Ovarian Cancer

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Original Editors - Trisha Counce & Brandy Hirsch from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Brandy Hirsch, Trisha Counce, Lucinda hampton, Aminat Abolade, Vidya Acharya, WikiSysop, Kim Jackson, Elaine Lonnemann, Wendy Walker, Rishika Babburu and 127.0.0.1  

Definition/Description

The term "ovarian cancer" encompasses several types of cancer that all arise from the cells of the ovaries in the female reproductive system. Ovarian cancer commonly manifests as three different types including epithelial (cells on the surface of the ovary), fallopian tube, and primary periotoneal (lining inside the abdomen). Epithelial ovarian cancer accounts for about 70% of all ovarian cancers, making it the most common type. The four most common subtypes of epithelial ovarian cancer are serous, mucinous, clear cell, and endometrioid, with serous being the most common variety. Ovarian cancer is believed to occur due to changes in cell DNA. Unfortunately, ovarian cancer often goes undiagnosed until advanced stages of the disease when it is hardest to identify the initial source.

                                                          

STAGES 

 Stage I - Growth of the cancer is limited to the ovary or ovaries.

• Stage IA - Growth is limited to one ovary and the tumor is confined to the inside of the ovary. There is no cancer on the outer surface of the ovary. There are no ascites present containing malignant cells. The capsule is intact.
• Stage IB - Growth is limited to both ovaries without any tumor on their outer surfaces. There are no ascites present containing malignant cells. The capsule is intact.
• Stage IC - The tumor is classified as either Stage IA or IB and one or more of the following are present: (1) tumor is present on the outer surface of one or both ovaries; (2) the capsule has ruptured; and (3) there are ascites containing malignant cells or with positive peritoneal washings.

Stage II - Growth of the cancer involves one or both ovaries with pelvic extension.

• Stage IIA - The cancer has extended to and/or involves the uterus or the fallopian tubes, or both.
• Stage IIB - The cancer has extended to other pelvic organs.
• Stage IIC - The tumor is classified as either Stage IIA or IIB and one or more of the following are present: (1) tumor is present on the outer surface of one or both ovaries; (2) the capsule has ruptured; and (3) there are ascites containing malignant cells or with positive peritoneal washings.

Stage III - Growth of the cancer involves one or both ovaries, and one or both of the following are present: (1) the cancer has spread beyond the pelvis to the lining of the abdomen; and (2) the cancer has spread to lymph nodes. The tumor is limited to the true pelvis but with histologically proven malignant extension to the small bowel or omentum.

• Stage IIIA - During the staging operation, the practitioner can see cancer involving one or both of the ovaries, but no cancer is grossly visible in the abdomen and it has not spread to lymph nodes. However, when biopsies are checked under a microscope, very small deposits of cancer are found in the abdominal peritoneal surfaces.
• Stage IIIB - The tumor is in one or both ovaries, and deposits of cancer are present in the abdomen that are large enough for the surgeon to see but not exceeding 2 cm in diameter. The cancer has not spread to the lymph nodes.
• Stage IIIC - The tumor is in one or both ovaries, and one or both of the following is present: (1) the cancer has spread to lymph nodes; and/or (2) the deposits of cancer exceed 2 cm in diameter and are found in the abdomen.
  

Stage IV - This is the most advanced stage of ovarian cancer. Growth of the cancer involves one or both ovaries and distant metastases (spread of the cancer to organs located outside of the peritoneal cavity) have occurred. Finding ovarian cancer cells in pleural fluid (from the cavity which surrounds the lungs) is also evidence of stage IV disease.

