Methodological assessment of HCC literature.

Despite the fact that the hepatocellular carcinoma (HCC) represents a major health problem, very few interventions are available for this disease, and only sorafenib is approved for the treatment of advanced disease. Of note, only very few interventions have been thoroughly evaluated over time for HCC patients compared with several hundreds in other, equally highly lethal, tumours. Additionally, clinical trials in HCC have often been questioned for poor design and methodological issues. As a consequence, a gap between what is measured in clinical trials and what clinicians have to face in daily practice often occurs. As a result of this scenario, even the most recent guidelines for treatment of HCC patients use low strength evidence to make recommendations. In this review, we will discuss some of the potential methodological issues hindering a rational development of new treatments for HCC patients.

Teorema de Noether do Cálculo das Variações e Controlo Óptimo Estocásticos

Neste trabalho começamos por apresentar os problemas clássicos do cálculo das variações e controlo óptimo determinísticos, dando ênfase ás condições necessárias de optimalidade de Euler-Lagrange e Princípioípio do Máximo de Pontryagin (Capítulo 1). No Capítulo 2 demonstramos o Teorema de Noether do cálculo das variações e uma sua extensão ao controlo óptimo. Como exemplos de aplicação mencionamos as leis de conservação de momento e energia da mecânica, válidas ao longo das extremais de Euler-Lagrange ou das extremais de Pontryagin. Numa segunda parte do trabalho introduzimos o cálculo das variações estocástico (Capítulo 3) e demonstramos um teorema de Noether estocástico obtido recententemente por Jacky Cresson (Capítulo 4). O Capítulo 5 ´e dedicado á programação dinâmica: caso discreto e contínuo, caso determinístico e estocástico.

Rapid prototyping of compliant human aortic roots for assessment of valved stents.

Adequate in-vitro training in valved stents deployment as well as testing of the latter devices requires compliant real-size models of the human aortic root. The casting methods utilized up to now are multi-step, time consuming and complicated. We pursued a goal of building a flexible 3D model in a single-step procedure. We created a precise 3D CAD model of a human aortic root using previously published anatomical and geometrical data and printed it using a novel rapid prototyping system developed by the Fab@Home project. As a material for 3D fabrication we used common house-hold silicone and afterwards dip-coated several models with dispersion silicone one or two times. To assess the production precision we compared the size of the final product with the CAD model. Compliance of the models was measured and compared with native porcine aortic root. Total fabrication time was 3 h and 20 min. Dip-coating one or two times with dispersion silicone if applied took one or two extra days, respectively. The error in dimensions of non-coated aortic root model compared to the CAD design was <3.0% along X, Y-axes and 4.1% along Z-axis. Compliance of a non-coated model as judged by the changes of radius values in the radial direction by 16.39% is significantly different (P<0.001) from native aortic tissue--23.54% at the pressure of 80-100 mmHg. Rapid prototyping of compliant, life-size anatomical models with the Fab@Home 3D printer is feasible--it is very quick compared to previous casting methods.

Comportamiento de las redes de arrastre pelágicas utilizadas en el crucero BIC Humboldt y BIC Jose Olaya Balandra 9808-09 de Paita a Tacna.

Resultados del comportamiento de las redes de arrastre pelágica modelo alemán Engel 988/400 utilizadas para la Evaluación de Recursos Pelágicos: Anchoveta (Engraulis ringens), Sardina (Sardinops sagax sagax), Jurel (Trachurus picturatus murphyi), Caballa (Scomber japonicus peruanus) y Samasa (Anchoa nasus) durante el crucero Hidroacústico 9808-09 a bordo de los BICs Humboldt y José Olaya Balandra entre Paita - Callao - Los Palos (Tacna). Se determinó la distancia entre puertas, el área de la boca de la red y el volumen de agua filtrada que tuvieron las redes en los arrastres efectivos de una milla náutica de distancia durante los 188 lances de comprobación, obteniéndose un rendimiento; se capturó un total de 18.357,87 kg; correspondiendo para la anchoveta 653,51 kg; sardina 108,05; jurel 24,84 kg; caballa 299,77 kg; samasa 228,95 kg y otros recursos hidrobiológicos 17.042,76 kg; con un índice de captura (CPUE) de 249,31 kg. Los valores de datos de comportamiento de la red como la abertura horizontal de la boca, abertura vertical, profundidad de la red y distancia entre la relinga inferior al fondo, etc., se obtuvo en forma directa por medio de una net sonda FS 900 SIMRAD, y SCANMAR RX 400, los arrastres tuvieron en promedio una duración de 21 minutos con una velocidad de 3,4 nudos.

