7.

OVARIAN TUMORS
General considerations
Tumors of the ovary are benign, borderline or malignant. Benign tumors require operative
intervention but do not recur or metastasize, nor do they generally decrease survival. Borderline tumors, in
contrast, are associated with a small risk of recurrence, may have invasive implants and thus may decrease
survival. Malignant tumors recur, metastasize and decrease survival.
Benign ovarian neoplasms do not produce any symptoms that readily differentiate them from
malignant tumors or from a variety of other pelvic diseases. Indeed, one of the most unfortunate features of
benign tumors is that they are indistinguishable clinically from their malignant counterparts.
lthough it is not known whether malignant ovarian tumors arise de novo or develop from
benign tumors, there is strong inferential evidence that at least some benign tiunors
will become malignant.
7.1. BENIGN TUMORS
Classification
A satisfactory classification of ovarian tumors must precede any discussion of
this comple! and variegated group of neoplasm. The following tabulation has proven
satisfactoiy in our practice "
. #ystic tumors
$. %onneoplastic &functional cysts'
(. %eoplastic serous mucinous dermoid &benign cystic teratoma'
B. )olid tumors
$. *unctioning tumors &with characteristics'
(. +ndocrinological inert feminizing or mascuinizing
Nonneo!astic or functiona c"sts of t#e o$ar"
mong the most frequently found masses involving the adne!a &anatomically, the adne!a consist
of the fallopian tubes, round ligament, ovaries and structures within the round ligament that were formed
from embryologic rests' are the nonneoplastic cysts that are related to the process of ovulation and are
sometimes referred to as functional cysts. They are by far the most common clinically detectable
enlargements of the ovary occurring during the reproductive years.
1
They are of great significance primarily because they cannot be readily distinguished from true
neoplasms on clinical grounds alone. mong the noneoplastic cysts and hyperplasias of the ovary are"
, functional cysts, both follicular and corpus luteum types-
, theca lutein cysts- pregnancy
luteoma-
, sclerocystic ovaries-
, endometriotic cysts.
If ovulation does not occur, a clear fluid,filled follicular cyst lined by
granulosa cells may result and can reach sizes as large as $.cm in diameter. These
cysts usually resolve spontaneously within a few days to ( weeks but can persist
longer.
/hen ovulation occurs, a corpus luteum is formed that may become
abnormally enlarged through internal hemorrhage or cyst formation. )uch cysts are
often associated with variable delays in the onset of menses and confusion regarding
the possibility of an ectopic pregnancy.
Theca lutein cyst result from overstimulation of the ovary by 0#1 and are
characterized by e!tensive luteinization of the stroma surrounding the follicle. They
are often associated with hydatidiform moles and choriocarcinoma.
#oipus luteum, follicular and theca lutein cysts are benign, represent an
e!aggerated physiologic response of the ovary and, in most instances, involute over
time.
Neo!astic tumors
There are three main varieties of these tumors " serous, mucinous, dermoid.
)erous cystadenomas are more common and as a rule do not attain a very large size. lthough
most of the inner wall of the cyst may be smooth it may also contain a large number of papillary pro2ections.
ssociated fibrosis may lead to the so,called cystadenofibroma.
The serous cyst is usually unilocular, containing a serocitrine, clear fluid. Bilaterality may be in as
$.3 of patients with serous cystadenomas.
2
Mucinous cystadenomas may become huge &several have been reported to weigh
$.. to (.. pounds'. 1rossly, they are round or ovoid masses with smooth capsules
that are usually translucent and bluish,whitish gray.
The interior is divided into a number of discrete septa or locules containing
generally a clear, viscid fluid. 4f ma2or concern are mucinous cysts that perforate and
initiate intraabdominal transformation of the peritoneal mesothelium to a mucin,
secreting epithelium with gradual accumulation in peritoneal cavity of large amounts
of gelatinous material, constituting the pseudomyxoma peritonei!
Incidence of bilaterality in mucinous cysts is no significant.
