Ovarian cancer

Ovarian cancer (human)
Classification and external resources

Micrograph of a low malignant potential mucinous ovarian tumour. H&E stain.
ICD-10 C56., D27.
ICD-9 183, 220
ICD-O: varied
DiseasesDB 9418
MedlinePlus 000889
eMedicine med/1698
MeSH D010051

Ovarian cancer is a cancerous growth arising from different parts of the ovary.

Most (>90%) ovarian cancers are classified as "epithelial" and were believed to arise from the surface (epithelium) of the ovary.[1][2] However, recent evidence suggests that the Fallopian tube could also be the source of some ovarian cancers.[3] Since the ovaries and tubes are closely related to each other, it is hypothesized that these cells can mimic ovarian cancer.[4] Other types arise from the egg cells (germ cell tumor) or supporting cells (sex cord/stromal).

In 2004, in the United States, 25,580 new cases were diagnosed and 16,090 women died of ovarian cancer. The risk increases with age and decreases with pregnancy. Lifetime risk is about 1.6%, but women with affected first-degree relatives have a 5% risk. Women with a mutated BRCA1 or BRCA2 gene carry a risk between 25% and 60% depending on the specific mutation.[5] Ovarian cancer is the fifth leading cause of death from cancer in women and the leading cause of death from gynecological cancer.[6]

In early stages ovarian cancer is associated with abdominal distension.[7]

10-year relative survival ranges from 84.1% in stage IA to 10.4% in stage IIIC.[8]

Ovarian cancer causes non-specific symptoms.[9] Early diagnosis would result in better survival, on the assumption that stage I and II cancers progress to stage III and IV cancers (but this has not been proven). Most women with ovarian cancer report one or more symptoms such as abdominal pain or discomfort, an abdominal mass, bloating, back pain, urinary urgency, constipation, tiredness and a range of other non-specific symptoms, as well as more specific symptoms such as pelvic pain, abnormal vaginal bleeding or involuntary weight loss.[10][11][12] There can be a build-up of fluid (ascites) in the abdominal cavity.

Diagnosis of ovarian cancer starts with a physical examination (including a pelvic examination), a blood test (for CA-125 and sometimes other markers), and transvaginal ultrasound. The diagnosis must be confirmed with surgery to inspect the abdominal cavity, take biopsies (tissue samples for microscopic analysis) and look for cancer cells in the abdominal fluid. Treatment usually involves chemotherapy and surgery, and sometimes radiotherapy.[13]

In most cases, the cause of ovarian cancer remains unknown. Older women, and in those who have a first or second degree relative with the disease, have an increased risk. Hereditary forms of ovarian cancer can be caused by mutations in specific genes (most notably BRCA1 and BRCA2, but also in genes for hereditary nonpolyposis colorectal cancer). Infertile women and those with a condition called endometriosis, those who have never been pregnant and those who use postmenopausal estrogen replacement therapy are at increased risk. Use of combined oral contraceptive pills is a protective factor. The risk is also lower in women who have had their uterine tubes blocked surgically (tubal ligation).[14][15]

Contents

Classification

A benign tumor of the ovary, discovered during a C-section; this is a 4 cm teratoma

Ovarian cancer is classified according to the histology of the tumor, obtained in a pathology report. Histology dictates many aspects of clinical treatment, management, and prognosis.

According to SEER, types of ovarian cancers in women age 20+ are as follows:[8]

Percent of
ovarian cancers
in women
age 20+		 Histology 5 year
RSR
89.7 Surface epithelial-stromal tumor (Adenocarcinoma) 54.4
26.4 Papillary serous cystadenocarcinoma 21.0
15.9 "Borderline" adenocarcinoma
(underestimated b/c short data collection interval)		 98.2
12.6 Adenocarcinoma, not otherwise specified 18.3
9.8 Endometrioid tumor 70.9
5.8 Serous cystadenocarcinoma 44.2
5.5 Papillary 21.0
4.2 Mucinous cystadenocarcinoma 77.7
4.0 Clear-cell ovarian tumor 61.5
3.4 Mucinous adenocarcinoma 49.1
1.3 Cystadenocarcinoma 50.7
5.5 Carcinoma
4.1 Carcinoma not otherwise specified 26.8
1.1 Sex cord-stromal tumour 87.8
0.3 Other carcinomas, specified 37.3
1.7 Mullerian tumor 29.8
1.5 Germ cell tumor 91.0
0.8 Teratoma 89.1
0.5 Dysgerminoma 96.8
0.3 Other, specified 85.1
0.6 Not otherwise specified 23.0
0.5 Epidermoid (Squamous cell carcinoma) 51.3
0.2 Brenner tumor 67.9
0.2 Other, specified 71.7

