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There is no simple and reliable way to test for ovarian cancer in women who do not have any signs or symptoms. The Pap test does not screen for ovarian cancer.
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.
Ovarian cancer is usually only palpable in advanced stages. Screening is not recommended using CA-125 measurements, HE4 levels, ultrasound, or adnexal palpation in women who are at average risk. Risk of developing ovarian cancer in those with genetic factors can be reduced. Those with a genetic predisposition may benefit from screening. This high risk group has benefited with earlier detection.
Ovarian cancer has low prevalence, even in the high-risk group of women from the ages of 50 to 60 (about one in 2000), and screening of women with average risk is more likely to give ambiguous results than detect a problem which requires treatment. Because ambiguous results are more likely than detection of a treatable problem, and because the usual response to ambiguous results is invasive interventions, in women of average risk, the potential harms of having screening without an indication outweigh the potential benefits. The purpose of screening is to diagnose ovarian cancer at an early stage, when it is more likely to be treated successfully.
Screening with transvaginal ultrasound, pelvic examination, and CA-125 levels can be used instead of preventative surgery in women who have BRCA1 or BRCA2 mutations. This strategy has shown some success.
Cases of GTD can be diagnosed through routine tests given during pregnancy, such as blood tests and ultrasound, or through tests done after miscarriage or abortion. Vaginal bleeding, enlarged uterus, pelvic pain or discomfort, and vomiting too much (hyperemesis) are the most common symptoms of GTD. But GTD also leads to elevated serum hCG (human chorionic gonadotropin hormone). Since pregnancy is by far the most common cause of elevated serum hCG, clinicians generally first suspect a pregnancy with a complication. However, in GTD, the beta subunit of hCG (beta hCG) is also always elevated. Therefore, if GTD is clinically suspected, serum beta hCG is also measured.
The initial clinical diagnosis of GTD should be confirmed histologically, which can be done after the evacuation of pregnancy (see «Treatment» below) in women with hydatidiform mole. However, malignant GTD is highly vascular. If malignant GTD is suspected clinically, biopsy is contraindicated, because biopsy may cause life-threatening haemorrhage.
Women with persistent abnormal vaginal bleeding after any pregnancy, and women developing acute respiratory or neurological symptoms after any pregnancy, should also undergo hCG testing, because these may be signs of a hitherto undiagnosed GTD.
Women with a hydatidiform mole have an excellent prognosis. Women with a malignant form of GTD usually have a very good prognosis.
Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumour and a life-threatening disease, it is very sensitive to chemotherapy. Virtually all women with non-metastatic disease are cured and retain their fertility; the prognosis is also very good for those with metastatic (spreading) cancer, in the early stages, but fertility may be lost. Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. Only a few women with GTD have a poor prognosis, e.g. some forms of stage IV GTN. The FIGO staging system is used. The risk can be estimated by scoring systems such as the "Modified WHO Prognostic Scoring System", wherein scores between 1 and 4 from various parameters are summed together:
In this scoring system, women with a score of 7 or greater are considered at high risk.
It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre. There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in developing countries.
People with strong genetic risk for ovarian cancer may consider the surgical removal of their ovaries as a preventative measure. This is often done after completion of childbearing years. This reduces the chances of developing both breast cancer (by around 50%) and ovarian cancer (by about 96%) in people at high risk. Women with "BRCA" gene mutations usually also have their Fallopian tubes removed at the same time (salpingo-oophorectomy), since they also have an increased risk of Fallopian tube cancer. However, these statistics may overestimate the risk reduction because of how they have been studied.
People with a significant family history for ovarian cancer are often referred to a genetic counselor to see if they if testing for BRCA mutations would be beneficial. The use of oral contraceptives, the absence of 'periods' during the menstrual cycle, and tubal ligation reduce the risk.
There may an association of developing ovarian cancer and ovarian stimulation during infertility treatments. Endometriosis has been linked to ovarian cancers. Human papillomavirus infection, smoking, and talc have not been identified as increasing the risk for developing ovarian cancer.
A widely recognised method of estimating the risk of malignant ovarian cancer based on initial workup is the "risk of malignancy index" (RMI). It is recommended that women with an RMI score over 200 should be referred to a centre with experience in ovarian cancer surgery.
The RMI is calculated as follows:
There are two methods to determine the ultrasound score and menopausal score, with the resultant RMI being called RMI 1 and RMI 2, respectively, depending on what method is used:
An RMI 2 of over 200 has been estimated to have a sensitivity of 74 to 80%, a specificity of 89 to 92% and a positive predictive value of around 80% of ovarian cancer. RMI 2 is regarded as more sensitive than RMI 1.
The diagnosis is made in asymptomatic pregnant women by obstetric ultrasonography. On pelvic examination a unilateral adnexal mass may be found. Typical symptoms are abdominal pain and, to a lesser degree, vaginal bleeding during pregnancy. Patients may present with hypovolemia or be in circulatory shock because of internal bleeding.
