-cadherin, CLEC2 and for a panel of 82 microRNA associated with regulation of angiogenesis, cell proliferation, cell signaling, immune control and autophagy. Original microarray data were also explored. Serum samples were analyzed for a panel of 19 cytokines. Data were associated with biochemical data, histopathology and survival. Patients with a more aggressive disease and shorter survival, who we named fast-growing accordingly to the tumor doubling time, at presentation had significantly higher AFP levels, TGF-β1 and Cyphra 21-1 levels. Transcriptomic analysis evidenced a significant downregulation of CLEC2 and upregulation of several metalloproteinases. A marked local upregulation of both PD-1 and PD-L1, a concomitant FoxP3-positive lymphocytic infiltrate, a loss of E-cadherin, gain of epithelial-mesenchymal transition (EMT) phenotype and extreme poor differentiation at histology were also present. Upregulated microRNA in fast-growing HCCs are associated with TGF-β signaling, angiogenesis and inflammation. Our data show that fast HCCs are characterized not only by redundant neo-angiogenesis but also by unique features of distinctively immunosuppressed microenvironment, prominent EMT, and clear-cut activation of TGFβ1 signaling in a general background of long-standing and permanent inflammatory state

Role of High total protein in gallbladder bile in the formation of cholesterol gallstones.

While it is generally accepted that cholesterol supersaturation of bile is of key importance in the rapid formation of cholesterol crystals, the role of total biliary protein and pH in the pathogenesis of cholesterol gallstones is less well understood. The relation of cholesterol saturation, total protein, and pH was studied in 73 gallbladder bile samples with and 35 gallbladder bile samples without cholesterol crystals. In samples containing crystals, a trend to higher values of cholesterol and to a higher cholesterol saturation index was observed. However, significantly (P = 0.02) higher concentrations of total protein were found in samples with crystals [0.80 +/- 0.40 g/dL (8.0 +/- 4.0 g/L)] than in samples without crystals [0.63 +/- 0.26 g/dL (6.3 +/- 2.6 g/L)]. Moreover, of 22 bile samples with total protein concentrations greater than 10.0 g/L, cholesterol crystals were detected in all but 2. Total lipids, bile acids, phospholipids, and pH values were not significantly different in the two groups of bile samples. It was concluded that high biliary protein concentrations are frequently associated with cholesterol crystals and may, therefore, be a possible risk factor in the pathogenesis of cholesterol gallstones

Budd-Chiari syndrome

Le syndrome de Budd-Chiari (SBC) est une affection rare ; sa prévalence est estimée à 1/1000 000 habitants/an dans le monde. En Algérie, la prévalence du SBC n’est pas connue, cependant 115 cas de SBC ont été colligés dans notre seul centre hospitalier entre 2004 et 2010. Le SBC primitif relève de pathologies thrombogènes diverses, congénitales ou acquises. Elles sont dominées par les syndromes myéloprolifératifs (SMP), retrouvés dans 50 % des cas. Dans notre série, l’affection prothrombotique la plus fréquente était comme attendu le SMP. Hormis la fréquence de l’association maladie cœliaque et Syndrome de Budd-Chiari, Il n’y avait pas de particularité concernant la répartition étiologique du SBC chez nos patients. La prise en charge thérapeutique du Budd-Chiari repose sur le traitement symptomatique des complications de la cirrhose, le traitement anticoagulant, les techniques de désobstruction vasculaire, notamment le shunt intrahépatique porto-systémique par voie trans-jugulaire (TIPSS). A un stade avancé, la transplantation hépatique doit être envisagée. Cet arsenal thérapeutique a permis d’améliorer considérablement le pronostic du SBC, avec une survie à 5 ans de 90 %. Nos patients n’ont pu bénéficier des techniques de radiologie interventionnelles, ce qui a lourdement grevé leur pronostic. Ainsi, la survie à 3 ans était de 54 % seulement. La mise en place des techniques de radiologie interventionnelle permettrait de façon certaine, l’amélioration du pronostic du SBC chez nos patients.Budd-Chiari syndrome (SBC) is a rare disease. Its frequency is estimated at 1/1000 000 inhabitants/year worldwide. In Algeria, the prevalence of SBC is not known; however, 115 cases of SBC were collected only in our hospital between 2004 and 2010. Etiologies of BCS are dominated by myeloproliferative disorders (MPD), found in 50% of cases. Other congenital or acquired prothrombotic disorders may be involved. In our patients, the most common prothrombotic condition was, as expected MPD. Apart from the frequency of the association of celiac disease and Budd-Chiari syndrome, there was no distinction regarding the etiological distribution of SBC in our patients. Therapeutic management of BCS is based on the symptomatic treatment of cirrhosis complications, anticoagulant therapy, endo-vascular techniques, including transjugular intrahepatic porto-systemic shunt (TIPSS). In advanced stage, liver transplantation should be considered. These treatments have greatly improved the prognosis of SBC, with 5-year survival rate of 90%. Our patients did not benefit from interventional radiology techniques, which heavily worsened prognosis. Thus, the 3-year survival was only 54%. The development of interventional radiology will certainly improve prognosis of SBC in our country