Ovarian cancer can also be a secondary cancer, the result of metastasis from a primary cancer elsewhere in the body. 7% of ovarian cancers are due to metastases while the rest are primary cancers. Common primary cancers are breast cancer and gastrointestinal cancer (a common mistake is to name all peritoneal metastases from any gastrointestinal cancer as Krukenberg cancer , but this is only the case if it originates from primary gastric cancer). Surface epithelial-stromal tumor can originate in the peritoneum (the lining of the abdominal cavity), in which case the ovarian cancer is secondary to primary peritoneal cancer, but treatment is basically the same as for primary surface epithelial-stromal tumor involving the peritoneum.

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 cytopathology. The AJCC stage is the same as the FIGO stage. The AJCC staging system describes the extent of the primary Tumor (T), the absence or presence of metastasis to nearby lymph Nodes (N), and the absence or presence of distant Metastasis (M). [16]

Para-aortic lymph node metastases are considered regional lymph nodes (Stage IIIC).

The AJCC/TNM staging system includes three categories for ovarian cancer, T, N and M. The T category contains three other subcategories, T1, T2 and T3, each of them being classified according to the place where the tumor has developed (in one or both ovaries, inside or outside the ovary). The T1 category of ovarian cancer describes ovarian tumors that are confined to the ovaries, and which may affect one or both of them. The sub-subcategory T1a is used to stage cancer that is found in only one ovary, which has left the capsule intact and which cannot be found in the fluid taken from the pelvis. Cancer that has not affected the capsule, is confined to the inside of the ovaries and cannot be found in the fluid taken from the pelvis but has affected both ovaries is staged as T1b. T1c category describes a type of tumor that can affect one or both ovaries, and which has grown through the capsule of an ovary or it is present in the fluid taken from the pelvis. T2 is a more advanced stage of cancer. In this case, the tumor has grown in one or both ovaries and is spread to the uterus, fallopian tubes or other pelvic tissues. Stage T2a is used to describe a cancerous tumor that has spread to the uterus or the fallopian tubes (or both) but which is not present in the fluid taken from the pelvis. Stages T2b and T2c indicate cancer that metastasized to other pelvic tissues than the uterus and fallopian tubes and which cannot be seen in the fluid taken from the pelvis, respectively tumors that spread to any of the pelvic tissues (including uterus and fallopian tubes) but which can also be found in the fluid taken from the pelvis. T3 is the stage used to describe cancer that has spread to the peritoneum. This stage provides information on the size of the metastatic tumors (tumors that are located in other areas of the body, but are caused by ovarian cancer). These tumors can be very small, visible only under the microscope (T3a), visible but not larger than 2 centimeters (T3b) and bigger than 2 centimeters (T3c).

This staging system also uses N categories to describe cancers that have or not spread to nearby lymph nodes. There are only two N categories, N0 which indicates that the cancerous tumors have not affected the lymph nodes, and N1 which indicates the involvement of lymph nodes close to the tumor.

The M categories in the AJCC/TNM staging system provide information on whether the ovarian cancer has metastasized to distant organs such as liver or lungs. M0 indicates that the cancer did not spread to distant organs and M1 category is used for cancer that has spread to other organs of the body.

The AJCC/TNM staging system also contains a Tx and a Nx sub-category which indicates that the extent of the tumor cannot be described because of insufficient data, respectively the involvement of the lymph nodes cannot be described because of the same reason.

