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w:type="continuation-separator"><w:p><w:r><w:continuationSeparator/></w:r></w:p></w:endnote></w:endnotePr><w:compat><w:dontAllowFieldEndSelect/><w:useWord2002TableStyleRules/></w:compat></w:docPr><w:body><wx:sect><w:p><w:pPr><w:pStyle w:val="Meta-Titre"/></w:pPr><w:r><w:t>Les cancers de l’ovaire (153a)</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Meta-Auteur"/></w:pPr><w:r><w:t>Professeur Pierre BERNARD</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Meta-DateCreation"/></w:pPr><w:r><w:t>Décembre 2002 (Mise à jour avril 2005)</w:t></w:r></w:p><w:p/><w:p><w:pPr><w:sectPr><w:pgSz w:w="11906" w:h="16838"/><w:pgMar w:top="180" w:right="1417" w:bottom="1417" w:left="1417" w:header="708" w:footer="708" w:gutter="0"/><w:cols w:space="708"/><w:docGrid w:line-pitch="360"/></w:sectPr></w:pPr></w:p></wx:sect><wx:sect><w:p><w:pPr><w:pStyle w:val="Annexe-Resume"/><w:rPr><w:b/><w:b-cs/></w:rPr></w:pPr><w:r><w:rPr><w:b/><w:b-cs/><w:u w:val="single"/></w:rPr><w:t>Résumé</w:t></w:r><w:r><w:rPr><w:b/><w:b-cs/></w:rPr><w:t> : </w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-Resume"/><w:rPr><w:b-cs/></w:rPr></w:pPr></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-Resume"/><w:rPr><w:b-cs/></w:rPr></w:pPr><w:r><w:rPr><w:b-cs/></w:rPr><w:t>Le cancer de l’ovaire reste, malgré les progrès de l’imagerie, de la biologie et thérapeutiques, de mauvais pronostic avec 48,4% de survie à cinq ans, tous stades confondues (5).</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-Resume"/><w:rPr><w:b-cs/></w:rPr></w:pPr><w:r><w:rPr><w:b-cs/></w:rPr><w:t>Le diagnostic repose sur l’examen clinique et l’imagerie : échographie, scanner,et/ou IRM.</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-Resume"/><w:rPr><w:b-cs/></w:rPr></w:pPr><w:r><w:rPr><w:b-cs/></w:rPr><w:t>Le diagnostic positif est histologique.</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-Resume"/><w:rPr><w:b/><w:b-cs/></w:rPr></w:pPr><w:r><w:rPr><w:b-cs/></w:rPr><w:t>Les facteurs de risque, les modalités du dépistage et les principaux facteurs pronostiques sont étudiés.</w:t></w:r></w:p><w:p/><w:p><w:pPr><w:sectPr><w:type w:val="continuous"/><w:pgSz w:w="11906" w:h="16838"/><w:pgMar w:top="180" w:right="1417" w:bottom="1417" w:left="1417" w:header="708" w:footer="708" w:gutter="0"/><w:cols w:space="708"/><w:docGrid w:line-pitch="360"/></w:sectPr></w:pPr></w:p></wx:sect><wx:sect><w:p><w:pPr><w:pStyle w:val="Annexe-Index"/><w:rPr><w:b/><w:b-cs/></w:rPr></w:pPr><w:r><w:rPr><w:b/><w:b-cs/><w:u w:val="single"/></w:rPr><w:t>Mots-clés</w:t></w:r><w:r><w:rPr><w:b/><w:b-cs/></w:rPr><w:t> : </w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-Index"/></w:pPr></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-Index"/></w:pPr><w:r><w:t>Cancer des ovaires, cystadénocarcinome séreux, , cystadénocarcinomes mucineux, tumeurs à cellules lipidiques, tumeurs des cellules germinales gonadoblastomes.</w:t></w:r></w:p><w:p/><w:p><w:pPr><w:sectPr><w:type w:val="continuous"/><w:pgSz w:w="11906" w:h="16838"/><w:pgMar w:top="180" w:right="1417" w:bottom="1417" w:left="1417" w:header="708" w:footer="708" w:gutter="0"/><w:cols w:space="708"/><w:docGrid w:line-pitch="360"/></w:sectPr></w:pPr></w:p></wx:sect><wx:sect><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:rPr><w:b/><w:b-cs/></w:rPr></w:pPr><w:r><w:rPr><w:b/><w:b-cs/><w:u w:val="single"/></w:rPr><w:t>Références</w:t></w:r><w:r><w:rPr><w:b/><w:b-cs/></w:rPr><w:t> : </w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:rPr><w:b/><w:b-cs/></w:rPr></w:pPr></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="23"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="270"/><wx:font wx:val="Symbol"/></w:listPr><w:rPr><w:lang w:val="EN-GB"/></w:rPr></w:pPr><w:r><w:rPr><w:lang w:val="EN-GB"/></w:rPr><w:t>JACOBS.I et Al : Prevalence screening for ovarian cancer in post menopausal women by </w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="23"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="270"/><wx:font wx:val="Symbol"/></w:listPr><w:rPr><w:lang w:val="EN-GB"/></w:rPr></w:pPr><w:r><w:rPr><w:lang w:val="EN-GB"/></w:rPr><w:t>CA 125 seasurement and ultrasonography. BMJ. 1993 ; 306 : 1030.