Incidence des cancers et polypes colorectaux dans le canton de Vaud, 1983-2007: tendances et déterminants

Le cancer colorectal atteint, chaque année, plus d'un million de personnes dans le monde et plus de 500'000 en meurent [1]. Il affecte de manière très inégalitaire les différentes parties du monde. En effet, s'il constitue un problème de santé publique majeur dans des régions telles que l'Amérique du Nord, l'Europe ou l'Océanie (incidence supérieure à 50 pour 100'000), il est nettement plus rare dans certains pays d'Asie, d'Afrique ou d'Amérique du Sud (incidence inférieure à 10 pour 100'000) [2]. Aux Etats-Unis, on estime que 5 à 6% de la population générale présentera un cancer colorectal au cours de sa vie [3]. En Suisse, le cancer colorectal est le deuxième cancer le plus mortel, avec quelque 1'600 décès par an, après le cancer du poumon [4]. Avec 4'000 nouveaux cas annuels, il représente 11% de tous les cancers chez l'homme et chez la femme [5]. Le cancer colorectal est le troisième cancer le plus fréquent après celui du poumon et de la prostate chez l'homme, alors qu'il n'est précédé chez la femme que par le cancer du sein. Pour la période 2003-07, l'incidence en Suisse est estimée à 50 cas/100'000 hommes et 32 cas/100'000 femmes (taux standardisés selon la population européenne) [5] et son taux de survie relative à 5 ans est de 60%, ce qui en fait le taux le plus élevé d'Europe [6]. Le fait que l'incidence chez les migrants ait tendance à rattraper celle des indigènes en moins d'une génération suggère que les facteurs environnementaux jouent un rôle prédominant dans la carcinogénèse des tumeurs colorectales [7]. Cependant, d'autres facteurs, notamment génétiques, interviennent dans la survenue des cancers colorectaux. En effet, dans des conditions de vie similaires, on observe une incidence de cancers colorectaux différente entre différentes ethnies. Des études américaines ont par exemple montré une incidence plus élevée chez les noirs (48 pour 100'000) que chez les blancs (40/100'000) ou les hispaniques (26/100'000) [8]. Les hommes sont plus fréquemment touchés par le cancer colorectal que les femmes, avec un sexe ratio de 1,5 [9]. Les premiers cas de cancers colorectaux apparaissent à partir de 25 ans et l'incidence augmente de manière quasi exponentielle jusqu'à un âge de 75-80 ans, puis se stabilise [10]. L'âge moyen au diagnostic se situe entre 65 et 70 ans. Environ 66% des cancers colorectaux sont localisés dans le côlon (dans l'ordre décroissant: au niveau du sigmoïde, du côlon ascendant, descendant et transverse), 27% dans le rectum, 4% dans l'anus tandis qu'environ 4% restent multiples et indéfinis [10]. Notons encore, qu'à des fins de comparaisons épidémiologiques, les cancers du côlon, du rectum et de l'anus sont souvent regroupés dans l'unique groupe des tumeurs colorectales.

Incidence, prevalence and clinical significance of abnormal hematological indices in compensated cirrhosis.

Background & Aims: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prog-nostic significance. Methods: We analyzed a database of 213 subjects with compensated cirrhosis without esopha-geal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglo-bin,<13.5 g/dL for men and 11.5 g/dL for women), leuko-penia (white blood cell counts,<4000/mm 3 ), or thrombo-cytopenia (platelet counts, < 150,000/mm 3 ). The primary end points were death or transplant surgery. Results: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P .0191) and leukope-nia (P.0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years,a significant difference in death or transplant, mortality,and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at base- line compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r 0.35, P < .0001; white blood cell count, r 0.31, P < .0001). Conclusions: Thrombocy-topenia is the most common and first abnormal HI to occurin patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baselin predicted increased morbidity and mortality.

Incidence and outcomes of symptomatic neonatal arterial ischemic stroke.

