Recent=20 Advances in OVARIAN = CANCER

Manoj=20 Sharma, Raksha Arora, Reva Tripathi, Vijay Zutsi =

Departments=20 of Radiation Oncology and OBG, =20 Maulana Azad Medical College and Associated Lok Nayak=20 Hospital

Ovarian cancer accounts for 10-15% of = gynaecological=20 malignancies. It has a high fatality to case ratio as it is diagnosed in = advanced stages, because of being asymptomatic in early stages. Ovarian = cancer=20 represents a major surgical challenge and requires complex multimodality = therapy=20

Pathological=20 types

&nbs= p; =20 Primary (80%) &nbs= p; = ; = &= nbsp; &n= bsp; =20 Secondary (20%)

Epithelial &nbs= p; =20 Non-epithelial &nbs= p; = ; =20 Typical =20 Atypical

=20 (90%) &nbs= p; =20 - Germ cell &nbs= p; = ; = &= nbsp; &n= bsp; =20 (Krukenberg)

-Sex=20 cord stromal

-Unclassified

Cystic = Solid

Epithelial ovarian=20 cancer

Approximately 90% of ovarian cancers are epithelial = in type=20 and are derived from coelomic epithelium or mesothelium. Serous=20 cystadenocarcinoma is the most common epithelial ovarian tumour.

Genetic risk=20 factors for epithelial ovarian cancer

Most epithelial ovarian cancers occur sporadically; = familial=20 or hereditary patterns account for <5% of all malignancies. Genetic = risks=20 are:

Site = specific=20 familial ovarian cancer=20
Breast / = ovarian=20 familial cancer syndrome=20
Lynch II = syndrome:=20 Which includes multiple adenocarcinomas, involves a combination of = familial=20 colon cancer (Lynch I) and a high rate of ovarian, endometrial and = breast=20 cancers and other malignancies of gastrointestinal and genitourinary = systems=20

Females with genetic risk factors should undergo = screening=20 with Trans vaginal sonography (TVS) every 6 months followed by = prophylactic=20 bilateral oophorectomy at completion of child bearing.

Clinical features=20

More than 80% cases occur in postmenopausal women. = The peak=20 age incidence is 62 years. As epithelial ovarian cancers remain = asymptomatic for=20 long periods of time, 70% of patients present in advanced stages (III or = IV).

=20 Symptoms are often vague and nonspecific- lower abdominal pain = and=20 discomfort, distension, pressure on a variety of gastro-intestinal = problems.=20

In advanced stages- = abdominal=20 distension due to presence of ascites, bloating

Signs:=20

Cachexia=20
Ascites=20
Solid, = irregular,=20 fixed pelvic mass.=20
Cul de sac = nodules.=20
Edema of=20 legs/varicose veins.

Investigations:

Includes Preanaesthetic work up.

Blood investigations

CBC=20
LFT=20
KFT

Tumour markers

1-CA125- For=20 postmenopausal patients with an adnexal mass and a serum. CA 125 level=20 >95U/ml, there is a 96% positive predictive value for malignancy. In=20 premenopausal patients specificity of the test is low because CA 125 = hence tends=20 to be elevated in common benign conditions also.

2-P53 EGFR-Studies in early borderline low risk malignancy cases. = This is=20 done to decide the = positive=20 cases that turned into = high=20 risk poor prognosis cases , whether chemotherapy = should be=20 given in these cases or = not .

Occult blood in stool

Chest X-Ray

ECG

USG abdomen and pelvis

To know the = origin,=20 size and nature of tumours.=20
Presence of = free=20 fluid=20
Metastases. =

CT scan/ MRI

Can be useful in suspected cases of ovarian = malignancy-

If the = origin of mass=20 is doubtful=20
To plan = management=20 i.e. surgery/ neoadjuvant chemotherapy followed by surgery.=20
To know the = extent of=20 spread and localize metastatic deposits=20
Status of = lymphnodes=20
For follow = up after=20 treatment

Barium enema/ colonoscopy

Indicated = in patients=20 over 45 years of age to exclude a primary colonic lesion with ovarian=20 metastasis=20
In all the = patients=20 with occult blood in stool.=20
In presence = of=20 intestinal obstruction. =

Upper GI endoscopy

To rule out primary gastric malignancy

IVP

In case of moderately large growth to see the path = of ureters=20 (in case CT scan/ MRI is not done) prior to surgical intervention.

