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ovarian cancer
Ovarian cancer is a malignant ovarian neoplasm
(an abnormal growth located on the ovaries).
Causes
Ovarian cancer is the fifth leading cause of cancer death in women,
the leading cause of death from gynecological malignancy, and the
second most commonly diagnosed gynecologic malignancy [1].
It is idiopathic, meaning that the exact cause is usually unknown. The
disease is more common in industrialized nations, with the exception
of Japan. In the United States, females have a 1.4% to 2.5% (1 out of
40-60 women) lifetime chance of developing ovarian cancer.
Older women are at highest risk. More than half of the deaths from
ovarian cancer occur in women between 55 and 74 years of age and
approximately one quarter of ovarian cancer deaths occur in women
between 35 and 54 years of age.
The risk for developing ovarian cancer appears to be affected by
several factors. The more children a woman has, the lower her risk of
ovarian cancer. Early age at first pregnancy, older ages of final
pregnancy and the use of low dose hormonal contraception have also
been shown to have a protective effect. Ovarian cancer is reduced in
women after tubal ligation.
The link to the use of fertility medication, such as Clomiphene
citrate, has been controversial. An analysis in 1991 raised the
possibility that use of drugs may increase the risk for ovarian
cancer. Several cohort studies and case-control studies have been
conducted since then without providing conclusive evidence for such a
link. [2] It will remain a complex topic to study as the infertile
population differs in parity from the "normal" population.
There is good evidence that in some women genetic factors are
important. Carriers of certain mutations of the BRCA1 or the BRCA2
gene, more frequent in some populations (e.g. Ashkenazi Jewish women)
are at a higher risk of both breast cancer and ovarian cancer, often
at an earlier age than the general population. Patients with a
personal history of breast cancer or a family history of breast and/or
ovarian cancer, especially if at a young age, may have an elevated
risk. A strong family history of uterine cancer, colon cancer, or
other gastrointestinal cancers may indicate the presence of a syndrome
known as hereditary non-polyposis colon cancer (HNPCC, also known as
Lynch II syndrome), which confers a higher risk for developing ovarian
cancer. Patients with strong genetic risk for ovarian cancer may
consider the use of prophylactic oophorectomy after completion of
child-bearing.
A Swedish study, which followed more than 61,000 women for 13 years,
has found a significant link between milk consumption and ovarian
cancer. According to the BBC, "[Researchers] found that milk had the
strongest link with ovarian cancer - those women who drank two or more
glasses a day were at double the risk of those who did not consume it
at all, or only in small amounts." [3] Recent studies have shown that
women in sunnier countries have a lower rate of ovarian cancer, which
may have some kind of connection with exposure to Vitamin D. [citation
needed]
Other factors that have been investigated, such as talc use, asbestos
exposure, high dietary fat content, and childhood mumps infection, are
controversial and have not been definitively proven.
"Associations were also found between alcohol consumption and cancers
of the ovary and prostate, but only for 50 g and 100 g a day."[4]
Classification
Ovarian cancer is classified according to the histology of the tumor.
Lesions differ significantly in clinical features, management, and
prognosis (ICD-O codes provided where available):
Surface epithelial-stromal tumours are the most common and prototypic
ovarian cancers. They are thought to originate from the ovarian
surface lining, and include serous cystadenocarcinoma (8441/3), and
mucinous cystadenocarcinoma (8470/3).
Sex cord-stromal tumors include lesions that are hormonally active
such as the estrogen-producing granulosa cell tumor (8620/3) and the
virilizing Sertoli-Leydig cell tumor or arrhenoblastoma.
Germ cell tumors originate from dysplastic germ material and tend to
occur in young women and girls. Lesions include the dysgerminoma
(9060/3), a form of the choriocarcinoma (9100/3), and the malignant
form of the teratoma (9083/3).
Other lesions include metastasis to the ovary, for instance from
breast cancer. Krukenberg cancer is ovarian cancer originating from
gastrointestinal cancer.
Staging
Ovarian cancer staging is by the FIGO staging system and uses
information obtained after surgery, which can include a total
abdominal hysterectomy, removal of (usually) both ovaries and
fallopian tubes, (usually) the omentum, and pelvic (peritoneal)
washings for cytology. The AJCC stage is the same as the FIGO stage.
Stage I - limited to one or both ovaries
IA - involves one ovary; capsule intact; no tumor on ovarian surface;
no malignant cells in ascites or peritoneal washings
IB - involves both ovaries; capsule intact; no tumor on ovarian
surface; negative washings
IC - tumor limited to ovaries with any of the following: capsule
ruptured, tumor on ovarian surface, positive washings
Stage II - pelvic extension or implants
IIA - extension or implants onto uterus or fallopian tube; negative
washings
IIB - extension or implants onto other pelvic structures; negative
washings
IIC - pelvic extension or implants with positive peritoneal washings
Stage III - microscopic peritoneal implants outside of the pelvis; or
limited to the pelvis with extension to the small bowel or omentum
IIIA - microscopic peritoneal metastases beyond pelvis
IIIB - macroscopic peritoneal metastases beyond pelvis less than 2 cm
in size
IIIC - peritoneal metastases beyond pelvis > 2 cm or lymph node
metastases
Stage IV - distant metastases--in the liver, or outside the peritoneal
cavity
Para-aortic lymph node metastases are considered regional lymph nodes
(Stage IIIC).
