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Evaluación del impacto del perfil molecular de cáncer de endometrio en la predicción preoperatoria de afectación ganglionar, patrón de recidiva, y pronóstico tras la recidiva
No full textEl càncer d'endometri és la neoplàsia més freqüent del tracte genital inferior, i la seva incidència i mortalitat estan en augment. El tractament del càncer d'endometri en estadis inicials és principalment quirúrgic, i es basa en la realització d'una histerectomia total amb doble anexectomia, així com una estadificació quirúrgica que inclou l'avaluació de l'estat ganglionar, i que es pot realitzar mitjançant biòpsia selectiva de gangli sentinella (BSGC) únicament o associada a limfadenectomia pèlvica i aòrtica, en funció dels factors de risc prequirúrgics. Aquests factors de risc (histologia i grau en la biòpsia d'endometri i estadi per imatge) presenten limitacions a l'hora de predir preoperatòriament l'afectació ganglionar i extrauterina, amb variacions en la taxa d'afectació ganglionar que oscil·len entre l’1% i el 15% en tumors de baix risc, i entre el 15% i el 40% en tumors d’alt risc, cosa que comporta un infra o sobretractament en un nombre gens menyspreable de pacients.
La classificació molecular del càncer d'endometri ha emergit en els darrers deu anys com una eina important per classificar les pacients, amb una excel·lent correlació diagnòstica entre patòlegs en la biòpsia d'endometri i entre aquesta i la peça d'histerectomia. Els tumors es poden classificar en quatre grups: tumors POLE mutats (POLEmut), mismatch repair deficient (MMRd), p53 anormal (p53abn) i sense perfil molecular específic (NSMP). L'impacte pronòstic independent del perfil molecular ha estat àmpliament demostrat al llarg dels anys i per múltiples cohorts. Tanmateix, la seva capacitat per predir preoperatòriament l'afectació ganglionar i extrauterina és desconeguda.
D'altra banda, un cop realitzada la cirurgia, la classificació de risc postoperatòria que estableix el tractament adjuvant i el tipus de seguiment presenta també limitacions en la predicció de la recidiva: fins a un 15% de les pacients considerades de baix risc presentaran una recidiva i, per contra, entre el 40 i el 50% de les pacients considerades d'alt risc no presentaran mai una recidiva de la seva malaltia. Aquesta classificació es basava, fins a l'any 2021, en factors clàssics com l'histologia, l'estadi FIGO postoperatori i la invasió limfovascular (ILV). El paper del perfil molecular en la predicció del patró de recidiva encara no ha estat explorat. Finalment, també es desconeix l’impacte pronòstic que té el perfil molecular en l’evolució de les pacients després de presentar una recidiva.
L’objectiu principal del present projecte de tesi doctoral va ser establir la taxa d’afectació ganglionar en funció dels quatre grups moleculars mitjançant una revisió sistemàtica de la literatura i un metanàlisi. En segon lloc, vam voler avaluar la capacitat del perfil molecular per predir preoperatòriament l'afectació ganglionar i extrauterina mitjançant l’estudi d’una cohort de 658 pacients amb càncer d’endometri del nostre centre, sotmeses a cirurgia primària i amb perfil molecular realitzat retrospectivament sobre teixit tumoral. El tercer objectiu d’aquesta tesi va ser avaluar la capacitat del perfil molecular per predir el patró de recidiva en aquesta mateixa cohort de pacients. El nostre darrer objectiu va ser analitzar les característiques pronòstiques després de la recidiva associades al perfil molecular en una cohort de 64 pacients diagnosticades amb una primera recidiva a distància al pulmó.
Creiem que els resultats d’aquesta tesi poden aportar informació important respecte al paper del perfil molecular en l’escenari diagnòstic i preoperatori, així com en el moment del seguiment i de la recidiva.El cáncer de endometrio es la neoplasia más frecuente del tracto genital inferior, y su incidencia y mortalidad están en aumento. El tratamiento del cáncer de endometrio en estadios iniciales es principalmente quirúrgico, y se basa en la realización de una histerectomía total con doble anexectomía, así como una estadificación quirúrgica que incluye la evaluación del estado ganglionar, y que puede realizarse mediante biopsia selectiva de ganglio centinela (BSGC) únicamente o asociada a linfadenectomía pélvica y aórtica, en función de los factores de riesgo prequirúrgicos. Estos factores de riesgo (histología y grado en la biopsia de endometrio y estadio por imagen) presentan limitaciones a la hora de predecir preoperatoriamente la afectación ganglionar y extrauterina, con variaciones en la tasa de afectación ganglionar que oscilan de 1% a 15% en tumores de bajo riesgo, y de 15% a 40% en tumores de alto riesgo, lo que conlleva un infra o sobretratamiento en un número no despreciable de pacientes.