Mammography

In case of breast mass to rule out primary breast = cancer=20 metastatic to ovary

Endometrial Sampling / ECC

In case of irregular uterine bleeding / post = menopausal=20 bleeding to rule out uterine / cervical cancer metastatic to ovary or = presence=20 of co-existent carcinoma endometrium.

Liver-spleen scans=20
Bone = scans &nbs= p; = ; =20 Are unnecessary unless symptoms /signs suggest metastasis=20
Brain scans &nbs= p; = ; =20 to these sites

FIGO surgical staging for = ovarian=20 cancer

Stage = I:=20 Growth limited to the ovaries

Stage Ia: = Growth limited to=20 one ovary; no ascites containing malignant cells. No tumour on the = external=20 surface; capsule intact

Stage Ib: = Growth limited to=20 both ovaries no ascites containing malignant cells. No tumour on the = external=20 surfaces; capsules intact

Stage Ic: = Tumour either=20 stage Ia or Ib but with tumour on the surface of one or both ovaries or = with=20 capsules ruptured; or with ascites present containing malignant cells or = with=20 positive peritoneal washings.

Stage II: = Growth involving one or both ovaries with pelvic=20 extension

=20 Stage IIa: Extension and /or metastasis to the uterus and = /or=20 tubes.

Stage IIb: = Extension to=20 other pelvic tissues

Stage IIc: = Tumour either=20 stage IIa or IIb but with tumour on the surface of one or both ovaries = or with=20 capsules ruptured; or with ascites present containing malignant cells or = with=20 positive peritoneal washings.

Stage = III:=20 Tumour involving one or both ovaries with peritoneal implants outside = the=20 pelvis
           &n= bsp;    =20 and/or positive retroperitoneal or inguinal nodes. Superficial = liver=20 metastasis equals       =
           &n= bsp;    =20 stage III. Tumour is limited to the true pelvis, but with = histologically=20 proven malignant
          =20       extension=20 to small bowel or omentum.

Stage IIIa: = Tumour grossly=20 limited to the true pelvis with negative nodes but with histologically = confirmed=20 microscopic seedling of abdominal peritoneal surfaces.

Stage IIIb: = Tumour of one=20 or both ovaries with histologically confirmed implants of abdominal = peritoneal=20 surface, none exceeding 2cm in diameter, Nodes Negative.

Stage IIIc: = Abdominal=20 implants >2cm in diameter and /or positive retroperitoneal or = irregular=20 nodes.

Stage IV: = Growth involving one or both ovaries with distant metastasis. If = plural=20 effusion is
&n= bsp; =20 present, there must be positive cytologic test results to allot a = case to=20 stage IV.
&n= bsp; =20 Parenchymal liver metastasis equals stage IV.

&nbs= p; =20

Treatment

Surgery =96 it = is usually=20 the first phase of treatment. The surgical procedure include the = following

Surgical = staging for=20 presumed localized stage I or II disease.=20
Debulking = of primary=20 advanced stage III or IV disease.=20
Surgery = following=20 primary chemotherapy for stage III or IV disease.=20
Secondary = debulking=20 of recurrent or progressive disease.=20
Palliative = surgery=20 for ovarian cancer including intestinal obstruction.

Surgical staging in managing stage I and II = ovarian=20 cancer

Steps:

Vertical = midline=20 incision is made=20
Any free = fluid is=20 aspirated and sent for cytology. In absence of ascites, peritoneal = washings=20 are obtained from the pelvis and paracolic gutters by the instillation = of=20 about 100 ml saline into each area.=20
Because of = the large=20 volume of the diaphragm, random biopsies of normal appearing diaphragm = are=20 discouraged. Thorough cytologic sampling of the undersurface of the = diaphragm=20 can be obtained by cytobrush /Ayre=92s spatula.=20
The entire = pelvis and=20 abdomen are carefully explored and biopsy of any suspicious nodules is = taken.=20 If there is no evidence of disease, multiple intraperitoneal biopsies = should=20 be performed. The peritoneum of cul-de sac, both paracolic gutters, = over=20 bladder and intestinal mesenteries should be biopsied.=20
Ovarian = tumour is=20 resected. Frozen section is indicated if patient desires future = fertility and=20 malignancy is doubtful.=20
If = malignancy is=20 certain, total abdominal hysterectomy and bilateral = salpino-oophorectomy are=20 performed.=20
Infracolic=20 omentectomy is done.=20
Pelvic=20 lymphadenectomy is performed on the side of tumour. Sampling of only = enlarged=20 pelvic lymphnodes is discouraged since metastasis are frequently = microscopic=20 and unrecognized.=20
Paraaortic=20 lymphadenectomy is performed by removing the lymphnodes from the aorta = and=20 renal cava from bifurcation of aorta to just below the renal vessels. =