5ermoid cyst &benign cystic teratoma' is rarely large, often bilateral and frequent in the younger
individual. 4n opening the cyst, one frequently finds hair, bone and cartilage as well as a large amount of
greasy fluid.
Microscopically, one may find all types of mature ectoderm, mesoderm and endoderm elements
&gastro,intestinal, nervous, respiratory, thyroid tissue'.
Benign soi% tumors are usually of connective tissue origin &fibrom, Brenner
tumor'. They vaiy in size from very small nodules, found on the surface of the ovary,
to very large neoplasms.
4n physical e!amination these tumors are usually quite firm, slightly irregular
in contour and mobile. The Demons-Meigs syndrome is an uncommon clinical entity
in which a benign ovarian fibroma is seen with ascites and hydrothora!.
S"m!toms an% %iagnosis of &enign o$arian tumors
Most neoplasm of the ovary are asymptomatic unless they have been sub2ect to a complication, hi
many instances, the first symptom noted is a palpable pelvic mass or abdominal enlargement.
Pelvic examination remains the best method of identifying an ovarian mass in its
earliest stages. 6nowledge of the size, shape, contour and general location within the
pelvis helps the physician arrive at the most likely diagnosis.
Benign tumors are usually smooth walled, cystic, palpable in the lateral vaginal
cul,de,sac, mobile, unilateral, independent of the uterus.
ny mass that is larger than 7 to 8cm in diameter should usually be surgically
e!plored. 9:3 of ovarian cysts smaller than :cm in diameter are nonneoplastic. The
3
transitory e!istence of functional cysts is of prime importance in distiguishing them
from true neoplasms &tumor disappear in two months'.
Most neoplastic ovarian tumors produce few symptoms" sense of pelvic weight
or pressure, abdominal discomfort, urinary tract or intestinal disorders.
Feminizing tumors, that occur before the menarche, are clasically associated with
pseudoprecocious puberty &early breast development, appearance of pubic and a!illary hair and vaginal
bleeding'.
hi the menstrual years, the symptoms may be " amenorrhea, nausea, gastro,intestinal disturbances,
sensitive breasts, weigh gain and a general lack of well,being.
In the postmenopausal patient, the symptoms are often similar to those of patients of comparable
age who are receiving e!ogenous hormones &vaginal epithelium matures, the endometrium becomes
proliferative and bleeding may occur'.
1onadal stromal tumor with masculinization is characterized by amenorrhea, breast
atrophy, clitoromegaly, hirsutism.
#omplementary investigations, utilized especially in pelvic tumors, are"
, pregnancy test-
, roentgenologic e!amination of the abdomen &teratoma, calcifications'-
, intravenous pyelogram &to detect ureteral displacement or obstruction, which may be
caused by intraligamentary tumors'- ;< barium enema &if symptomatic'-
, pelvic ultrasound &to e!clude intrauterine or malignant characteristics of
the mass'-
, laparoscopy &may be helpful in distinguishing a uterine myoma from an
ovarian neoplasm and in any situation where the source of a pelvic mass is uncertain-
laparoscopy may be helpful, but laparotomy is necessary in the treatment of most
adne!al enlargements-
, usuall laboratory tests in vue of surgical treatment and careful evaluation
of general physical condition.
Differential diagnosis
lthough it is not unrealistic to consider every ovarian neoplasm or ovarian mass potentially
malignant, in truth only (.3 of all ovarian neoplasms are pathologically malignant. 4nly occasionally it is
possible to differentiate benign from malignant tumors on the basis of history and physical e!amination. /e
present pelvic findings in benign and malignant ovarian tumors"
4
&enign maignant
unilateral bilateral
cystic solid
mobile fi!ed
smooth irregular
no ascites ascites
no cul,de,sac nodules presence of cul,de,sac
nodules
long time asymptomatic rapid growth rate
ll persistent adne!al enlargements must be considered malignant until proved
otherwise. 4ther aspects which can be differentiated"
= pregnancy &intrauterine, ectopic'-
= myomas of the uterus &especially subserous pedunculated or intraligamentary'-
= hydrosalpin!-
= tubo,ovarian inflammatory mass-
= double uterus-
= endometriosis &ovarian cystic'-
= functional cyst-
= pelvic kidney-
= tuberculous peritonitis &encysted'-
= ascites &may cause marked enlargement of the abdomen similar to that seen
with large cysts'-
= liver, spleen, kidney or adrenal tumors.