The Pan American (2004-01-29)

https://scholarworks.utrgv.edu/panamerican/1564/thumbnail.jp

Hemodynamics

Hemodynamics is study of the mechanical and physiologic properties controlling blood pressure and flow through the body. The factors influencing hemodynamics are complex and extensive. In addition to systemic hemodynamic alterations, microvascular alterations are frequently observed in critically ill patients. The book "Hemodynamics: New Diagnostic and Therapeuric Approaches" is formed to present the up-to-date research under the scope of hemodynamics by scientists from different backgrounds

Vergleich der MR-Hydrometrie mit dem Sekretin-Cholecystokinin-Test zur Diagnostik der exokrinen Pankreasinsuffizienz.

Die MR-Hydrometrie zeigt eine hohe Sensitivität und Spezifität bei höhergradigen exokrinen Pankreasinsuffizienzen im Vergleich zum Sekretin-Cholecystokinin-Test. Bei leichtgradigen Insuffizienzen vor allem im ekbolen Bereich kommt es nur zu eingeschränkten Übereinstimmungen zwischen der MR-Hydrometrie und dem Sekretin-Cholecystokinin-Test

La caractérisation du flux artériel hépatique par la technique 4D Flow

Objectif : Déterminer la capacité de la séquence IRM 4D flow à mesurer la forme et le flot (débit, vélocité) de l’artère hépatique et de ses branches en trois dimensions. Méthodologie : Un fantôme de l’artère hépatique réaliste qui imite le flux sanguin et les mouvements respiratoires ainsi que 20 volontaires ont été imagés. La précision du 4D flow Cartésien avec navigateur et remplissage de l’espace-k selon la position respiratoire était déterminée in-vitro à quatre résolutions spatiales (0,5 à 1,0 mm isotropique) et fenêtres d’acceptation du navigateur (± 8 et ± 2 mm) avec un scanner IRM à 3T. Deux séquences centrées sur les branches hépatiques et gastroduodénales étaient évaluées in-vivo et comparés au contraste de phase 2D. Résultats : In vitro, l’augmentation de la résolution spatiale diminuait plus l’erreur qu’une fenêtre d’acceptation plus étroite (30.5 à -4.67% vs -6.64 à -4.67% pour le débit). In vivo, les artèreshépatiques et gastroduodénales étaient mieux visualisées avec la séquence de haute résolution (90 vs 71%). Malgré un accord interobservateur similaire (κ = 0.660 et 0.704), la séquence à plus haute résolution avait moins de variabilité pour l’aire, le débit, et la vélocité moyenne. Le 4D flow avait une meilleure cohérence interne entre l’afflux et l’efflux à la bifurcation de l’artère hépatique (1.03 ± 5.05% et 15.69 ± 6.14%) que le contraste de phase 2D (28.77 ± 21.01%). Conclusion : Le 4D flow à haute résolution peut évaluer l’anatomie et l’hémodynamie de l’artère hépatique avec une meilleure précision, visibilité, moindre variabilité et meilleure concordance interne.Objectives: To assess the ability of four-dimensional (4D) flow, an MRI sequence that captures the form and flow of vessels in three dimensions, to measure hepatic arterial hemodynamics. Methods: A dynamic hepatic artery phantom and 20 consecutive volunteers were scanned. The accuracies of Cartesian 4D flow sequences with k-space reordering and navigator gating at four spatial resolutions (0.5- to 1-mm isotropic) and navigator acceptance