The ovarian cancer stages are made up by combining the TNM categories in the following manner:

Ovarian cancer, as well as any other type of cancer, is also graded, apart from staged. The histologic grade of a tumor measures how abnormal or malignant its cells look under the microscope. [17] There are four grades indicating the likelihood of the cancer to spread and the higher the grade, the more likely for this to occur. Grade 0 is used to describe non-invasive tumors. Grade 0 cancers are also referred to as borderline tumors. [17] Grade 1 tumors have cells that are well differentiated (look very similar to the normal tissue) and are the ones with the best prognosis. Grade 2 tumors are also called moderately well differentiated and they are made up by cells that resemble the normal tissue. Grade 3 tumors have the worst prognosis and their cells are abnormal, referred to as poorly differentiated.

Symptoms

The signs and symptoms of ovarian cancer are most of the times absent, but when they exist they are nonspecific. In most cases, the symptoms persist for several months until the patient is diagnosed.

A prospective case-control study of 1,709 women visiting primary care clinics found that the combination of bloating, increased abdominal size, and urinary symptoms was found in 43% of those with ovarian cancer but in only 8% of those presenting to primary care clinics. [18]

Accuracy of symptoms

Two case-control studies, both subject to results being inflated by spectrum bias, have been reported. The first found that women with ovarian cancer had symptoms of increased abdominal size, bloating, urge to pass urine and pelvic pain.[12] The smaller, second study found that women with ovarian cancer had pelvic/abdominal pain, increased abdominal size/bloating, and difficulty eating/feeling full.[19] The latter study created a symptom index that was considered positive if any of the six (6) symptoms "occurred >12 times per month but were present for <1 year". For early-stage disease, they reported a 57% sensitivity and 87% to 90% specificity.

Consensus statement

In 2007, the Gynecologic Cancer Foundation, Society of Gynecologic Oncologists and American Cancer Society originated the following consensus statement regarding the symptoms of ovarian cancer.[20]

Ovarian cancer is called a “silent killer” because symptoms were not thought to develop until the disease had advanced and the chance of cure or remission poor. However, the following symptoms are much more likely to occur in women with ovarian cancer than women in the general population. These symptoms include:

Women with ovarian cancer report that symptoms are persistent and represent a change from normal for their bodies. The frequency and/or number of such symptoms are key factors in the diagnosis of ovarian cancer. Several studies show that even early stage ovarian cancer can produce these symptoms. Women who have these symptoms almost daily for more than a few weeks should see their doctor, preferably a gynecologist. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. Early stage diagnosis is associated with an improved prognosis.

Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these other symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women in the general population who do not have ovarian cancer.

Cause

The exact cause is usually unknown. The risk of 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 age 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.

Hormones

The relationship between use of oral contraceptives and ovarian cancer was shown in a summary of results of 45 case-control and prospective studies. Cumulatively these studies show a protective effect for ovarian cancers. Women who used oral contraceptives for 10 years had about a 60% reduction in risk of ovarian cancer. (risk ratio .42 with statistical significant confidence intervals given the large study size, not unexpected). This means that if 250 women took oral contraceptives for 10 years, 1 ovarian cancer would be prevented. This is by far the largest epidemiological study to date on this subject (45 studies, over 20,000 women with ovarian cancer and about 80,000 controls).[21]

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 of ovarian cancer. Several cohort studies and case-control studies have been conducted since then without demonstrating conclusive evidence for such a link.[22] It will remain a complex topic to study as the infertile population differs in parity from the "normal" population.

Genetics

There is good evidence that in some women genetic factors are important. Carriers of certain mutations of the BRCA1 or the BRCA2 gene are notably at risk. The BRCA1 and BRCA2 genes account for 5%-13% of ovarian cancers[23] and certain 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 diagnosed 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 nonpolyposis colorectal 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, i.e. preventative, oophorectomy after completion of childbearing.

Australia being member of International Cancer Genome Consortium is leading efforts to map ovarian cancer's complete genome.

