ovarian cancer

OVARIAN CARCINOMA

Student-learning Objectives:
At the end of this lecture the student should be able to know:
Epidemiology and etiology of ovarian cancer.
Familial ovarian cancer.
Classification of ovarian malignancy.
Stages and metastatic spread of epithelial ovarian cancer.
The management of ovarian neoplasms.
The prognosis and survival of ovarian cancer.
Classification, clinical features, treatment of non-epithelial tumors.

Malignant ovarian tumours

Dr.fatin shallal

Epidemiology and Risk Factors

It is more common in the wealthy nations of the world.
While the incidence is similar to that of endometrium &of cervix, more women die from ovarian cancer than from carcinoma of the cervix &body of the uterus combined because most of it discovered late.
Most of ovarian tumors are of epithelial origin.
Rare before 35years&incidence increase with age to a peak in the 50-70years old age group.
Only 3% of ovarian cancers are seen in women younger than 35years &most of these are non epithelial cancer such as germ cell tumours.
Numerous reproductive, environmental, and genetic risk factors have been associated with the development of ovarian cancer. For about 90 to 95 percent, no identifiable genetic link for their ovarian cancer, most risk factors are related to a pattern of uninterrupted ovulatory cycles during the reproductive years. Repeated stimulation of the ovarian surface epithelium is hypothesized to lead to malignant transformation. Approximately 5 to 10 percent of patients have an inherited genetic predisposition.


Table : Risk Factors for Developing Epithelial Ovarian Cancer

Nulliparity

Early menarche

Late menopause

White race

Increasing age

Residence in North America and northern Europe

Family history


Nulliparity is associated with long periods of repetitive ovulation, and women without children have double the risk of developing ovarian cancer . Those with a history of infertility have an even higher risk. Although the reasons are unclear, it is more likely to be an inherent ovarian predisposition than an iatrogenic effect of ovulation-inducing drugs. For example, women treated for infertility who achieve a live birth do not have an increased risk of ovarian cancer . In general, risks decrease with each live birth, eventually plateauing in women delivering five times. One interesting theory to explain this protective effect is that pregnancy may induce shedding of premalignant ovarian cells.

Early menarche and late menopause also have been associated with an increased risk of ovarian cancer. In contrast, breast feeding has a protective effect, perhaps by prolonging amenorrhea. Presumably by also preventing ovulation, long-term combination oral contraceptive use reduces the risk of ovarian cancer by 50 percent. The duration of protection lasts up to 25 years after the last use. In contrast, estrogen-replacement therapy after the menopause has an elevated risk.


White women have the highest incidence of ovarian cancer among all racial and ethnic groups. Compared with that of black and Hispanic women, the risk is elevated by 30 to 40 percent. Although exact reasons are unknown, racial discrepancies in parity and rates of gynecologic surgery may account for some of the differences. Other Factors increased risk of ovarian cancer:Endometeriosis Cigarette smoking(mucinos tumours only),Obesity.

Tubal ligation and hysterectomy each have been associated with a substantial reduction in the risk of developing ovarian cancer. It has been postulated that any type of gynecologic procedure that precludes irritants from reaching the ovaries via ascension from the lower genital tract plausibly might exert a similar protective effect. For example, women who regularly use perineal talc have an elevated risk .

The overall incidence of ovarian cancer rises with increasing age up to the mid-70s before declining slightly among women beyond 80 years . In general, aging allows an extended time to accumulate random genetic alterations within the ovarian surface epithelium.

Familial ovarian cancer

Forms 5-10% of women with ovarian cancer.
Might associate with epithelial ovarian cancer (usually serous adenocarcinoma).
Suggestive history At least 2 first degree relatives with ovarian, breast or colorectal carcinoma.
Cases usually diagnosed before 50 years of ages.
Defective genes include BRCA1 (81%) &BRCA2 (14%).
The risk of ovarian cancer (40%) in these families is less than the risk of breast cancer (80%).
Genetic testing cannot guarantee to detect all defective genes.
Annual ovarian u/s with color-flow Doppler studies & serum CA 125 estimation every 6-12 months are recommended.
Radical surgery is recommended in high risk once complete her family.

classification of ovarian malignancy:

According to the site of origin:

Primary ovarian tumours: can originate from the epithelium, the connective tissue of the ovary(sex cord stromal), or the germ cells.
Secondary ovarian tumours: include metastatic tumours form other site including krukenberg tumours, common sites include colon, stomach, breast.


