c It a pi e r Carcinoma of the ovary and Fallopian tube CanDEr of Ihe ovary 143 Cance<ofrliG Fallopian lube 152 OVERVIEW of tha ovary is mosl common ii 1 the 'ijeamiyridtirjri:.c-t 111 fc world There die lustundsr 6000 case!, each ysar in Ibs UK Wb ilfl ffiB incidence of ovarian cancer is si mi l&r to thai of endometri urn aridcf cervix, more women die from ovar&n cancer than fro-; 1 ^drtinnma nl fl>E.cerm anfl body of fbe ut?rue combined. Most wanan temours are ol epithelial (irigm. Tlie&E jre Mre befure Hit age of 35'years buttle incider-DE increases i<iitb age IG a peak in tbe 5Q-7Q-ypar-i;ld aae gmup (Fig. 13.1 j. Mo^tspltlieli?! amours art not discovered until they hava spread widely Some at fiiesE "nvariai'' lumouis prnoabiy arise frnm the fallopian ^bo.tumnurF of whmh arn .Dually racogriized only v/tien at a relatively early ^tage Surely and rjhemufherapy. mdirily v<A\\ carboplafir, DI cisplalm and paciilaxel, form lire mapnsfay nf iiBaf- DnJv 3 pEri:Hnln;nvanan cjnggrs are seen mwnm fin you ngerthan 35 yea rs and most of these are non ^jjltnelial cancers a& yerm ^11 luinuurs ^n conlrasf To epithelial fumpurs. germ DE!! lumouis can be Ireaterjvpry successfully 'Vifh Ferlilitycanoffen bu^jnaerved CANCER OF THE OVARY Aeliology " Incessant uunlation' theory Epithelial liimaura arc mosl trcqucntlv wilb nulli|iari[y, jr) t&tly rncnjrdic, ^ late age at menopju*,e and j high esrimjTeJ number of vewri ol o^iiliition. Grill contraceptive use reduces the rkk iouifuld (The Cancer and Steroid Hormont Sludy, 1997). lk>ive\er, even without urdl Lonlidceplives, inciej<.ingage at first birtli reduces tht risk of ovarian cancer. This and other anomialici ca^ldcubt upon the 'incessant ovulalicii* theor, 1 . Suhfertititylreatmenr Subfertiliry, especially when il is unexplained, isasso- aaccd with buth ovarian and cnddmdrial canitr. r, 1,-ist-coiii rolled Siiudies have sujy>eMed 1 1 Carcinoma of the ovary antf Fallopian lube UL>- Cn s c. 4C — & 3D 6 1 20- O 10 n- ,»"» • " • \ / \ pf • / y ' 10-14 25-33 40-44 55-74 >94 .Age iy£arsj Figure 13.1 The Incidence D! ovarian cancers England anO Wales iQffice of Population Censuses and Surveys, 1985|. there might possibly bed link between ovarian cancer and prolonged attempts at induction of ovulalion (VenneraL, Genetic factors F3inilial ovarian cancer • Familial ovarian cancer is rarfl -5-10% • Suggflstive history • fttlea5tt'"ofir&t-rtogree relatives mill u.'diidn or ti)loretlal carcmama • Casss usually diaynoaed before 50 vFarsotagH » Defective genss include 0flC4f and 8RCA2 t Th* risk of ovarian cancfii 1.40%) in Ihese lamilles is less than the r&k of breast cancer {80%| » Genetic testing cannot guarantee to defect all genes Familial ovarian cancer There is a family hinor? in between 5 and HI per cent of ^omtn ivith epithelial nvarian tantcrs - serous adenocardoornas (Kafipr/^k ul jl. t Av-umaii with one affectf d dose relati\ r e has a lifetime ctsk of 2-5 per cent, twice tht ribk in the general popuklion. With two affected clost reldLivt^ lhi L lite- time risk increases to 30-10 per cent iPonder, 19y4|. A partieular feature of familial unciT:> is the i elativelv early age dl ™hich thcv occur Most of these families rtl>o have ia&C;> of breast or (.olorectal cancer in the family. 'Itie defective gt;ne in (he breast/ovary families is most commonly the luinoiir-s.uppn:$ior gene BRCAl (#1 pei cent). BRCA2 is defective in aboiil 14 ntr^unl. Families Wffl i.olorettal cancer have defects in the J3NA repair genes but this is seldom found m association with tamilial ovarian cancer (Kaflpr/ak el al., 1999). A woman who has inheuied a detective RK.CA1 gene hi a weJl- ducumenlctl [dmilv ha;> a 60 per cent risk of breast cancer by .'ill years nl a^ and an &0 pel cent lifetime risk. However, the risk of ovarian earlier is much lower, he ing nearer JO per cent Management ot women with a family history of Dvarian cancer Genetic testing for BKCAl is. now pos&iblc bill is impracticable and unreliable because mutations are found far lesi often than expected, even in with a strong family bislorv. There jre very able problems in interpreting the resulis in with only one or li^o aftected relatives There maybe a spectrum of inulaliyrii, isith verv different lei'els of risk. Ei'en a negative test resnlr nid\ nol provide ihe expflded reassurance. Once idenlilied vvilh the help or a clinical geneticist, women with a hiph ri^k of ovarian and" bica&t cancer arc difiitult to advise. The main risk is bre&sl i-uiLer h but prophyldclk, bilalcral mastectoniy ifl a very drastic s^tep for any 'voilian 10 Lake. None of the available &tre.emng tests for ovarian cancer is vurv effective, and false-positive result* can result in unnecessary surgery. Annual ovarian ullrasonography with colour-flow Doppler studies and serum CA 1Z5 estimation evert 6-12 months are recommended, bui it is unierlaJB how much pro Let Lion this offei^. Prophylactic hilat eral oopho recto in y, iiiually combined v-nth