Carcinoma of the ovary and Fallopian tube doc

of tha ovary is mosl common ii 1 the 'ijeamiyridtirjri:.c-t 111 fc world There die lustundsr 6000 case!, each ysar in Ibs UKWb ilfl ffiB incidence of ovarian cancer is si mi l&r to thai

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 ovariancancer This and other anomialici ca^ldcubt upon the'incessant ovulalicii* theor,1

1 1 Carcinoma of the ovary antf Fallopian lube

• /

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

( V e n n e r a L ,

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 v F a r s o t a g H

» 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\re has a lifetime

ctsk of 2-5 per cent, twice tht ribk in the general

popuklion With two affected clost reldLivt^ lhiL

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 n t r ^ u n l Families Wffli.olorettal cancer have defects in the J 3 N A repair genesbut this is seldom found m association with tamilialovarian cancer (Kaflpr/ak el al., 1999) A womanwho has inheuied a detective RK.CA1 gene hi a weJl-

ducumenlctl [dmilv ha;> a 60 per cent risk of breastcancer by 'ill years nl a^ and an &0 pel cent lifetimerisk However, the risk of ovarian earlier is muchlower, 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 isimpracticable and unreliable because mutations arefound far lesi often than expected, even in

with a strong family bislorv There jre veryable problems in interpreting the resulis inwith only one or li^o aftected relatives There maybe

a spectrum of inulaliyrii, isith verv different lei'els ofrisk Ei'en a negative test resnlr nid\ nol provide iheexpflded 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-uiLerhbut prophyldclk, bilalcral mastectoniy ifl a very drastics^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-flowDoppler studies and serum CA 1Z5 estimation evert

6-12 months are recommended, bui it is unierlaJBhow much pro Let Lion this offei^ Prophylactic hilateral 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, nolrecnyvt the nsi; entirely, as c.lrcillonn of the pcrfl

toneum has occurred after this procedure

Class if i callon of nujrian tumouis

Ovarian i n m o i i r b lan be solid or cystic They nuyhfbenign r>r ma%nanl antl [n addition there are thc«

that, while havinglack am' evidence olcalled borderline lurai

ovarian |linorigcoid gonadal tyj>e laiso

Oi sex cord me.senchyi

«A cord iTie^nchmal

Simplified hi stole ovarian tumours

f U ill 'fferpniiated care

II Sex cord stromal turn

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 andajsociated with an

Cancer olthe ovary Ị

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]ịii 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 typẹ

Simplified hislologlcal classification of ovarian tumours

I Common epithelial liimours (Uiilgn, borderline or malignanl)

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

Ẹ 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 typẹ', Hyvcver,

»ucinnufl uid cndomeiriuid lesions, are likely to he

ivith an earlier j^agt; jnd lộ^r grade than cystadcnoi_-arcLnoiriạs.

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-omạ Occasional glandulai itiuctures may be present which tumble a diagnosis of đenenareinorna to be madẹ 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 nvarỵ'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 rẹa<-h enormous diniens-ions A cyst

diameter of 25 cm is quile

Endometrioid carcinoma

Ihesearc ovarian tumours that resemble etidome trinl cirdiionidị 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^ônuable 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.il1 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*quentlycoeristh 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, b u l

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 f l u i d , flowing to l y m p h a t i c 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 1-11Stage III-IV

Pcdvicnodes30

h7

H'ai'a-aorticnodes1965

peritonea] surface throughout the abdominal cavityand on the surface of the diaphiagm Mctasta^s on theundersuitiice otthc diaphragm m;ifrbe found in up to

44 per cent of whjt otherwise wenis to be stage 1-11disease

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 iruinmvolved 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 feelinglump the neil mo&L frequenl Patients may comJiif indigcslion, urinary frequency^ weight loss irarely, abnormal menses orpostmenopauaai bkesh"

A hard abdominal mass ansing from ihc pelvnhiglily suggestive, especially in the presence of ascit

A fixed, hard, irregular pelvic mass is usually fdl ITC*J!

combined \aginal and rectal KtammatioD f H g I.1

pii^l4S)/llie neck and groin should also be examnifor enlarged nodes

:n

Ilialllb

Ilk

Haeniaioln^iejl mvecount, ure.i, electrolyAdiestX lay isesBenlionyciut d barium cd

mm bowel involvemi

*rif ^n intravenous

•j- useful Ullrnsonogi

Trtblcl3,2 F1OO bilging for primary ovarian a

with ascites present containing malignant cells or

with positive peritoneal washings

Growth involving oncoi both ovaries ivithpelvii eAlcnsionExtension 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 yrwith ascites preheat conlaining malignant ceDi w

with positive peritoneal washing1,

Growth involving one or bolh ovariei with peritoneal implants outside the

pd'is or poiitivt rctropcriloncdl urin^uin^l nodesSuperticijl liver inetastuseii equals Stape ITI