Prevalence and Incidence 

Statistics 

• Over 22,000 new cases of ovarian cancer will be diagnosed this year
• Ovarian cancer will cause over 15,000 deaths this year
• In women age 35-74, ovarian cancer is the fifth leading cause of cancer-related deaths
• 1 woman in every 71 will develop ovarian cancer in her lifetime
• The 5-year survival rate is over 90% if treated in the earliest stages, however, only 19% of all cases are found at this stage
• If caught in stage III or higher, the survival rate can be as low as 30.6%
  
• Ovarian cancer is the leading cause of death from gynecological malignancies 
• 2nd most common reproductive cancer in women 

Characteristics/Clinical Presentation

Epithelial ovarian cancer presents with a wide variety of vague and nonspecific symptoms. Ovarian cancer may cause one or more of these signs and symptoms--

•      Bloating, which is when the area below your stomach swells or feels full 
•      Vaginal bleeding or discharge (not normal for individual) 
•      Pain in the pelvic or abdominal area, abdominal distension or discomfort, abdominal mass 
•      Back pain 
•      Feeling full quickly while eating 
•      Painful urinination or frequent urges, constipation, or diarrhea 
•      Indigestion and acid reflux 
•      Shortness of breath (SOB) 
•      Weight Loss
  
•      Persistent lack of energy 

Physical findings are uncommon in patients with early disease, but the more advanced the disease one may present with ovarian or pelvic mass, ascites, pleural effusion, or abdominal mass or bowel obstruction.  Pay attention to your body, and know what is normal for you. If you have vaginal bleedingand/or an abnormal menstral cycle that is not normal for you, see a physician right away. The key is early intervention so the earlier ovarian cancer is found and treated, the more likely treatment will be effective.

Below is a symptom chart differentiating gynecological cancers

Associated Co-morbidities

Breast cancer
     Women who have had breast cancer also have a higher risk of ovarian cancer. The risk is
even higher in women who have had breast cancer and also have a family history of
breast cancer.

Hypertension

Cerebrovascular Disease

Osteoarthritis

Infection

Anemia (article reg prevalence and incidence of comorbidities)

Medications

Common Drugs & Drug Combinations Used in Chemotherapy 

For platinum sensitive patients:

• Carboplatin & Paclitaxel
• Cisplatin & Paclitaxel
• Bevacizumab
• Paclitaxel & Bevacizumab

In patients who are platinum resistant, a single drug is often used including:

Pegylated liposomal doxoruicin, Docetaxel, Paclitaxel, Topotecan, Gemcitabine, Etoposide, or Bevacizumab

Other Drugs Approved for Ovarian Cancer 

Adriamycin PFS
Adriamycin RDF
Carboplatin
Clafen
Cisplatin
Cyclophosphamide
Cytoxan
Doxorubic in Hydrochloride
Dox-SL
DOXIL
Doxorubicin Hydrochloride Liposome
Evacet
Gemcitabine Hydrochloride
Gemzar
Hycamtin
LipoDox
Neosar
Paclitaxel
Paraplat
Paraplatin
Platinol
Platinol-AQ
Taxol
Topotecan Hydrochloride

Diagnostic Tests/Lab Tests/Lab Values

There are currently no reliable screening tools available to diagnose ovarian cancer. Annual pap smears will detect cervical cancer but NOT ovarian varieties. The current recommendations include an annual pelvic exam, transvaginal ultrasound, and CA-125 blood test. These are the best options for screening but even in combination, results have been found to be unreliable.

Screening Tools 

• Pelvic Exam: Women age 18 and above should have a mandatory annual vaginal exam. Women age 35 and above should receive an annual rectovaginal exam (physician inserts fingers in the rectum and vagina simultaneously to feel for abnormal swelling and to detect tenderness).
• Transvaginal Ultrasound: This ultrasound, performed with a small instrument placed in the vagina, is appropriate especially for women at high risk for ovarian cancer or for those with an abnormal pelvic exam.
• CA-125 Test: This blood test determines if the level of CA-125, a protein produced by ovarian cancer cells, has increased in the blood of a woman at high risk for ovarian cancer or with an abnormal pelvic examination. Some non-cancerous diseases of the ovaries also increase the CA-125 levels, and some ovarian cancers may not produce enough CA-125 levels to cause a positive test.