hv^iterec- lomy, i> recommended for dejrh ilelinuil h^h-rnt women aflcr Completion of their family at aN«*] 45 years of age (K,ii|ir^Hk ul al., 1999). This does, nol recnyvt the nsi; entirely, as c.lrcillonn of the pcrfl toneum has occurred after this procedure. Class if i callon of nujrian tumouis Ovarian inmoiirb lan be solid or cystic. They nuyhf benign r>r ma%nanl antl [n addition there are thc« that, while having lack am' evidence ol called borderline lurai ovarian | lin orig coid gonadal tyj>e laiso Oi sex cord me.senchyi «A cord iTie^nchmal Simplified hi stole ovarian tumours I Connirnii apfilielial hi A Serous rumour B MuGifious tumour C. EniJumetmid lumui D Clear cell f U ill 'fferpniiated care II Sex cord stromal turn A Grgnulo&dsn'niiac fl Andrablas'Oma: SH III Germ cell A Dy&ngrniincma C Embiyonalcelltumi E. Teratuma F Mlx IV MaiasiaLc Pathology of ep it he cpid ofteji rfM^i ihe dfgr.ee of dif vival, fflfLt-pt in the mo mniuui-3 tend [o be a^s<i and a bedii progrn Hin'rv^l between differa • .c i n on i and ajsociated with an Cancer olthe ovary I. in tumours that, while having sonic uf Lhc features oi malign an cy, lack anv evidence of s-tronidl invasion. These are called borderline turn ours. Primary ovdri-in turnout are divided into epithe]i.ii type l implying an origin frum surracc epithelium), sex cord gurwdai ti pc (also known assevcord slromal I; pc, or sev cord mesfn<.hvmal t}pc, and originating from y;.\ coid mesenchymAl elements), and germ cell type. Simplified hislologlcal classification of ovarian tumours I Common epithelial liimours (Uiilgn, borderline or malignanl) A. Serous Etrmour Ei Mu Din DUE turn nil r C. EndomeliiokJtumuur D CI™rcflN(me5nr>ep|iroldl tumour E Banner rumour F. UnOlfferenlidled eamnomjis II SBI cord -^iim.ii tumours A Granule strnma cell tumour B- Andriiblasturna Serin h-Lflydigcf II tumour C Gynand'o blastema III Germ cell him ours Setnus carcinoma 6. EndodKrm&l sinus tumour (yolk sac C. Embryonal cell lumour D Chonncaicinprna E. Teratoma F Ulixgd tumours IV MBla&tatic luiriDiirs Pathology ol epithelial lumaurs Well-differentiated epilhdial carcinomas tend to he more often associated with early-sisige disease, but the degrpu of differentiation does correlate with $ur- Ttval, except in the most advjncrd stages Diploid Tumours tend to be associated wilh earlier stage dis- cdM anil a better prognosis. Cell type is nol of itsell propnosntiilJy iiignificant. Comparing patients $U£e fcstage and grade fcr grade, iliere is no diifcrcncc m mrvi^sil between different epithelial type.',. Hyvcver, »ucinnufl .uid cndomeiriuid lesions, are likely to he ivith an earlier j^agt; jnd lo^.^r grade than cystadcnoi_-arcLnoiria.s. serous tilrcjnonia& have both solid and cystic elements, hut some may he rminl|' cptic. They often affect both ovaiies. Well-ditlerentiated rumours have a papUlarj 1 parltrn i^ith stujmal im'asion, Psanimoma bodies (calcos-pherdeO are often prcbtnt. At the other end of the spectrum is the anapUsHc luniunr C^mpOseel ul sheets of undiflerentiated neoplastic cells in masses- within j fib run i bli-oma. Occasional glandulai itiuctures may be present which tumble a diagnosis of ddenenareinorna to be made. All grad- ations, between these Ivu an: ^een, sometimes in the same tumour. Mutinous carcinoma Malignant niUi:Lnous.tiinioiirs.accoiin | for 10 per tent otthe malignant tumours of the nvary.'JTiev are usually imihilacular, ihin-ivalJed cyst^ with ii smooth extei- nal surface containing mutinous Quid. Muunou^ lumuihii aie amongst the laigest tumours, of The ovary and nwv re.a<-h enormous diniens-ions A cyst diameter of 25 cm is quile Endometrioid carcinoma Ihesearc ovarian tumours that resemble etidome trinl cirdiionidi. There ib liltk to characterize an ovarian tumour as being of endomelrioid typt by naked-cjc examination. Most are cystic, often unilocutar. -ind conlsiin lurbkl brown fluid. Five to 1(1 per cent are seen in continuity witJi n^o^nuable endometrio&is. Ovanan adenoacanthoma, with benign-jppearing bquamoLib elements^ accounts, tor almost Sll per cent of some series ti indomemcMd tumouis. It [& important to note rhat 1!> per cent of endometrfuid carcmonias oJ the ovary are associated with endomelrial carcinoma in tht body of the uleriB. la most cases these are two separate pri maty tumours. Clear cell carcinoma (mesonepliraid) t ihtkabl L^mniun of tht- malignant epuhe lialtumours-nf lheovary h accountijig for 5— 10 per cent of ovarian carcinomas. The appearance from which the lumuursulerive (heir name is the clear cell pattern but, in addition, some areas show a tubulo -cystic palter 11 with the chai aclei istic 'hub-nail' appearance of the lining epithelium. 