Ovarian Cancer


Ovarian Cancer

Ovarian cancer is cancerous growth that begins from the ovaries. Ovarian cancer often presents in late stages as it usually lack specific symptoms. As the patient usually presents at a very advance stage, the survival rate is poor.
Ovarian cancer is one of the top 10 cancers affecting women. The estimated lifetime risk is 1 case in 70 women. Epithelial ovarian cancers occur most commonly among whites in industrialized areas of North America, Northern and Western Europe and least frequently in Asia and India.

Types of ovarian cancer

Cancers of the ovaries are mainly primary tumors which started off at the ovaries. It can also be secondary tumors as a spread of cancer from other organs such as breast, colon, stomach, uterus and cervix.
The types of primary ovarian tumors include:
1.    Epithelial Ovarian Carcinoma: It forms 90% of primary ovarian cancers. These cancer starts off at the surface layers that cover the outside of the ovary.
2.    Germ Cell Tumor: This forms 2% of primary ovarian cancers. It usually affects younger women. The cancer cells originate from cells that make the eggs.
3.    Sex-cord Stromal Tumor: This accounts for 6% of primary ovarian cancers. These cancer cells start off from the ovarian tissue that produces hormones like progesterone, estrogen and testosterone.

The types of ovarian tumor will determine the prognosis and the treatment.
Primary Ovarian Cancers usually spread directly to the nearby organs in the peritoneal. It commonly will spread upwards to the peritoneal surfaces of the diaphragm, bowel, liver and omentum. It can also spread to the nearby bladder, uterus and the paracolic gutters. Spreading through the lymphatic system involving the lymph nodes and through blood to further organs e.g. liver is usually the later stages of the disease.

What causes Ovarian Cancer?

The exact cause of ovarian cancer is still unknown. However, there are several risk and contributing factors that render a woman more susceptible to it as compared with the rest.



Risk Factors of Ovarian Cancer

1.    Age: Risk increases with age. Most patients with ovarian cancers happen at age 50 years and older (post-menopausal)
2.    Nulliparity: Women who never had children. Women who have been pregnant are 50% less likely to develop ovarian cancer.
3.    Continuous ovulation: Menses start at a younger age and late menopause. During each ovulation, the egg needs to break out from the surface of the ovary. After which the ovary needs to repair. Each time during ovulation, there is an increase chance of abnormal cell repair which may lead to cancerous changes in cells.
4.    Ovulation Induction Agents: increase the risk due to over-stimulation of the ovaries increasing ovulation.
5.    Hormone Replacement Therapy: increases risk of ovarian cancers.
6.    Family and personal history of cancers: If there is a family or personal predisposition of cancers of the breast, uterus and colon the risk is increased.
7.    Inherited Genetic mutation: Families of BRACA1/BRCA2 gene mutations have increased risk of breast and ovarian cancer. Patients with family history of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) have increased risk of colorectal, ovary, uterus and stomach cancers.

Combined Oral Contraceptives, pregnancy, later age onset of menses and early menopause are protective factor against ovarian cancer. 


Symptoms of Ovarian Cancer

Symptoms of ovarian cancer are non-specific and very vague. The symptoms often resemble many common benign conditions that are not cancerous. Hence by the time the cancer is diagnosed, it is already in the late stage.


The more frequent symptoms ovarian cancer patients may have are:



1.    Increase in abdomen size, a mass in the lower abdomen or just bloatedness sensation
2.    Persistent pelvic and lower abdomen pain
3.    Persistent poor appetite with early satiety and nausea

The other non-specific symptoms that may occur include:

1.    Constipation
2.    Changes in urine habits: urgency and increase frequency
3.    Lethargy and fatigue
4.    Lower back pain that worsens
5.    Abnormal menstrual bleeding
6.    Weight gain (due to the enlarged ovary mass) or weight loss in the late stages of cancer
7.    Shortness of breath

Clinical findings of Ovarian Cancer patients

In the early stages, there may not be any physical signs. In the later stages, an abdomen mass and ascites (collection of fluid in the abdomen) may be present. Pelvic examination may reveal and enlarged ovary. The lymph nodes should also be palpated if present; it means that the cancer has spread to the lymphatic system.