In many instances incomplete = staging is=20 perform which can hamper subsequent management. To overcome this problem = the=20 following form is recommended to be filled up at the time of performing = staging=20 laparotomy. Its comprehensive nature ensures minimizing chances of = incomplete=20 surgery. =

Form to be filled up at the time of = surgical=20 staging

1. Ascites

=B7 =20 Yes

=B7 =20 No

=B7 =20 Aliquot to cytology

=B7 =20 Other (pseudomucinous fluid or ruptured cyst = fluid)

2. Peritoneal washing (if ascities absent)

=B7 =20 Yes

=B7 =20 No

3. Macroscopic tumour present: ovary

=B7 =20 Left

=B7 =20 Right

=B7 =20 Both

4. Capsule ruptured or tumour on capsule

=B7 =20 Yes

=B7 =20 No

5. Tumour on tube or broad ligament

=B7 =20 Yes

=B7 =20 No

6. Macroscopic tumour on uterus

=B7 =20 Yes

=B7 =20 No

=B7 =20 Uterus absent

7. Tumour in pelvic peritoneum

=B7 =20 Yes

=B7 =20 No

8. Lymph node enlargement

=B7 =20 Pelvic lymph node

=B7 =20 Para aortic lymph node

=B7 =20 Not inspected

9. Tumour on abdominal viscera

=B7 =20 Small bowel and/or mesentry

=B7 =20 Large bowel and/or mesentry

=B7 =20 Stomach/ duodenum

=B7 =20 Liver capsule

=B7 =20 Liver parenchyma

=B7 =20 Omentum

=B7 =20 Other abdominal viscera (specify)

10. Tumour on abdominal parietal surface

=B7 =20 Right paracolic gutter

=B7 =20 Left paracolic gutter

=B7 =20 Right diaphragm

=B7 =20 Left diaphragm

=B7 =20 Anterior abdominal wall

=B7 =20 Posterior abdominal wall

=B7 =20 None

11. Operation Type

=B7 =20 Primary laparotomy

=B7 =20 Early re-operation debulking

=B7 =20 Interval re-operation to debulk

12. Surgery Performed

=B7 =20 Unilateral salpingoophorectomy

=B7 =20 Bilateral salpingoophorectomy

=B7 =20 Total abdominal hysterectomy

=B7 =20 Omentectomy

=B7 =20 Bulk reduction

=B7 =20 Biopsy only

=B7 =20 Pelvic lymph node biopsy

=B7 =20 Bowel resection

=B7 =20 Other (specify)

13. Residual Tumour

=B7 =20 No macroscopic residual tumour

=B7 =20 <2 cm maximum diameter

=B7 =20 >2cm

Debulking or=20 cytoreductive surgery in stage III and IV = cancer

Surgery includes an initial exploratory laparotomy = with=20 removal of as much disease as possible. The operation includes = performance of=20 total abdominal hysterectomy and bilateral salpingoophorectomy, along = with a=20 complete omentectomy and resection of any metastatic lesions from the = peritoneal=20 surface or intestines.

=20 The principal goal of cytoreductive surgery is removal of all the = primary=20 cancer and if possible, = metastatic=20 disease. The goal is to reduce the tumour burden by resection of all = individual=20 tumours to an optimal status i.e. less than 0.5cm, which is associated = with a=20 superior survival rate.

=20 The performance of a pelvic lymphdenectomy in patients with stage = III=20 disease has been reported to prolong survival. But extensive = lymphadenectomy in=20 absence of clinically/ radiologically enlarged lymphnodes should be = considered=20 investigational.