13ciau.il 1 there k A ver> strong association between cle.ii cell tumours nt (he ovary and ovarian endo- mctnosiS:. and because ikar cell and ernlometrioid Tumours ft*quentlycoerist h it has t-rai suggested thai the- dear cell tumour in ay beavariantofendomctnoid tunioui. Borderline epithelial tumours Ten per cent of all epithelial tumours of the ,ire of borderline malignancy. These show varying degrees oi nuclear atypia and an mcrease in mitolK activity, multi-layering of E<x>[>laslit cells and forma- tion of cellular bud*,, bul no invasion of the stroma. Most boi'deihne tunioui s lemam confined tc? the ovanes and this. may account fur ihdr much better prognosis. Peritoneal lesions are present in some cases and, although ii few are true mnastascs, many do not progrc&s and some even regress after removal of the primary 1 union r. The historical diagnosis, ol borderline malignancy can be difficult, paiticularlym mucinous tumours. Most borderline Uimours arc serous or mutinous in type, Natural history Some two-thirds ol' patients with ova nan earner pr^M-nt >vith tliii-aw; that has sprwd beyond [be pelvis. I his is |irnbahiy due to llie insidious nature of the signs and symptoms, of carcinoma of the ovary, bul rnav sometimes b-: due to a rapidly growing I u [Hour. Due to the non-ipecillc nature of most of these symptomSj a diagnosis ol ovaiian cancer is seldom considered until the dibcabc is m an advanced Mela static spread 'The pelvic perilnneiim and other pelvic oigans bccomi: involved by dirftt spreaJ (Table 13.1). iTie peritoneal fluid, flowing to lymphatic channels on the undersurface of the diaphragm, earner malignant cells to the unurnlum, lo ihe peritoneal surfaces of Ihc snmL and iaige bowel and the liver, and to the parietal Table 13.1 Pelvic and para-aorlk node Nodes involved ; Stage 1-11 Stage III-IV Pcdvic nodes 30 h7 H'ai'a-aortic nodes 19 65 peritonea] surface throughout the abdominal cavity and on the surface of the diaphiagm. Mctasta^s. on the undersuitiice otthc diaphragm m;if r be found in up to 44 per cent of whjt otherwise wenis to be stage 1-11 disease Lymphatic spread commonlv involves the pelvic and the para-aoi-tiL node> r Spread rii^V also occur to nodes inthenOrl or inguinal region Haematogenous spread iisiiallv occurs late in tlie course of the disease. Tht iruin mvolved jrc the liver jnd the luna, although , to bone and brain are sometimes seen. Clinical Peiitoneal deposits on the surface of Ihc liver do not make the tumour Stage IV; the parenchyma must be involved i"lahle 13 Z]. Similarly, the presence of * pleural effusion Ls hifiufllcienl to put the tumour m Stage JV unless malignant tells <iro found on of the pleural fluid. Diagnosis pain or discomfort are the common* presenting complaints and distension or feeling lump the neil mo&L frequenl. Patients may comJ iif indigcslion, urinary frequency^ weight loss i rarely, abnormal menses orpostmenopauaai bkesh" A hard abdominal mass ansing from ihc pelvn higlily suggestive, especially in the presence of ascit A fixed, hard, irregular pelvic mass is usually fdl ITC*J! combined \aginal and rectal KtammatioD fHg I. 1 pii^l4S)/llie neck and groin should also be examni for enlarged nodes. •Iabkl3.2 FlC.Osta la JLi Ic II.i lib Ilk :n Ilia lllb Ilk Haeniaioln^iejl mve count, ure.i, electroly AdiestX lay isesBenli onyciut d barium cd mm bowel involvemi *rif ^n intravenous •j- useful. Ullrnsonogi Cancer of Hie ovary 147 Trtblcl3,2 F1OO bilging for primary ovarian a I.] Ih Ila lib Ilk Ilia lllb Hit F1GO definition CroMh]irnilei] iu ovaries Growth limited in one ovary Xo ascites Xo liimoiir on external surface Cdpsule intact Growth limited lo both ovaries No a^it<:& No Tumour on external surfaces Capsule intact Tumour eithei Stage Li 01 Ib but tumour on iurfara ofunt or both ovaries or with capsule ruplureil ur with ascites present containing malignant cells or with positive peritoneal washings Growth involving oncoi both ovaries ivithpelvii eAlcnsion Extension and '01 mctaitabtb lu iht uliTui or luhe*. bxlension to other pelvic ti^ue^ Tunioui either Stage Ib or lib but nunour on iurfd^u of one or hath ovaries or •vilh capsule ruptured yr with ascites preheat conlaining malignant ceDi w with positive peritoneal washing 1 , Growth involving one or bolh ovariei with peritoneal implants outside the pd'is or poiitivt rctropcriloncdl urin^uin^l nodes Superticijl liver inetastuseii equals Stape ITI Turn our grossly limited to (he true pelvis with negative noil« bill with hi«ologicalli-conlunn:ilmKro! 