1,721,077 research outputs found

    Results of salvage abdominoperineal resection for anal cancer after radiotherapy

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    PURPOSE: Nonsurgical treatment of anal cancer by radiotherapy alone or combined with chemotherapy is the standard therapy for epidermoid carcinoma of the anal canal Surgery is only recommended for treatment failures. Very few studies have been devoted to the outcome of this salvage surgery The aim of this study is to evaluate these results METHODS: A retrospective review from 1986 to 1995 revealed 21 patients with residual or recurrent anal canal carcinoma after initial radiotherapy, operated on by abdominoperineal resection. Patients were reviewed as to age, gender, initial treatment, any symptoms of recurrence, duration until recurrence, any diagnosis imaging, treatment, and outcome. RESULTS: None of these 21 patients had known lymph node involvement or metastases at radiotherapy or at salvage abdominoperineal resection Eleven patients had residual disease (positive biopsy less than 6 months after the end of radiotherapy) and 10 had tumor recurrence (more than 6 months after cessation of treatment) Recurrence occurred at a mean of 15 (range, 9-41) months after radiotherapy. All 21 patients underwent an abdominoperineal resection. Pathologic examination of the 21 specimens showed complete excision in all cases except one and lymph node metastases in two cases. There was no perioperative mortality. The mean follow-up after surgery was 40 months, no patients were lost to follow-up Of the 21 patients, 10 died and 11 lived, of whom 9 are disease free. The overall survival rate at three years after salvage abdominoperineal resection was 58 percent The overall survival rate for patients with residual disease (vs. recurrence) at three years was 72 percent (vs. 29 percent) and at five years was 60 percent (vs 0 percent, P = 0.06) CONCLUSIONS: Salvage abdominoperineal resection for anal cancer can be expected to yield a number of survivors from residual disease, but the low rate of survival after abdominoperineal resection for recurrent disease suggests the need for additional postoperative treatment if salvage abdominoperineal resection is performed.</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Vectorization of photodynamic therapy using extracellular vesicles in the treatment of peritoneal metastasis. Preclinical data