Treatment
Surgery is the preferred treatment and is frequently necessary for
diagnosis. Studies have shown that surgery performed by a specialist
in gynecologic oncology usually result in an improved outlook.
Improved survival is attributed to more accurate staging of the
disease and a higher rate of aggressive surgical excision of tumor in
the abdomen by gynecologic oncologists as opposed to general
gynecologists and general surgeons.
The type of surgery depends upon how widespread the cancer is when
diagnosed (the cancer stage), as well as the type and grade of cancer.
The surgeon may remove one (unilateral oophorectomy) or both ovaries
(bilateral oophorectomy), the fallopian tubes (salpingectomy), and the
uterus (hysterectomy). For some very early tumors (stage 1, low grade
or low-risk disease), only the involved ovary and fallopian tube will
be removed (called a "unilateral salpingo-oophorectomy," USO),
especially in young females who wish to preserve their fertility. In
advanced disease as much tumor as possible is removed (debulking
surgery). In cases where this type of surgery is successful, the
prognosis is improved compared to patients where large tumour masses
(more than 1 cm in diameter) are left behind.
Chemotherapy is used as after surgery to treat any residual disease.
At present many oncologists are still recommending systemic
chemotherapy including a platinum derivative with a taxane as a
preferred method of treating advanced ovarian cancer. However,
randomized, multicenter clinical trials are beginning to clearly show
that Intra-peritoneal chemotherapy produces longer survival times. As
this therapy may not always be available in local hospitals, women
should consult doctors based in nationally recognized centers as soon
after diagnosis as possible in order to select the most effective
treatment plan. Chemotherapy can also be used to treat women who have
a recurrence.
Three large randomized studies of the Gynecologic Oncology Group have
suggested that chemotherapy regimens delivered partly via direct
infusion into the abdominal cavity (intraperitoneal or "IP") improve
median survival time over regimens that are only given intravenously
(in the vein or "IV"). Reported toxicities are generally higher and
the advantages of IP chemotherapy are still debated among specialists.
Radiation therapy is not effective for advanced stages because a high
dose can not be delivered because vital organs are in the radiation
field.
Pre-clinical chemosensitivity and chemoresistance testing is being
done by laboratories in the USA, Europe, and Asia.
Symptoms
sense of pelvic heaviness
vaginal bleeding
weight gain or weight loss
abnormal menstrual cycles
unexplained back pain that worsens over time
increased abdominal girth
non specific gastrointestinal symptoms:
vague lower abdominal discomfort
increased gas
indigestion
lack of appetite
nausea and vomiting
Bloody stool
inability to ingest usual volumes of food
bloating
Additional symptoms that may be associated with this disease:
increased urinary frequency/urgency
excessive hair growth
Fluid buildup in the lining around the lungs (Pleural effusions)
Positive pregnancy readings (in the absence of pregnancy. This is for
germ cell tumors only)
Note: There may be no symptoms until late in the disease.
Diagnosis
Ovarian cancer at its early stages(I/II) is difficult to diagnose
until it spreads and advances to later stages(III/IV). This is due to
the fact that most of the common symptoms are non-specific.
The blood test called CA-125 is useful in differential diagnosis and
in follow up of the disease, but it has not been shown to be an
effective method to screen for early-stage ovarian cancer and is
currently not recommended for this use.
A study funded by the American Cancer Society conducted at the H. Lee
Moffitt Cancer Center & Research Institute has found a correlation
between high levels of lysophospholipids (a type of fatty acid) with
ovarian cancer patients and low levels of lysophospholipids with
healthy women. This potential biomarker can be detected by a simple
blood test. The blood test was 93% accurate as predictor of ovarian
cancer with less than 4% false positives of the 117 women studied.[5]
Current research is looking at ways to combine tumor markers along
with other indicators of disease (i.e. radiology and/or symptoms) to
improve accuracy. The challenge in such an approach is that the very
low population prevelance of ovarian cancer means that even testing
with very high sensitivity and specificity will still lead to
unacceptable numbers of false positive results. This is exemplified by
the recent discovery of proteomic predictors that showed 100%
sensitivity and 95% specificity. [6]
A pelvic examination, including CT scan, trans-vaginal ultrasound, is
also of utility. Physical examination may reveal increased abdominal
girth and /or ascites (fluid within the abdominal cavity). Pelvic
examination may reveal an ovarian or abdominal mass. The pelvic exam
can include a rectovaginal component for better palpation of the
ovaries.