Alcohol

A pooled analysis of ten (10) prospective cohort studies conducted in a number of countries and including 529,638 women found that neither total alcohol consumption nor alcohol from drinking beer, wine or spirits was associated with ovarian cancer risk."[24] The results of a case-control study in the region of Milan, Italy, "suggests that relatively elevated alcohol intake (of the order of 40 g per day or more) may cause a modest increase of epithelial ovarian cancer risk"[25]. "Associations were also found between alcohol consumption and cancers of the ovary and prostate, but only for 50 g and 100 g a day."[26] "Statistically significant increases in risk also existed for cancers of the stomach, colon, rectum, liver, female breast, and ovaries."[27]

Other

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." [28] 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.[29]

Other factors that have been investigated, such as talc use,[30] asbestos exposure, high dietary fat content, and childhood mumps infection, are controversial and have not been definitively proven; moreover, such risk factors may in some cases be more likely to be correlated with cancer in individuals with specific genetic makeups.[31]

Diagnosis

Micrograph of serous carcinoma, a type of ovarian cancer, diagnosed in peritoneal fluid.

Ovarian cancer at its early stages(I/II) is difficult to diagnose until it spreads and advances to later stages (III/IV). This is because most symptoms are non-specific and thus of little use in diagnosis.[32]

When an ovarian malignancy is included in the list of diagnostic possibilities, a limited number of laboratory tests are indicated. A complete blood count (CBC) and serum electrolyte test should be obtained in all patients.

The serum BHCG level should be measured in any female in whom pregnancy is a possibility. In addition, serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) should be measured in young girls and adolescents with suspected ovarian tumors because the younger the patient, the greater the likelihood of a malignant germ cell tumor.

A blood test called CA-125 is useful in differential diagnosis and in follow up of the disease, but it by itself has not been shown to be an effective method to screen for early-stage ovarian cancer due to its unacceptable low sensitivity and specificity. However, this is the only widely-used marker currently available.

Current research is looking at ways to combine tumor markers proteomics 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 prevalence of ovarian cancer means that even testing with very high sensitivity and specificity will still lead to a number of false positive results (i.e. performing surgical procedures in which cancer is not found intra-operatively). However, the contributions of proteomics are still in the early stages and require further refining. Current studies on proteomics mark the beginning of a paradigm shift towards individually tailored therapy.

A pelvic examination and imaging including CT scan and trans-vaginal ultrasound are essential. 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 examination can include a rectovaginal component for better palpation of the ovaries. For very young patients, magnetic resonance imaging may be preferred to rectal and vaginal examination.

To definitively diagnose ovarian cancer, a surgical procedure to take a look into the abdomen is required. This can be an open procedure (laparotomy, incision through the abdominal wall) or keyhole surgery (laparoscopy). During this procedure, suspicious areas will be removed and sent for microscopic analysis. Fluid from the abdominal cavity can also be analysed for cancerous cells. If there is cancer, this procedure can also determine its spread (which is a form of tumor staging).

Prevention

There are a number of ways to reduce or eliminate the risk of ovarian cancer. Pregnancy before the age of 25 as well as breastfeeding provides some reduction in risk. Tubal ligation and hysterectomy reduce the risk and removal of both tubes and ovaries (bilateral salpingo-oophorectomy) dramatically reduces the risk of not only ovarian cancer but breast cancer also[33]. The use of oral contraceptives (birth control pills) for five years or more decreases the risk of ovarian cancer in later life by 50%.[34]

Tubal ligation is believed to decrease the chance of developing ovarian cancer by up to 67% while a hysterectomy may reduce the risk of getting ovarian cancer by about one-third. [35] Moreover, according to some studies, analgesics such as acetaminophen and aspirin seem to reduce one's risks of developing ovarian cancer. Yet, the information is not consistent and more research needs to be carried on this matter.

Screening

Routine screening of the general population is not recommended by any professional society. This includes the U.S. Preventive Services Task Force, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the National Comprehensive Cancer Network.[36]

No trial has shown improved survival for women undergoing screening.[36]

Screening tests include the CA-125 marker, transvaginal ultrasound, and combinations of markers such as OvaSure (LabCorp). A definitive diagnosis requires surgical excision of the ovaries and fallopian tubes, so a positive screening test must be followed up by surgery.[36]

The purpose of screening is to discover ovarian cancer in early stages, when it is more curable, on the hypothesis that early-stage cancer develops into later-stage cancer. However, it is not known whether early stage ovarian cancer evolves to later stage cancer, or whether stage III (peritoneal cavity involvement) arises as a diffuse process.[36]

The goal of ovarian cancer screening is to detect ovarian cancer at stage I.[37] Several large studies are ongoing, but none have recommended screening.[38] In 2009, however, Menon et al. reported from the UKCTOCS that utilizing mutimodal screening, in essence first performing annual CA-125 testing, followed by ultrasound imaging on the secondary level, the positive predictive value was 35.1% for primary invasive epithelial ovarian and tubal carcinoma, making such screening feasible.[39] However, it remains to be seen if such screening is effective to reduce mortality.