Complications
Torsion of the pedicle
In appro!imately $:3 of cases, ovarian cyst may twist on its pedicle and produce rather
acute initial symptoms. Torsion may be complete or incomplete. /hen complete
torsion occurs, gangrene of the cyst rapidly results.
)evere nausea and vomiting, rigidity of the lower abdomen appear promptly
and if the tumor is on the right side the simulation to an acute appendicitis is marked.
5
4ther differential diagnosis are" hemoperitoneum from complicated ectopic
pregnancy, intestinal obstruction, peritonitis. )urgery, of course, is the rule.
upture of the cyst
4varian cyst may rupture or be associated with intracystic or intraperitoneal bleeding. There may
be acute symptoms with the rapid development of shock as in a ruptured ectopic pregnancy.
)hould the rupture of a cyst involve only a single locule, or should bleeding be less severe, the
abdominal symptoms may be mild and transitory.
benign mucinous cyst rupture may produce pseudomy!oma peritonei.
!upuration
#ertain cysts, particularly dermoids, are prone to undergo infection, especially if there is partial
twisting of the pedicle. This will produce symptoms similar to those seen in a pelvic inflammatory disease
&pain, tenderness, rigidity, fever'. /ithout surgical intervention a frank peritonitis may ensue.
Malignant change
This occurs in only :,$.3 of the mucinous cysts. The problem is much more serious with the
papillary serous tumors because the histological differentiation between the benign and malignant is often
comple!. Malignant degeneration of serous tumors occurs in appro!imately (:3. Malignant transformation
of dermoid cysts is relatively uncommon &$,>3'.
There are some clinical characteristics of malignant change" age more than ?.. rapid increase in
volume of a known tumor, benign tumor becomes rigid and fi!ed, ascites.
Treatment of benign ovarian tumors
AN indicated earlier, small adne!al masses of less than :,@cm in diameter should be treated
e!pectantly over the course of two or three months, particularly in a younger woman. )hould this not regress
and particularly if it should increase in size, laparotomy must be performed.
Aarge ovarian cysts are unlikely to be functional and deserve immediate laparotomy as do solid
tumors, which carry a much larger hazard of being malignant.
s to the type of surgery performed, there seems little question that in the average
woman who has completed her family, total hysterectomy with removal of both
adne!ae is the safest procedure.
/here conservation of one ovary andBor the uterus is desired &to avoid
menopausal symptoms or for further pregnancy' this is permissible if careful
inspection &frozen sections and peritoneal washings' suggests that the lesion is benign.
6
s a rule, complete operation is desirable in the parous woman and after ?. years &the
menopause is really a minor problem today now that replacement therapy is available.
7.'. OVARIAN (AN(ER
General considerations
4varian cancer accounts for only ?3 of cancers in women, but it is the leading cause of death
from gynecologic malignancies. This tumor is the seventh most common cancer in women worldwide, after
cancers of the breast, cervi!, colon and rectum, stomach, corpus uteri and lung.
4ne interesting fact about ovarian cancer is that the highest incidence rates are in developed
countries and the lowest rates are in developing countries. In the Cnited )tates, ovarian cancer is the second
most common gynecologic cancer.
The lifetime risk among women with no history of familial ovarian cancer is estimated to be $.?3
&$ in 7. women' and that of women with positive family histories is higher.
4varian cancer incidence appears to be the highest in %orth merica and %orthern +urope and
lowest in Dapan and it occurs more commonly in white women. The mean age at diagnosis is :9 years and
the incidence with age and peaks in the eighth decade.