Información básica de los principales peces de consumo

Complementa la información sobre los aspectos de mayor interés referidos a la pesca de consumo y las investigaciones biológicas y pesqueras sobre algunos peces de valor comercial, con el objetivo de ampliar los estudios sobre la bionomía e historia natural de cada especie, conocer la distribución general en tiempo y espacio de las principales especies, estimar la magnitud de los stocks y sus fluctuaciones.

Chirurgie [Surgery].

The evolution of visceral surgery is characterized by defining with ever increasing precision the real role of new techniques. Hernia repair, abdominal compartment syndrome, pancreatic and colorectal cancers, as well as haemorrhoids, confirm this reality. Although laparoscopy has clear indications in hernia repairs, many still prefer open approach. The abdominal compartment syndrome, now better understood thanks to laparoscopy, is increasingly important in intensive care. The role of laparoscopy for pancreatic and colorectal cancers is still limited. The development of minimally invasive techniques has led to a reduced morbidity of surgery for haemorrhoids and better results. The economic impact of new technologies must remain a primary concern.

Red meat and cancer risk in a network of case-control studies focusing on cooking practices.

BACKGROUND: Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. METHODS: We analyzed data from a network of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. RESULTS: Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29; 95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46; 95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95% CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95% CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29; 95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52; 95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). CONCLUSIONS: Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countries.

Venous cannula performance assessment in a realistic caval tree model.

OBJECTIVES: A new caval tree system was designed for realistic in vitro simulation. The objective of our study was to assess cannula performance for virtually wall-less versus standard percutaneous thin-walled venous cannulas in a setting of venous collapse in case of negative pressure. METHODS: For a collapsible caval model, a very flexible plastic material was selected, and a model with nine afferent veins was designed according to the anatomy of the vena cava. A flow bench was built including a lower reservoir holding the caval tree, built by taking into account the main afferent vessels and their flow provided by a reservoir 6 cm above. A cannula was inserted in this caval tree and connected to a centrifugal pump that, in turn, was connected to a reservoir positioned 83 cm above the second lower reservoir (after-load = 60 mmHg). Using the same pre-load, the simulated venous drainage for cardiopulmonary bypass was realized using a 24 F wall-less cannula (Smartcanula) and 25 F percutaneous cannula (Biomedicus), and stepwise increased augmentation (1500 RPM, 2000 and 2500 RPM) of venous drainage. RESULTS: For the thin wall and the wall-less cannulas, 36 pairs of flow and pressure measurements were realized for three different RPM values. The mean Q-values at 1500, 2000 and 2500 RPM were: 3.98 ± 0.01, 6.27 ± 0.02 and 9.81 ± 0.02 l/min for the wall-less cannula (P <0.0001), versus 2.74 ± 0.02, 3.06 ± 0.05, 6.78 ± 0.02 l/min for the thin-wall cannula (P <0.0001). The corresponding inlet pressure values were: -8.88 ± 0.01, -23.69 ± 0.81 and -70.22 ± 0.18 mmHg for the wall-less cannula (P <0.0001), versus -36.69 ± 1.88, -80.85 ± 1.71 and -101.83 ± 0.45 mmHg for the thin-wall cannula (P <0.0001). The thin-wall cannula showed mean Q-values 37% less and mean P values 26% more when compared with the wall-less cannula (P <0.0001). CONCLUSIONS: Our in vitro water test was able to mimic a negative pressure situation, where the wall-less cannula design performs better compared with the traditional thin-wall cannula.

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group.

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models.Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m(2) over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points.Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination.Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.

Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features.