Turn our grossly limited to (he true pelvis with negative noil« bill withhi«ologicalli-conlunn:ilmKro!1copic5i:nlinsl>f"''bili>ininjl peritoneal surfacesTumour 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 i n g u i n a l nodesGrowth 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 < n j i | ^ !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 nancy ttorc' In moal women, the diagnosis is lar

malig-from tirlain before the laparotomy and the ation is undertaken on the basu ( h a t (here is a largemass that nradb to be [Amoved regardless of itsnature

oper-I oper-I " Carcinoma ol (he ovary and Fallopian lube

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

screening purposcs So far, none has become ,i^<iil.ible

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

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 c a n c e r

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

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

Cancer of Ihe ovary 143

Kploration of the- upper

dtic tkiid or peritoneal

ac shinild he taken for

ei abdomen are explored

fiiiit spread c?l tumour

•virvand the

rem.perito-osits will persis! iri almost

roscopit tumour appear?

while surgery alone may

cases, additional therapy

disease and curettage ol the uterine cavity'to exclude

a synchronous endomctriaF tumoui If the tumour [&

subsequently found ro be pnorK differentiated or ifthe washings are positive, a second operation 10 denttllt-petMb mil be neLesaan

Borderline disease usimlly pr^^nlbB^ a Slage La our confined to one ovary It is often nol recognized

tum-as malignant II an ovaiian cystectomy htum-as been formed in IVL.HIII& woman <uidiisei.Tnb likely chat Ihedisease has been removed completely, thi're i:> prol?-abh' little to be gained from further surgery hul the

per-risk of rti-urreno; (36 per oentj i; highei than afteroophorectomy ;li pCT«nO urpelvicclcarancei.2.5 per

Ccnl) In cases of doubt, a second laparntomy should

l>e performed lo explore Ihe abdomen thoroughlyand to remove the res( uf (he affected ovaiy Olderwomen who have no wish lo h-nt children ha.'e little

to gam from conservative surgery, and it K probablystill p r u d e n t lo rciornmend bilateral oophorcccormand hysterectomy

When bulky disease remains after initial sui^ery, asecond Laparoiomy may be performed on Iliose \\f>men

who respond after ivvo lo fuur lourjis ol apy.The chemotherapy is ihen resinned i^oon ^SpOi-

themothei-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-prognoiiigroup ma;1 be increased by 6 months and that the sur-vival n 3 ytiirjiniiy be improved Irani 10 per cent to 20percent f v a n d e r frergei al.t 1995! Thi& has led lo theu>eof[nitialchemotheiapyin women in whom t l i e d i ^ -

fawii unlikely lu be rebecuible Clefnfinnation of mahg

•anq1 is made by q-tolog^1 yr guided bfops^ and

Hirgeiy follows il the tumour resfionds Itrenminslubeictn il'this is an effective strategy

Second-look sur&erv ib defined as a plannedjparotomy at the end of chemotherapy Hie obpcel-

^cbi are, Hrbt, to determine Ihe response to previousdierdpy in order lo douimenl aicurately itb efficacy

md to plan subsequent management, and second, lo

ocise anv residual disease While there is no dotlblAat second-look surgery gives the most accurate

•idication of the disease starns, (lie f^identi; su^^eilsdial neither the surgical resection of itsidual t u m o u r

•nr ihe opportunity to change ihe treatment has anyrfecton [he patient's survival Second-look procedures

therefore have no place Outside clinical trials at thepresent time

Selecting patients for postoperative treatment

Women with Stage la orlb disease and well or alelv diflcrcnlialcd tumours ma; nol require furtherireaonenL The benefil of adjuvant therapy for women

moder-with Slage Ic disease lemams unceitam, hut manyuntolu£i:>ts adviae chemotherapy M other palientiwith invasive ovarian carcinoma require ^iiuvanltherapy There i.s no evidence that adjuvant therapyalfeclb.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 radioactiveyllrium is linked lo d monoclonal antibody i^hichrecognizes an antigen found on innflt nvari^n cancers

This is given intraperitoneally It remains an expenmenial treatment

Chemotherapy

ChemciNerapy lor epithelial ovarian cancer

Slape IHV-possibly Slags Ic

Chemotherapy i& gi^'en both (o prolong clinicalremission 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\ral&