BACKGROUND AND OBJECTIVES: Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as cerebral palsy, epilepsy, and cognitive impairment. Prospective epidemiologic studies that include outcome assessments are scarce. This study aimed to provide information on the epidemiology, clinical manifestations, infarct characteristics, associated clinical variables, treatment strategies, and outcomes of NAIS in a prospective, population-based cohort of Swiss children. METHODS: This prospective study evaluated the epidemiology, clinical manifestations, vascular territories, associated clinical variables, and treatment of all full-term neonates diagnosed with NAIS and born in Switzerland between 2000 and 2010. Follow-up was performed 2 years (mean 23.3 months, SD 4.3 months) after birth. RESULTS: One hundred neonates (67 boys) had a diagnosis of NAIS. The NAIS incidence in Switzerland during this time was 13 (95% confidence interval [CI], 11-17) per 100 000 live births. Seizures were the most common symptom (95%). Eighty-one percent had unilateral (80% left-sided) and 19% had bilateral lesions. Risk factors included maternal risk conditions (32%), birth complications (68%), and neonatal comorbidities (54%). Antithrombotic and antiplatelet therapy use was low (17%). No serious side effects were reported. Two years after birth, 39% were diagnosed with cerebral palsy and 31% had delayed mental performance. CONCLUSIONS: NAIS in Switzerland shows a similar incidence as other population-based studies. About one-third of patients developed cerebral palsy or showed delayed mental performance 2 years after birth, and children with normal mental performance may still develop deficits later in life.

May increasing incidence of breast cancer be related to overdiagnosis? : a population-based study

Background: Breast cancer is the first cause of cancer in women in Switzerland. While breast cancer mortality has sharply decreased in the two last decades in Switzerland, the incidence of breast cancer has increased during the same period. Various reasons for this increase have been hypothesized, such as the increase in the prevalence of obesity, the use of postmenauposal hormone replacement therapy, or a later age for having a first child. Overdiagnosis secondary to screening and any other forms of early detection procedures could be also involved. Analyses of breast cancer by stage can help evaluate if overdiagnosis could have contributed to the increase in the incidence of breast cancer. Methods: We used data from the Valais cancer registry at the Observatoire valaisan de la santé (www.ovs.ch). This population based registry collects data on all new (incident) cases of cancer diagnosed in women living in one canton of Switzerland, Valais. Cancers are coded according to the International Classification of Diseases for Oncology (ICD-O-3) and the stages are coded according to the TNM classification. Information on breast cancer stage (in situ: 0; invasive: I, II, III, IV) was available for all cases recorded between 1993 and 2011 (N=4246). Standardized rates of breast cancer were computed (direct standardization on European population).

Three-step pathway engineering results in more incidence rate and higher emission of nerolidol and improved attraction of Diadegma semiclausum

The concentration and ratio of terpenoids in the headspace volatile blend of plants have a fundamental role in the communication of plants and insects. The sesquiterpene (E)-nerolidol is one of the important volatiles with effect on beneficial carnivores for biologic pest management in the field. To optimize de novo biosynthesis and reliable and uniform emission of (E)-nerolidol, we engineered different steps of the (E)-nerolidol biosynthesis pathway in Arabidopsis thaliana. Introduction of a mitochondrial nerolidol synthase gene mediates de novo emission of (E)-nerolidol and linalool. Co-expression of the mitochondrial FPS1 and cytosolic HMGR1 increased the number of emitting transgenic plants (incidence rate) and the emission rate of both volatiles. No association between the emission rate of transgenic volatiles and their growth inhibitory effect could be established. (E)-Nerolidol was to a large extent metabolized to non-volatile conjugates.

Traitement percutané de la thrombose veineuse profonde aiguë [Catheter-based treatment for acute deep vein thrombosis].

Plus de la moitié des patients présentant une thrombose veineuse profonde des membres inférieurs développent un syndrome post-thrombotique. Le risque est particulièrement élevé en cas de thrombose de l'axe principal de drainage veineux comprenant la veine fémorale commune et les veines iliaques. Plusieurs études ont démontré que l'incidence du syndrome post-thrombotique peut être diminuée si une recanalisation des veines ilio-fémorales est obtenue dans la phase aiguë. A l'heure actuelle, des techniques de recanalisation percutanées sont proposées à des patients sélectionnés présentant une thrombose ilio-fémorale. Cet article a pour but de résumer les connaissances actuelles sur la recanalisation percutanée de la thrombose veineuse profonde aiguë. Nearly half of patients with acute lower limb deep vein thrombosis (DVT) develop a post-thrombotic syndrome (PTS). This risk is particularly high in case of proximal DVT of the common femoral and iliac vein, the major lower limbs venous outflow vessel. Several studies have demonstrated that PTS incidence can be reduced with early vein recanalisation. Currently, catheter-based recanalisation therapies can be offered to selected patients with acute ilio-femoral deep vein thrombosis. Aim of the present article is to summarize current knowledge on these catheter-based recanalisation therapies.

JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro.

Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina.

Incidence and Risk Factors of Abdominal Complications After Lung Transplantation.

BACKGROUND: Due to the underlying diseases and the need for immunosuppression, patients after lung transplantation are particularly at risk for gastrointestinal (GI) complications that may negatively influence long-term outcome. The present study assessed the incidences and impact of GI complications after lung transplantation and aimed to identify risk factors. METHODS: Retrospective analysis of all 227 consecutively performed single- and double-lung transplantations at the University hospitals of Lausanne and Geneva was performed between January 1993 and December 2010. Logistic regressions were used to test the effect of potentially influencing variables on the binary outcomes overall, severe, and surgery-requiring complications, followed by a multiple logistic regression model. RESULTS: Final analysis included 205 patients for the purpose of the present study, and 22 patients were excluded due to re-transplantation, multiorgan transplantation, or incomplete datasets. GI complications were observed in 127 patients (62 %). Gastro-esophageal reflux disease was the most commonly observed complication (22.9 %), followed by inflammatory or infectious colitis (20.5 %) and gastroparesis (10.7 %). Major GI complications (Dindo/Clavien III-V) were observed in 83 (40.5 %) patients and were fatal in 4 patients (2.0 %). Multivariate analysis identified double-lung transplantation (p = 0.012) and early (1993-1998) transplantation period (p = 0.008) as independent risk factors for developing major GI complications. Forty-three (21 %) patients required surgery such as colectomy, cholecystectomy, and fundoplication in 6.8, 6.3, and 3.9 % of the patients, respectively. Multivariate analysis identified Charlson comorbidity index of ≥3 as an independent risk factor for developing GI complications requiring surgery (p = 0.015). CONCLUSION: GI complications after lung transplantation are common. Outcome was rather encouraging in the setting of our transplant center.

Characterization of hepatic fatty acids in mice with reduced liver fat by ultra-short echo time (1)H-MRS at 14.1 T in vivo.

Alterations in the hepatic lipid content (HLC) and fatty acid composition are associated with disruptions in whole body metabolism, both in humans and in rodent models, and can be non-invasively assessed by (1)H-MRS in vivo. We used (1)H-MRS to characterize the hepatic fatty-acyl chains of healthy mice and to follow changes caused by streptozotocin (STZ) injection. Using STEAM at 14.1 T with an ultra-short TE of 2.8 ms, confounding effects from T2 relaxation and J-coupling were avoided, allowing for accurate estimations of the contribution of unsaturated (UFA), saturated (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty-acyl chains, number of double bonds, PU bonds and mean chain length. Compared with in vivo (1) H-MRS, high resolution NMR performed in vitro in hepatic lipid extracts reported longer fatty-acyl chains (18 versus 15 carbons) with a lower contribution from UFA (61 ± 1% versus 80 ± 5%) but a higher number of PU bonds per UFA (1.39 ± 0.03 versus 0.58 ± 0.08), driven by the presence of membrane species in the extracts. STZ injection caused a decrease of HLC (from 1.7 ± 0.3% to 0.7 ± 0.1%), an increase in the contribution of SFA (from 21 ± 2% to 45 ± 6%) and a reduction of the mean length (from 15 to 13 carbons) of cytosolic fatty-acyl chains. In addition, SFAs were also likely to have increased in membrane lipids of STZ-induced diabetic mice, along with a decrease of the mean chain length. These studies show the applicability of (1)H-MRS in vivo to monitor changes in the composition of the hepatic fatty-acyl chains in mice even when they exhibit reduced HLC, pointing to the value of this methodology to evaluate lipid-lowering interventions in the scope of metabolic disorders.

Marked increase in incidence for bloodstream infections due to Escherichia coli, a side effect of previous antibiotic therapy in the elderly.