It is also important to have a comprehensive family history taken by a physician who can identify risk factors associated with ovarian cancer since 5-10% of cases have a familial link. If a women is considered to be at high risk for ovarian cancer, the following tool can also be used:

• Genetic testing: This testing identifies mutations in BRCA1 and BRCA2. Mutations in these proteins increased a womans risk of ovarian cancer greatly. About 1.4 percent of women in the general population will develop ovarian cancer sometime during their lives. By contrast, approximately 39 percent of women who inherit a harmful BRCA1 mutation and 11 to 17 percent of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years.

Positive Tests 
If any of these tests are positive, a woman should consult with a gynecologic oncologist who may conduct a CT scan and X-Rays and study the results. However, the only way to more accurately confirm ovarian cancer is with a biopsy, a procedure in which the doctor takes a sample of the tumor and examines it under a microscope.

New research on ovarian cancer screening tests is ongoing and the Natioinal Ovarian Cancer Coalition monitors the latest scientific developments. Updated information can be found here: www.ovarian.org/

Etiology/Causes

Typically cancer begins when healthy cells acquire a genetic mutation that turns normal cells into abnormal cells. Healthy cells grow and multiply at a set rate, eventually dying at a set time. Unlike normal, healthy cells, cancerous cells grow and multiply at an abnomally high rate, and they don't die-off when they should. These abnormal cells come together to form a mass or tumor. Cancer cells invade nearby tissues and can break off from an initial tumor to spread elsewhere in the body which is called metastasizing.  

There is no way to know for sure if you will get ovarian cancer because the causes remain unclear.  Most women get ovarian cancer without being at high risk. However, several factors may increase a woman’s risk for ovarian cancer, including the following:

• Middle-aged (50) or older 
• Close family members (such as your mother, sister, aunt, or grandmother) on either your mother's or your father's side, who have had ovarian cancer 
• Genetic mutation (abnormality) called BRCA1 or BRCA2, or one associated with Lynch syndrome 
• History of breast, uterine, colorectal (colon), or cervical cancer, or melanoma. 
• Eastern European (Ashkenazi) Jewish background 
• Never given birth or have had trouble getting pregnant 
• Diagnosed with endometriosis 
  

Although you may have one or more of the above risk factors, it does not mean you will get ovarian cancer.  Besides the above mentioned risk factors it is important to know certain facts as well:1) All women are at risk for ovarian cancer, 2) although vague, symptoms exist and increase over time, 3) early detection increases survival rate, 4) and a Pap test DOES NOT detect ovarian cancer. Therefore, speaking with your physician about your risk is always in your best interest. 

Systemic Involvement

Ovarian cancer can effect several different systems including the gastrointestinal, urogenital, cardiovascular, pulmonary, and musculoskeletal. Systemic issues that occur with ovarian cancer consist of abdominal bloating, discomfort, pain, distension, indigestion, and acid reflux. Pelvic pain or discomfort, back pain, painful urination, constipation, and/or diarrhea are additional symptoms of ovarian cancer. A sensation of shortness of breath can also occur which can be confused with a cardiopulmonary dysfunction.  In addition, it has been found that patients with ovarian cancer demonstrate an altered lipid metabolism. This finding may lead to an eventual epidemiology. 

Medical Management (current best evidence)

There are three main treatment types for ovarian cancer:

1) Surgery - Surgery to remove the cancerous growth is the most common method of diagnosis and therapy for ovarian cancer. It is best performed by a qualified gynecologic oncologist.
2) Chemotherapy - Chemotherapy is the treatment of cancer using chemicals (medications) that travel through the bloodstream to destroy cancer cells or stop them from growing both in and outside the ovaries. Chemotherapy is used in the majority of cases as a follow-up therapy to surgery.
3) Radiation Therapy - Radiation therapy uses high-energy X-rays to kill cancer cells and shrink tumors (only rarely used in the treatment of ovarian cancer in the United States).

Physical Therapy Management (current best evidence)

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Alternative/Holistic Management (current best evidence)

Complementary Therapies 

Complementary therapies are diverse practices and products that are used in conjunction with conventional medicine. This should not be confused with alternative medicine which refers to alternative treatment method used in place of a standard treatment.