Examination of the lungs may reveal pleural effusion (malignant collection of fluids in the lungs) in the late stages. Examination of the breasts is important especially for patients with BRCA1/BRCA2 and HNPCC as breast and ovarian cancers are associated with such genetic disorders. Examination of the rectum to make sure it is not involved as ovarian cancers in advance stage will spread to surrounding organs like the rectum and bladder. 
Investigations in Ovarian Cancer


1.    Blood test :

-         CA125: It is a protein found on the surface of ovarian cancer cells, other cancer cells as well as other healthy tissues. Hence it is not a specific marker for ovarian cancer and not widely used as a screening tool. It can be raised in non-cancerous conditions like endometriosis, pelvic inflammation, menstruation, pregnancy, liver, kidney and lung diseases. It can also be raised in other cancers such as liver, stomach, lung, pancreas, uterus, breast and colon.

-         Tumor markers: B-Hcg, alpha-fetoprotein and lactate dehydrogenase can be measured if suspected of germ cell tumors.

-         Karyotyping of chromosomes: In pre-pubertal patients before onset of menses who are suspected to have ovarian cancer, should undergo karyotyping of the sex chromosomes.

2.    Imaging:
-         Ultrasound: it is a non-invasive initial assessment of the pelvic mass. High frequency sound waves are used to image the ovaries and the surroundings.
-         Chest X-ray: to look for cancerous spread to the lungs
-         CT scan: It is used for staging of the ovarian cancer and to look for distant spread to other organs.
-         MRI scan: MRI is able to characterize the tissue of the ovaries allowing physicians to determine if it is benign or malignant. It is also used in staging of the disease to look for distant spread of the cancer to other organs.

3.    Aspiration of ascites fluid: ascites is the build-up of fluid in the abdomen, often in ovarian cancer it is a late presentation. The fluid can be aspirated and sent for cytology to look for cancer cells.

4.    Laparotomy: If clinical suggestion of ovarian cancer, the surgeon may proceed with an abdomen operation for confirmation of the disease as well as staging of the disease. The ovarian tissue and ascetic fluid is then sent to the pathologist to confirm presence of cancer cells. Fine needle transcutaneous biopsy is not recommended as it will only delay diagnosis and treatment.
  
5.    Upper gastrointestinal workup: For patient with gastrointestinal symptoms and diffuse carcinomatosis (condition whereby the cancer has disseminates throughout the body), upper gastrointestinal workup is necessary. The investigations a barium enema, upper and/or lower endoscopy and upper gastrointestinal series. 



Staging of Ovarian Cancer


Staging of ovarian cancer usually involves imaging findings and laparotomy surgery findings to establish the size of the cancer and how far it has spread. The staging system used is FIGO (International Federation of Gynecology & Obstetrics). The stages determine the prognosis and survival outcomes of the patients.



Stage 1: Cancer confined to one or two ovaries

1A- confined to 1 ovary, capsule of ovary intact with no ascites
1B- confined to both ovaries, capsule of ovary intact with no ascites
1C- confined to1 or both ovaries with ascites or positive peritoneal washings for cancer cells

Stage 2: Cancer involving 1 or both ovaries has spread to the pelvis (such as uterus, fallopian tubes)

2A- cancer has spread to the uterus and/or the fallopian tubes
2B- cancer has spread to other pelvic tissues
2C- stage 2a or 2b plus ascites with positive peritoneal washings for cancer

Stage 3: cancer involving 1 or both ovaries has spread to the peritoneum (lining of the abdomen) outside the pelvis OR the cancer limited to the pelvis has extended to the small bowels or omentum or lymph nodes

Stage 4: cancer has spread to distant organs outside the abdomen such as liver or lungs or bones. 


Grading of the cancer

Low grade: Cells look abnormal but are usually slow growing

Moderate grade: Cells look more abnormal than the low grade cells

High Grade:  Cells look very abnormal and are usually fast growing 


Treatment of ovarian cancer



Surgery is still the treatment of choice. For those medically unfit for operation they may be given chemotherapy first and surgery later. Surgery is used for confirmation of the diagnosis, determine the extent of the disease, stage the disease and resect all visible tumor. Chemotherapy and radiotherapy may be an adjuvant add on therapy depends on the stage of the disease.

Surgery

Surgery staging laparotomy involves total abdominal hysterectomy, bilateral salpingo-oophorectomy, lymph nodes sampling for cancer plus omentectomy (removal of the uterus, both ovaries, lymph nodes and the omentum), peritoneal washings and as much debulking as possible. When more of the tumor can be removed, the better the outcome.

In cases when the patient present in advance stages of the cancer and the cancer is too advanced for surgery, neo-adjuvant chemotherapy (pre-operation) chemotherapy can be given to shrink the cancer before surgery.
If fertility is an issue, consult a gynecologist to discuss further on the appropriate treatment.


