Prise en charge du carcinome hépatocettulaire en 2010 [Management of hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.

Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial : B-240

Purpose: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead? versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods and Materials: This prospective, randomized, multicentre study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads? or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. The results of the two groups were compared using the chi-square test and Student`s t-test. Results: Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p < 0.001) and 59% for aspartate transaminase (p < 0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89 µmol/L. Concerning gastrointestinal disorders, 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders, serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. Conclusion: PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group.

Basidiomicets de les torberes dels Pirineus catalans. Primera contribució

Es donen a conèixer els primers resultats dels estudis sobre la flora dels Basidiomicets que fructifiquen a les torberes d'esfagnes dels vessants catalans dels Pirineus. Es citen i comenten 9 espècies noves o poc conegudes a la Península Ibèrica, com són: Hygrocybe coccineo crenata (Ort.) Mos., H. lepida Arnolds, Hypholoma elongatum (Pers.: Fr.) Ricken, H. udum (Pers.: Fr.) Kühner, Omphalina oniscus (Fr.: Fr.) Quél., Hebeloma helodes Favre, Cortinarius palustres Moser, C. sphagneti P.D. Orton i C. uliginosus Berk.

Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and chronic infection with hepatitis C virus is one of the main risk factors for HCC. This study analyses the characteristics of the patients with chronic hepatitis C participating in the Swiss Hepatitis C Cohort Study who developed HCC. METHODS: Analysis of the database of the Swiss Hepatitis C Cohort Study, a multicentre study that is being carried out in eight major Swiss hospitals since the year 2000. Patients with chronic hepatitis C and HCC were regrouped and compared to the patients without HCC. RESULTS: Among the 3,390 patients of the cohort, 130 developed an HCC. Age was one of the determining factors. Cirrhosis and its complications ascites and porto-systemic encephalopathy were associated with HCC. Males presented a higher risk for HCC than females. Alcohol consumption was associated with HCC. Diabetes mellitus was an important risk factor, especially in patients with low fibrosis. Patients with Hepatitis C genotype 2 had significantly less HCC than patients with other genotypes. A low socioeconomic status (income, education, profession) was associated with HCC. CONCLUSIONS: Beside the expected characteristics (age, gender, cirrhosis, alcohol), these data stress the role of diabetes mellitus and reveal the importance of low socioeconomic status as a risk factor for HCC in Swiss patients infected with hepatitis C virus. This vulnerable population should be closely monitored.

AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint eff ort.

Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data.

The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the PNPLA3 gene is associated with liver damage in chronic liver diseases. Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear. We performed a meta-analysis of individual participant data including 2,503 European patients with cirrhosis to assess the association between rs738409 and HCC, particularly in ALD and CHC. We found that rs738409 was strongly associated with overall HCC (odds ratio [OR] per G allele, additive model=1.77; 95% confidence interval [CI]: 1.42-2.19; P=2.78 × 10(-7) ). This association was more pronounced in ALD (OR=2.20; 95% CI: 1.80-2.67; P=4.71 × 10(-15) ) than in CHC patients (OR=1.55; 95% CI: 1.03-2.34; P=3.52 × 10(-2) ). After adjustment for age, sex, and body mass index, the variant remained strongly associated with HCC. Conclusion: Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development.

Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004.

Upward trends in mortality from hepatocellular carcinoma (HCC) were recently reported in the United States and Japan. Comprehensive analyses of most recent data for European countries are not available. Age-standardized (world standard) HCC rates per 100,000 (at all ages, at age 20-44, and age 45-59 years) were computed for 23 European countries over the period 1980-2004 using data from the World Health Organization. Joinpoint regression analysis was used to identify significant changes in trends, and annual percent change were computed. Male overall mortality from HCC increased in Austria, Germany, Switzerland, and other western countries, while it significantly decreased over recent years in countries such as France and Italy, which had large upward trends until the mid-1990s. In the early 2000s, among countries allowing distinction between HCC and other liver cancers, the highest HCC rates in men were in France (6.8/100,000), Italy (6.7), and Switzerland (5.9), whereas the lowest ones were in Norway (1.0), Ireland (0.8), and Sweden (0.7). In women, a slight increase in overall HCC mortality was observed in Spain and Switzerland, while mortality decreased in several other European countries, particularly since the mid-1990s. In the early 2000s, female HCC mortality rates were highest in Italy (1.9/100,000), Switzerland (1.8), and Spain (1.5) and lowest in Greece, Ireland, and Sweden (0.3). In most countries, trends at age 45-59 years were consistent with overall ones, whereas they were more favorable at age 20-44 years in both sexes. CONCLUSION: HCC mortality remains largely variable across Europe. Favorable trends were observed in several European countries mainly over the last decade, particularly in women and in young adults.