)ome of the geographic differences in the ovarian cancer incidence rates are e!plained by
intercountry differences in reporting systems, socioeconomic development, fertility rates, patterns of oral
contraceptive use and hysterectomy rates. Because a genetic link has been observed, another possible
e!planation is that the prevalence of the gene may be higher in some ethnic groups than in others. More than
7:3 of cases of ovarian cancer are still diagnosed in advanced stages of the disease.
Risk factors
The causes of ovarian cancer are poorly understood, but several factors have
been associated with an increased or decreased risk of the disease. ge, race,
nulliparity, infertility, history of endometrial or breast cancer and family history of
ovarian cancer have been consistently found to increase the risk for invasive epithelial
cancer. Age
The incidence rate of ovarian cancer increases from $:.7 per $..,... per year in the ?. to ?? age
group to a peak rate of :? per $..,... per year in the 7: to 79 age group.
4varian cancer is a rare disease before the age of ?., but its incidence increases steeply with age.
7
The relationship between age at menarche and menopause and the risk of ovarian cancer is
inconclusive. )ome studies reported that women e!periencing menarche before the age of $8 had a three to
four times higher risk of developing ovarian cancer than those e!periencing menarche at older ages.
The data on the association between ovarian cancer risk and age at natural menopause show
similar inconsistencies. )ome studies have detected an increased risk of ovarian cancer with increasing age
at menopause that ranges from $.? to ?.@.
eproductive and menstrual factors
Parity has been associated with a decreased risk for ovarian cancer. The risk of
tumor decreases with each increase in the number of pregnancies. The effects of age at
first birth and incomplete pregnancies &spontaneous abortions' on the risk of ovarian
cancer are still unresolved. )ome studies showed a protective effect for incomplete
pregnancies similar to that of full term pregnancies.
"reast feeding suppresses ovulation. /omen with a history of breast feeding have
been reported to have a lower risk for ovarian cancer &@.3 reduction in lifetime risk
compared with nulliparous women'.
#nfertility and fertility drugs utilized in treatment of anovulation may cause increased
ovulation and the risk of ovarian cancer.
$xogenous hormones, e!pressed by combined oral contraceptives, have been
shown to reduce the risk of ovarian cancer and this protective effect is one of the best
established and most consistent findings in the epidemiologic studies of ovarian
cancer.
The risk also decreases with increasing duration of oral contraceptive use &$$3
with each year of use'.
)tudies of the association between estrogen replacement therapy and ovarian
cancer have not shown consistent results.
Palpa%le postmenopausal ovary 5uring the postmenopausal years, when the ovary
becomes smaller &size of $.:!$!..:cm' the presence of a palpable ovary must alert the
physician to the possibility of an underlying malignancy &0. Barber'.
8
Family history
t least two well described familial ovarian cancer syndromes e!ist" the hereditary breast,ovarian
cancer syndrome &BE# $ gene, located on the long arm of chromosome $7' and Ainch syndrome II
&familial predisposition to ovarian cancer, endometrial and colon cancer without polyposis'
*amilial ovarian cancer accounts for less than :3 of all ovarian cancers. *or women with a strong
family history of ovarian cancer, management typically includes frequent screening and consideration of
prophylactic oophorectomy after the age of >: and when childbearing is complete.
Dietary factors
+cologic studies showed a positive correlation between consumption of animal fat, proteins and
total calories and the incidence of ovarian cancer.
&ther ris' factors 4ther risk factors for ovarian cancer that are inconclusive or have been
less studied include the following " obesity, thyroid disease, use of antidepressant,
anticonvulsants or psychotropic drugs, ionizing radiation and occupational e!posure to
benzene, asbestos or metals.
Pathogenesis
Three hypotheses have been proposed to e!plain the etiopathogenesis of ovarian cancer"
= the incessant ovulation-
= the gonadotropin-
= the pelvic contamination.
The incessant ovulation theory postulates that repeated minor trauma to the epithelial surface of
the ovary caused by continuous ovulation increases the likelihood of ovarian cancer. This hypothesis
suggests that factors which suppress ovulation &parity, oral contraceptives, lactation' reduce the risk of
ovarian cancer.