1 copic5i:nlinsl>f"''bili>ininjl peritoneal surfaces Tumour with hibLologitallv to-cifinnod impljnlson abdomiHsl peritoneal •vurtaces, none evceeding 2 cm in diameter Nodes aie negative Abdombalitupladts >2 cm fn diameter or positive retropericonejl or inguinal nodes Growth involving one or both ovaries with distant mctastaiti II pleural eft'usfon is present, there mint bs poaitivi qlology lo alloi a case to Stage IV Ljl liver mcinslrf&i^ e<nji|^ !jl^i,e- !V Haemato logical iiivestigations include a full blood count, urea, electroltes and livci function tots. cjrry out a barium enema 01 colonoscopyto difieitn- Hn between aa ovarian add n coloniLlumourdinl (u awei^ bovnc] Itivnlveinent fmm the ovarian tumour ibelf. An intravenous pvelogram (IVP) ia occasfon- Jl>' useful. Ultrasonogiaphymav hdp to ountirm the piesenccol a pelvic maw and detect ascites before it is clmicalK apparcfll- ITI conjunction with CA 125 esti- ill^lion. it may be used to calculate a 'risk of malig- nancy ttorc'. In moal women, the diagnosis is lar from tirlain before the laparotomy. and the oper- ation is undertaken on the basu (hat (here is a large mass that nradb to be [Amoved regardless of its nature. II" Carcinoma ol (he ovary and Fallopian lube Surgery infrj colic omen 13.2 Abdominal distension 'Mth underlying ovarian mass and ascites (Courtesy nf Mr K Metcalf.) Markers far epithelial tumours FA 125 is Ihe only marker in common elm leal use. It can also be raised in benign conditions such as endometriosfc. CA 125 is useful for monitoringivn men receivingc-hemoLherdp^ Lo aise*s response. A persist- ent rise m CA 125 may precede diukhi] evidence ofrecurrcnl dismast by stveral months in some cjiies, However, the values can be normal in the presence of small tarn our depns its. Screening carcinoma ot ihe ovary rends to be: a symptom- atic in ihu cnrly Mages and most patients, presenl "'ilh adduced disease, ninth effort has been made to define a tunuiui marker which could be used for screening purposcs. So far, none has become ,i^<iil.ible that K truly specific and that is suitable for the eaily detection of epithelial carcinoma (Cram and |ei'dinj!ih> 1994). Ultrasound is not suitable as i pri- mary screening tool because of expense and a higli falb<;-positive rate The most promising approach is a combination of CA 125 with ultrasound fur ihosc i"Omi L n »vithpcrs]i.tentlv raised values. In our present stale of knowledge and with the Inikbir technology, screening tlie ycnciiil popula- tion is neither useful nor safe. Patients should be enrolled in trials to .i-jses:, n<^ iorttning techniques, but should not be led in believe (hii proven Surgery far epithelial ovarian cancer Pnmaiy ^JFflery-ln delermlra diagiosis and mil GYP III mom • Total abdominal hysterectomy • Bihnfaral sal Dingo-oopno recto my • Infracolic omeniectomy priinarysLrgerv hpari!u&". l om3nivl evident of synchronous endomotnal can ^ r I rile™,! | deb Hiking surgery * Womeiwlthbuky dl • Cheniiithtirapy resumed after surgery Second-look surgery * Atflieendofdiemorlitrapy • No place incurrsnt management Eturclerlme tumours * Ovarian cvEtectoinv or DOplmr-ectamy adequate in ynung '"omfln and hila'eral ^alpingo-ncphorectomv In -women Surgery is die maiiulay of both the diagnosis and td ticatnienc ol ovanan cancer A vertical incision is required lor an adequate exploration of [lie upper abdomen. A Mmplc: of ascitic fluid 01 peiitoneal washings, with normal saline should be Idk^n for cytology. The pdvis. and upper ahdonie n a re explored carefully to ideniifv mrt<i>tatic disease. The therapeutic objetlive of surgery for oianan cancer is the removal of all Hitimur. While this is achieved in ihu maiont} of Stage 1 cases, and in smine Stage IT, it k muaih/ impo^iiiblc: in moic advanced dJBQSb Decatise ol the diffuse spread of tumour throughout lh<; pentoncaJ cavity and the retroperilo- neal Dodu» mi Lniiiupic deposits will persist in alnioa all cases., eren when all macroscopic tumour appear* id hav* been ocibcd. Thus, while surgerv alone mar he curative in many Mjge I eabcs, ;uklitional thcrap» [s tsvcntial lor mos.t of the remainder. r lh£ resection of divisible tumour us.ua.lly require* a total hyHerectoniy, bikleral salpmgo-oophorectoni* ^, unilateral salp eaiefule aifiease and curftlaj^c s eudon v found t fte pelvis \vill be nccc RonJ^rline diseaw u our cnnfiried to one c as malignant. If an <jv lorrned 1 in a young wo disease hji bei:n iemi *lily little to be gninc riik of recurrence (3f pophorectoroy (I5pj cent], Incjsesof doul he pcrfoiined to enp and to remove the re women i^ho have nni to gain from oonscrva itill prudent In recfln* and nyflterectoiny. \\lien buJkv disease stiond laparolom^ ma; who riipond alter twi a.pv. The cliemotherap^ able after the second o : A laige Eii that the mediai nuv be- increase vivjl at 3 years may bci percent (Van der Berg use ol i n i r i ,iU hemothei rase ii unlikely lube res nanc) 1 is niade by cy surgerv follows if the tu vxn if th i"; !