The platinum druj?*,, cisplatin and its analogue

car-boplann, aie hcav} metal compounds which cause

cross-linkage o f l ' 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

cvtotovic drug^s either alone or in combination

I i Carcinoma til the ovary and Fallopian lulie

Cibpktm is a very to^k drugr 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£>nnl&> 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^lhi1 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 recurir II ib usuallv given

as a 4-hour inriision nftera prernedicarion regimen of

* inx^asive tumours -5-ygai survival riife&

- 90% f c r Slage la and l t > 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 tlost1^ 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 w h c c l e h d v e

uverall

Borderline epithelial tumours

Women wilh buukiline ovarian epilhelijl tumounjconfined 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 -Mfoi sernoji borderline epithelial tumours i.s around 90per cent For Stage Tlf niudnou& tumours, ihe 15-year

*,urvivji|rdleibonly44percern Mosthave p&eudomy\oma pentonei With the exceptinnol' thc-se with pseudortipDnia pentonei, the oven!

is good

pflntonel

Invasive epithelial ovarian cancer

Survival for epithelial yvanan cancer is dependedm^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 womenMage I disease to 111 perienl for Slage 1II-IV Since tinnidjorily 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'erc^ni, those wilh pyorly differentiated tumoursmuch worse In more advanced tumours, Ihe

of residual tunioui at [lie end of initial surgeijsignificrtnl in terms ol prognosis

The survival figures for cancer of thethanked little over tbe la^i 2Q vuars and leinainfor women wilh advanced disease despite moreical surgery and irapryi'cmcnts in cheniolheMost Mudieji do shois ionn improvemenl m msurvival m patients with minimal residualfollowing surgery and why respond to post-Iredtrnent However, lhi$ benelil hat, not beencie-rHly long labtmg to affecr ^-vear

There is nodoubl lhat even if long-termnot 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 i n i t i a l 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 ^iadvanced 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 ihuirraricyand their •ieiuiti^jtv to imen^ive chanothcrapTi

it is especially appropriate to refer ihese patients forspecidlisl 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;' oflcnhormones, in pnrlicuhir oejtro^nj,

•hicli can cause po^tnienopaii^al bleeding in nlderw^iun iind bCKual prccocit.1 in pre-pubeital girla

Grainilos.i ^ell mtmiurs usually ittrcle inhibin Thiican he used to monitor the effect1; of 1 realm entrTheca cell tumoms are usual ly benign Granulosa

<cll luraoiiu c u i u r a t all agti, but arc tound

prcdom-•tinrly in poJitinenopausa] women, 'Ihc Caging fcm for (nc.se tumours h ihe same as tor epithelialfeinont^ Most presem as ^lag^ 1 BiLileial turnourb

s>'&-|IH present in only 5 per ocnl of

•iholugyCiaiiulo^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 grouph the cut surface is

•Clcn yellow because of neutral lipid relaled to sev

hormone prndoctioiL Areai, nfare also common

by chemotherapy in advanced or recurrent cases

In ca'.ci of late recurrence, furlhcr siirgerv should

be considered before any oilier therapy is ^iven 'Ilie5-year survival is around £U per cent overalL butrecurrence is associated with a high mortality

Sertoli—Leydig cell

Hall of these rare ucoptasia produce male horrnoneii-in <.au&i: ^irili^linn Rarely oeslrnften', are, 'iTie nroftiiosis for the majority who havedisease isgoodi, and treatment is the same asfor 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 spreadmainly bi lymphatics All IJISLS d«d a ihcsl X-rayand rf coni[HJteriH-n] loiiHigra|ihy |TT) scan Serumalpba-feloprolein (AFP! and beta-human ckorionicgonadotmpliin ||i-hCG) mint he asi,3icd to excludetheommoiisprc^aiteofelernentflofchoriocarcinoma,endodermflJ flinui t u m o u r or teratoma Gccasjonallvsome cases of pure dyBgcrmrnoma ha.'e raised

of ^-hCG.Puredys^eriniiioin^ha\e^yousiidithey are nornialli1 JitaKe I tumours (7S per cent),most being Stage la

PathologyDysyennmoma^ are bohd tumuurb which luvt asmooth 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 t e r a t o m a , volk we t u m o u r or

152 Carcinoma of Hie ovary and Fallopian tube

aic found in a bunt Jti per cent ofdvspier.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

w a r j , making up 10-15 percenl overall and reaching

a higher proportion in ihildren lr nlay present M an

acute ahdoriien due to rupTujecfthe T u m o u r

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\ren \\-hen the t u m o u r 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 t u m o u r 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 womenwild Stage la distase unildlt-rdl uopbo recto my rrwysuffice, but in okler patients, hyslereclomy and bilat-eral ^alpingo-oophorM.lumy is recommended Womenare suil-ible for conservative surgery if ihey have aunilateral 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-jmay be fallowed up closely wi(houl further treal-inenl For Ihe remainder, chemotherapy b^s replacedradiotherapy, particularly in Iho young age gronpj inwhich (hia tumour is most common, as fertility

is likely to be preserved, ^hort courses of risplaunchemolherapi, given in combination with bleornyciftandetoposidc |B£P) are curative in the 90 per cent rfpHtients without adverse features, MOR' mtensneregiinens are u^ed for patients with adverse features, ]