</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="23"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="270"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>BERNARD P et Al : Le traitement des tumeurs ovariennes à malignité atténuée. REAL. GYN.OBST - 2001. 66 : 13-21.</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="23"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="270"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>BERNARD P. et Al : La surveillance post thérapeutique des cancers ovariens. REAL.GYN. OBST- 1998. 36 : 15-21.</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="23"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="270"/><wx:font wx:val="Symbol"/></w:listPr><w:rPr><w:lang w:val="EN-GB"/></w:rPr></w:pPr><w:r><w:t>DARGENT.D : Le dépistage des cancers de l’ovaire. </w:t></w:r><w:r><w:rPr><w:lang w:val="EN-GB"/></w:rPr><w:t>REAL.GYN.OBST- 2001. 66 : 8-12.</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Annexe-References"/><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="23"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="270"/><wx:font wx:val="Symbol"/></w:listPr><w:rPr><w:lang w:val="EN-GB"/></w:rPr></w:pPr><w:r><w:rPr><w:lang w:val="EN-GB"/></w:rPr><w:t>Annual Report on the results of treatment in gynecological cancer. 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</w:binData><v:shape id="_x0000_i1025" type="#_x0000_t75" style="width:336pt;height:215.25pt"><v:imagedata src="wordml://03000001.png" o:title="image6"/></v:shape></w:pict></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:hlink w:dest="image6.gif"><w:r><w:rPr><w:rStyle w:val="Lienhypertexte"/></w:rPr><w:t>Tableau : Répartition générale des tumeurs ovariennes selon la classification de l’O.M.S.</w:t></w:r></w:hlink></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:r><w:t>(statistique personnelle de F.Cabanne)</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:r><w:t>(P.Bernard)</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Les pré-dispositions génétiques sont en relation avec la mutation du gène BRC A1 ou BRC A2.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau1"/><w:listPr><wx:t wx:val="2." wx:wTabBefore="0" wx:wTabAfter="75"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Epidémiologie </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>L’incidence en France est de 12 nouveaux cas pour 100 000 et par an ; les  cancers de l’ovaire sont responsables de 5,8% des décès par cancer. Les cancers de l’ovaire représentent 4% des cancers de la femme et sont au 5ème rang des causes de mortalité par tumeur maligne. Cette fréquence peut paraître faible, mais ces tumeurs sont la première cause de mortalité par cancer gynécologique. De plus, leur incidence est en constante augmentation depuis 25 ans. Le traitement est basé sur une chirurgie qui peut être conservatrice en cas de tumeur de stade précoce survenant chez une femme jeune, le plus souvent suivie d’une chimiothérapie. La surveillance des patientes traitées est importante pour tenter  de dépister et de traiter plus précocement une éventuelle récidive et donc, idéalement, d’améliorer la survie. Les modalités de cette surveillance dépendent des facteurs pronostiques de la tumeur.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau1"/><w:listPr><wx:t wx:val="3." wx:wTabBefore="0" wx:wTabAfter="75"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Etude clinique</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>La relative pauvreté des signes fonctionnels en début de développement fait que souvent, la tumeur n’est découverte qu’à un stade avancé de son évolution, ce qui fait que nous envisageons son diagnostic successivement au stade pelvien, puis au stade pelvi-abdominal et ascitique, et enfin à l’occasion d’une complication chimique révélatrice.</w:t></w:r></w:p><w:p/><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="3.1." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Le stade pelvien</w:t></w:r></w:p><w:p/><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau3"/><w:listPr><wx:t wx:val="3.1.1." wx:wTabBefore="1425" wx:wTabAfter="180"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Les signes fonctionnels</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Ils peuvent se retrouver dans toutes les affections pelviennes,  et leur banalité, et leur caractère supportables font qu’ils n’ont aucune spécificité :</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="24"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>des métrorragies, des irrégularité menstruelles,</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="24"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>des douleurs pelviennes à type de pesanteur, parfois plus aiguë en cas de distension ou de torsion,</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="24"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>plus que la pollakiurie, ce sont les troubles digestifs à type de flatulence et de constipation qui traduisent la compression pelvienne.</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="24"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>Le plus souvent, la découverte se fait à l’occasion d’un examen gynécologique systématique ou d’une échographie pelvienne et abdominale.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau3"/><w:listPr><wx:t wx:val="3.1.2." wx:wTabBefore="1425" wx:wTabAfter="180"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>L’examen clinique</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Au spéculum, le col est sain. Au toucher vaginal, on perçoit une masse annexielle dont il faut préciser les caractères : kystique ou mi-solide, mi- kystique ou solide.</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="25"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>son indépendance ou non par rapport à l’utérus,</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="25"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>son caractère fixé ou non à la paroi pelvienne latérale.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau3"/><w:listPr><wx:t wx:val="3.1.3." wx:wTabBefore="1425" wx:wTabAfter="180"/><wx:font wx:val="Times New Roman"/></w:listPr><w:spacing w:line="240" w:line-rule="auto"/></w:pPr><w:r><w:t>Les examens complémentaires</w:t></w:r></w:p><w:p/><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau4"/><w:listPr><wx:t wx:val="3.1.3.1." wx:wTabBefore="1980" wx:wTabAfter="120"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>L’échographie vaginale avec évaluation doppler</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>L’échographie pelvienne est d’une bonne sensibilité : 81%.</w:t></w:r></w:p><w:p><w:r><w:t>Elle conduit a un certain nombre de faux positif  1,1%, et donc parfois à des opérations abdominales initiales. 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</w:binData><v:shape id="_x0000_i1033" type="#_x0000_t75" style="width:240pt;height:200.25pt"><v:imagedata src="wordml://02000009.jpg" o:title="image5"/></v:shape></w:pict></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:hlink w:dest="image5.jpg"><w:r><w:rPr><w:rStyle w:val="Lienhypertexte"/></w:rPr><w:t>Photo : IRM en coupe axiale du pelvis : 1 cm au dessus de la coupe précédente</w:t></w:r></w:hlink></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:r><w:t>envahissement de la paroi antérieure du rectum.</w:t></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:r><w:t>(P. Bernard)</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Le scanner abdomino-pelvien précise l’état des nœuds lymphatiques pelviens et lombo-aortiques.</w:t></w:r></w:p><w:p/></wx:sub-section></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau1"/><w:listPr><wx:t wx:val="4." wx:wTabBefore="0" wx:wTabAfter="75"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Le dépistage des cancers ovariens</w:t></w:r></w:p><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="4.1." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Stratégies de dépistage en fonction du risque</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Deux situations sont à distinguer quand il s’agit d’appliquer une stratégie de dépistage des cancers de l’ovaire. Sont à considérer à part les sujets à risque et la population générale.</w:t></w:r></w:p><w:p><w:r><w:t>S’agissant des sujets à risque, on sait que certains facteurs individuels (puberté précoce, stérilité, ménopause tardive…) interviennent, mais il est impossible, en pratique, de les prendre en compte. Seule peut être exploitée la notion de risque familial.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="4.2." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Les familles à risque</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Les études épidémiologiques démontrent que le risque cumulatif d’être atteint d’un cancer de l’ovaire avoisine 1% : 1 femme sur 100 fera, au cours de sa vie (life time risk), un cancer de l’ovaire. Chez les femmes apparentées au premier degré (fille, sœur ou mère) avec un sujet atteint d’un cancer de l’ovaire, le risque est de 4%. Si deux parentes de premier degré ont été atteintes, le risque passe à 15%. Il en est de même si la parentèle du premier degré comporte un cas de cancer de l’ovaire et un cas de cancer du sein survenus avant l’âge de 50 ans ou deux cas de cancer du sein survenus avant  l’âge de 60 ans. Chez les femmes, enfin , apparentées au premier degré avec trois femmes atteintes de cancer de l’ovaire, le risque atteint 25%.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Ces notions épidémiologiques n’ont pas, au plan individuel, une grande signification. Leur intérêt est surtout de permettre l’identification des « familles à risque ». Quand on trouve dans une famille chez des sujets  apparentés au premier degré, soit deux cas de cancer de l’ovaire, soit un cas de cancer de l’ovaire et un cas de cancer du sein apparus avant l’âge de 50 ans ou deux cas de cancer de l’ovaire, on doit considérer qu’on est en présence d’une famille à risque et l’on doit suspecter un syndrome « sein-ovaire », soit un syndrome « ovaire spécifique de site », syndromes qui peuvent être liés à une mutation du gène BRCA1 ou du gène BRCA2.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>En présence d’une mutation du gène BRAC1,  le risque cumulatif (life time risk) de cancer de l’ovaire est de 45% (et le risque de cancer du sein de 80%). En présence de mutation du gène BRCA2, le risque cumulatif est de 25%. En l’absence de mutation de BRAC1 ou de BRCA2, le risque est celui observé dans la population générale.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Sur le plan pratique, la recherche d’une mutation doit être proposée dans tous les cas où on est en droit de suspecter un syndrome sein-ovaire ou un syndrome ovaire spécifique de site. On doit y ajouter les sujets appartenant à une famille classée HNPCC (Hereditary Non Polypous Colorectal Cancer). Le test génétique permet d’identifier les vrais sujets à risque qui ne sont pas forcément les parents de premier degré d’une femme atteinte de cancer de l’ovaire. Après les tests génétiques, deux situations sont à distinguer . Si la personne est porteuse d’une mutation, il faut, dès l’âge de 30 ans, la soumettre au dépistage double semestriel (échographie et dosage du CA125 tous les 6 mois) et proposer, à l’âge de 40 ans au plus tard, une annexectomie  bilatérale. Si la personne n’est pas porteuse d’une mutation, son risque est en principe le même que celui observé dans la population générale. Mais il peut être difficile de faire accepter l’absence de dépistage. Il en de même chez les femmes dont une seule parente de premier degré, la mère le plus souvent, a été affecté d’un cancer de l’ovaire.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="4.3." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Population générale </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>L’expérience londonienne suggère que le dépistage systématique est susceptible de faire reculer la mortalité imputable au cancer l’ovaire. Aux 22 000 femmes enrôlées dans le bras « dépistage » ont été comparées </w:t></w:r></w:p><w:p><w:r><w:t>22 000  femmes qui n’ont bénécifié d’aucun examen paraclinique systématique. On a observé 16 cancers dans le bras « dépistage » et 20 dans le bras « pas de dépistage ».</w:t></w:r></w:p><w:p><w:r><w:t>Les résultats obtenus par les Anglais ne sont pas suffisamment probants pour que des campagnes de dépistage  systématique soient d’ores et déjà lancées. Mais ils incitent fortement à rejoindre l’UKTOCS (United Kingdom Trial on Ovarian Cancer Screening) qui deviendrait l’ITOCS (International Trial on Ovarian Cancer Screening). Cette étude permettrait  à la fois de savoir, quelle est des deux méthodes à disposition,la plus sensible et la plus spécifique, et d’évaluer l’impact du dépistage sur la mortalité par cancer de l’ovaire. Les statisticiens ont calculé que l’objectif à atteindre était de 200 000 sujets. Cette étude ne portera que sur les femmes ménopausées.