Ovarian cancer warning signs include ongoing pain or cramps in the belly or back, abnormal vaginal bleeding, nausea, and bloating. Depending on the cancer stage, ovarian cancer treatment includes surgery and chemotherapy.
Ovarian cancer
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Micrograph of a mucinous ovarian carcinoma stained by H&E.
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Ovarian cancer is a cancer that forms in an ovary. It results in abnormal cells that have the ability to invade or spread to other parts of the body When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, pelvic pain, abdominal swelling, and loss of appetite, among others.[3] Common areas to which the cancer may spread include the lining of the abdomen, lining of the bowel and bladder, lymph nodes, lungs, and liver.
The risk of ovarian cancer increases in women who have ovulated more over their lifetime. This includes those who havenever had children, those who begin ovulation at a younger age or reach menopause at an older age Other risk factors include hormone therapy after menopause, fertility medication, and obesity.actors that decrease risk include hormonal birth control, tubal ligation, and breast feeding.About 10% of cases are related to inherited genetic risk; women with mutations in the genes BRCA1 or BRCA2 have about a 50% chance of developing the disease. The most common type of ovarian cancer, comprising more than 95% of cases, is ovarian carcinoma. There are five main subtypes of ovarian carcinoma, of which high-grade serous carcinoma is the most common. These tumors are believed to start in the cells covering the ovaries, though some may form at the Fallopian tubes. Less common types of ovarian cancer include germ cell tumors and sex cord stromal tumors.A diagnosis of ovarian cancer is confirmed through a biopsy of tissue, usually removed during surgery.
Screening is not recommended in women who are at average risk, as evidence does not support a reduction in death and the high rate of false positive tests may lead to unneeded surgery, which is accompanied by its own risks.Those at very high risk may have their ovaries removed as a preventive measure. If caught and treated in an early stage, ovarian cancer may be curable. Treatment usually includes some combination of surgery, radiation therapy, and chemotherapy. Outcomes depend on the extent of the disease and the subtype of the cancer present.[7] The overall five-year survival rate in the United States is 45%.Outcomes are worse in the developing world.
In 2012, ovarian cancer occurred in 239,000 women and resulted in 152,000 deaths worldwide. This makes it, among women, the seventh-most common cancer and the eighth-most common cause of death from cancer. The typical age of diagnosis is 63. Death from ovarian cancer is more common in North America and Europe than in Africa and Asia.
Signs and symptoms
Signs and symptoms of ovarian cancer are frequently absent in early stages; even when they do exist, they may be subtle. In most cases, symptoms exist for several months before being recognized and diagnosed, or they may initially be misdiagnosed as a condition such as irritable bowel syndrome. The early stages of ovarian cancer tend to be painless unless the growing mass causes ovarian torsion. Early symptoms can include bloating, abdominopelvic pain, and pain in the side. The most typical symptoms of ovarian cancer include bloating, abdominal or pelvic pain or discomfort, back pain, irregular menstruation or postmenopausal vaginal bleeding, pain or bleeding after or duringsexual intercourse, difficulty eating, loss of appetite, fatigue, diarrhea, indigestion, heartburn, constipation, nausea, early satiety, and possibly urinary symptoms (includingfrequent urination and urgent urination); typically these symptoms are caused by a mass pressing on the other abdominopelvic organs or from metastases. If these symptoms start to occur more often or more severely than usual, especially after no significant history of such symptoms, ovarian cancer should be considered.Metastases may cause a Sister Mary Joseph nodule.]
In adolescents or children with ovarian tumors, the presenting symptoms can include severe abdominal pain, irritation of the peritoneum, or bleeding. As the cancer becomes more advanced, it can cause an accumulation of fluid in the abdomen. If the malignancy has not been diagnosed by the time it causes ascites, it is typically diagnosed shortly thereafter. Advanced cancers can also cause abdominal masses, lymph node masses, or pleural effusion.