Management

Surgical treatment may be sufficient for malignant tumors that are well-differentiated and confined to the ovary. Addition of chemotherapy may be required for more aggressive tumors that are confined to the ovary. For patients with advanced disease a combination of surgical reduction with a combination chemotherapy regimen is standard. Borderline tumors, even following spread outside of the ovary, are managed well with surgery, and chemotherapy is not seen as useful.

Surgery is the preferred treatment and is frequently necessary to obtain a tissue specimen for differential diagnosis via its histology. Surgery performed by a specialist in gynecologic oncology usually results in an improved result[40]. 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 presumed 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 malignancy, where complete resection is not feasible, as much tumor as possible is removed (debulking surgery). In cases where this type of surgery is successful (i.e. < 1 cm in diameter of tumor is left behind ["optimal debulking"]), the prognosis is improved compared to patients where large tumor masses (> 1 cm in diameter) are left behind. Minimally invasive surgical techniques may facilitate the safe removal of very large (greater than 10 cm) tumors with fewer complications of surgery.[41]

Chemotherapy has been a general standard of care for ovarian cancer for decades, although with highly variable protocols.[42] Chemotherapy is used after surgery to treat any residual disease, if appropriate. This depends on the histology of the tumor; some kinds of tumor (particularly teratoma) are not sensitive to chemotherapy. In some cases, there may be reason to perform chemotherapy first, followed by surgery.

For patients with stage IIIC epithelial ovarian adenocarcinomas who have undergone successful optimal debulking, a recent clinical trial demonstrated that median survival time is significantly longer for patient receiving intraperitoneal (IP) chemotherapy.[43] Patients in this clinical trial reported less compliance with IP chemotherapy and fewer than half of the patients received all six cycles of IP chemotherapy. Despite this high "drop-out" rate, the group as a whole (including the patients that didn't complete IP chemotherapy treatment) survived longer on average than patients who received intravenous chemotherapy alone.

Some specialists believe the toxicities and other complications of IP chemotherapy will be unnecessary with improved IV chemotherapy drugs currently being developed.

Although IP chemotherapy has been recommended as a standard of care for the first-line treatment of ovarian cancer, the basis for this recommendation has been challenged.[44]

Radiation therapy is not effective for advanced stages because when vital organs are in the radiation field, a high dose cannot be safely delivered. Radiation therapy is then commonly avoided in such stages as the vital organs may not be able to withstand the problems associated with these ovarian cancer treatments. [45]

Prognosis

Ovarian cancer usually has a poor prognosis. It is disproportionately deadly because it lacks any clear early detection or screening test, meaning that most cases are not diagnosed until they have reached advanced stages. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries. Ovarian cancers shed cells into the naturally occurring fluid within the abdominal cavity. These cells can then implant on other abdominal (peritoneal) structures, included the uterus, urinary bladder, bowel and the lining of the bowel wall (omentum ) forming new tumor growths before cancer is even suspected.

The five-year survival rate for all stages of ovarian cancer is 45.5%. For cases where a diagnosis is made early in the disease, when the cancer is still confined to the primary site, the five-year survival rate is 92.7%.[46]

Germ cell tumors of the ovary have a much better prognosis than other ovarian cancers, in part because they tend to grow rapidly to a very large size, hence they are detected sooner.

Complications

These cells can implant on other abdominal (peritoneal) structures, including the uterus, urinary bladder, bowel, lining of the bowel wall (omentum) and, less frequently, to the lungs.

Epidemiology

Age-standardized death from ovarian cancer per 100,000 inhabitants in 2004.[47]
     no data      less than 0.6      0.6-1.2      1.2-1.8      1.8-2.4      2.4-3      3-3.6      3.6-4.2      4.2-4.8      4.8-5.4      5.4-6      6-7      more than 7

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.