The gonadotropin hypothesis considers that the e!posure of the ovary to continuous, high
circulating levels of pituitary gonadotropin increases the risk of malignancy.
The pelvic contamination theory suggests that carcinogens may come in contact with the ovary
after passage through the genital tract.
Classification
The student of ovarian pathology is often confused by the prodigious variation in histologic
structure, and biologic behaviour. #urrently, the most popular and practical scheme of classification is based
on the histogenesis of the ovary"
I. %eoplasms derived from coelomic epithelium &serous, mucinous,
endometrioid etc'-
II. %eoplasms derived from germ cells &teratoma, dysgerminoma, gonadoblastoma'-
9
III. %eoplasms derived from specialized gonadal stroma &granulosa,theca cell tumors,
arrhenoblastoma, gynandroblastoma, lipid cell tumors'-
IF. %eoplasms derived from nonspecific mesenchyme &fibroma,
sarcoma'-
F. %eoplasms metastatic to the ovary &gastro,intestinal tract, breast,
endometrium, lymphoma'.
The histologic type of tumor varies with age. Most tumors in postmenopausal patients are of
epithelial origin. #ommon epithelial tumors, which account for about 9.3 of all ovarian cancers, arise from
the surface epithelium of the ovary.
)erous carcinomas are the most common histologic type of ovarian malignancy accounting for
about :.3 of all epithelial ovarian cancers. Mucinous tumors represent the second most common type of
epithelial ovarian malignancy.
The pathogenesis of epithelial ovarian cancer is unknown. Theoretically, malignant ovarian
neoplasms may arise de novo from benign lesions or from changes in tumors of low
malignant potential.
The primary mode of dissemination of epithelial ovarian cancer is by
implantation on peritoneal surfaces, pelvis, right paracolic space to the right
hemidiaphragm, pleural surfaces. Involvement of .the omentum is e!tremely common
&more than 8. 3'. Implantation on the serosa of the small intestine is also common.
scites frequently accompanies peritoneal metastases.
4ther ways of dissemination can be"
) direct local e!tension &cul,de,sac and bladder peritoneum, uterus, fallopian
tubes and rectosigmoid colon'-
) hematogenous spread &especially as a late manifestation'- ) lymphatic
metastases &pelvic or para,aortic nodes'.
Clinical evaluation. Diagnosis. Staging classification.
The high mortality rate of ovarian cancer is due primarily to the difficulty in detecting the disease
in early stages. If diagnosed when the cancer is confined to the ovary &stage I', the : year survival rate
approaches 8.3 compared with only $93 for stage IF disease. Cnfortunately, fewer than (:3 of cases are
stage I at diagnosis. The disease tends to be asymptomatic until it is well advanced.
10
+arly symptoms are often nonspecific, such as vague abdominal discomfort, nausea, dyspepsia,
which may be present for several months before the diagnosis. )uch complaints are usually not recognized
as anything more than Gmiddle,age indigestionG.
high inde! of suspicion is warranted in all women between the ages of ?. and 7. who have
persistent gastrointestinal symptoms that cannot be diagnosed. The possibility of ovarian cancer is often
dismissed.
s the ovarian tumor enlarges, it causes compression of surrounding pelvic structures, resulting in
such symptoms as constipation, urinary frequency or pelvic pressure. Menstrual irregularity is also
occasionally associated.
4f course, malignant tumors may undergo changes similar to benign tumors including torsion,
hemorrhage or rupture which may result in acute abdominal pain, constituting a surgical emergency.
s ascites develops or the tumor metastasizes, abdominal distension becomes more pronounced.
Hain is usually a late complication and is seen with early disease only when associated with a torsion,
rupture or infection.
Pelvic examination remains the most reliable means of detecting early disease. ny ovary palpated
in a patient > or more years after menopause should raise a high inde! of suspicion of an early ovarian
neoplasm.
pelvic or pelvic,abdominal mass is palpable in most patients with ovarian cancer. There are no
pathognomonic findings on physical e!amination that distinguish a malignant from a benign tumor.