Role=20 of conservative surgery

The uterus and contralateral ovary can be preserved = in women=20 with stage Ia, grade I disease who desire to preserve fertility. The = patient=20 should be monitored carefully with routine periodic pelvic examinations = and=20 determinations of serum CA125 levels. Generally, the other ovary and = uterus are=20 removed at completion of child bearing.

Chemotherapy =

All stage of tumours except stage Ia and Ib grade I = require=20 post operative chemotherapy. How ever clinically early=20 borderline ,low risk = cases that are P53 EGFR positive and now have turned into high risk poor prognosis cases , the chemotherapy should be = given in these cases too .

=20

Drugs=20 currently used as first-line treatment

Drugs under=20 evaluation for first-line = treatment

Carboplatin=20
Cisplatin =
Paclitaxel=20

Docetaxel =
Irinotecan=20
Gemcitabine=20
Pegylated liposomal=20 doxorubicin=20
Topotecan =

Combination chemotherapy has been shown to be = superior to=20 single agent chemotherapy for most patients with epithelial ovarian = cancer. But=20 recent study shows that single agent carboplatin is as effective as = combination=20 of carboplatin plus paclitaxel as first line chemotherapy.

=20 For stage Ia and Ib (grade 2 and 3) and stage Ic epithelial = ovarian=20 cancer treatment with = carboplatin or=20 combination therapy with paclitaxel for 3 to 4 cycles seems desirable. =

Chemotherapeutic=20 Recommendation in advanced ovarian cancer

Combination chemotherapy with cisplatin and = paclitaxel for=20 4-6 cycles every 3-4 weeks is the treatment of choice for patients with = advanced=20 epithelial ovarian cancer. = ; despite the fact that a large = trial,=20 ICON-3, failed to show superiority of this combination to single agent=20 carboplatin or the CAP regimen. ⁶

Chemotherapeutic=20 Regimens

PT =20 Cisplatin (75-100mg /m²) + Paclitaxel (175-210 mg/=20 m²)

CT = Carboplatin=20 (AUC=3D5) + Paclitaxel (135-175 mg/ m²)

PC = Cisplatin=20 (75-100mg /m²) + Cyclophosphamide (650-1000 mg/ = m²)

CC = Carboplatin=20 (AUC=3D5-7) + Cyclophosphamide (600 mg/ m²)

PAC =20 Cisplatin (50 mg/ m²) + Doxorubicin (50 mg/ = m²) +=20 Cyclophosphamide (500 mg/ m²)

=20 Area=20 Under Curve (AUC)

Neoadjuvant=20 Chemotherapy

It is the use of chemotherapy as the initial = treatment for=20 patients for whom the alternative is cytoreductive surgery. It is used = when the=20 risks of surgery are judged to be excessive or tumour is thought to be=20 unresectable. FNAC/ paracentesis can obtain the cytological diagnosis in = such=20 cases. Although there are no randomized controlled studies, there is = suggestive=20 evidence that Neoadjuvant chemotherapy does not compromise survival, = provided=20 that effective cytoreductive surgery can be incorporated into the = treatment=20 plan.

Treatment=20 Assessment &n= bsp; =20

Careful = pelvic=20 examinations=20
CA 125 = levels: An=20 elevated CA 125 level predicts persistent disease at second look = surgery in=20 97% of the cases but CA 125 level is not sensitive enough to exclude=20 subclinical disease.=20
Radiological=20 Assessment:=20
- USG=20
- CT scan: = False=20 negative rate of CT scan is about 45% =20

Second = Look=20 Surgery

This is an operation performed on a patient who has = no=20 clinical, biochemical or radiological evidence of disease after = prescribed=20 course of chemotherapy in advanced ovarian cancer. The technique of = second look=20 laparotomy is same as that of staging laparotomy.

=20 As second look laparotomies have not been shown to influence = patient=20 survival, they should be performed only in a research setting in which = second=20 line or =93salvage=94 therapies are undergoing clinical trials. Second = look=20 laparoscopy is less invasive but is associated with high false negative = rates.=20