We conducted a survey including 3334 bloodstream infections (BSIs) due to E. coli diagnosed in 2005-2014 at a stable cohort of hospitals. Marked increases in incidence were observed for community-acquired (CA) BSIs in patients aged >75 years, CA-BSIs of digestive origin in patients aged 60-74 years, healthcare-associated BSIs, and BSIs associated with ESBL (extended-spectrum B-lactamase)-producing E. coli (ESBLEc). Using MLST, we studied the genetic diversity of 412 BSI isolates recovered during the 2014 survey: 7 major sequence type complexes (STCs) were revealed in phylogenetic group B2, 3 in group A/B1 and 2 in group D. Among the 31 ESBLEc isolates, 1/3 belonged to STC 131. We searched for possible associations between clonal groups, clinical determinants and characteristics of BSIs: isolates from groups B2 (except STC 131) and D were susceptible to antibiotics and associated with BSIs of urinary origin in patients <60 years. STC 131 and group A/B1 isolates were multi-drug resistant and associated with CA-BSIs of digestive origin in patients aged 60-74 with a recent history of antibiotic treatment. STC 131 isolates were associated with HCA-BSIs in patients with recent/present hospitalization in a long-stay unit. We provide a unique population-based picture of the epidemiology of E. coli BSI. The aging nature of the population led to an increase in the number of cases caused by the B2 and D isolates generally implicated in BSIs. In addition, the association of a trend toward increasing rates of gut colonization with multi drug-resistant isolates revealed by the rise in the incidence of BSIs of digestive origin caused by STC 131 and A/B1 (STCs 10, 23, and 155) isolates, and a significant increase in the frequency of BSIs in elderly patients with recent antibiotic treatment suggested that antibiotic use may have contributed to the growing incidence of BSI.

A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.

UNLABELLED: Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll-like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction. CONCLUSION: Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity. (Hepatology 2015;62:1375-1387).

Veränderung von Inzidenz und Mortalität von Kopf-Hals-Malignomen in Rheinland-Pfalz, 2000-2009 [Changes in Incidence and Mortality Trends of Head and Neck Cancer in Rhineland-Palatinate, 2000-2009].

BACKGROUND: Epidemiological data on HNC are often reported aggregated despite their anatomical and histological heterogeneity. In Germany, few studies have analyzed incidence and mortality trends separately for specific anatomic sites. Furthermore, little is known about whether the incidence of HPV-associated tumour entities of the head and neck region has increased. METHODS: Based on cancer registry data from Rhineland-Palatinate from 2000 to 2009, age-standardized incidence and mortality rates were calculated for all HNC sites and localisation groups that might be HPV-associated according to the literature. Trends were analyzed by Joinpoint regression and reported as the annual percentage change (APC). RESULTS: Throughout the study period, 8 055 incident cases and 3 177 deaths were identified. The incidence rates of overall HNC increased among women (APC:+2.2%) and declined slightly among men (- 0.9%). Significantly increasing incidence rates among women were seen for tumours of the oral cavity (+2.7%) and the oropharynx (+3.6%). Among men, a significant decrease in incidence rates for tumours of the hypopharynx (-3.4%) and the larynx (-2.7%) are noteworthy. Cancers at HPV-associated sites showed increased incidence rates in men (+3.3%) and women (+4.3%). A decrease in mortality was found for tumours of the larynx in both sexes (-5.8% men,-9.1% women). CONCLUSIONS: A detailed analysis by localisation of HNC showed significant and often opposing trends for men and women regarding incidence and mortality.

Incidence and consequence of major bleeding in primary percutaneous intervention for ST-elevation myocardial infarction in the era of radial access: an analysis of the international randomized Acute myocardial infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up trial.

AIMS: The aims of the study are to compare the outcome with and without major bleeding and to identify the independent correlates of major bleeding complications and mortality in patients described in the ATOLL study. METHODS: The ATOLL study included 910 patients randomly assigned to either 0.5 mg/kg intravenous enoxaparin or unfractionated heparin before primary percutaneous coronary intervention. Incidence of major bleeding and ischemic end points was assessed at 1 month, and mortality, at 1 and 6 months. Patients with and without major bleeding complication were compared. A multivariate model of bleeding complications at 1 month and mortality at 6 months was realized. Intention-to-treat and per-protocol analyses were performed. RESULTS: The most frequent bleeding site appears to be the gastrointestinal tract. Age >75 years, cardiac arrest, and the use of insulin or >1 heparin emerged as independent correlates of major bleeding at 1 month. Patients presenting with major bleeding had significantly higher rates of adverse ischemic complications. Mortality at 6 months was higher in bleeders. Major bleeding was found to be one of the independent correlates of 6-month mortality. The addition or mixing of several anticoagulant drugs was an independent factor of major bleeding despite the predominant use of radial access. CONCLUSIONS: This study shows that major bleeding is independently associated with poor outcome, increasing ischemic events, and mortality in primary percutaneous coronary intervention performed mostly with radial access.