Benign ovarian tumors tend to be cystic, smooth, unilateral and mobile.
Malignant tumors tend to be solid, nodular, bilateral, immobile or fi!ed.
The finding of ascites suggests malignant tumor but may also be found in
MeigIs syndrome. lthough ascites may be distinguishable from a pelvic,abdominal
mass by percussion &central tympany associated with ascites, central dullness and
lateral tympany associated with a mass' this distinction is not always possible. scites
without the presence of a pelvic mass should lead one to consider liver disease or other
primary malignancies &colon, pancreas, stomach or breast'.
+!amination of the upper abdomen in patients with advanced disease may
reveal hepatomegaly, massive omental involvement.
#areful chest auscultation and percussion may aid in the diagnosis of pleural
effusions.
The differential diagnosis of a pelvic mass includes benign ovarian tumors,
functional cysts, endometriosis, pelvic inflammatory disease. #ommon
11
nongynecologic causes include diverticular disease, tumors of the colon or appendi!,
retroperitoneal tumors, metastatic cancer and a pelvic kidney.
(a%oratory tests
Eoutine blood studies, including a complete blood count, differential blood count, platelet count
and chemistry survey, should be part of the preoperative evaluation.
serum # $(: determination is recommended because an estimated 8.3 of patients with
epithelial ovarian cancer have an abnormal value at diagnosis. # $(: is the most e!tensively studied
antigen and is the e!pression of cells derived from embryonal coelomic epithelium and
Mullerian duct. )erum # $(: levels are greater than >:CBml in 8.3 of women with nonmucinous
epithelial ovarian cancer.
# $(: levels may be elevated in a significant proportion of women destined to develop ovarian
cancer sometimes years prior to the onset of clinical disease.
Eecent work has concentrated on the evaluation of new tumor markers that may be complementary
to # $(:" # $:,>, T1 7(.>.
Eadiographic studies are realised in different teritories " abdominal &calcifications, indication of
associated ascites or intestinal obstruction', chest &pleural effusions, pulmonary metastases', e!cretory
urography, barium enema &to eliminate the diagnosis of conditions such as diverticular disease, cancer of the
colon, inflammatory bowel disease or involvement of the rectosigmoid by ovarian cancer'.
)onography is used to differentiate benign from malignant ovarian tumors. Malignant tumors are
generally multiloculated, more solid or echogenic, larger than :cm, with thick septae and solid nodules.
scites is easily detected, mesenteric or peritoneal involvement may also be noted.
#T has a superior ability to detect disease in the liver, retroperitoneum and omentum. /hen
indicated, fine,needle aspiration under #T guidance may be performed.
MEI may be used but it is not determined if it is superior to #T or C).
Aymphography may be used to delineate lymph node involvement but is not
been used routinely.
4ther categories of investigations may be" Hap smear, cystoscopy, cytology of
peritoneal lavage, Iaparoscopy.
The primary care physician needs to be alert to the possibility of an ovarian
malignancy in all women with intact ovaries who present with abdominal or pelvic
complaints. The primary care physician can also play an important role in identifying
patients at high risk for ovarian cancer and in helping patients understand the risks and
12
benefits of the various screening methods, prevention strategies and treatment options.
!taging
)tage of disease is determined by the e!tent of tumor at the initial diagnosis. The staging
classification for ovarian cancer is a surgico,pathologic system, last modified by *I14 in $98:. n
exploratory laparotomy is often necessary to diagnose ovarian cancer, since ovarian masses
may also be caused by benign cysts, by other primary ovarian tumors or by metastases
to the ovary from a primary gastrointestinal or breast cancer.
Aaparotomy permits a careful e!amination of all serosal surfaces, biopsies of
grossly involved areas, collection of ascites or peritoneal washings for cytologic
studies.