Ideally, ultrasound will show the location of the gestational sac in the ovary, while the uterine cavity is "empty", and if there is internal bleeding, it can be identified. Because of the proximity of the tube, the sonographic distinction between a tubal and an ovarian pregnancy may be difficult. Serial hCG levels generally show not the normal progressive rise.
In a series of 12 patients the mean gestation age was 45 days.
Histologically, the diagnosis has been made by Spiegelberg criteria on the surgical specimen of the removed ovary and tube. However, the tube and ovary are not usually removed as sonography allows for earlier diagnosis and surgeons strive to preserve the ovary. Prior to the introduction of Spiegelberg's criteria in 1878, the existence of ovarian pregnancy was in doubt; his criteria helped to identify the ovarian pregnancy from other ectopics:
- The gestational sac is located in the region of the ovary.
- The gestational sac is attached to the uterus by the ovarian ligament.
- Ovarian tissue is histologically proven in the wall of the gestational sac.
- The oviduct on the affected side is intact (this criterion, however, holds not true for a longer ongoing ovarian pregnancy).
An ovarian pregnancy can be mistaken for a tubal pregnancy or a hemorrhagic ovarian cyst or corpus luteum prior to surgery. Sometimes, only the presence of trophoblastic tissue during the histologic examination of material of a bleeding ovarian cyst shows that an ovarian pregnancy was the cause of the bleeding.
Follow-up imaging in women of reproductive age for incidentally discovered simple cysts on ultrasound is not needed until 5 cm, as these are usually normal ovarian follicles. Simple cysts 5 to 7 cm in premenopausal females should be followed yearly. Simple cysts larger than 7 cm require further imaging with MRI or surgical assessment. Because they are large, they cannot be reliably assessed by ultrasound alone because it may be difficult to see the soft tissue nodularity or thickened septation at their posterior wall due to limited penetrance of the ultrasound beam. For the corpus luteum, a dominant ovulating follicle that typically appears as a cyst with circumferentially thickened walls and crenulated inner margins, follow up is not needed if the cyst is less than 3 cm in diameter. In postmenopausal patients, any simple cyst greater than 1 cm but less than 7 cm needs yearly follow-up, while those greater than 7 cm need MRI or surgical evaluation, similar to reproductive age females.
For incidentally discovered dermoids, diagnosed on ultrasound by their pathognomonic echogenic fat, either surgical removal or yearly follow up is indicated, regardless of patient age. For peritoneal inclusion cysts, which have a crumpled tissue-paper appearance and tend to follow the contour of adjacent organs, follow up is based on clinical history. Hydrosalpinx, or fallopian tube dilation, can be mistaken for an ovarian cyst due to its anechoic appearance. Follow-up for this is also based on clinical presentation.
For multiloculate cysts with thin septation less than 3 mm, surgical evaluation is recommended. The presence of multiloculation suggests a neoplasm, although the thin septation implies that the neoplasm is benign. For any thickened septation, nodularity, or vascular flow on color doppler assessment, surgical removal should be considered due to concern for malignancy.
The diagnosis is strongly suggested by ultrasound (sonogram), but definitive diagnosis requires histopathological examination. On ultrasound, the mole resembles a bunch of grapes ("cluster of grapes" or "honeycombed uterus" or "snow-storm"). There is increased trophoblast proliferation and enlarging of the chorionic villi. Angiogenesis in the trophoblasts is impaired as well.
Sometimes symptoms of hyperthyroidism are seen, due to the extremely high levels of hCG, which can mimic the normal Thyroid-stimulating hormone (TSH).
Ovarian pregnancies are dangerous and prone to internal bleeding. Thus, when suspected, intervention is called for.
Traditionally, an explorative laparotomy was performed, and once the ovarian pregnancy was identified, an oophorectomy or salpingo-oophorectomy was performed, including the removal of the pregnancy. Today, the surgery can often be performed via laparoscopy. The extent of surgery varies according to the amount of tissue destruction that has
occurred. Patients with an ovarian pregnancy have a good prognosis for future fertility and therefore conservative surgical management is advocated. Further, in attempts to preserve ovarian tissue, surgery may involve just the removal of the pregnancy with only a part of the ovary. This can be accomplished by an ovarian wedge resection.
Ovarian pregnancies have been successfully treated with methotrexate since it was introduced in the management of ectopic pregnancy in 1988.
An ovarian pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as not to endanger the intrauterine pregnancy.
For surface epithelial-stromal tumors, the most common sites of metastasis are the pleural cavity (33%), the liver (26%), and the lungs (3%).
A prospective study of ovarian sex cord–stromal tumours in children and adolescents began enrolling participants in 2005.