Management of=20 persistent / recurrent disease

Second line = therapy

Secondary=20 cytoreduction: Patients with persistent or recurrent pelvic = and=20 abdominal tumours after primary therapy for ovarian cancer may be = candidates=20 for surgical excision of their disease.=20
Second line or=20 =93Salvage=94 chemotherapy: If the disease persists at the = time of second=20 look laparotomy or disease progresses clinically during primary = therapy,=20 patient can be switched over to second line therapy. Oral Etoposide therapy , = I.V.=20 infusions with Cisplatin, carboplatin, paclitaxel, ifosfamide or=20 hexamethylmalamine with or without other agents can be used. Response = rate is=20 in the range of 20-30%.=20
Intraperitoneal=20 chemotherapy:-It provides a high, prolonged and direct = concentration=20 of the drug to micro and macroscopic tumour tissue in the peritoneal = cavity.=20 The bioavailability of intraperitoneally administered drugs is around = 10 times=20 higher than the same drugs administered systemically. It acts both by = topical=20 and systemic effect. The various drugs which can be used = intraperitoneally are=20 Cisplatin, 5FU, Carboplatin, Paclitaxil, Adriamycin, Cyclophosphamide, = Mitomycin-C, Mitoxantron, Methotrexate, Gemicitabin. Intraperitoneal=20 instillation can be done preoperatively, intraoperatively, within 48 = hours=20 post surgery or 2-3 weeks after surgery.
The advantages of=20 intraperitoneal chemotherapy are:
1. Complication free = instillations=20
2. Excellent control of ascites and steep fall in CA 125 levels =
3.=20 Much lesser systemic toxicities
4. Prolongation of treatment to = time of=20 disease progression
5. Lower rate of abdominal recurrence =
The=20 disadvantages of intraperitoneal chemotherapy are:
1. Not all = drugs can=20 be instilled intraperitoneally.

= 2. May=20 not create a desired systemic concentration of the drug.
3. Due = to=20 advanced disease or due to post operative adhesions compartmentalization = of=20 peritoneal cavity may occur leading to unsatisfactory dissemination of = drug in=20 whole peritoneal cavity. =20

Role of Radiation = Therapy=20

There is a = reemergence of role of=20 Radiotherapy in recent = times and in=20 the literature and that = can be given in two ways:

1- The Whole = pelvic=20 Radiation therapy: To a Dose of 50 Gy in 25 fractions over 5 = weeks time=20 and

2-Whole = abdominal=20 radiation: Given as a supplement to the chemotherapy or as = salvage=20 treatment . How ever it is associated with very high morbidity rates = especially=20 intestinal obstructions when compared to whole pelvic radiation.

Follow = up

Every 3 months for first two years then every 4 = monthly for 1=20 year followed by six monthly for 2 years. At each visit following is = done:

General = physical and=20 pelvic examination=20
Serum CA = 125 levels=20
USG pelvis=20
CT scan = needs to be=20 individualized

5-year survival rates

Stage I /II =20 80-100%

Stage IIIa =20 30-40%

Stage IIIb =20 20%

Stage IIIc/IV 5%

Follow up and management of recurrent disease

Stage = I, II, III=20 and IV

Complete response=20

Ovarian=20 tumours of low malignant potential (LMP)

This is a subset of epithelial ovarian tumours, = which has a=20 far better prognosis than epithelial ovarian cancer. They occur = predominantly in=20 premenopausal (30-50years) women, remain confined to the ovary for long = periods=20 and have a very good prognosis.

The criteria for the diagnosis of borderline = tumours are=20 mainly histopathological and as follows:

Epithelial=20 proliferation with papillary formation and pseudostratification.=20
Nuclear = atypia and=20 increase mitotic activity=20
Absence of = true=20 stromal invasion (i.e. without tissue destruction)

Treatment=20

When the appearance of an ovarian tumour suggests = that is may=20 be of low malignant potential and this is reinforced by frozen section, = then=20 conservative principles may be followed.

Because of less aggressive nature of LMP tumours, = the staging=20 laparotomy should be modified as follows:

Resect all = visible=20 disease.=20
If=20 the omentum is clinically uninvolved, an omental biopsy rather that = total=20 omentectomy is sufficient.=20
If=20 a mucinous LMP tumour is present, an appendectomy should be performed. =
There is no = benefit in=20 resecting clinically normal lymphnodes.=20
There is no = benefit in=20 removing clinically uninvolved tissue (e.g. uterus, other ovary)=20
There is no = benefit in=20 taking random peritoneal biopsies.