BACKGROUND: Differences exist between the proximal and distal colon in terms of developmental origin, exposure to patterning genes, environmental mutagens, and gut flora. Little is known on how these differences may affect mechanisms of tumorigenesis, side-specific therapy response or prognosis. We explored systematic differences in pathway activation and their clinical implications. MATERIALS AND METHODS: Detailed clinicopathological data for 3045 colon carcinoma patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for analysis. A subset of 1404 samples had molecular data, including gene expression and DNA copy number profiles for 589 and 199 samples, respectively. In addition, 413 colon adenocarcinoma from TCGA collection were also analyzed. Tumor side-effect on anti-epidermal growth factor receptor (EGFR) therapy was assessed in a cohort of 325 metastatic patients. Outcome variables considered were relapse-free survival and survival after relapse (SAR). RESULTS: Proximal carcinomas were more often mucinous, microsatellite instable (MSI)-high, mutated in key tumorigenic pathways, expressed a B-Raf proto-oncogene, serine/threonine kinase (BRAF)-like and a serrated pathway signature, regardless of histological type. Distal carcinomas were more often chromosome instable and EGFR or human epidermal growth factor receptor 2 (HER2) amplified, and more frequently overexpressed epiregulin. While risk of relapse was not different per side, SAR was much poorer for proximal than for distal stage III carcinomas in a multivariable model including BRAF mutation status [N = 285; HR 1.95, 95% CI (1.6-2.4), P < 0.001]. Only patients with metastases from a distal carcinoma responded to anti-EGFR therapy, in line with the predictions of our pathway enrichment analysis. CONCLUSIONS: Colorectal carcinoma side is associated with differences in key molecular features, some immediately druggable, with important prognostic effects which are maintained in metastatic lesions. Although within side significant molecular heterogeneity remains, our findings justify stratification of patients by side for retrospective and prospective analyses of drug efficacy and prognosis.

Lettres de Nicolas COLBERT. — Mélanges historiques.

Contient : Onze lettres adressées à Baluze par Nicolas Colbert, évêque de Luçon et d'Auxerre (16 mars 1667-30 avril 1675) ; Deux lettres de Philippe IV, roi d'Espagne, à Louis XIV (3 novembre 1661) ; « Traduction de ce que M. le marquis de Fuentes doit dire au Roi. » ; Liste des couvents de Paris avant et après 1600 ; « Pour rendre compte à Monseigneur du discours latin adressé au pape, » sur les propositions du clergé de France ; « Articles pour la pacification des troubles du Berry » (23-24 octobre 1650) ; Délibérations des assemblées tenues par l'archevêque de Paris, à la suite du projet d'établissement de Monts-de-Piété en France (27 juin 1630) ; Extraits et collations de quelques pièces d'Avitus ; « Catalogue des auteurs contemporains qui ont escrit l'histoire des rois de France depuis le roy Robert jusqu'à présent » (1685), de la main de Baluze ; Pronostics tirés de la comète de 1578, en italien ; « Tractatus de votis » par [Jules-César ?] Boulanger ; Liste des traités de paix et d'alliance concernant les rois de France ; Epitaphes de Henri et Charles de Schomberg ; Fragment de poème latin sur la quatrième croisade ; Mémoire sur la succession de Philippe IV, roi d'Espagne (incomplet de la fin) ; Fragment de chronique des événements parisiens de la première partie de l'année 1597 ; Lettre de M. de Thou au comte de Brienne (12 septembre 1661) ; « Discours au Roi » (la suite est au f. 144) ; « Harangue de M. le Cardinal, par lui prononcée en Parlement le 18 janvier 1634. » ; « Récit véritable de ce qui s'est passé à Paris depuis le 24e avril 1617. » ; Pièces concernant divers négociants de Lyon et la Compagnie des Indes (1666) ; Lettre de M. de Briel à « M. le comte de Tremese », capitaine des gardes (21 septembre 1635) ; Liste de surintendants, contrôleurs généraux, etc., tirée des comptes de l'Epargne (1608-1635) ; Notes sur l'histoire des Juifs à Paris ; Notes sur les séjours des princes et des rois à Nesle ; « Extrait d'une lettre du patriarche d'Ethiopie, religieux de la Compagnie de Jesus » (14 décembre 1637) ; deux copies ; Extrait d'une lettre de la prieure de Loudun à un Père Jésuite (19 novembre 1638) ; Corrections pour le recueil des Conciles ; Notes, de la main de Baluze, sur les écrits de divers Pères de l'Eglise ; Notes sur diverses affaires ecclésiastiques ; « Il Badoaro di Francesco Patritio » (1558) ; Lettre, en latin, de Jean Maury à Colbert ; « Narratio rei nuper gestae in Parnasso, » en vers latins, adressée à Perrault ; Responsio cur Mecaenas litteratorum laudari abnuat », en vers latins, adressée à Quinault ; Lettre de P. Danès, évêque de Lavaur, à son neveu George Danès (18 avril 1566) ; Lettre de l'abbé Gamurrini, sans adresse (22 janvier 1680) ; Lettre de [Samuel] Sorbière [à Baluze] (2 juillet 1662) ; Samuelis Sorberii ad Stephanum Baluzium allocutio in funere... Petri de Marca ; imprimé de 4 pages ; Lettre de M. Lefranc à Baluze (Montauban), (27 février 1667) ; Lettre de [Henri] d'Aguesseau au même (Limoges, 6 avril 1668) ; Deux lettres de M. Devaubourg à Baluze (5 et 29 décembre 1638)