CANCER OF THE FALLOPIAN TUBE

Primary carcinoma of the Fallopian tuberare, comprising only 0.3 per cent ofmalignancies However, only t-arly Fallopiancarcinomas mn be distinguished with certaintyovarian disease ^ Study of screening for ovariancer detected three cases of early F a l l o p i a n lubeoma and 19 ovarian tumoun, a relative prev

15 limes greater Mian expected 'iTiis surges

hallopian tube carcinoma may he more cothan is realized

PiimarvLardiiomais usually unilatcial Theage ri| diagnosis is 5fr y^ars Many of the p^

nulfiparou!.''15percent)laildinkiilaliti-isre

up to 71 per o;nt of these women Tumouridenlkal to thai of ovarian cancer, and met

in peKk and para-aorlk nodes are cnnimo-n

Table U.3 THJOsta

Cancer ol the

same regimtiis

[fie patienls.are

Nghly

ingcry In vuimg women

rral flopbnrectomy may

hvsleiecloLny and

bilal-s recommended Womun

• surgery if ihti1 have a

ir noasdtes, no evidence

I surgery and ii negative

Hies

as and dysge-rniinomas

1 without hirthei

lieal-mothcrapy has replaced

the young ,i£f grim])1; in

t common, as fertilily

Bit courses of cisnlalin

nnation mlh blt'ormcin

u h r in |be9(| percent of

am res More intensive

Is with adverse feature!

IPIAN TUBE

Ilo|>ian lube is extremely

y ceni ol' gi naecological

\Y early Fallopian

shid ivilh ccrldiiity

Teen ing far ovarian

can-iv Fallopian lube

curdn-ns P re-liHin' [ire-valence

cted Thi^ suggests lha[

may be more common

dry unil<]ier<il Tlie mean

Manv oi ihe patients are

I'lierc nuv be dldenu: of m-situ ease in lhetuba.1 epithelium

dis-Cdrunoma of ibe Fallopian lube! usuallythe lumen with lumour The tumour may j>rolrudethrough the fimbri&l tnil and the tube may be retortshaped, resemblmp a hydroailpinSs Ii [s usually very

r lo ihc serous adcnocarcinoma of [be ovarv

The F1GO clinical staging is similar to that usedfur ovarian cancer {Table 13.3J Probably because ofthe difTiaillj in ijlstin^ni^hin^ between ad^'anccdovarian and advanced Fallopian lube carcinoma, 74per cent of Fallopian tube carcinomas, are diagnosed atStage l-Ma, ( h e renuining 2fi per ccnl jrt Stage llb-lV"

Table 13,3 FTGO staging r^r ^allnpi^Ll lubi: carcinoma

0 Carcinoma in sim-limiied lo the tubal rnucosa

1 Growth limited to the Fallopian tubes

la One tube involved wilh extension into thesnbnuicosaor

Not penecnling Ihe aerosal surface

No ascites

Hi Both tubes mvolved but otherwise a*, for fa

lc One urboth lubes with extension through or onto thetubal seros.i or

ascites with malignant cells orpositive peritoneal washings

II Growth involving one or botb Fallopian tubes with pelvic extension

lla Extension or metasMses 10 ihe ulerns or ovarieslib Extension to other pelvic or&diis

Ilk Sldgc lla or lib plus ascites with malignant cells or

positive peritoneal washings

I II Tumour involves one or both Fallopian tubes with peritoneal implants outside the

pelvis or positive retroperitoneal or i n g u i n a l nodes;

Superficial liver melastases equals Stage 111Tumour appears l i m i t e d lo (he Irue pel' is but with historically proven malignantextension to tbe small bowel or oincntum

I l i a Tumour 15 grossly limited to the true pelvis with n e g a t i v e K m p J i mxlri but

wilh historically confirmed microscopic seeding of abdominal peritonealsurfaces

lllh l u m o u r involving one 01 both Fallopian tubes with histologicaUvconfinneil

implants Of abdominal peritoneal surfaces., none exceeding 2 c m in diame[erLymph node^ are negative

lllc Abdominal implant! >2cm in diameter or posit he relropcriloneal or inguinal

nodesGrowth involving one or bolh Fdllupian lubes with distanl mctastases

11 pleural effusion is present, there musl bepusili'u cytology

melastases equals Slage TV'