In other animals

Ovarian tumors have been reported in mares. Reported tumor types include teratoma,[48][49] cystadenocarcinoma,[50] and particularly granulosa cell tumor.[51][52][53][54][55]

See also

References

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  8. ↑ 8.0 8.1 Kosary, Carol L. (2007). "Chapter 16: Cancers of the Ovary". In Lin, LAG; Young, JL; Keel, GE et al.. SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988-2001, Patient and Tumor Characteristics. SEER Program. NIH Pub. No. 07-6215. Bethesda, MD: National Cancer Institute. pp. 133–144. http://seer.cancer.gov/publications/survival/surv_ovary.pdf. 
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  26. ↑ "Alcohol consumption and cancer risk". Bandolier. 2007-04-01. http://www.jr2.ox.ac.uk/bandolier/booth/hliving/alccan.html. 
  27. ↑ Bagnardi V, Blangiardo M, La Vecchia C, Corrao G (2001). "Alcohol consumption and the risk of cancer: a meta-analysis". Alcohol Research & Health 25 (4): 263–70. PMID 11910703. http://pubs.niaaa.nih.gov/publications/arh25-4/263-270.htm. 
  28. ↑ BBC News Milk link to ovarian cancer risk 29 November 2004
  29. ↑ Lefkowitz ES, Garland CF (December 1994). "Sunlight, vitamin D, and ovarian cancer mortality rates in US women". Int J Epidemiol 23 (6): 1133–6. doi:10.1093/ije/23.6.1133. PMID 7721513. http://ije.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=7721513. 
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  31. ↑ E.g., http://www.cancerhelp.org.uk/type/ovarian-cancer/about/ovarian-cancer-risks-and-causes#talcum
  32. ↑ Rossing, Mary Anne; Wicklund, Kristine G.; Cushing-Haugen, Kara L.; Weiss, Noel S. (2010-01-28). "Predictive Value of Symptoms for Early Detection of Ovarian Cancer". J Natl Cancer Inst. 102 (4): djp500v1. doi:10.1093/jnci/djp500. PMID 20110551. PMC 2826180. http://jnci.oxfordjournals.org/cgi/content/full/djp500v1. 
  33. ↑ Finch A, Beiner M, Lubinski J, et al. (July 2006). "Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation". JAMA 296 (2): 185–92. doi:10.1001/jama.296.2.185. PMID 16835424. http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=16835424. 
  34. ↑ Bast RC, Brewer M, Zou C, et al. (2007). "Prevention and early detection of ovarian cancer: mission impossible?". Recent Results Cancer Res. 174: 91–100. doi:10.1007/978-3-540-37696-5_9. PMID 17302189. 
  35. ↑ "What are the risk factors for ovarian cancer?". http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-risk-factors. Retrieved July 27, 2010. 
  36. ↑ 36.0 36.1 36.2 36.3 Clarke-Pearson DL (July 2009). "Clinical practice. Screening for ovarian cancer". N. Engl. J. Med. 361 (2): 170–7. doi:10.1056/NEJMcp0901926. PMID 19587342. http://content.nejm.org/cgi/content/full/361/2/170. 
  37. ↑ Kurman RJ, Visvanathan K, Roden R, Wu TC, Shih IeM (April 2008). "Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis". Am. J. Obstet. Gynecol. 198 (4): 351–6. doi:10.1016/j.ajog.2008.01.005. PMID 18395030. PMC 2532696. http://linkinghub.elsevier.com/retrieve/pii/S0002-9378(08)00020-3. 
  38. ↑ Partridge E, Kreimer AR, Greenlee RT, et al. (April 2009). "Results from four rounds of ovarian cancer screening in a randomized trial". Obstet Gynecol 113 (4): 775–82. doi:10.1097/AOG.0b013e31819cda77 (inactive 2010-03-17). PMID 19305319. PMC 2728067. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0029-7844&volume=113&issue=4&spage=775. 
  39. ↑ Menon U, Gentry-Maharaj A, Hallett R, et al. (April 2009). "Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)". Lancet Oncol. 10 (4): 327–40. doi:10.1016/S1470-2045(09)70026-9. PMID 19282241. http://linkinghub.elsevier.com/retrieve/pii/S1470-2045(09)70026-9. 
  40. ↑ Junor EJ, Hole DJ, McNulty L, Mason M, Young J (November 1999). "Specialist gynaecologists and survival outcome in ovarian cancer: a Scottish national study of 1866 patients". Br J Obstet Gynaecol 106 (11): 1130–6. PMID 10549956. 
  41. ↑ Ehrlich, P.F., Teitelbaum, D.H., Hirschl, R.B., Rescorla, F. (2007). "Excision of large cystic ovarian tumors: combining minimal invasive surgery techniques and cancer surgery—the best of both worlds". J. Pediatr. Surg. 42 (5): 890–3. doi:10.1016/j.jpedsurg.2006.12.069. PMID 17502206. 
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  43. ↑ Armstrong DK, Bundy B, Wenzel L, Huang HQ, et al. (January 2006). "Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer". NEJM 354 (1): 34–43. doi:10.1056/NEJMoa052985. PMID 16394300. http://content.nejm.org/cgi/content/full/354/1/34. 
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  46. ↑ Survival rates based on SEER incidence and NCHS mortality statistics, as cited by the National Cancer Institute in SEER Stat Fact Sheets — Cancer of the Ovary
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  52. ↑ Hoque S, Derar RI, Osawa T, Taya K, Watanabe G, Miyake Y (June 2003). "Spontaneous repair of the atrophic contralateral ovary without ovariectomy in the case of a granulosa theca cell tumor (GTCT) affected mare" (– Scholar search). J. Vet. Med. Sci. 65 (6): 749–51. doi:10.1292/jvms.65.749. PMID 12867740. http://joi.jlc.jst.go.jp/JST.JSTAGE/jvms/65.749?from=PubMed. 
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  54. ↑ Moll HD, Slone DE, Juzwiak JS, Garrett PD (1987). "Diagonal paramedian approach for removal of ovarian tumors in the mare". Vet Surg 16 (6): 456–8. doi:10.1111/j.1532-950X.1987.tb00987.x. PMID 3507181. http://www3.interscience.wiley.com/journal/119849124/abstract. 
  55. ↑ Doran R, Allen D, Gordon B (January 1988). "Use of stapling instruments to aid in the removal of ovarian tumours in mares". Equine Vet. J. 20 (1): 37–40. doi:10.1111/j.2042-3306.1988.tb01450.x. PMID 2835223. 
Tumors: female urogenital neoplasia · (C51-C58/D25-28, 179-184/218-221)
Adnexa
Ovaries
Glandular and epithelial/
surface epithelial-
stromal tumor