windows (± 8 to ± 2 mm) were assessed in vitro at 3 T. Two sequences centered on gastroduodenal and hepatic artery branches were assessed in vivo for intra - and interobserver agreement and compared to 2D phase-contrast (0.5-mm in -plane). Results In vitro, higher spatial resolution led to a greater decrease in error than narrower navigator window (30.5 to −4.67% vs−6.64 to −4.67% for flow). In vivo, hepatic and gastroduodenal arteries were visualized more frequently with the higher resolution sequence (90 vs 71%). Despite similar interobserver agreement (κ = 0.660 and 0.704), the higher resolution sequence had lower variability for area, flow, and average velocity. 4D flow had lower differences between inflow and outflow at the hepatic artery bifurcation (11.03 ± 5.05% and 15.69 ± 6.14%) than 2D phase-contrast (28.77 ± 21.01%). Conclusion: High-resolution 4D flow can assess hepatic artery anatomy and hemodynamics with improved accuracy, greater vessel visibility, better interobserver reliability, and internal consistency

The role of genetic variation in predisposition to alcohol-related chronic pancreatitis

Background Chronic pancreatitis (CP) is a disease of fibrosis of the pancreas for which alcohol is the main causative agent. However, only a small proportion of alcoholics develop chronic pancreatitis. Genetic polymorphism may affect pancreatitis risk. Aim To determine the factors required to classify a chronic pancreatic population and identify genetic variations that may explain why only some alcoholics develop chronic pancreatitis. Methods The most appropriate method of diagnosing CP was assessed using a systematic review. Genetics of different populations of alcohol-related chronic pancreatitics (ACP) were explored using four different techniques: genome-wide association study (GWAS); custom arrays; PCR of variable nucleotide tandem repeats (VNTR) and next generation sequencing (NGS) of selected genes. Results EUS and sMR were identified as giving the overall best sensitivity and specificity for diagnosing CP. GWAS revealed two associations with CP (identified and replicated) at PRSS1-PRSS2_rs10273639 (OR 0.73, 95% CI 0.68-0.79) and X-linked CLDN2_rs12688220 (OR 1.39, 1.28-1.49) and the association was more pronounced in the ACP group (OR 0.56, 0.48-0.64)and OR 2.11, 1.84-2.42). The previously identified VNTR in CEL was shown to have a lower frequency of the normal repeat in ACP than alcoholic liver disease (ALD; OR 0.61, 0.41-0.93). Homozygosity of the normal variant was more common in ALD than ACP (OR 0.53, 0.3-0.96) or Healthy Controls (OR 0.55, 0.3-1.00)). The NGS discovery phase lead on to validation of the 21 most significant SNPs with Sequenom array. This showed significance difference between ACP and ALD in allele frequency of the synonymous SNP, PRSS1_rs6666, (OR 1.99, 1.46-2.72) Conclusion A range of potential exonic and intronic sites have been identified that have association with a predisposition to developing chronic pancreatitis. These findings show that further work is justified to fully assess the interaction of the different polymorphisms and their phenotypic significance in development of the disease