Ovarian cancer symptoms can vary based on the subtype Low malignant potential (LMP) tumors, also known as borderline tumors, do not cause an increase in CA125 levels and are not identifiable with an ultrasound. The typical symptoms of a LMP tumor can include abdominal distension or pelvic pain. Particularly large masses tend to be benign or borderline,
Rarely, teratomas can cause growing teratoma syndrome or peritoneal gliomatosis.[16] The symptoms of sex cord-stromal tumors belie their ability to produce hormones. In prepubertal children, early puberty is the main symptom; abdominal pain and distension are also common. Rather than early puberty, adolescents with sex cord-stromal tumors may experience amenorrhea. Adults instead experience menometrorrhagia and abnormal vaginal bleeding after menopause in most cases. Other common symptoms include hirsutism, abdominal pain, virilization, and an adnexal mass.
Ovarian cancer facts
- Ovarian cancer is a relatively uncommon type of cancer that arises from different types of cells within the ovary.
- The most common ovarian cancers are known as epithelial ovarian cancers (EOC).
- Other types of ovarian cancer include ovarian low malignant potential tumor (OLMPT), germ cell tumors, and sex cord-stromal tumors.
- Inherited mutations in the BRCA1 and BRCA2 genes greatly increase a woman's risk of developing ovarian cancer.
- A gynecologic oncologist is a specialist with expertise in the management of ovarian cancer.
- Most ovarian cancers are diagnosed in advanced stages because there are no reliable early symptoms and signs of ovarian cancer. Even in more advanced tumors, symptoms and signs are vague and nonspecific.
- There are no reliable screening tests for ovarian cancer.
- Treatment of ovarian cancer involves surgery to remove as much of the tumor as possible andchemotherapy.
Risk factors
Most of the risk for ovarian cancer is related to the amount of time spent in ovulation. Thus not having children is a risk factor for ovarian cancer, likely because ovulation is not suppressed via pregnancy. Both obesity and hormone replacement therapy also raise the risk.
Things that halt ovulation: breast feeding, oral contraceptive use with estrogen/progesterone combination meds, multiple pregnancies, and pregnancy at an early age, all decrease risk of ovarian cancer. These conditions decrease the overall time during one's lifetime spent ovulating. A positive family history of ovarian cancer is a risk factor for ovarian cancer. People with hereditary nonpolyposis colon cancer (Lynch Syndrome), and those with BRCA-1 and BRCA-2 genetic abnormalities are at increased risk.
Hormones
Use of fertility medication may contribute to borderline ovarian tumor formation, but the link between the two is disputed and difficult to study. Fertility drugs may be associated with a higher risk of borderline tumors. Those who have been treated for infertility but remain nulliparous are at higher risk for epithelial ovarian cancer; however, those who are successfully treated for infertility and subsequently give birth are at no higher risk. This may be due to shedding of precancerous cells during pregnancy but the cause remains unclear. The risk factor may instead be infertility itself, not the treatment.
Hormonal conditions such as polycystic ovary syndrome and endometriosis are associated with ovarian cancer, but the link is not completely confirmed. Postmenopausal hormone replacement therapy (HRT) with estrogen likely increases the risk of ovarian cancer. The association has not been confirmed in a large-scale study,but notable studies including the Million Women Study have supported this link. Postmenopausal HRT with combined estrogen and progesterone may increase contemporaneous risk if used for over 5 years, but this risk returns to normal after cessation of therapy. Estrogen HRT with or without progestins increases the risk of endometrioid and serous tumors but lowers the risk of mucinous tumors. Higher doses of estrogen increase this risk.
Long periods of continuous ovulation are thought to be the main non-genetic cause of epithelial ovarian cancer. This is because during the cells are constantly stimulated to divide while ovulatory cycles continue. Therefore, people who have not borne children are at twice the risk of ovarian cancer than those who have. A longer period of ovulation caused by early first menstruation or late menopause is also a risk factor.