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    Les métastases péritonéales (MP) sont particulières tant par leur nombre que par leur dispersion à l'ensemble de la cavité péritonéale. Elles surviennent à un stade avancé des cancers digestifs et ovariens, et le pronostic des patients est limité malgré une cytoréduction complète. La thérapie photodynamique (PDT), du fait de la faible sélectivité tumorale des photosensibilisateurs (PS), a vu son développement freiné dans le traitement des MP. La nanovectorisation, notamment liposomale, a récemment démontré l'optimisation de la biodistribution intra tumorale des médicaments. L'intégration de la méta-tétra(hydroxyphényl)chlorine (mTHPC), l'un des PS les plus utilisés en clinique, au sein des vésicules extracellulaires issues de cellules souches mésenchymateuses (EVs), a permis in vitro et dans un modèle murin de xénogreffe sous cutanée, l'amélioration de l'efficacité de la PDT. L'objectif de ce travail était d'évaluer la nanovectorisation vésiculaire de la mTHPC (EVs-mTHPC) dans un modèle murin de MP d'origine colique, et de la comparer à la vectorisation liposomale (Foslip®). La reproductibilité était analysée dans un modèle ovarien de MP. Les EVs ciblaient les MP, avec une concentration intra tumorale de mTHPC 24h après injection intra péritonéale de EVs-mTHPC, 3 et 8 fois supérieure par rapport à la formulation libre et vectorisée par des liposomes respectivement (p<0.01). Le ratio moyen de mTHPC dans les tumeurs/tissus non tumoraux était de 44 pour la formulation vésiculaire vs 1.5 et 5.5 pour les formulations libres, et liposomales respectivement. En moyenne le ciblage tumoral par les EVs était 8 fois plus important. La vectorisation vésiculaire potentialisait la cytotoxicité tumorale de la PDT (55 % des nodules tumoraux nécrotiques versus 18 % pour Foslip, p < 0,0001) sans affecter les tissus sains, et modulait le microenvironnement tumoral. Elle favorisait une réponse immunitaire antitumorale, principalement pro-inflammatoire M1-like CD80+ et lymphocytaire T CD8+, dans les modèles immunocompétents de MP. De plus, la PDT vectorisée par les EVs réduisait significativement la prolifération intratumorale et prolongeait la survie des souris (KI67 : 9% vs 48, 26 et 18%, p<0.0001; et médiane survie : 28, vs 22,16 et 26 jours pour la PDT vectorisée par les EVs, vs les contrôles, la PDT non vectorisée et la PDT vectorisée par les liposomes, respectivement, p<0.0001). La sélectivité tumorale des EVs était confirmée dans un modèle ovarien de MP. Notamment dans l'ascite, on observait des clusters de cellules tumorales avec colocalisation du signal de fluorescence de la mTHPC. L'ensemble de ces résultats présente les EVs comme un nanovecteur biologique efficace de la mTHPC, supérieur aux liposomes, permettant une PDT sélective et efficace dans un modèle murin de MP.Peritoneal metastasis (PM) are particular both in their number and in their dispersion throughout the peritoneal cavity. PM occur in advanced digestive and ovarian cancers, and the prognosis of patients is limited despite complete cytoreduction. The development of photodynamic therapy (PDT) in PM treatment was not important, due to the low tumor selectivity of photosensitizers (PS). Nanovectorization, especially with liposome, recently demonstrate the optimization of tumor accumulation of drugs. The integration of meta(tetrahydroxyphenyl)-chlorin (mTHPC), one of the most clinically used PS, into extracellular nanovesicles derived from mesenchymal stem/stromal cells (EVs), improved PDT efficacy in vitro and in mouse xenograft model. The objective of this work was to evaluate the vesicular vectorization of mTHPC (EVs-mTHPC) in a mouse model of PM from colic origin, and to compare with liposomal vectorization (Foslip®). These analyzes were reproduced in an ovarian model of PM. The EVs targeted the PM. mTHPC tumoral concentration, 24 hours after intraperitoneal injection of EVs-mTHPC, was 3 and 8 times higher compared to the free and liposomal formulations respectively (p <0.01). The mean ratio of mTHPC in tumor/non-tumor tissue was 44 for EVs formulation vs 1.5 and 5.5 for the free and liposomal formulations respectively. Tumor targeting by EVs was approximately 8 times higher. EVs vectorization potentiated PDT cytotoxicity at the tumor site (55% of necrotic tumor nodules versus 18% for Foslip, p <0.0001) without affecting healthy tissues, and modulated the tumor microenvironment of immunocompetent colorectal and ovarian carcinomatosis models. EVs promoted antitumor immune cell infiltration, mainly proinflammatory M1-like CD80+ and CD8+ T cell effector. In addition, intratumor proliferation was significantly decreased after PDT with EVs-mTHPC (KI67: 9% vs 48, 26 and 18%, p <0.0001 for EVs-mTHPC, vs controls, free PDT and Foslip®, respectively). Overall EVs vectorization of mTHPC afforded important tumor selectivity while overcoming the PDT toxicity of the free drug and prolonged mice survival in the colorectal carcinomatosis model (median survival: 28, vs 22, 16 and 26 days for for EVs-mTHPC, vs controls, free PDT and Foslip®, respectively, p <0.0001). Tumor selectivity of EVs was confirmed in an ovarian model of MP. Particularly, mice presented important ascitis. Tumor cells observed on ascitis smears were mainly observed as clusters and colocalized with a mTHPC fluorescence signal, in favor of PS internalization in tumor cells present in ascites. EVs appears like the clinically relevant fourth-generation PDT vehicle to overcome current limitations of PDT in the treatment of PM and promote a hot tumor immune environment in PM. EVs tumor selectivity appears superior to liposomal targetting