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>En attendant que les résultats en soient connus, il serait préjudiciable de se lancer dans le dépistage « individuel » dont les résultats, en termes de réduction de mortalité par cancer, ne sont pas prouvés alors qu’il est amplement démontré qu’il aboutit à un grand nombre d’opérations chirurgicales inutiles.</w:t></w:r></w:p><w:p/></wx:sub-section></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau1"/><w:listPr><wx:t wx:val="5." wx:wTabBefore="0" wx:wTabAfter="75"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Les principaux facteurs pronostiques </w:t></w:r></w:p><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="5.1." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Facteurs pronostiques cliniques </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Le stade d’extension tumorale : la classification de la Fédération Internationnale des Gynécologues Obstétriciens (FIGO) est la plus utilisée. La détermination du stade (surtout dans les stades précoces) nécessite une chirurgie complète qui doit comporter, outre la chirurgie pelvienne, une cytologie péritonéale systématique, une lymphadénectomie pelvienne et lombo-aortique, des biopsies péritonéales multiples et une omentectomie. Les taux de survie à 5 ans varient entre 80% et 90%, 60% et 70% pour les stades II, 20% et 30% pour les stades III et 10% à 25% pour les stades IV.</w:t></w:r></w:p><w:p><w:r><w:t>Le volume du reliquat tumoral après la première intervention chirurgicale : il est le facteur pronostique le plus important dans les cancers de l’ovaire de stade avancé (IIIc ou IV). L’intervention chirurgicale initiale est donc fondamentale et doit assurer l’exérèse du maximum de lésions mascroscopiquement visibles. Le volume du résidu est dépendant des caractéristiques de la tumeur et la qualité de la chirurgie d’exérèse initiale. 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</w:binData><v:shape id="_x0000_i1034" type="#_x0000_t75" style="width:376.5pt;height:204pt"><v:imagedata src="wordml://0300000A.png" o:title="image10"/></v:shape></w:pict></w:r></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:hlink w:dest="image10.gif"><w:r><w:rPr><w:rStyle w:val="Lienhypertexte"/></w:rPr><w:t>Tableau : classification FIGO (1987) </w:t></w:r></w:hlink></w:p><w:p><w:pPr><w:pStyle w:val="Media-Legende"/></w:pPr><w:r><w:t>(Fédération Internationale des Gynécologues et Obstétriciens)</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="5.2." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Facteurs histologiques </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Les tumeurs ovariennes à malignité atténuée ont un excellent pronostic après la chirurgie d’exérèse. Elles ne représentent que 13% de l’ensemble des tumeurs malignes.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Le degré de différenciation cellulaire (=grade histologique) de la tumeur est un facteur pronostique majeur. Dans le stade précoce (stade I), il est un facteur décisionnel important pour discuter d’un éventuel traitement adjuvant.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Le type histologique de la tumeur : les tumeurs à cellules claires et indifférenciées sont de plus mauvais pronostic.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="5.3." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Facteurs biologiques </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Ces facteurs sont discutés : décroissance du CA 125 après la chirurgie et lors de la chimiothérapie, ploïdie des cellules tumorales, hyperexpression de l’her-2/neu, de la p 21 ou de la p 53. Hormis la cinétique du CA 125, les autres facteurs biologiques ont peu d’impact en pratique quotidienne.</w:t></w:r></w:p><w:p/></wx:sub-section></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau1"/><w:listPr><wx:t wx:val="6." wx:wTabBefore="0" wx:wTabAfter="75"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Le traitement est décidé en fonction du stade et du grade histologique </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Les moyens sont chirurgicaux et chimiothérapeutiques. </w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau1"/><w:listPr><wx:t wx:val="7." wx:wTabBefore="0" wx:wTabAfter="75"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>La surveillance post-thérapeutique </w:t></w:r></w:p><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="7.1." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>La laparotomie ou cœlioscopie de second look </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Elle fut systématique dans les années 80. L’objectif était alors de diagnostiquer la récidive péritonéale infra-clinique accessible sur le plan thérapeutique à la chimiothérapie par les sels de platine. Mais l’évolution dépendait en réalité beaucoup plus du stade initial et de l’évolution métastatique ganglionnaire.</w:t></w:r></w:p><w:p><w:r><w:t>Il apparut aussi clairement que pour les stades IA, le traitement chirurgical initial apportait 80 à 90% de survie à 5 ans. Le caractère répétitif du second look fut mis en discussion dès lors que la majorité des récidives péritonéales surviennent au cours des deux années post-chirurgicales. Les situations de départ déterminent en fait l’indication de la laparotomie de second look : le stade FIGO d’une part, les critères histologiques et les options thérapeutiques d'autre part. </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Pour tous les stades I avec une exérèse complète, une cytologie péritonéale négative, la seule justification de la laparotomie de contrôle un an après serait le contrôle histologique des ganglions lombo-aortiques, un scanner abdomino-pelvien remplacera le plus souvent le geste invasif.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>A l’exception du stade Ia, c’est à dire pour les stades Ib, Ic et II, le geste chirurgical initial a dû comporter un curage lombo-aortique.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>La laparotomie, ou cœlioscopie de second look, a pour but de réaliser des biopsies péritonéales multiples et de visualiser une récidive éventuelle dans la cavité péritonéale.</w:t></w:r></w:p><w:p><w:r><w:t> </w:t></w:r></w:p><w:p><w:r><w:t>Si la préférence va à la cœlioscopie, celle-ci doit être aussi performante que la laparotomie, et son choix doit être indépendant du stade initial (elle reste opérateur dépendant).</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Les résultats des biopsies orientent la thérapeutique à suivre.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Dans le cas des biopsies péritonéales positives, on propose une chimiothérapie.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Dans le cas d’un curage lombo-aortique positif, le traitement de choix reste la chimiothérapie de première ligne.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>La laparotomie de contrôle est surtout indiquée après le traitement des tumeurs de stade III. En effet, après la chirurgie de première intention et les six cures de chimiothérapie (protocole PC ou PAC) et actuellement le protocole franco-allemand Taxol-Carboplatine (TC) versus Taxol-épirubicine-carboplatine (TEC), la laparotomie de second look permet de compléter et de réaliser une chirurgie maximaliste, si celle-ci n’avait pu être pratiquée lors de la première laparotomie avec hytérectomie et annexectomie bilatérale, omentectomie, curage lombo-aortique, biopsie multiples, et d’éventuelles réactions digestives.</w:t></w:r></w:p><w:p><w:r><w:t>Les interventions de second look ne concernent, pour la période 1990-1992, que 14,8% des stades III et IV ; ce faible nombre devrait augmenter au cours des prochaines années en raison de l’introduction du paclitaxel en association aux sels de platine dans la chimiothérapie de première ligne. Nous reviendrons sur ces résultats dans les commentaires de la publication de l’Annual Report à laquelle  nous participons et apportons notre contribution depuis 1997.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="7.2." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>L’imagerie </w:t></w:r></w:p><w:p/><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau3"/><w:listPr><wx:t wx:val="7.2.1." wx:wTabBefore="1425" wx:wTabAfter="180"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>L’échographie</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Elle concerne trois indications dans la surveillance :</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="27"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>Exploration de l’ovaire restant pour les stades I</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="27"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>Recherche des métastases hépatiques</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="27"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>Reconnaissance des zones liquides, et en particulier d’une lame d’ascite débutante. L’examen permet alors la ponction et l’identification de cellules malignes confirmant la récidive péritonéale</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau3"/><w:listPr><wx:t wx:val="7.2.2." wx:wTabBefore="1425" wx:wTabAfter="180"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Le scanner </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Il a fait l’objet de controverses. En effet, il pourrait paraître illusoire de lui demander de rechercher une récidive péritonéale infra-clinique. B.Nelson a fait une étude afin de préciser, lors du bilan initial, l’existence de métastases inférieures et supérieures à 2 cm sur le diaphragme, la surface et le parenchyme hépatique, le mésentère, la plèvre, l’épiploon et les ganglions aortiques supra-rénaux. Il conclut que le scanner est la meilleure méthode d’évaluation de l’extension tumorale.</w:t></w:r></w:p><w:p><w:r><w:t>L’imagerie par le scanner représente un excellent procédé de surveillance de la cavité abdomino-pelvienne, mais surtout des gnaglions latéro-aortiques infra et supra-rénaux. Notre position est de réaliser dans les six mois post-thérapeutiques, un scanner de référence, puis un contrôle annuel pendant les quatre années suivant la laparotomie de second look.</w:t></w:r></w:p><w:p/></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau3"/><w:listPr><wx:t wx:val="7.2.3." wx:wTabBefore="1425" wx:wTabAfter="180"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>L’imagerie de résonance magnétique nucléaire (IRM)</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Elle ne sera indiquée que sur un signe d’appel, élévation des marqueurs tumoraux, échographie ou scanner avec une anomalie.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>L’avantage de l’IRM est de donner une imagerie tridimensionnelle avec la taille de la lésion et son extension viscérale pelvienne ou abdominale. Le coût de cet examen, trois fois plus élevé que le scanner, en limite l’utilisation aux patientes pour lesquelles une élévation des marqueurs tumoraux est constatée.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>L’IRM, pas plus que le scanner n’est spécifique de la récidive, les deux permettent uniquement de mesurer l’augmentation de la taille d’une localisation pelvienne ou abdominale.</w:t></w:r></w:p><w:p/></wx:sub-section></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau2"/><w:listPr><wx:t wx:val="7.3." wx:wTabBefore="735" wx:wTabAfter="195"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>Les marqueurs tumoraux </w:t></w:r></w:p><w:p/><w:p><w:r><w:t>L’évolution des marqueurs tumoraux sériques et tissulaires représente les éléments nouveaux de la surveillance post-thérapeutique.</w:t></w:r></w:p><w:p><w:r><w:t>Au cours de la chimiothérapie post-opératoire, la chute du taux de CA 125 correspond dans 75% des cas à une réponse favorable, selon G.J.S. Rustin. L’élévation secondaire du taux sérique de CA 125 doit être retenue comme le signe d’alerte pour la recherche d’une localisation métastatique intra-péritonéale ou à distance. Un taux élevé de CA 125 au départ représente un élément majeur pour la surveillance ultérieure, il apparaît élevé dans 80% des cas de cancer épithélial de l’ovaire. Dans toutes nos observations, l’ascension secondaire du CA 125 correspond à une reprise évolutive du cancer ovarien.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Un autre marqueur sérique peut avoir de l’intérêt pour le clinicien, il s’agit de l’antigène carcino-embryonnaire (ACE), glycoprotéine dont le taux est élevé dans 73% des cancers ovariens, en particulier dans les cystadénocarcinomes mucineux, mais le taux est influencé par le degré d’extension de la tumeur.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Son taux est établi par radio-immunologie, un taux supérieur ou égal à 15 ng/ml est considéré comme pathologique. La normalisation est obtenue en deux semaines après une exérèse chirurgicale complète, selon A. Gorins. La réascension des taux après le traitement indique une récidive locale ou l’apparition des métastases. Le dosage des marqueurs sériques sera proposé tous les mois la première année, puis tous les six mois pendant 5 ans.