•> nn 'jftcdiv Seiond-lonk surgei •paroiumy at tiie end ivcb are, fir^t, Ly detcn •terapy in order lo da and m plan sulxsequen mcise any residua) di* thjl stcond-Jook pUcation of the fct neither the nor the opportunity to effect on the patient 1 ? «i Cancer of Ihe ovary 143 - an cancer j a Demand remove Hi Stage I a sndomelrial canter •my chemDlherapy surgery Kill Ufa the diagnosis and the t A vertical incision is Kploration of the- upper dtic tkiid or peritoneal ac shinild he taken for ei abdomen are explored DC disease. • of b-urgCry for ovarian H uimnnr While ihi' 1* Edge I caw& and in some cible in mure advanced fiiiit spread c?l tumour •virvand the rem.perito- osits will persis! iri almost roscopit tumour appear? while surgery alone may cases, additional therapy njuinder. Murnnurusualh' require* d salpingo-oophorectomy and mJracohc omentectoinv However, in a foiiiig nullipjroub i^oman with a unilateral tumour and no iscites, unildterdlsalpmgo-uuphortTtoniy may be]us- nllable alter careful exploration lo collide metabtatii. disease and curettage ol the uterine cavity'to exclude a synchronous endomctriaF tumoui. If the tumour [& subsequently found ro be pnorK differentiated or if the washings are positive, a second operation 10 dent tllt-petMb mil be neLesaan. Borderline disease usimlly pr^^nlbB^ a Slage La tum- our confined to one ovary. It is often nol recognized as malignant. II an ovaiian cystectomy has been per- formed in .IVL.HIII& woman <uidiisei.Tnb likely chat Ihe disease has been removed completely, thi're i:> prol?- abh' little to be gained from further surgery hul the risk of rti-urreno; (36 per oentj i; highei than after oophorectomy ;li pCT«nO urpelvicclcarancei.2.5 per Ccnl). In cases of doubt, a second laparntomy should l>e performed lo explore Ihe abdomen thoroughly and to remove the res( uf (he affected ovaiy. Older women who have no wish lo h-nt children ha.'e little to gam from conservative surgery, and it K probably still prudent lo rciornmend bilateral oophorcccorm and hysterectomy. When bulky disease remains after initial sui^ery, a second Laparoiomy may be performed on Iliose \\f>men who respond after ivvo lo fuur lourjis ol themothei- apy.The chemotherapy is ihen resinned .i^oon ^SpOi- whlc after Ihe becond opcralion. This is called 'intei val dehulking' "i large f u"ipeari &ludy of Ihis approach suggests that the median survival in "hispoor-prognoiii group ma; 1 be increased by 6 months and that the sur- vival .n 3 ytiirjiniiy be improved Irani 10 per cent to 20 percent fvander frergei al. t 1995!. Thi& has led lo the u>eof[nitialchemotheiapyin women in whom tliedi^- fawii unlikely lu be rebecuible. Clefnfinnation of mahg •anq 1 is made by q-tolog^ 1 yr guided bfops^ and Hirgeiy follows il the tumour resfionds. Itrenminslube ictn il'this is an effective strategy. Second-look sur&erv ib defined as a planned jparotomy at the end of chemotherapy. Hie obpcel- ^cbi are, Hrbt, to determine Ihe response to previous dierdpy in order lo douimenl aicurately itb efficacy md to plan subsequent management, and second, lo ocise anv residual disease While there is no dotlbl Aat second-look surgery gives the most accurate •idication of the disease starns, (lie f^identi; su^^eils dial neither the surgical resection of itsidual tumour •nr ihe opportunity to change ihe treatment has any rfecton [he patient's survival. Second-look procedures therefore have no place Outside clinical trials at the present time. Selecting patients for postoperative treatment Women with Stage la orlb disease and well or moder- alelv diflcrcnlialcd tumours ma; nol require further ireaonenL The benefil of adjuvant therapy for women with Slage. Ic disease lemams unceitam, hut many untolu£i:>ts adviae chemotherapy. M other palienti with invasive ovarian carcinoma require ^iiuvanl therapy. There i.s no evidence that adjuvant therapy alfeclb.the outcome in women with borderline tumours. R a tho therapy Radiotherapy is now dlmosl never used in die rouiine manage ment of ovarian carcinoma. \ pote'iitiiil exeep- tLon ii radio-[mmunotheiapi in which radioactive yllrium is linked lo d monoclonal antibody i^hich recognizes an antigen found on innflt nvari^n cancers This is given intraperitoneally. It remains an expen menial treatment. Chemotherapy ChemciNerapy lor epithelial ovarian cancer Slape IHV-possibly Slags Ic Chemotherapy i& gi^'en both (o prolong clinical remission and survival, and for pal li at ion in advanced and lecurrcnt disease. Chemotherapy is commenced us &oon ib possible after bur^eiy dnd is usuallv given for five or^iv cycle*, at 1—4-weekly inter\ r al&. The platinum druj?*,, cisplatin and its analogue car- boplann, aie hcav} metal compounds which cause cross-linkage ofl'N^ srrjnd? in a similar fashion m alkyLiting agents. They are considered to be The most effective drugs [n general uhc in (he management of ovarian carcinoma, and are the most widely used cvtotovic drug^s either alone or in combination. I .i Carcinoma til the ovary and Fallopian lulie Cibpktm is a very to^k drug r L'mil the advent of Ihe S-hydru^ylryplamine (SHTj antagonist !gane- setion and nrid,ini.ctroii), severe nausea jpul vymit- ing> sometimes la&rinj: itverai days, were a serious problem. Permanent renal da nidge will occur unless cisplatin is given with adequale hydration with intra- venous lluids. Peripheral ricuropalhy and hearing loss Aft reported ivitli increasing. iiimulative doses Elec- trolyte disturbances:. inch as. hypomagnesaemia, arc seen occasionally, Unlike most chemotherapfulk .j£> n nl&> marrow tnxicity Lsnol UiUdlh a problem, with the except inn of anaemia. Carboplatin is ,1$ effective: as cisplatm in tbe (real- mem of o'arian cancer find I* Ihe mosl commonly used firsl-line drag, either alone or in combination with paclitaxeL II caubfs less nausea and vomiting lhan cisplalm and h,i$ oo significant renal rovidlv, Neuroloj,iuty is rare and hearing lus^ j^ subclmicaf. The lack of renjl luALily means that there is flu need to gi^'e catbopislin wilh intravenous, hvdraiinn. 