Internationa *e%eration of G"necoogic Oncoogists +*IGO, staging s"stem for e!it#eia cancer
of t#e o$ar"
STAGE TUMOR (-ARA(TERISTI(S
I tumor limited to the ovaries
IA one ovary, no ascites, intact capsule
IB both ovaries, no ascites, intact capsule
I( ruptured capsule, capsular involvement, positive peritoneal washings or
malignant ascites
II ovarian tumor with pelvic e!tension
IIA pelvic e!tension to uterus or tubes
IIB pelvic e!tension to other pelvic organs &bladder, rectum' or vagina
II( pelvic e!tension plus findings indicated for I#
III tumor outside the pelvis or with positive nodes
IIIA microscopic seeding outside the true pelvis
II.B /
gross deposits &implants' none e!ceeding (cm in diameter, node negative
III( abdominal implants greater than (cm, positive retroperitoneal or
inguinal nodes
IV distant organ involvement, including liver parenchyma or pleural space
Early detection of ovarian cancer
The mortality from ovarian cancer has changed little in the last >. years. The overall five,year
survival for this disease is variably quoted between (. and >.3. 4varian cancer has a higher mortality than
all the other gynecological malignancies combined. Thus, the need for the development of tests to aid the
early detection of ovarian cancer is important.
The time course of the progression of early disease is an important aspect that is poorly understood
but is crucial to the design of any protocol for the early detection of ovarian cancer.
13
It can be seen that target screening of high risk populations, although important on an individual
basis, is unlikely to have a significant impact on ovarian cancer statistics. 4ver 9.3 of cases of ovarian
cancer are sporadic tumors and need to be detected by screening techniques. )everal methods have been
tested for ovarian cancer screening.
Pelvic examination is currently the standard for screening. It has a sensitivity of
@73 for detecting a ?!@cm mass. Therefore, the pelvic e!amination alone is of limited
value as a screening tool for the detection of early ovarian cancer.
Tumor mar'ers are substances which include enzymes, hormones, nonspecific
inflammatory proteins and placental and fetal antigens. They may reflect an alteration
in ovarian function or surface molecular structure or a general response to malignancy.
)ince the original description of tumor,associated antigens in ovarian cancer over >.
years ago, over $.. potential tumor,associated markers have been reported in the
literature.
The most e!tensively studied ovarian cancer,associated antigen is #,$(:, a
high molecular weight glycoprotein of which intense e!pression is found in more than
8.3 of epithelial ovarian cancers. # ,$(: has been used in three different situations"
J< follow,up of patients with ovarian cancer-
JK< preoperative evaluation of benign versus malignant neoplasms-
J< ovarian screening &in postmenopausal women, a value greater than >:CBml
is highly suggestive of malignant process'.
Transvaginal ultrasonography can detect early morphologic changes accompanying
oncogenesis &size, papillary pro2ections from the cyst wall and cyst comple!ity'. Most
recently, transvaginal color 5oppler blood flow studies were suggested as a highly
accurate way to screen women for ovarian cancer.
Transvaginal screening is optimal in postmenopausal women in whom ovarian
volume does not vary on a physiologic basis. Eoutine screening for ovarian cancer in
the general population is not recommended by the merican #ollege of 4bstetrics and
1ynecology.
14
)creening is recommended for some very high risk patients &advanced age and
family history of ovarian cancer'. The current recommendation for those patients is
annual rectovaginal e!amination, serum #,$(: and TF) until childbearing is
complete or the woman reaches >: years of age. t that point, prophylactic
oophorectomy is recommended.
Treatment of ovarian cancer
Ear" stage %isease
*or older women who have completed childbearing, standard surgical management includes
total hysterectomy and %ilateral salpingo-oophorectomy
complete surgical staging operation must be performed to identify the significant proportion of
patients who will harbor occult metastatic disease. This surgical staging should include a through abdominal
e!ploration with biopsies and cytologic washings from multiple sites, omentectomy and sampling of the
pelvic and paraaortic lymph nodes.