Chemotherapy

Very small percentage of patient does not require follow up post-surgery chemotherapy to ensure eradication of remaining disease. Patients with low grades Stage 1A & 1B can be treated with chemotherapy alone but however follow up regular pelvic examinations, ultrasound examination, CA125 and follow ups are necessary. If any of the tests reveal persistence of disease or progression of disease, surgery is the mainstay of treatment.

High grade Stage 1A, 1B, 1C and anything above Stage 2 ovarian cancer needs adjuvant chemotherapy post operation. This involves 6cycles of injections given every 3 weeks. Common chemotherapy agents used are Cisplatin, carboplatin and paclitaxel. Besides injectable forms of chemotherapy, chemotherapy can also be instilled into the peritoneal to target cancer cells in the abdomen and pelvis. This has less adverse systemic effects.

Neo-adjuvant chemotherapy given pre-operation is used to shrink advanced tumors that are initially inoperable or if the patient is medically unfit for surgery. If the patient responds well to chemotherapy, debulking surgery to remove the tumor is then conducted.

In cases whereby, there is recurrence of ovarian cancer, a second line of chemotherapy is induced.


Radiotherapy

Radiotherapy is rarely used in the treatment of ovarian cancer.

Prognosis of Ovarian Cancer

The estimated 5 years survival rates for epithelial ovarian cancer are based on the FIGO staging system:

Stage 1A: 87%
Stage 1B: 71%
Stage 1C: 79%
Stage 2A: 67%
Stage 2B: 55%
Stage 2C: 57%
Stage 3: 23-41%
Stage 4: 11%

Follow up

After surgery and chemotherapy, follow up with your gynecologists is important. Initially it is at 2-3 monthly intervals for the first 2 years then 4-6 monthly for next 3 years then annually.

During each visit, a comprehensive history on any suggestive symptoms and well-being of patient is taken. A pelvic examination is also conducted to look out for any masses or signs of recurrence. Tumor marker CA125 if raised is highly suspicious of recurrence. If there is any suggestion of recurrence imaging via CT or MRI of the abdomen and pelvis is warranted.

Prevention and screening for Ovarian Cancer

Protective factors against ovarian cancer include pregnancy, breast feeding, combined oral contraceptives and also surgical removal of the ovaries.
Screening for ovarian cancer in the general average risk population who has no symptoms is not recommended as it may lead to unnecessary interventions that may bring more harm than benefits.

However, for patients with high risk of ovarian cancer like those with BRCA1/BRCA2 and HNPCC gene mutations, surveillance for ovarian cancer is highly recommended. At the specialist centre: Annual pelvic examination, transvaginal ultrasound with or without Ca125 serum testing is carried out.  

American College of Obstetrics and Gynecologists recommend prophylactic removal of the fallopian tubes and ovaries for BRCA1/BRCA2 patients before any development of ovarian cancer. Usually this surgery is conducted after 40 years old and when the patient has completed a family. Prophylactic surgery reduces the risk of such patients developing cancer by 90%.

References

1.      Li J, Abushahin N, Pang S, et al. Tubal origin of 'ovarian' low-grade serous carcinoma. Mod Pathol. Nov 2011; 24(11):1488-99. [Medline].
2.      Hippisley-Cox J, Coupland C. Identifying women with suspected ovarian cancer in primary care: derivation and validation of algorithm. BMJ. Jan 4 2011;344:d8009. [Medline]. [Full Text].
3.      Integrated genomic analyses of ovarian carcinoma. Nature. Jun 29 2011; 474(7353):609-15. [Medline].
4.      Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. Comprehensive molecular portraits of human breast tumors. Nature. Sep 23 2012;[Medline].
6.      www.mayoclinic.com

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Ovary Diseases

The female reproductive system consists of the ovaries, fallopian tubes, uterus, cervix and the vagina.

Ovaries produce eggs and female hormones (estrogen and progesterone). These are important in the regulation of menstrual cycles, pregnancy as well as feminine characteristics such as breasts. Each ovary is about the size of an almond.

From menarche to menopause, the ovaries will release eggs and the female hormones. When menopausal the ovaries will stop releasing the eggs and make lower levels of the female hormones resulting in post-menopausal symptoms.

Ovarian diseases involved any disorders with the ovaries. It includes Ovarian Cancer, Ovarian Cyst, Polycystic Ovary Syndrome, Premature Ovarian Failure and also Ovarian Torsion. We will discuss each condition in details in this blog.