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>L’aspect de la courbe de décroissance des marqueurs en cours de chimiothérapie est un indicateur de la sensibilité de la tumeur aux agents chimiothérapiques. Une tumeur agressive conserve un taux relativement élevé pendant les 4 premiers mois de la chimiothérapie, une normalisation très tardive du marqueur incitera à poursuivre le traitement pendant 3 cures supplémentaires, même si le second look n’a pas retrouvé de foyer tumoral évolutif.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Les marqueurs tissulaires utilisent des anticorps, par exemple les anticorps épithéliaux polymorphiques de la mucine : BC2.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Il s’agit d’une détection immuno-histocytochimique par un anticorps monoclonal dont l’expression dans plus de 10% de cellules apparaît dans 98% des récidives cancéreuses.</w:t></w:r></w:p><w:p><w:r><w:t>D’autres auteurs, et en particulier J.A. Schueler, ont évalué la signification de l’indice d’ADN par cytométrie de flux :</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="28"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>IA &gt; 1,40 : 61% de survie</w:t></w:r></w:p><w:p><w:pPr><w:listPr><w:ilvl w:val="0"/><w:ilfo w:val="28"/><wx:t wx:val="·" wx:wTabBefore="360" wx:wTabAfter="240"/><wx:font wx:val="Symbol"/></w:listPr></w:pPr><w:r><w:t>IA &lt; 1,40 : 96% de survie</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Un indice initial élevé justifie une surveillance par les marqueurs sériques et une laparotomie de contrôle dans les 18 mois post-opératoires.</w:t></w:r></w:p><w:p/></wx:sub-section></wx:sub-section><wx:sub-section><w:p><w:pPr><w:pStyle w:val="Niveau1"/><w:listPr><wx:t wx:val="8." wx:wTabBefore="0" wx:wTabAfter="75"/><wx:font wx:val="Times New Roman"/></w:listPr></w:pPr><w:r><w:t>La conduite à tenir</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Au cours de la première année après le traitement initial, un examen clinique tous les trois mois avec un dosage du ou des marqueur(s) tumoral(aux) initialement élevé sera demandé, et un seul scanner abdomino-pelvien de référence avant le 6ème mois. Pour les quatre années suivantes, les consultations seront programmées tous les six mois avec un dosage des marqueurs, et une fois par an, un scanner abdomino-pelvien et une radiographie pulmonaire.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Après cinq ans et en l’absence de récidive, un examen clinique semestriel et un dosage annuel des marqueurs seront suffisants.</w:t></w:r></w:p><w:p/><w:p><w:r><w:t>Comme le démontrent les publications de l’Annual Report, 90% des récidives surviennent au cours des deux premières années.</w:t></w:r></w:p><w:p/><w:sectPr><w:hdr w:type="odd"><w:p><w:pPr><w:pStyle w:val="En-tte"/><w:jc w:val="center"/><w:rPr><w:rFonts w:ascii="Verdana" w:h-ansi="Verdana"/><wx:font wx:val="Verdana"/><w:sz w:val="18"/><w:sz-cs w:val="18"/></w:rPr></w:pPr><w:r><w:rPr><w:rFonts w:ascii="Verdana" w:h-ansi="Verdana"/><wx:font wx:val="Verdana"/><w:sz w:val="18"/><w:sz-cs w:val="18"/></w:rPr><w:t>Corpus Médical – Faculté de Médecine de Grenoble</w:t></w:r></w:p></w:hdr><w:ftr w:type="odd"><w:p><w:pPr><w:pStyle w:val="En-tte"/></w:pPr><w:r><w:rPr><w:rStyle w:val="Numrodepage"/></w:rPr><w:pict><v:shapetype id="_x0000_t75" coordsize="21600,21600" o:spt="75" o:preferrelative="t" path="m@4@5l@4@11@9@11@9@5xe" filled="f" stroked="f"><v:stroke joinstyle="miter"/><v:formulas><v:f eqn="if lineDrawn pixelLineWidth 0"/><v:f eqn="sum @0 1 0"/><v:f eqn="sum 0 0 @1"/><v:f eqn="prod @2 1 2"/><v:f eqn="prod @3 21600 pixelWidth"/><v:f eqn="prod @3 21600 pixelHeight"/><v:f eqn="sum @0 0 1"/><v:f eqn="prod @6 1 2"/><v:f eqn="prod @7 21600 pixelWidth"/><v:f eqn="sum @8 21600 0"/><v:f eqn="prod @7 21600 pixelHeight"/><v:f eqn="sum @10 21600 0"/></v:formulas><v:path o:extrusionok="f" gradientshapeok="t" o:connecttype="rect"/><o:lock v:ext="edit" aspectratio="t"/></v:shapetype><w:binData w:name="wordml://0200000B.jpg">/9j/4AAQSkZJRgABAQEASABIAAD/2wBDAAUEBAQEBAUEBAUIBQQFCAoHBQUHCgsJCQoJCQsOCwsL
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