• Acupuncture - An ancient Chinese method of healing in which small sterilized needles are inserted into the body's energy centers to promote healing.
• Aromatherapy - The use of essential oils from flowers, herbs and trees to promote health and well being.
• Herbal Medicine- Use of remedies using plant parts to treat symptoms and illnesses. (Consult your healthcare professional prior to using herbal medicine).
• Massage - Manipulating the body's muscle and connective tissue through rubbing, kneading and patting to promote relaxation and well being.
• Meditation - Conscious relaxation and focused breathing to relax the mind and body.
• Qi Gong (chee-GUNG) - A type of Chinese medicine that combines movement, meditation and breathing to enhance the flow of qi (an ancient term given to what is believed to be vital energy) in the body, improve blood circulation and enhance immune function.
• Stress Reduction - Use of stress reduction methods such as exercise, meditation, etc. which have been found to be beneficial in reducing cancer progression and recurrence.
• Yoga, Tai Chi - Postures, movements and breathing exercises to strengthen and heal the body, mind and spirit.

Before beginning any complementary therapy, it is important to discuss the approach with your healthcare team and complementary therapy practitioner. More information about complementary and alternative treatments can be found in the Ovarian Cancer Guide to Quality of Life Issues and can be ordered by calling 1-888-OVARIAN (1-888-682-7426)/

Differential Diagnosis

Extraovarian Primary Peritoneal Carcinoma (EOPPC) and adnexal masses (ovarian cysts) present a diagnostic dilemma; the differential diagnosis is extensive, with most masses representing benign processes.  EOPPC is an abdominal cancer without ovarian involvement. It mimics the signs and symptoms of ovarian cancer as well as the microscopic appearance and pattern of spread. Ovarian cysts are difficult to differentiate without histopathologic tissue diagnosis, a definitive diagnosis is generally precluded. Physicians must evaluate the likelihood of a pathologic process using clinical and radiologic information and balance the risk of surgical intervention for a benign versus malignant process. 

Ovarian carcinoma will sometimes present first with a paraneoplastic syndrome such as polyarthritis syndrome, carpal tunnel, myopathy, plantar fasciitis, or palmar fasciitis (swelling, digital stiffness or contractures, palmar erythema). The condition may be misdiagnosed as chronic regional pain syndrome (CRPS), Dupuytren’s contracture, or a rheumatologic disorder. Hand and upper extremity manifestations often appear before the tumor is clinically evident.  

Additional Differential Diagnosis: 

Malignant gastric tumors
Anovulation
Appendiceal tumors
Appendicitis, Acute
Ascites
Benign lesions of the uterine corpus
Bladder distention/urinary retention
Borderline Ovarian Cancer
Cervicitis
Colon cancer
Embryologic remnants
Endometriosis
Gastric Cancer
Irritable Bowel Syndrome
Low-lying cecum
Metastatic gastrointestinal carcinoma
Ovarian torsion
Pancreatic Cancer
Pelvic abscess
Pelvic Inflammatory Disease
Pelvic kidney
Peritoneal Cancer
Peritoneal cyst
Rectal Cancer
Retroperitoneal mass
Urachal cyst
Urinary Tract Obstruction
Uterine Cancer
Uterine fibroids

Case Reports/ Case Studies

Physical Activity and Ovarian Cancer

 Early Symptoms of Ovarian Cancer In Young Patients

Recreational Activity and Ovarian Cancer

Fertility Drugs and Ovarian Cancer

Resources

Stages of Ovarian Cancer Video

www.ovariancancer.orgNational Ovarian Cancer Coalition Clinical Trials

[1][2]

Womens Health Website--Ovarian Cancer Fact Sheet

Social Media Support Group Healthheo 

Ovarian Cancer National Alliance 

Gilda Radner Familial Ovarian Cancer Registry

WebMd Website--Ovarian Cancer

Daily Rx Website--Ovarian Cancer

Internet MD 1

Internet MD 2

Recent Related Research (from Pubmed)

see tutorial on Adding PubMed Feed

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References

see adding references tutorial.