Expectations (prognosis)
Ovarian cancer has a poor prognosis. It is disproportionately deadly
because symptoms are vague and non-specific. More than 60% of patients
presenting with this disease already have stage III or stage IV
disease, when it has already spread beyond the ovaries.
Ovarian cancers shed malignant cells into the naturally occurring
fluid within the abdominal cavity. These cells then have the potential
to float in this fluid and frequently implant on other abdominal
(peritoneal) structures included the uterus, urinary bladder, bowel,
and lining of the bowel wall (omentum). These cells can begin forming
new tumor growths before cancer is even suspected.
More than 50% of women with ovarian cancer are diagnosed in the
advanced stages of the disease because no cost-effective screening
test for ovarian cancer exists. The five-year survival rate for all
stages is only 35% to 38%. If, however, diagnosis is made early in the
disease, five-year survival rates can reach 90% to 98%.
Germ Cell Ovarian Cancer has a much better prognosis, but is rarer.
Complications
spread of the cancer to other organs
progressive function loss of various organs
ascites (fluid in the abdomen)
blockage of the intestines
Notable women with ovarian cancer
Evelyn Ankers, actress (died at age 67); (see [1])
Raelene Boyle, Australian athlete; surviving
Laurie Beechman, actress/singer (died at age 43)
Marcheline Bertrand, actress and mother of Angelina Jolie (died age
56)
Clare Boylan, Irish writer (died at age 58)
Jill Chaifetz, American lawyer and children's right advocate (died at
age 41)
Elizabeth Connors- teacher and women's rights activist(died at age 43)
Carol Channing, actress/entertainer; surviving
Caitlin Clarke, actress (died at age 52)
Sister Sarah Clarke, County Galway, Ireland-born Roman Catholic nun
and London-based political activist during The Troubles (1980s-1990s);
survived; died of natural causes.
Helen Cresswell, British writer and author (died at age 71)
U.S. Congresswoman Rosa DeLauro, surviving (see [2])
Mildred Dean, mother of American actor James Dean; she died when Dean
was 9 years old (see[3]).
Sandy Dennis, Oscar-winning actress (died at age 54)
Rosalind Franklin, British physical chemist and crystallographer,
linked with the discovery of the shape of the double helix of DNA
(died at age 37)
Diana Dors, actress, also known as Diana d'Ors (died at age 52)
Patricia C. Dunn, embattled former chair of Hewlett-Packard, currently
battling ovarian cancer.
Robert Eads, American female to male transsexual who was refused
medical treatment for the cancer in the state of Georgia (died at age
53)
Jeannie Ferris, Senator for South Australia; surviving
Susan Fleetwood, British actress (died at age 51)
Ella Grasso, former Connecticut governor, and the first woman ever to
be elected governor in her own right (died at age 61)
Cassandra Harris, Australian actress/wife of Pierce Brosnan (died at
age 43)
Dolly Haas, actress/singer; wife of Al Hirschfeld (died at age 84)
Joan Hackett, actress (died at age 49)
Madeline Kahn, actress, singer and comedienne (died at age 57)
Coretta Scott King, wife of civil rights activist Rev. Martin Luther
King, Jr. (died at age 78)
Joyce Kulhawik, film critic and Boston television personality; former
TV co-host of movie critic Leonard Maltin; surviving.
Sarabeth Kusick, wife of baseball player Craig Kusick (who died from
leukemia nine months following his wife's death)
Dixie Lee, actress/singer; converted to marry Bing Crosby (died at age
40)
Janet Margolin, actress (died at age 50)
Mary I of England, née Mary Tudor; British Queen Mary I (died either
of uterine cancer or ovarian cancer at the age of 42)
Heather Menzies, Canadian actress, most famous for portraying Louisa
in The Sound of Music and widow of Robert Urich; surviving
Mary Millar, British actress, most famous as "Rose" from Keeping Up
Appearances (died at age 62)
Helen Simpson Morosini, mother of the late singer/actress/activist
Dana Reeve (died at age 71)
Bess Myerson, former Miss America, surviving
Laura Nyro, singer (died at age 49; her own mother, Gilda Nigro, also
died of ovarian cancer and at the same age as Nyro)
Alice Pearce, actress (died at age 48)
Gilda Radner, actress/comedienne/Saturday Night Live alumna (died at
age 42)
Patsy Ramsey, mother of the late JonBenét Ramsey (died at age 49)
Janet Sandell, South African social activist (died at age 70)
Dinah Shore, actress/singer (died at age 77)
Linda Smith, comedienne, actress; head of the British Humanists'
Association (died at age 48)
Jessica Tandy, actress (died at age 85)
Elizabeth Tilberis, Harper's Bazaar Editor-in-Chief (died at age 51)
Angela Winbush, American rhythm and blues vocalist, surviving
Loretta Young, Oscar-winning actress (died at age 87)
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