Large gypsum nodules in the Paleogene and Neogene evaporites of Spain: distribution and palaeogeographic significance

Sabkha and deep burial set tings are the most com mon sites where diagenetic anhydrite forms. In a sabkha setting, displacive facies (iso lated nodules, bed ded nodules, enterolithic levels) of early diagenetic or primary anhydrite are generated (Shearman, 1966; Hardie, 1967). These anhydrite facies are commonly foundat the top of shoal ing cycles representing the evolution from subaqueous depositional conditions at the base (carbonates, lutites) to exposure conditions at the top where in ter stitially-grown gypsum/anhydrite de velops ( sabkha cy cles). In a deep burial setting, gypsum transforms to tally to anhydrite with in creas ing temperature and lithostatic pressure (Murray, 1964). Al though this mineral transformation usually preserves the depositional gypsum facies, a significant textural change is in volved in other cases, resulting in replacive anhydrite with a nodular-mosaic or"chicken-wire" fabric (Warren, 2006). In the two settings, how ever, the size of the individual anhydrite nodules is relatively small, rarely reaching some tens of centimetres across. More over, bedding is preserved or little disturbed, al though minor de formation is caused by the displacive sabkha nodules.

Occurrence of a new sulphate mineral: Ca7Na3K(SO4)9 in the Emet borate deposits, western Anatolia (Turkey)

This paper is a preliminary report on the petrographic and geochemical characteristics of a new sulphate mineral associated with lacustrine glauberite layers. This mineral is present in two boreholes recently drilled in the Emet borate district (Mio-cene; western Anatolia , Turkey). The evaporitic succession in these boreholes is mainly formed of a glauber ite-probertiteal-ternation. We suggest the name"emetite", after the town of Emet, for the new sulphate mineral, although the fine crystal size hinders the appropriate chemical and crystallographic characterization required to propose it as a new mineral to the International Mineralogical Association. .

Occurrence of a new sulphate mineral: Ca7Na3K(SO4)9 in the Emet borate deposits, western Anatolia (Turkey)

This paper is a preliminary report on the petrographic and geochemical characteristics of a new sulphate mineral associated with lacustrine glauberite layers. This mineral is present in two boreholes recently drilled in the Emet borate district (Mio-cene; western Anatolia , Turkey). The evaporitic succession in these boreholes is mainly formed of a glauber ite-probertiteal-ternation. We suggest the name"emetite", after the town of Emet, for the new sulphate mineral, although the fine crystal size hinders the appropriate chemical and crystallographic characterization required to propose it as a new mineral to the International Mineralogical Association. .

Ausgegraben! Schweizer Archäologen erforschen die griechische Stadt Eretria. Eine Ausstellung der Schweizerischen Archäologischen Schule in Griechenland in Zusammenarbeit mit dem Antikenmuseum Basel und Sammlung Ludwig (22.09.2010-30.01.2011).