'Llm dose i& calculated ID relation to iheglonierularfiliratifiii rate, usin^lhi 1 area under/ the curve (AUC) formula. Pachtaxel f'lavolj ii gi^'en in combination \vj[h cis- pletin or cui boplaim as. firsi-lint ircaimcnt, but may he ii vd alone when the disease recuri r II ib usuallv given as a 4-hour inriision nftera prernedicarion regimen of * inx^asive tumours -5-ygai survival riife& - 90% fcr Slage la and lt> wtll or lumeurt improved ihe quality advanced o^rian cam ranitidine or cimetidini to inactions. Paclkixel i> derived fiom the bdrk of the Paafic yew tree ('laxitt beevifolia) and has a meclia- nis-m of nction lhat is unique among cytotoxic drugq. Sensory neuropathy and neiitropenij are more common with higher tlost 1 ^ 3nd inrnsions for 24 honrb itsull in a higher incidence of grade 4 neutropeiiia. Otber formi of loxicity such as mya^iu ,md arthrafgia ait do^e dependent but riei'cr severe. Nausea and Jliii^areveiyniild, hut loss of body hair is usually irrespective of dose anil schedule, Bradycardia and hypotension uinall; do riotcau.se fiy Results - epithelial tumours Results or treatment ol epithelial tumours • Borderline turn durs -e*cellpnUQng^er -rnntf nt those whcclehdve uverall Borderline epithelial tumours Women wilh buukiline ovarian epilhelijl tumounj confined to the ovaries Iwve a good loiig-ttiin piog- noiii, with very few women dyin^ frum iheir disease. Kveri *vilh eMra-ovarian surea*], ibe 15-ye^r -M foi sernoji borderline epithelial tumours i.s around 90 per cent For Stage Tlf niudnou& tumours, ihe 15-year *,urvivji|rdleibonly44percern. Most have p&eudomy\oma pentonei. With the exceptinn ol' thc-se with pseudortipDnia pentonei, the oven! is good. pflntonel Invasive epithelial ovarian cancer Survival for epithelial yvanan cancer is depended m^inlv onstage, size of residuaf lumyur at the end initial surgery and grade ot tumour. The! 5-ytAf vival range*, from flO m 70 per cent tor women Mage I disease to 111 perienl for Slage 1II-IV. Since tin nidjorily of patients, present with advanced the overall 5-vear survival in the UK is only H. UTiile women with Sl^ge I tumours with grade 1 2 Ilislodygy have a 5-year survk^l rale of cf'er c^ni, those wilh pyorly differentiated tumours much worse. In more advanced tumours, Ihe of residual tunioui at [lie end of initial surgeij significrtnl in terms ol prognosis. The survival figures for cancer of the thanked little over tbe la^i 2Q vuars and leinain for women wilh advanced disease despite more ical surgery and irapryi'cmcnts in cheniolhe Most Mudieji do shois ionn improvemenl m m survival m patients with minimal residual following surgery and why respond to post- Iredtrnent. However, lhi$ benelil hat, not been cie-rHly long labtmg to affecr ^-vear There is nodoubl lhat even if long-term not been improved, modern q-totoxic therapy aid rhfca mosl common sa and Ihec ce sicroid honnoi can cause postm n and semsil pre iiifosa cell tumoun be used |y monitor l Tbcca cell tumyurs ai occur j[ all postmenopau these tumours i. Mos^t presenl i presenl in only 5 per cell (umours; may develop whe preriiiminanlly c^tk cord slromal tumou yellowy because of wal -alas or moderately ours ian epithelial tumours i good long-term prog- ymg from their diseajfl id. (lie 15-ve.ar survival il tumours is around 90 os tumours, the 15-fear L Most of those who die la. With ilie excepnon a peritonei, [lie overall in cancer in cancer is depcnde.nl nal tumour at the end erf wiioui. The. 5-vear sur- er ctril fur women br Stage HI-TV. Since willl advanced disease, he L'K ii unlv 23 per ccnU lmnoiir:> with grade l« -vi%al rate ol over 411 pa ierennktetk Uimour^ do *d. tumour.";, the amour* pud of initial surgery ii ancer of the ovaiy 0 years -md remain poor lisease despite more rad- nenls in ibnnotherap*. improvement in oiiiimal residual respond to pos'-suij aicfit lias not been uni- tl 5-year survival rates. if long-term ill rvival m cytoluik therapy c quality of life for many paticnti ^i advanced ovarian cancer in spite of the side effects Nan-epithelial tumours iai tumouis constilute approviinalely ID per cent yf all ovarian ^nctr&. Bec^iiit of ihuir raricyand their •ieiuiti^jtv to imen^ive chanothcrapTi it is especially appropriate to refer ihese patients for specidlisl tjre. Sex card sNmallumaurs Nan-epithelial tumnnrs " £tx-e.or(Jstrorndltuiiidur • Gianuluss rail Itimour • The^a eel I tumour • Eertnli-LEydni Himour • Germ e.ell lumaur • Vfilk sar {gndodBrmal gmusl (fimour • lerjluma sa and theca cett e mwst common sex cord stromal tumours are and. lhei;i o^ll tumours. The;' oflcn hormones, in pnrlicuhir oejtro^nj, •hicli can cause po^tnienopaii^al bleeding in nlder w^iun iind. bCKual prccocit. 