Simplified histological classification of ovarian malignancy:
1.epithelial
Serous carcinoma.
Mucinous carcinoma.
Endometrioid carcinoma.
Clear cell carcinoma(mesonephroid)
2. Sex cord stromal tumours
Granulose cell tumours
Androblastoma:Sertoli Leyding cell tumours
Gynandroblastoma.
Germ cell tumours
Dysgerminoma
Endodermal sinus tumours
Choriocarcinoma
Teratoma
Mixed tumours
Metastatic tumours

stages of Ovarian Cancer

Stage I: This is the earliest form of ovarian cancer. Cancer is found in one or both  HYPERLINK "http://cancer.about.com/od/cancerglossary/g/ovarydefinition.htm" ovaries. Stage I ovarian cancer is divided into three stages.
Stage IA: Cancer is present in one ovary.
Stage IB: Cancer is present in both ovaries.
Stage IC: Cancer is present in one or both ovaries and cancer is found on the outside surface of one or both ovaries, or the outer covering of the tumor has ruptured, or cancer cells are found in the fluid or tissue linings of the abdomen.
Stage II:In stage II ovarian cancer, cancer is present in one or both ovaries, and has spread to other parts of the pelvic region. There are three stages in stage II ovarian cancer.
Stage IIA: Cancer has spread to the uterus and/or fallopian tubes.
Stage IIB: Cancer is in one or both ovaries and has spread to other organs in the pelvic region such as the bladder, rectum, or sigmoid colon.
Stage IIC: Cancer is found in one or both ovaries and has spread to the uterus, fallopian tubes, bladder, sigmoid colon, or rectum. Cancer may also be present is tissue and fluid samples of the lining of the abdominal cavity.

Stage III: In stage III ovarian cancer, cancer is found in one or both ovaries and has spread to the abdomen. Stage III ovarian cancer is divided into three different stages.
Stage IIIA: Cancer is found in one or both ovaries and has spread to a small part of the abdomen.
Satge IIIB: Cancer is present in one both ovaries and has spread to the peritoneum in an amount less than 2 centimeters. The peritoneum is the lining of the abdominal cavity.
Stage IIIC: Cancer is found in one or both ovaries, and has spread to the pertinoneum more than 2 centimeters and/or has spread to the lymph nodes.
Stage IV: Stage IV ovarian cancer is the most advanced stage of the disease. In this stage, cancer is found in one or both ovaries and has spread to parts of the body beyond the abdomen, like the lungs and liver.


Metastatic spread
2/3 of patient with ovarian cancer present with disease that has spread beyond the pelvis.
1.direct spread
2.peritoneal fluid (large&small bowel,parietal peritoneal surface,liver)
3.lymphatic spread(pelvic¶-aortic lymphnodes,cervical nodes)
4.haematogenous spread :usually occurs late(liver,lung,bone,brain).
Management :

Clinical features:

Ovarian Cancer Symptoms:
Ovarian cancer is difficult to detect in its earlier stages. Symptoms are often associated with the location of the tumor and its impact on the surrounding organs. They tend to be non-specific and can mimic other conditions.
Most common symptoms:
Bloating, abdominal pressure and/or discomfort
Lower abdominal and/or pelvic pain
Frequent and/or urgent urination (in absence of an infection)
Feeling full quickly and/or difficulty eating
Additional possible symptoms:
Vague, but persistent gastrointestinal upsets (gas, nausea, indigestion)
Change in bowel habits (constipation, diarrhea)
Abnormal bleeding, pain during intercourse
Unusual fatigue, shortness of breath
Unexpected weight loss or gain


On examination:Proper pelvic and abdominal examination may reveal a fixed hard mass arising from the pelvis in combination with the presence of ascites , a diagnosis of ov. CA is highly likely.
investigations of patient with epithelial ovarian tumour:
Ultrasound is the most useful non invasive test of a suspected malignancy. US characterizes the morphology of the cyst,presence of bilateral tumours,ascites and omemtal deposit. To differentiate benign tumors and early-stage ovarian cancers, transvaginal sonography is typically the most useful imaging test. In general, malignant tumors are multiloculated, solid or echogenic, large (>5 cm), and have thick septa with areas of nodularity. Other features may include papillary projections or neovascularizationdemonstrated by Doppler flow. In patients with advanced disease, sonography is less helpful. The pelvic sonogram may be particularly difficult to interpret when a large mass encompasses the uterus, adnexa, and surrounding structures. Ascites, if present, is easily detected, but abdominal sonography has limited use.
blood test(CBC,LFT,RFT)
CXR is important to assess pleural fluid and groin should be examined for enlarged nodes.
Sometimes:barium enema,colonoscopy,IVP CT scan of the abdomine and MRI if bowel symptoms are present or there is a possibility of a primary colorectal tumour.
Ideally women with a strong family history should be referred to clinical genetics for assessment of the family tree. If the pedigree suggests a hereditary cancer genetic testing for BRCA1 and BRCA2 may be offered. At present screening is offererd to women aged 35 and over. This is usually yearly TVU and CA125 however this strategy is not very sensitive or specific. Prospective studies are being carried out looking at 4-6 mn measurement of CA125.