Chemotherapy=20

There is no role for post-operative therapy in the = treatment=20 of patients with advanced stage LMP tumours unless there are invasive = implants=20 or micro invasive disease in the primary tumours or they are positve for P53 EGFR=20 marker.Clinically early borderline ,low risk cases that are P53 EGFR positive are considered high risk and have now turned into high risk poor prognosis cases , the chemotherapy should be = given in these cases .

Chemotherapy can be used in patients with invasive = or micro=20 invasive implants. =

Management of=20 recurrent disease

Secondary cytoreductive surgery appears to be the = only=20 effective treatment for recurrent disease. There is no data available to = support=20 the use of chemotherapy.

Germ cell=20 cancer

Germ cell tumours are derived from the primordial = germ cell=20 of the ovary. In patients under 20 years of age, 70% of ovarian tumours = are of=20 germ cell origin and around 2/3^rd of these are malignant. = Dysgerminoma the most common = germ cell=20 malignancy. Around 10-15% is bilateral. Approximately 5% of = dysgerminomas occur=20 in phenotypic females with abnormal karyotype and gonads.

Clinical features=20

Rapid = abdominal=20 distension due to tumour and ascites=20
Subacute = pelvic pain=20 related to capsular distension, hemorrhage or necrosis=20
Pressure = symptoms=20 related to bladder or rectum=20
Torsion or = rupture of=20 adnexa can lead to acute abdomen

Physical=20 examination

Abdominal = examination=20 may reveal pelvic mass or ascites.=20
Pervaginal=20 examination: Adnexal mass=20
Some = patients may=20 require examination under anaesthesia.

Investigations

Blood investigations

Complete = blood count=20
KFT=20
LFT =

Tumours markers

S.a=20 feto protein=20
S.b=20 human chorionic gonadotropin=20
S. lactate = de=20 hydrogenase

Karyotyping: It should be done in all = prepubertal=20 girls because of the propensity of these tumours to
&n= bsp; =20 arise in dysgenetic gonads.

Chest X-Ray

Abdominal X-Ray

It may reveal calcification due to bone/tooth = formation in=20 dermoid cyst

USG Pelvis and abdomen

CT scan/ MRI

Treatment

Around 2/3^rd of dysgerminomas are stage = I at the=20 time of diagnosis. Because they occur mainly in young females special=20 consideration should be given to preserve fertility whenever = possible.

Surgery

This involves staging laparotomy as in epithelial = ovarian=20 cancers. If there is desire to preserve fertility, unilateral = oopherectomy=20 should be done while preserving the contralateral ovary, fallopian tube = and=20 uterus. For patients not desirous of fertility total abdominal = hysterectomy with=20 bilateral salpingoopheractomy with pelvic and paraaortic Lymphadenectomy = with=20 infracolic omenetectomy should be done.

For premenarcheal = girls whose=20 karyotype reveals Y chromosome both ovaries should be removed. As around = 15% of=20 dysgerminomas are bilateral, bisection of contralateral ovary and = excisional=20 biopsy of any suspicious lesion should be done.

Adjuvant chemotherapy

All patients except for stage I grade I/II tumours = should=20 receive 4-6 cycles of post op chemotherapy comprising of bleomycin, = etoposide=20 and cisplatin. The 5 year survival rate with chemotherapy and surgery is = 85-90%.

Neoadjuvant chemotherapy

In patients with advanced disease and diagnosed by = FNAC=20 staging laparotomy should be preceded by preoperative chemotherapy to = improve=20 operatability.

Radiation therapy

Dysgerminomas are highly radiosensitive tumours. = But=20 radiotherapy leads to loss of fertility so should rarely be used.

Follow up

Abdominal and pelvic examinations, chest X-Ray, AFP = or b=20 hCG (if initially elevated), USG pelvis, CT scan (to be individualized) = every=20 three months for 2 years, every 4 months for 1 year followed by every 6 = months=20 for 2 years.

Recurrent disease

Patients who have not received postoperative = chemotherapy=20 should receive BEP chemotherapy. If prior BEP has been given, POMB-ACE = should be=20 used.

Sex Cord=20 Stromal Tumours

Sex cord stromal tumours of ovary account for about = 5-8% of=20 all ovarian malignancies. They may be derived from female cells that = secrete=20 estrogens (i.e. granulosa and theca cells) and male cells that secrete = androgens=20 (i.e. sertoli and leydig cells).