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Étude des effets de l’implantation de prothèses intra-abdominales dans un modèle murin de carcinose péritonéale de type ovarien

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    This study was carried out in order to categorize visual signs of peritoneal cacirnomatosis after mesh implantation following resection and/or cytoreduction. Using the murine model of ovarian-type peritoneal cancer (PC) which is induced by intraperitoneal injection of ID8 – Luc ovarian cancer cells in immunocompetent C57BL/6 mice in the presence or the absence of intraabdominal prostheses (Surgimend or Ventralex) shows that these prostheses promote pro-tumor development assessed by bioluminescence. The biosynthetic mesh (Ventralex) decreases the survival of the animals whatever the experimental time of prosthesis implantation. Moreover, Ventralex is completely invaded by tumor nodules. In contrast, a vascular network was well visible naked eye on the biological mesh (Surgimend). However, it seems to be devoid of tumor nodules. Using scanning electron microscopy (SEM) allowed us to deny this macroscopic observation. In addition, these SEM observations revealed a probable epithelial-mesenchymal (TEM) transition. In other hand, the in vitro ID8-Luc cell interaction with both protheses assessed by SEM showed similar modified cell phenotype. Using such murine PC model, the safety of this pre-clinical prosthesis implantation strategy shows us that our incompetence to reduce tumor growth and to obtain better tumor control after resection or cytoreduction. The results obtained with prostheses encourage us not to recommend their use in case of intraabdominal pathology (hernia, evisceration, carcinosis). This should prompt providers to change the structure and composition of intra-abdominal prostheses to improve survival and prevent tumor development

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    Microenvironment and angiogenesis : impact on onco-surgical management of synchronous colorectal liver metastases.

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    Lors du diagnostic de cancer colorectal, près d’un quart des patients ont des métastases hépatiques dites synchrones. Lorsque la tumeur primitive est asymptomatique, la stratégie chirurgicale (chirurgie première de la tumeur primitive versus chirurgie première des métastases hépatiques) reste débattue. Les recommandations actuelles ne reposent que sur des accords d’experts qui elles-mêmes sont basées sur des études cliniques rétrospectives. L’étude du microenvironnement tumoral a pris ces dernières années une place majeure dans la recherche sur le cancer. Elle a permis de changer de paradigme avec une nouvelle conception du processus métastatique : une tumeur primitive peut agir sur le microenvironnement du futur site métastatique pour créer une "niche pré-métastatique". Cette niche pré-métastatique permettrait secondairement la croissance des cellules tumorales via une angiogénèse tumorale et la formation de métastases. Par une triple approche à la fois fondamentale, translationnelle et clinique, nous avons obtenu des données qui suggèrent qu’une chirurgie première de la tumeur colique ou rectale permet de moduler l’angiogénèse au sein du microenvironnement hépatique. Cette stratégie chirurgicale permettrait également d’améliorer le pronostic oncologique des malades et l’efficacité des anti-angiogéniques.At the time of the diagnosis of colorectal cancer, nearly 25% of patients have synchronous liver metastases. When this tumor is asymptomatic, the question of surgical strategy (primary tumor first versus liver-first strategy) remains debated. Current recommendations are based on agreements of experts which are by themselves based on retrospective clinical studies. The study of the tumor microenvironment has taken in recent years a major place in the field of cancer research. It leads to new paradigm with a new conception of the metastatic process. It may be possible that the microenvironment of the metastatic sites can be modulated by the primary tumor to promote the formation of the pre-“metastatic niche”. This leads to promote the growth of cancer cells and increase the metastatic potential of primary tumor. By a multidisciplinary research including fundamental, translational and clinical approaches, we have shown that primary tumor first strategy could modulate tumor angiogenesis and liver metastatic process. It is associated with improved survival of patients and efficacy of the anti-angiogenic therapy
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