La clasificación molecular del cáncer de endometrio ha emergido en los últimos diez años como una importante herramienta para clasificar a las pacientes, con una excelente correlación diagnóstica entre patólogos en la biopsia de endometrio y entre ésta y la pieza de histerectomía. Los tumores se pueden clasificar en cuatro grupos: tumores POLE mutados (POLEmut), mismatch repair deficient (MMRd), p53 abnormal (p53abn) y no specific molecular profile (NSMP). El impacto pronóstico independiente del perfil molecular ha sido ampliamente demostrado a lo largo de los años y por múltiples cohortes. Sin embargo, su capacidad para predecir preoperatoriamente la afectación ganglionar y extrauterina es desconocida.
Por otro lado, una vez realizada la cirugía, la clasificación de riesgo postoperatoria que establece el tratamiento adyuvante y el tipo de seguimiento presenta también limitaciones en la predicción de recidiva: hasta un 15% de pacientes consideradas de bajo riesgo presentarán una recidiva, y, por el contrario, 40-50% de las pacientes consideradas de alto riesgo no presentarán nunca una recidiva de su enfermedad. Esta clasificación se basaba, hasta el año 2021, en factores clásicos como la histología, el estadio FIGO postoperatorio y la invasión linfovascular (ILV). El rol del perfil molecular en la predicción del patrón de recidiva todavía no ha sido explorado. Por último, se desconoce también el impacto pronóstico que tiene el perfil molecular en la evolución de las pacientes tras presentar una recidiva.
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El primer objetivo del presente proyecto de tesis doctoral fue el de establecer la tasa de afectación ganglionar en función de los cuatro grupos moleculares realizando una revisión sistemática de la literatura y un metaanálisis. En segundo lugar, quisimos evaluar la capacidad del perfil molecular para predecir preoperatoriamente la afectación ganglionar y extrauterina mediante el estudio de una cohorte de 658 pacientes afectas de cáncer de endometrio en nuestro centro sometidas a cirugía primaria y con perfil molecular realizado retrospectivamente sobre tejido tumoral. El tercer objetivo de esta tesis fue evaluar la capacidad del perfil molecular para predecir el patrón de recidiva en esta misma cohorte de pacientes. Nuestro último objetivo fue analizar las características pronósticas tras la recidiva asociadas al perfil molecular en una cohorte de 64 pacientes diagnosticadas con una primera recidiva a distancia en el pulmón.
Creemos que los resultados de esta tesis pueden aportar importante información respecto al papel del perfil molecular en el escenario diagnóstico y preoperatorio, así como en el momento del seguimiento y la recidiva.Endometrial cancer is the most common neoplasm of the lower genital tract, and its incidence and mortality are increasing. Treatment of early-stage endometrial cancer is primarily surgical and is based on performing a total hysterectomy with bilateral salpingo-oophorectomy, as well as surgical staging that includes the assessment of nodal status. This can be carried out through sentinel lymph node biopsy (SLNB) alone or combined with pelvic and para-aortic lymphadenectomy, depending on preoperative risk factors. These risk factors (histology and grade on endometrial biopsy, and stage based on imaging) have limitations when it comes to preoperatively predicting lymph node and extrauterine involvement, with nodal involvement rates ranging from 1% to 15% in low-risk tumors and 15% to 40% in high-risk tumors, which can lead to under- or overtreatment in a significant number of patients.
The molecular classification of endometrial cancer has emerged over the past ten years as an important tool for patient stratification, with excellent diagnostic concordance between pathologists when assessing the endometrial biopsy and between the biopsy and the hysterectomy specimen. Tumors can be classified into four molecular subgroups: POLE-ultramutated (POLEmut), mismatch repair deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP). The independent prognostic impact of the molecular profile has been widely demonstrated over the years and across multiple cohorts. However, its ability to preoperatively predict lymph node and extrauterine involvement remains unknown.
On the other hand, once surgery has been performed, the postoperative risk classification that guides adjuvant treatment and follow-up strategies also has limitations in predicting recurrence: up to 15% of patients classified as low-risk will experience recurrence, while 40–50% of patients considered high-risk will never have a recurrence. Until 2021, this classification was based on traditional factors such as histology, postoperative FIGO stage, and lymphovascular space invasion (LVSI). The role of the molecular profile in predicting recurrence patterns has not yet been explored. Lastly, the prognostic impact of the molecular profile on patient outcomes after a recurrence is also unknown.
The primary objective of this doctoral thesis project was to establish the rate of lymph node involvement according to the four molecular subtypes through a systematic review of the literature and meta-analysis. Secondly, we aimed to evaluate the ability of the molecular profile to preoperatively predict lymph node and extrauterine involvement by studying a cohort of 658 patients with endometrial cancer treated with primary surgery at our center, for whom the molecular profile was retrospectively analyzed on tumor tissue. The third objective of this thesis was to assess the ability of the molecular profile to predict recurrence patterns in the same patient cohort. Our final objective was to analyze the prognostic characteristics following recurrence associated with molecular subtypes in a cohort of 64 patients diagnosed with a first distant pulmonary recurrence.
We believe that the results of this thesis can provide valuable insight into the role of molecular profiling in the diagnostic and preoperative setting, as well as in follow-up and recurrence management.Universitat Autònoma de Barcelona. Programa de Doctorat en Pediatria, Obstetrícia i Ginecologi
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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