Extraits de manuscrits de COLBERT.

Contient : Colb. 1548 [lat. 3858 B] : collection de canons ; Colb. 1562 [lat. 4172] : formulaire de lettres pontificales, XIVe-XVe siècle ; Colb. 1701 [lat. 4863] : catalogue en vers des archevêques de Rouen ; Colb. 1713 [lat. 937] : formulaire de la chancellerie des papes d'Avignon ; Colb. 1995 [lat. 4667] : catalogue des rois goths ; Colb. 2052 [lat. 2259] : bulles et diplômes du XIIIe siècle ; Colb. 2089 [lat. 4241] : traité de Jean Schadlant sur les cardinaux ; Colb. 2104 [lat. 5990] : bulles en faveur des rois de France ; Colb. 2262. [lat. 5244] : martyrologe de l'église du Puy ; Colb. 2275 [lat. 9996] : registre de la sénéchaussée de Carcassonne ; Colb. 2446 [lat. 8567] : Etienne de Saint-Georges ; Colb. 2479 [lat. 1772] : « planctus in obitum Constantii Luxoviensis » ; Colb. 2509 [lat. 5294] : miracles de saint Mansuy ; Colb. 2546 [lat. 5373 A] : procès de canonisation de Philippe, archevêque de Bourges ; Colb. 2576 [lat. 1458] : « Gesta Romanorum pontificum » ; Colb. 2578 [lat. 4955] : catalogues épiscopaux ; Colb. 2607 [lat. 673] : extrait de Guibert de Nogent ; Colb. 2835 [lat. 4991 A] : Aimeri de Peyrat ; Colb. 2958 [lat. 5302] : lettre de Jésus-Christ tombée du ciel ; Colb. 3126 [lat. 5954] : traités entre les rois de France et d'Angleterre ; Colb. 3280 [lat. 1745] : « Herberti, De hereticis » ; Colb. 3352 [lat. 8121 A] : satire de Garnier de Rouen ; Colb. 3969 [lat. 6042] : catalogues épiscopaux de la province de Reims ; Colb. 4001 [lat. 7185] : « Arithmomachia » ; Colb. 4047 [lat. 3881] : recueil de canons ; Colb. 4064 [lat. 1682] : recueil de décrétales ; Colb. 4085 [lat. 2731 A] : lettre d'Alcuin ; Colb. 4305 et 4309 [lat. 4280 AA et 2240] : traité contre les hérétiques ; Colb. 4374 [lat. 4889] : chronique d'Ekkehard ; Colb. 4467 [lat. 4350] : lettres de Boniface VIII ; Colb. 4799 [lat. 3555] : recueil d'Exempla ; Colb. 4822 [lat. 8654] : formulaire de Boncompagni ; Colb. 4967 [fr. 5909] : pièces relatives au règne de Charles III ; Colb. 5016 [lat. 2498] : vie de sainte Hélène ; Colb. 5080 [lat. 11015] : chartes de Narbonne ; Colb. 5222 [lat. 2858] : pièces concernant la marche d'Espagne ; Notes écrites par François Bohier, évêque de Saint-Malo [1535-1569] sur les feuillets blancs d'un pontifical ; Chartes de Philippe-Auguste pour Baudouin, comte de Flandre, 1195 et 1200 [Delisle, nos 447 et 579], d'après les originaux ; Bulle de Jean XXII, 7 juillet 1316, relative à la division du diocèse de Toulouse ; Fragment de synode sénonais de la fin du Xe siècle, d'après l'original ; Lettre d'Alcuin, feuillet mutilé d'un ms. du IXe siècle, avec transcription (cf. Bibl. de l'Ecole des chartes, t. XLII, p. 8-10)