Endometriosis is another risk factor for ovarian cancer,]s is pain with menstruation. Endometriosis is associated with clear-cell and endometrioid subtypes, low-grade serous tumors, stage I and II tumors, grade 1 tumors, and lower mortality.[16]efore menopause, obesity can increase a person's risk of ovarian cancer, but this risk is not present after menopause. This risk is also relevant in those who are both obese and have never used HRT. A similar association with ovarian cancer appears in taller people.
Genetics
Further information: Hereditary breast–ovarian cancer syndrome
In general, a family history of ovarian cancer can indicate a predisposition to developing it. The major genetic risk factor for ovarian cancer is a mutation in BRCA1 or BRCA2 DNA mismatch repair genes, which is present in 10% of ovarian cancer cases. Only one allele need be mutated to place a person at high risk, because the risky mutations are autosomal dominant. The gene can be inherited through either the maternal or paternal line, but has variable penetrance.Though mutations in these genes are usually associated with increased risk of breast cancer, they also carry a substantial lifetime risk of ovarian cancer, a risk that peaks in a person's 40s and 50s. The lowest risk cited is 30% and the highest 60%. Mutations in BRCA1 have a lifetime risk of developing ovarian cancer of 15-45%.[16] Mutations in BRCA2 are less risky than those with BRCA1, with a lifetime risk of 10% (lowest risk cited) to 40% (highest risk cited). On average, BRCA-associated cancers develop 15 years before their sporadic counterparts, because people who inherit the mutations on one copy of their gene only need one mutation to start the process of carcinogenesis, whereas people with two normal genes would need to acquire two mutations.
In the United States, five of 100 women with a first-degree relative with ovarian cancer will eventually get ovarian cancer themselves, placing those with affected family members at triple the risk of women with unaffected family members. Seven of 100 women with two or more relatives with ovarian cancer will eventually get ovarian cancer. In general, 5-10% of ovarian cancer cases have a genetic cause. BRCA mutations are associated with high-grade serous nonmucinous epithelial ovarian cancer.
A strong family history of endometrial cancer, colon cancer, or other gastrointestinal cancers may indicate the presence of a syndrome known as hereditary nonpolyposis colorectal cancer (also known as Lynch syndrome), which confers a higher risk for developing a number of cancers, including ovarian cancer. Lynch syndrome is caused by mutations in mismatch repair genes, including MSH2, MLH1, MLH6, PMS1, and PMS2. The risk of ovarian cancer for an individual with Lynch syndrome is between 10 and 12 percent.People of Icelandic descent, European Jewish descent/Ashkenazi Jewish descent, and Hungarian descent are at higher risk for epithelial ovarian cancer.Other genes that have been associated with ovarian cancer are BRIP1, MSH6, RAD51C and RAD51D. CDH1, CHEK2, PALB2 and RAD50 have also been associated with ovarian cancer.
Several rare genetic disorders are associated with specific subtypes of ovarian cancer. Peutz–Jeghers syndrome, a rare genetic disorder, also predisposes people to sex cord tumour with annular tubules. Ollier disease and Maffucci syndrome are associated with granulosa cell tumors in children and may also be associated with Sertoli-Leydig tumors. Benign fibromas are associated with nevoid basal cell carcinoma syndrome.
Environmental factors
Industrialized nations, with the exception of Japan, have high rates of epithelial ovarian cancer, which may be due to diet in those countries. White people are at a 30–40% higher risk for ovarian cancer when compared to Black and Hispanic people, likely due to socioeconomic factors; white women tend to have fewer children and different rates of gynecologic surgeries that affect risk for ovarian cancer.
Cohort studies have found a correlation between dairy consumption and ovarian cancer, but case-control studies do not show this correlation. There is mixed evidence regarding the effect of red meat and processed meat in ovarian cancer.