CA125 is the most common and is elevated in over 80% of EOC.CA125 blood test is used to measure the level of cancer antigen 125, a substance in the blood that can increase when ovarian cancer is present. However, because the CA125 level can be elevated by other conditions,and is not always increased in ovarian cancer patients, it is not an effective screening tool. Most doctors use the CA125 after the diagnosis of ovarian cancer has been surgically confirmed, as it can be an indicator of persistent or recurrent disease.
Paracenthesis and pleural fluid aspiration may be required.

Treatment:

This depends on the women age, reproductive plans and individual risk.
Surgery:
Provided the patient is fit for anesthesia ,surgery remain necessary for diagnosis , staging and treatment of epithelial ovarian cancer. malignant tumors are multiloculated, solid, large (>5 cm), and bilateral. Other features may include papillary projections, nodurlaity, omental deposite and presence of ascitis. radical surgery is total abdominal hystrectomy & SALPANGIOOOPHRECTOMY + INFRACOLIC OMENTECTOMY.
Fertility sparing surgery may also be performed in young patients with early stage epithelial ovarian cancer. In these cases unilateral salpingooopherectomy, omentactomy, peritoneal biopsies and pelvic /paraaortic node dissection can be performed with endomaterial sampling to exclude tumour.
Second look surgery is a planned laparotomy at the end of chemotherapy. The main function is to assess and resect any residual disease.

Chemotheropy can be given as primary treatment ,as an adjunct following surgery or for relapse of disease. It can be used to prolong clinical remission and survival or for palliation.
Carboplatin or cisplatin are platinum compounds are the most effective chemotherapeutic agent in ovarian cancer.Carboplatin is less renal toxic and causes less nausea and vomiting than platinum so it is most commonly used. The dose is calculated according to glomerular filtration rate (GFR).


Paclitaxel works by causing microtubar damage to the cell. This prevents replication and cell division. Pre-emptive steroid are given due to high sensitivty reaction. Side effects of peripheral neuropathy, neutopenia and myalgia are common and dose dependant. It also causes loss of total body hair irrespective of dose. After chemotherapy ,the patient may have a further CT scan to assess the response. The follow up of patient is usually by clinical examination and CA125 level assessment.
Prophylactic bilateral salpingooopherectomy has a role in patients who are fund to be carrying a gene mutation and have complete their family.
Prognostic factors in OV. CA:
- Stage of disease.
-Volume of residual disease post surgery.
-histological type and grade of tumour.
- Age at presentation.

5 years survival for stage 1 is 70-90%.

5 years survival for stage 11is 80%.
5 years survival for stage 111 is 30%.
And for 1V is 10-20%.

Non epithelail tumours:

Constitute about 10% of all ovarian tumours.
Sex cord stromal tumour:
1-Granulose and theca cell tumours:
Which is the most common sex cord tumour. They produce steroid hormones in particular oestrogen which can cause postmenapausal bleeding in older women and sexual precocity in prepubertal girl.
The surgical treatment is the same as for epithelail tumours. Unilateral oopherectomy is indicated in young women with stage 1a disease.
2-sertoli leydig cell tumours:
Half of these rare neoplasia produce male hormones which can cause virilization. The treatment the same of granulose cell tumours.


Germ cell tumours:
1-dysgerminoma:
Account for 2-5% of all primary malignant OV. Tumours. All occur in young women less than 30 years old. They spread mainly by lymphatic. All cases need CXR and CT . serum AFP and BHCG must be assayed to exclude the presence of choriocarcinoma ,endodermal sinus tumour or teratoma.
2-yolk sac tumors:
Also called endodermal sinus tumours making up 10-15% over all and reaching higher proportion in children. It may present as acute abdomine due to rupture of tumour following necrosis or hge. Often secrete AFP.
3-teratoma:
Mature teratoma are benign ,the most common being the cystic teratoma or dermoid cyst found at all ages but particularly in the third and fourth decades.
The treatment of all germ cell tumours mainly conservative surgery because the patients are usually young.
Combination chemotherapy is highly effective when required.