In young women with early ovarian cancers who wish to preserve the potential for childbearing, a
number of possibilities e!ist. If the patient has a cancer likely to be cured by surgery alone &stage $' it is
appropriate to preserve the uterus and the opposite tube and ovary, provided this ovary has been found free
of tumor by wedge biopsy and frozen section.
Most authorities agree that women who have had conservative surgery for epithelial ovarian cancer
should undergo removal of their remaining reproductive organs when they have completed childbearing.
Hatients with stage I, well differentiated tumors, have a : year survival rate of 9:3. *or patients
with grade > tumors, clear cell histologic type, or possibly dense adherence and large volume ascites
postoperative therapy is indicated because of the higher risk of recurrence. The most popular current
ad2uvant therapy for stage I high risk disease is platinum based chemotherapy.
A%$ance% stage %isease
Cnfortunately, the typical patient with ovarian cancer presents with advanced stage III or IF
disease, with large pelvic masses, ascites and upper abdominal masses.
Agressive cytoreductive surgery remains standard surgical management for patients
with metastatic ovarian cancer. Its goal is to reduce the amount of tumor as much as
possible &the concept of the Gma!imum surgical effortG'.
The standard cytoreductive procedure for patients with disseminated ovarian
cancer consists of a%dominal hysterectomy, %ilateral adnexectomy and omentectomy)
15
In the course of attempting to resect as much tumor as possible, other procedures may
be necessary, such as resection of the colon, small intestine, a portion of urinary tract,
the spleen, diaphragmaytic metastases, retroperitoneal lymph nodes.
4ptimal residual disease has come to denote minimal residual disease no greater
than $ to (cm in diameter. The removal of large tumor masses may enhance the
response to subsequent chemotherapy.
)ince the mid,$98.s, the most popular chemotherapy regimen for advanced ovarian cancers has
been the combination of *#!P(AT#+ and *,*(&P-&!P-AM#D$, 4ther combinations
include *A"&P(AT#+ and D&.&/"#*#+)
4ne of the most promising new drugs has been PA*(#TA.$( &TL4A', perhaps the most active
agent since cisplatin for patients with ovarian cancer.
The optimal length of chemotherapy remains to be determined. It appears that there is no
advantage to treatment with more than @ cycles of an intensive chemotherapy regimen.
Eadiation therapy techniques include intraperitoneal radioactive gold or chromium phosphate and
e!ternal beam therapy to the abdomen and pelvis. )everal institutions abandoned the use of irradiation as
postoperative therapy in patients with bulky residual epithelial cancers of the ovary.
These same institutions continued to test the applicability of irradiation in patients with minimal
residual disease after surgery.
)urgical re,e!ploration after completion of a planned program of chemotherapy to attempt to
detect residual disease, referred to as second loo' laparotomy has been a part of many treatment
programs for ovarian cancer.
The findings at )AA clearly correlate with survival and this has served as an
important end point in the evaluation of both surgical and chemotherapeutic
interventions.
In practice, a )AA includes multiple washings for cytology, a thorough
e!ploration of the abdominal cavity, removal of any remaining internal reproductive
organs, biopsy of any suspicious areas and biopsy of retroperitoneal lymph nodes.
4ther innovative approaches to the first,line postoperative treatment of
advanced ovarian cancer have included such treatments as concomitant chemotherapy
and radiotherapy in patients with minimal residual disease.
16
#ntraperitoneal chemotherapy in patients with minimal residual disease consists in introduction of
dose,intensity strategies using either autologous bone marrow rescue or peripheral stem cell support.
Ctilization of hematopoietic gro0th factors &granulocyte,macrophage colony,stimulating factor or
granulocyte colony,stimulating factor' into clinical trials has enabled clinicians to ameliorate some of the
myelosuppressive effects of chemotherapy.
4ther agents and modalities that are receiving considerable attention include
biologic therapy using"
;M autologous tumor,infiltrating lymphocytes-
;< monoclonal antibodies-
;< hormonal agents &1nE0 analogues'.
Innovative therapies using information from molecular biologic and genetic
studies are also rapidly emerging.
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