Other
Alcohol consumption does not appear to be related to ovarian cancer, Other factors that have been investigated, such as smoking, low levels of vitamin D in the blood,presence of inclusion ovarian cysts, and infection with human papilloma virus (the cause of some cases of cervical cancer), have been disproven as risk factors for ovarian cancer.The carcinogenicity of perineal talc is controversial, because it can act as an irritant if it travels through the reproductive tract to the ovaries, Case-control studies have shown that use of perineal talc does increase the risk of ovarian cancer, but using talc more often does not create a greater risk, Use of talc elsewhere on the body is unrelated to ovarian cancer, Sitting regularly for prolonged periods is associated with higher mortality from epithelial ovarian cancer. The risk is not negated by regular exercise, though it is lowered.
Increased age (up to the 70s) is a risk factor for epithelial ovarian cancer because more mutations in cells can accumulate and eventually cause cancer. Those over 80 are at slightly lower risk.
Smoking tobacco is associated with a higher risk of mucinous ovarian cancer; after smoking cessation, the risk eventually returns to normal.A diet high in animal fats may be associated with ovarian cancer, but the connection is unclear. Diet seems to play a very small role, if any, in ovarian cancer risk.
Trans men who have ovaries may be at higher risk of ovarian cancer, but the reason for this is unknown. Potential factors include testosterone therapy and lower rates of protective factors.
Higher levels of C-reactive protein are associated with a higher risk of developing ovarian cancer.
Protective factors
Suppression of ovulation, which would otherwise cause damage to the ovarian epithelium and, consequently, inflammation, is generally protective. This effect can be achieved byhaving children, taking combined oral contraceptives, and breast feeding, all of which are protective factors.A longer period of breastfeeding correlates with a larger decrease in the risk of ovarian cancer.[21] Each birth decreases risk of ovarian cancer more, and this effect is seen with up to five births. Combined oral contraceptives reduce the risk of ovarian cancer by up to 50%, and the protective effect of combined oral contraceptives can last 25–30 years after they are discontinued. Regular use of aspirin oracetaminophen (paracetamol) may be associated with a lower risk of ovarian cancer; other NSAIDs do not seem to have a similar protective effect,
Tubal ligation is protective because carcinogens are unable to reach the ovary and fimbriae via the vagina, uterus, and Fallopian tubes. Tubal ligation is also protective in women with the BRCA1 mutation, but not the BRCA2 mutation. Hysterectomy reduces the risk, and removal of both Fallopian tubes and ovaries (bilateral salpingo-oophorectomy) dramatically reduces the risk of not only ovarian cancer, but breast cancer as well.] This is still a topic of research, as the link between hysterectomy and lower ovarian cancer risk is controversial. The reasons that hysterectomy may be protective have not been elucidated as of 2015.
A diet that includes large amounts of carotene, fiber, and vitamins with low amounts of fat—specifically, a diet with non-starchy vegetables (e.g. broccoli and onions)—may be protective,though research is still ongoing in this area. Higher caffeine intake and consumption of more than two cups of tea a day have both been associated with lower ovarian cancer risk. Smoking tobacco is protective for sex cord-stromal tumors.
Ovarian low malignant potential tumor (OLMPT; borderline tumor)
Ovarian tumors of low malignant potential (OLMPT; formerly referred to as borderline tumors) account for about 15% of EOC. They are most often serous or mucinous cell types. They often develop into large masses that may cause symptoms, but they only rarely metastasize, that is, spread to other areas. Often, removal of the tumor, even at more advanced stages, can be a cure.
Germ cell ovarian cancers
Germ cell tumors arise from the reproductive cells of the ovary. These tumors are uncommon and are seen most commonly in teens or young women. This type of tumor includes different categories: dysgerminomas, yolk sac tumors, embryonal carcinomas, polyembryomas, non-gestational choriocarcinomas, immature teratomas, and mixed germ cell tumors.
Stromal ovarian cancers
Another category of ovarian tumor is the sex cord-stromal tumors. These arise from supporting tissues within the ovary itself. As with germ cell tumors, these are uncommon. These cancers come from various types of cells within the ovary. They are much less common than the epithelial tumors. Stromal ovarian cancers include granulosa-stromal tumors and Sertoli-Leydig cell tumors.
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