Eretria war eine der grossen Städte des antiken Griechenland. Zahlreiche Monumente und Kunstwerke zeugen noch heute von ihrer bedeutenden Vergangenheit. 1964 haben Archäologen aus der Schweiz die Erforschung der antiken Stadt, die vor über einem Jahrhundert begonnen hatte, in enger Zusammenarbeit mit den zuständigen griechischen Behörden aufgenommen. Zum ersten Mal sollen nun die bisherigen Ergebnisse in der Schweiz präsentiert werden: Die Ausstellung lässt anhand von etwa 500 Ausgrabungsfunden eine blühende griechische Stadt wieder aufleben. Eretria war von Anfang an ein wichtiger Knotenpunkt zwischen Ost und West. Die Stadt liegt am östlichen Ufer des Golfes von Euböa gegenüber von Attika. Von diesem zentralen Punkt in der Ägäis brachen eretrische Abenteurer ab dem 8. Jh. v. Chr. auf, um das gesamte Mittelmeer zu durchkreuzen. Obschon Eretria zur Zeit der Perserkriege um 490 v. Chr. und unter der athenischen Herrschaft im 5. Jh. gelitten hatte, erlebte die Stadt in den folgenden Jahrhunderten eine neue Blütezeit, die sich bis in die römische Kaiserzeit fortsetzte. Erst im 6. Jh. n. Chr. wird der Ort vollständig verlassen. Die Stadt der Lebenden stellt anschaulich die verschiedenen Bereiche des Lebens in einer antiken griechischen Stadt vor. Anhand der Wohnhäuser der eretrischen Aristokratie wird das Privatleben thematisiert. Im Gegensatz zu den Privathäusern, die nach aussen geschlossen sind, öffnen sich die öffentlichen Gebäude auf grosse Plätze. Die Agora, die Säulenhallen, das Theater, die Palästren und das Gymnasion bieten den Einwohnern genügend Raum, um sich zu treffen, über Politik und Kultur zu debattieren und Neuigkeiten auszutauschen. Die Stadt der Götter zeigt, welche Götter man in Eretria verehrte. Im Zentrum Eretrias befand sich das Heiligtum des Apollon Daphnephoros (= <des Lorbeerträgers>). Der Stadtgott Apollon teilte sich mit seiner Zwillingsschwester Artemis die Vorrangstellung im eretrischen Pantheon. Daneben hatten aber auch andere Götter ihren Platz: Athena auf der Akropolis, Demeter und Kore an deren Abhängen und Dionysos beim Theater. Die Stadt der Toten geht auf die Jenseitsvorstellungen und auf die Bestattungsbräuche der damaligen Menschen ein. Die oberirdischen Monumente sind seit langem verschwunden. Die eigentlichen Gräber in der Tiefe der Erde mit den sterblichen Überresten und den Grabbeigaben blieben indes intakt. Sie lehren uns viel über die Gesellschaft Eretrias und über das Verhältnis der Menschen zum Tod. Begleitpublikation zur Ausstellung "ausgegraben! Schweizer Archäologen erforschen die griechische Stadt Eretria", die vom 22. September 2010 bis zum 30. Januar 2011 im Antikenmuseum Basel und Sammlung Ludwig gezeigt wurde.

5

Die auJlerkörperliche Erfaltrung (AKE) hat in den letztenJahren Forscher vieler Fachrichtungen beschäftigt. Vor allem hat das Verständnis der Neurowissenschaften und experimentellen Psychologie zu diesem Boom entscheidend beigetragen. Um zu verdeutlichen, wie bereits wenige klinische Studien ein Feld verändern können, werden im Folgenden phänomenologische, neurologische, psychophysiologische, experimentelle und pharmakologische Studien zur AKE aufgefi:hrt, vor allem jene der Ietzten 20 Jahre. Von besonderer Bedeutung werden Hirnstimulationsstudien bei Patienten mit Epilepsie sein, da bei diesen Patienten das Hirn bei vollem Bewusstsein direk elektrisch stimuliert wird, Weiterhin werden Studien zur AKE vorgestellt, die Hirnströme bei Gesunden und Patienten messen; hinzu kommen Studien, mit denen versucht wird, den Ort einer Hirnschädigung mit dem Auftreten von AKE in Verbindung zu bringen, Die Schlussfolgerungen aus diesen Studien und aus experimentellen Verhaltensstudien sollen aufzeigen, dass man ein zuvor mystifiziertes Phänomen untersuchen kann, aber dass es einen genaueren Anhaltspunkt benötigt, anhand dessen man gezielt Studien planen und durchfi.rhren kann. Ebenfalls soll aufgezeigt werden, welche vielen Fragen zu diesem Phänomen noch immer offen sind und die Forschenden mindestens weitere 20 Jaltre beschäftigen werden.