1 in pre-pubeital girla. Grainilos.i ^ell mtmiurs usually ittrcle inhibin. Thii can he used to monitor the effect 1 ; of 1 realm ent r Theca cell tumoms are usual ly benign Granulosa <cll luraoiiu cuiurat all agti, but arc tound prcdom- •tinrly in poJitinenopausa] women, 'Ihc Caging s>'&- fcm for (nc.se tumours h ihe .same as. tor epithelial feinont^. Most presem as ^lag^ 1. BiLileial turnourb |IH present in only 5 per ocnl of •iholugy Ciaiiulo^a cell tumours are norinally solid, butq?stic ^•«'b may develop ivhen they become large. Some ^: |>reduminanlly cyclic. Likv mo^i tumuur& of the KI cord stromal tumour group h the cut surface is. •Clcn yellow because of neutral lipid relaled to sev hormone prndoctioiL Areai, nf are also common Treatment The s-urgical treatment is the mmt as for epithelial tumouis. Unilateral oophon:ilomy LJ inducted only in young women with Stage la disease. 'Ihe effect of adiunctive tKerapy is difficult to aiseaSj as granulo.sa cell tumours can recur up 10 20 years dfler. the iililldl dia^no&is. Radiotherapy has been largely replaced by chemotherapy in advanced or recurrent cases. In ca'.ci of late recurrence, furlhcr siirgerv should be. considered before any oilier therapy is ^iven. 'Ilie 5-year survival is around £U per cent overalL but recurrence is associated with a high mortality. Sertoli—Leydig cell Hall of these rare ucoptasia produce male horrnonei i-in <.au&i: ^irili^linn. Rarely oeslrnften', are , 'iTie nroftiiosis for the majority who have disease isgoodi, and treatment is the .same as for gran uloia cclltumouiur Germ cell tumours Dysgerminomas Dysgerminomds j^tounl fur 2-5 per tent of all primary malignant ovarian tumours. Nearly all occur in young women lcs;> than 30 years old. They spread mainly bi lymphatics. All IJISLS d«d a ihcsl X-ray and rf coni[HJteriH-n] loiiHigra|ihy |TT) scan. Serum alpba-feloprolein (AFP! and beta-human ckorionic gonadotmpliin ||i-hCG) mint he asi,3icd to exclude theommoiisprc^aiteofelernentflofchoriocarcinoma, endodermflJ flinui tumour or teratoma. Gccasjonallv some cases of pure dyBgcrmrnoma ha.'e raised of ^-hCG.Puredys^eriniiioin^ha\e^you siidithey are nornialli 1 JitaKe I tumours (7S per cent), most being Stage la. Pathology Dysyennmoma^ are bohd tumuurb. which luvt a smooth or nodul.ir, bosselaicil <j\lernrfl surface. The-y •IK sufl or rubbery in consistency, depending upon the pro]sortion of fibious tissue contained in them. They may reach a considerable iii/e. iliu meari diam- eter is 15cm Appivrximacely 111 per cent are bilateral; they are alone among malignant gam cell tumouib in havmg a significant incidence of bilaleralily. Hementi of [mm d In re teratoma, volk we tumour or 152 Carcinoma of Hie ovary and Fallopian tube aic found in a bunt Jti per cent of dvsp i er.mmoma.s. Very [horough sampling of all dyi- geruiinomifi must be undertaken by the hi*topatholo- gibt to cTicludi; the present uf these more malignant perm i ell elements, ab (his indicates a Other getrfft ioJk sac [eiidodiimal sinus! Hun.ou.is Yolk SdC ^ndoderrrm] sinus) tumour is the .second most common malign a nl g<:rm cell tumour of the warj, making up 10-15 percenl overall and reaching a higher proportion in ihildren. lr nlay present M an acute ahdoriien due to rupTujecfthe Tumour follow- ing necrosis and haemorrhage, I he tumour i.s usually well encapsulated and solid Areab of necrosis dnd haemorrhage are ofl en seen, as are small cystic spacei. Irs consistency vanes from bull to firm arid rubber}' and its cut surface ib slippery and rnucoid. IT often secretes APR wmch tan be used to iririnilurlrcatnieiiT. Teratonia Mature teratnmas dct benign, the muit common being the tjbticteratonid tu dcnnoidcysl Ibimd at all jgei but particularly ill ihe lliird ^nd fourth dc^dcs. NoT ^11 bolid teratomas are i m mat iff e type, Immatm* leratomas arc composed of a wide var- iety of tissue:, and comprise rfbout 1 per cent of alf ovarian terJTom^s, They are unilateral in alcno>l all cases dnj jppear as solid m;i3&e^ thai have iinoonh and bo&seUli'd surfaces. The culsui race shiihimamly solid (issue, aliliough .small cvslk spaces are visible. Blood levels of p-liCG and AFP should bu es-tima red, e\ r en \\-hen the tumour appeals tore a Slwightfoi ward immature TVeatment A malign a nl germ cell tumour should be suspected prior to surfer,' if a young \\oman has what appears to he j prcJoininanQy solid tumour on ultrasound examination. Such .n . i • should be refined to a oncologist Trpnlmenl of rmn-epitlielial rumours Sev rn'd ^'idilidl '-miurs Mainly Irdated by sirgarv-fiysittnictomv and bilateisl • Chemotherapy (when required) same reglmans uasfl tot apimwigj • Germ cell lumD » Mainl; conservative surgery because thti cheminthergpvl^ highly efi required Umliitpr.il ^Iplngu-oDphorKTomy only in young ivornen with Slge fa harlv diica&e is treated by biirgery. In young women wild Stage la