CMS: Ovarian serous cystadenoma · Mucinous cystadenoma · Cystadenocarcinoma (Papillary serous cystadenocarcinoma) · Krukenberg tumor

Endometrioid tumor · Clear-cell ovarian carcinoma · Brenner tumour
Sex cord-gonadal stromal
Leydig cell tumour · Sertoli cell tumour · Sertoli-Leydig cell tumour · Thecoma · Granulosa cell tumour · Luteoma
Germ cell
Dysgerminoma · Nongerminomatous (Embryonal carcinoma, Endodermal sinus tumor, Gonadoblastoma, Teratoma/Struma ovarii, Choriocarcinoma)
Fibroma
Meigs syndrome
Fallopian tube
Adenomatoid tumor
Uterus
Myometrium
Uterine fibroids/leiomyoma · Leiomyosarcoma · Adenomyoma
Endometrioid tumor · Uterine papillary serous carcinoma · Clear cell carcinoma · Endometrial intraepithelial neoplasia
SCC · Cervical intraepithelial neoplasia
Choriocarcinoma · Gestational trophoblastic disease
General
Uterine sarcoma · Mixed Müllerian tumor
Vagina
SCC · Botryoid rhabdomyosarcoma · Clear cell adenocarcinoma of the vagina · Vaginal intraepithelial neoplasia
Vulva
SCC · Melanoma · Papillary hidradenoma · Extramammary Paget's disease · Vulvar intraepithelial neoplasia

: ♀ FRS

anat/phys/devp

noco//npls, /

proc/asst, drug (G1/G2B/G3CD)

External links