El Joc tradicional a la iconografia filatèlica

Des del Grup de Recerca i Investigació sobre Esport i Societat (GRIES) ha semblat escaient iniciar un projecte de recerca que permeti aprofundir en l’estudi de la “Cultura lúdica com a patrimoni”. Aquest projecte de recerca i la dedicada a “Esport i modernització a Catalunya en el segle XX” són els dos projectes que sostenen una de les quatre línies d’investigació desplegades per aquest grup de recerca, en concret aquella que fa referència a “Cultura, esport i patrimoni”. Doncs bé, el present article dóna a conèixer els resultats obtinguts en tres estudis en relació a la utilització d’una de les fonts iconogràfi ques que al nostre entendre no ha merescut la sufi cient atenció per part dels investigadors malgrat disposar d’informacions força valuoses, si més no, en l’àmbit de l’estudi dels jocs populars i tradicionals. Ens estem referim a la iconografi a fi latèlica. El primer dels estudis mostra els resultats obtinguts en la investigació d’una emissió fi latèlica que aplegava força manifestacions lúdiques, la “Serie Europa -Juegos infantiles - 1989”. El segon ha consistit en l’elaboració d’un catàleg fi latèlic de jocs tradicionals d’Europa i el seu corresponent anàlisi. Per últim, el tercer, pretén consolidar aquest projecte, amb la realització d’una tesi doctoral que pretén estudiar els jocs i esports tradicionals d’arreu del món a través de la fi latèlia.

Genetic association analyses reveal a role for vitamin D insufficiency in hepatitis C virus-associated hepatocellular carcinoma development

Background: V itamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. Methods: Associations between t he r isk o f HCV-related HCC development and CYP2R1 , GC, and DHCR7 genotypes, which are genetic determinants of reduced 25-OH-vitamin D3 (25[OH]D3) serum levels, were determined. Results: A t otal of 5604 HCV-infected patients, 1279 with a nd 4325 without progression to HCC, w ere identified. The well-known association between 25(OH)D3 s erum levels and variations in CYP2R1 ( rs1993116, rs10741657), GC ( rs2282679), a nd DHCR7 ( rs7944926, rs12785878) g enotypes was also apparent in patients w ith chronic hepatitis C. The same genotypes of t hese single nucleotide polymorphisms (SNPs), w hich are associated with reduced 25(OH)D3 s erum levels, were significantly associated with HCV-associated HCC (P=0.07 [OR=1.13] for CYP2R1 , P=0.007 [OR=1.56] for GC, P=0.003 [OR=1.42] for DHCR7; ORs for risk genotypes). In contrast, no association between t hese genetic variations and the o utcome of antiviral therapy with pegylated interferon-α and ribavirin ( P>0.2 for e ach SNP) or liver fibrosis progression rate (P>0.2 for each SNP) was observed, s uggesting a specific influence o f the genetic d eterminants of 25(OH)D3 s erum levels o n hepatocarcinogenesis. Conclusions: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related HCC development. Controlled clinical trials to assess the benefit of vitamin D supplementation in HCVinfected patients with advanced liver fibrosis or cirrhosis are warranted.

Re-writing and Its Pedagogical Value: A Case Study

Tenint en compte el temps i la energia que els mestres i professors dediquen a la correcció de redaccions i produccions escrites i el poc efecte que aquestes semblen tenir en altres produccions dels aprenents, es va dissenyar la recerca que es presenta en aquest article. Els resultats de l'estudi semblen suggerir que les correccions no faciliten l'aprenentatge. Com presentem aquesta activitat de retroalimentació a l'alumnat i la posició que li donem dins d'un enfocament basat en el procés de l'escriptura seran clau per fer que les correccions siguin facilitadores de l'aprenentatge de la producció escrita.