distase. unildlt-rdl uopbo recto my rrwy suffice, but in okler patients, hyslereclomy and bilat- eral ^alpingo-oophorM.lumy is recommended. Women are suil-ible for conservative surgery if ihey have a unilateral eni^psulated tumour uo abates, no e\'irfenu: oi abnormal lymph nodes ai surgery jnJ a negative CT scan of the para-aor|i<. nodes. Stage 1 malignant lerarom^i iind dy.sgerminoin-j may be fallowed up closely wi(houl further treal- inenl. For Ihe remainder, chemotherapy b^s replaced radiotherapy, particularly in Iho young age gronpj in which (hia tumour is most common, as fertility is likely to be preserved, ^hort courses of risplaun chemolherapi, given in combination with bleornycift andetoposidc |B£P) are curative in the 90 per cent rf pHtients without adverse features, MOR' mtensne regiinens are u^ed for patients with adverse features, ] CANCER OF THE FALLOPIAN TUBE Primary carcinoma of the Fallopian tube rare, comprising only 0.3 per cent of malignancies. However, only t-arly Fallopian carcinomas mn be distinguished with certainty ovarian disease. ^ Study of screening for ovarian cer detected three cases of early Fallopian lube oma and 19 ovarian tumoun, a relative prev 15 limes greater Mian expected. 'iTiis surges hallopian tube carcinoma may he more co than is realized. PiimarvLardiiomais usually unilatcial. The age ri | diagnosis is 5fr y^ars. Many of the p^ nulfiparou!.''15percent) l aildink i ilaliti-isre up to 71 per o;nt of these women. Tumour idenlkal to thai of ovarian cancer, and met in peKk and para-aorlk nodes are cnnimo-n. Table U.3 THJOsta [...]... includes the nionfl pubisj the rtiid minorn, the clitoris, the vestibule nf the vj the hulb of the veslibuk- ^nd tht greater glands i,Bariholin n s; Thcmons pubiiib.a padol tai anieiinriothe pubic sym physis and covered bv hjir-bvunng skin The labia majora evtend poflokdyftom tlie niona un either bide 1.1 f ihepudnrndal deft into which ihe urethra and v j g i n j npen The; niei^e witli one anntliei and. .. penis, fjitlv hidden the anterior fol^s o f t h u labia minurj, ihe ditorii sista of a bndyoftwo noi'pnra cavernn.'iJ lying side and connected to the pubic and ischial ranii, J glani of «n$itfVtt> ipongv erectile tissue The veidt i< that area hePveen the Ubij minor,] inlrj w urethra and vapna open The hulhs nl the ve^si lie on cither sidt of the vaginal opening and areeli ated masfies of erectile tissue... D Bieasl The CanDRi and Steroid Hnirnone Study of the Cen;rpic.rDisaa^e Contrc-l and the Manorial Institute of Child Healinand Human and ovarian cancer in Did Rnce after Inlertilny and in vitro tertilisatnjn.Isflfflf199S.336 E^S 1000 Additional reading Burger HG Clin'cal util-ly nl inhihin measurements JGitn R 76 1391-6 CannistraSA CariLsr of the o'.'aty , 329 Hell Strom AC, Carcinoma of the l rev**... magnetic resonance imaging ( M K I ) of the pelvis may sometimes • helpful Thorough exam in at inn uiiderrfTijiLitheiiia and a fu 11-1 hickncis, generous, biops-v are the most imrjnrtant investigations The evAmuwlion should note pnlltnLirl v the size and distribution of the primary lesio*v especially the involvement oftheuretbraoranus., and iecondar>- lesions in the vulval vi p^rincal ikin mua be nought... tissue 'iTie greater veslihi glands, lie posterior to ihe hulh*, nf the vestibule are connected to the surface by short ducts Benign conditions of the vulva Patients with vulval symptoms j quently in gynaecological pracrke 'I'he com pi _ often brig-standing and distresbingand often induces, feeding of despair in both palienl and doctor A care fijl syiiipalhelic approach and a readiness [ir cunsuk colleagues... disease) occur an Mie vulva The latter is very K Condition? affecling ine vulva and vagina rare The hi&tolugical 1'eatures and termiimlogv of VTN ace analogous lo ihuic- of corvical intraepithelial ncoplasia fCINi and vaginal intr, often prti^nt in c;, baic daik skin and the lesions, are usually caL* papular and pigmented However, progression tc?... from sympathetic iuppurt and understanding, and lime must bi &tt tfiidc for lhi& Vidvalpain These synnplonis cause considerable diatreas In the sufferers, who Jie often young women The cause is frtquefltty elusive and Irejlment is empiricaL Steroid cream or ointment will help some of these miinen, but a mull idisciplinan' approach is required lor many is rarely hdpTul Ncn-neoplastic disorders of the vulva . r Carcinoma of the ovary and Fallopian tube CanDEr of Ihe ovary 143 Cance<ofrliG Fallopian lube 152 OVERVIEW of tha ovary is mosl common ii 1 the 'ijeamiyridtirjri:.c-t 111 fc world There. insidious nature of the signs and symptoms, of carcinoma of the ovary, bul rnav sometimes b-: due to a rapidly growing I u [Hour. Due to the non-ipecillc nature of most of these symptomSj. adverse features, ] CANCER OF THE FALLOPIAN TUBE Primary carcinoma of the Fallopian tube rare, comprising only 0.3 per cent of malignancies. However, only t-arly Fallopian carcinomas mn be distinguished