Granulosa- stromal=20 cell tumours

They are associated with estrogen production and = may cause=20 sexual psuedoprecocity in prepubertal girls, menstrual irregularities in = females=20 in reproductive age group and postmenopausal bleeding in postmenopausal = females.=20 Endometrial carcinoma is associated with 5% of cases and 25-50% is = associated=20 with endometrial hyperplasia.

Treatment

Surgery is the mainstay of treatment and includes a = staging=20 laparotomy with total abdominal hysterectomy and bilateral = salpingoopherectomy.=20 If a conservative surgery is performed in early stage disease and uterus = is left=20 in situ then endometrial curettage should be performed to rule out = associated=20 endometrial carcinoma.

Chemotherapy

There is no evidence that adjuvant chemotherapy = will prevent=20 recurrence of disease. Recurrences can be treated with VAC (vincristine=20 doxorubicin, cyclophosphamide) and PAC (cisplatin, doxorubicin,=20 cyclophosphamide).

Sertoli - leydig=20 cell tumours

They are associated with androgen production and = resultant=20 virilization. Management is same as that of granulosa cell tumours.

Ovarian=20 tumours and pregnancy

Most ovarian tumours occurring during pregnancy are = benign=20 the common types of ovarian masses found in pregnant females are corpus = luteum=20 cyst, dermoid cysts and serous cystadenoma.

Complications

Torsion of = the=20 pedicle of tumours during pregnancy and puerpurium.=20
Retention = of urine=20 due to impaction of tumour in pelvis=20
Obstructed = labour=20
Fetal = malpresentation=20
Rupture of = the cyst=20

Management

1^st Trimester

A benign appearing cyst on USG should be followed = up=20 conservatively, as corpus luteum cysts usually disappear on their own. =

2^nd Trimester

Persisting benign appearing cyst/solid mass can be = removed in=20 2^nd trimester by cystectomy at around 16-18 weeks with out = any harm=20 to fetus. A tumour diagnosed at around 28 weeks of pregnancy should be = removed=20 at the time of caesarian section or in the puerpurium.

Obstructed labour

An ovarian tumour causing obstructed labour should = be managed=20 by caesarean section and removal of tumour.

Complicated tumour

If a tumour has undergone torsion, rupture, = hemorrhage or=20 shows signs of malignancy, it should immediately be dealt with = appropriate=20 surgery.

Stage IA tumours = should be treated=20 by ovariectomy at the time of diagnosis followed by caesarian = hysterectomy,=20 bilateral salpingo-opherectomy and omentectomy at term.

Suggested=20 Readings

Berek JS, = Fu YS,=20 Hacker NF. Ovarian Cancer, In Berek JS, Rinehart RD, Hillard PJA, = Adashi EY=20 (ed.). Novak=92s Gynaecology 13^th edition. Willams & = Wilkins.=20 2002,1245-1320.=20
Hempling = RE, Piver=20 MS. Ovarian Cancer: Etiology, Screening, prophylactic oopherectomy and = surgery. In: Rock JA, James III HW (ed). Telinde=92s operative = Gynaecology=20 9^th edition. Lippincott-Raven. 2003; 1557-1568.=20
National=20 Comprehensive cancer Network. Practice Guidelines in Oncology = version1. 2006.=20
Schwarz PE, = Rutherford TJ, Chamber JT et al. Neoadjuvant chemotherapy for advanced = ovarian=20 cancer: long term survival. Gynaecol oncol 1999;72(1):93-99.=20
Paclitaxel = plus=20 carboplatin versus standard chemotherapy with either single-agent = carboplatin=20 or cyclophosphamide, doxorubicin and cisplatin in women with ovarian = cancer:=20 the ICON3 randomized trial. Lancet 2002;360:505-15.=20
Hacker NF, = Berek JS.=20 Cytoreductive surgery in ovarian cancer. In: Albert PS, Surmit EA, = eds.=20 Ovarian cancer. Boston; Martinus Nijhoff, 1986;53-67.=20
International Collaborative = Ovarian=20 Neoplasm (ICON) Group. Paclitaxel plus carboplatin versus standard=20 chemotherapy with either single- agent carboplatin or = cyclophosphamide,=20 doxorubicin, cisplatin in women with ovarian cancer: the ICON3 = randomised=20 trial. Lancet 2002; 360: 505.

=20