Surgical exploration and of possible ovarian tissue is required for the definitive diagnosis of ORS, and treatment by excision of the remnant ovarian tissue may be performed during the same procedure. For women who are not candidates for surgery, a clinical diagnosis can be made based on the symptoms and levels (follicle-stimulating hormone and estradiol, after bilateral oophorectomy) and/or findings consistent with the presence of residual ovarian tissue. Laparoscopy and histological assessment can aid in diagnosis.
A laparoscopy or laparotomy can also be performed to visually confirm an ectopic pregnancy. This is generally reserved for women presenting with signs of an acute abdomen and/or hypovolemic shock. Often if a tubal abortion or tubal rupture has occurred, it is difficult to find the pregnancy tissue. A laparoscopy in very early ectopic pregnancy rarely shows a normal looking fallopian tube.
Culdocentesis, in which fluid is retrieved from the space separating the vagina and rectum, is a less commonly performed test that may be used to look for internal bleeding. In this test, a needle is inserted into the space at the very top of the vagina, behind the uterus and in front of the rectum. Any blood or fluid found may have been derived from a ruptured ectopic pregnancy.
Progesterone levels of less than 20 nmol/l have a high predictive value for failing pregnancies, whilst levels over 25 nmol/l are likely to predict viable pregnancies, and levels over 60 nmol/l are strongly so. This may help in identifying failing PULs that are at low risk and thereby needing less follow-up. Inhibin A may also be useful for predicting spontaneous resolution of PUL, but is not as good as progesterone for this purpose.
In addition, there are various mathematical models, such as logistic regression models and Bayesian networks, for the prediction of PUL outcome based on multiple parameters. Mathematical models also aim to identify PULs that are "low risk", that is, failing PULs and IUPs.
Dilation and curettage is sometimes used to diagnose pregnancy location with the aim of differentiating between an EP and a non-viable IUP in situations where a viable IUP can be ruled out. Specific indications for this procedure include either of the following:
- no visible IUP on transvaginal ultrasonography with a serum hCG of more than 2000 IU/ml
- an abnormal rise in hCG level. A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.
- an abnormal fall in hCG level, such as defined as one of less than 20% in 2 days
Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rate, even for metastatic gestational choriocarcinoma, is around 90–95%.
At present, treatment with single-agent methotrexate is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.
Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding.
Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers.
The risk of ovarian remnant (ORS) is increased by incomplete removal of the ovarian at the time of oophorectomy. Surgical factors that contribute to incomplete removal include those that limit surgical exposure of the ovary, or compromise surgical technique. Factors may include:
- adhesions – these can limit visualization of the ovary and may also cause it to adhere to surrounding tissues. Adhesions are often present due to preexisting conditions and/or prior surgeries. In the majority of cases reported since 2007, endometriosis was the most common indication for the initial oophorectomy in patients who subsequently had ORS. Endometriosis increases the risk for functional ovarian tissue being embedded into adjacent structures, making complete excision of tissue challenging.
- Anatomic variations - unusual location of ovarian tissue, for example
- Intraoperative bleeding
- Poor surgical technique – this may include failure to obtain adequate exposure or restore adequate anatomy, or imprecise choice of incision site
Ovarian remnant (ORS) may first be considered in women who have undergone oophorectomy and have suggestive symptoms, the presence of a mass, or evidence of persistent ovarian function (by symptoms or laboratory testing). A history of oophorectomy is required, by definition, to make the diagnosis. Notes regarding the indication for the procedure and the procedure itself should be reviewed and may include prior abdominal or pelvic surgery, endometriosis, and/or poor surgical visualization. If ORS is possible, pelvic should be performed to evaluate for a pelvic mass.[1]
Most women with a PUL are followed up with serum hCG measurements and repeat TVS examinations until a final diagnosis is confirmed. Low-risk cases of PUL that appear to be failing pregnancies may be followed up with a urinary pregnancy test after 2 weeks and get subsequent telephone advice. Low-risk cases of PUL that are likely intrauterine pregnancies may have another TVS in 2 weeks to access viability. High-risk cases of PUL require further assessment, either with a TVS within 48 h or additional hCG measurement.
A retrospective study of 83 women with sex cord–stromal tumours (73 with granulosa cell tumour and 10 with Sertoli-Leydig cell tumour), all diagnosed between 1975 and 2003, reported that survival was higher with age under 50, smaller tumour size, and absence of residual disease. The study found no effect of chemotherapy. A retrospective study of 67 children and adolescents reported some benefit of cisplatin-based chemotherapy.
Fertility subsequent to treatment of surface epithelial-stromal tumors depends mainly on histology and initial
staging to separate it into early borderline (or more benign) versus advanced stages of borderline (or more malignant). Conservative management (without bilateral oophorectomy) of early stage borderline tumors have been estimated to result in chance of over 50% of spontaneous pregnancy with a low risk of lethal recurrence of the tumor (0.5%). On the other hand, in cases of conservative treatment in advanced stage borderline tumors, spontaneous pregnancy rates have been estimated to be 35% and the risk of lethal recurrence 2%.
Surgical treatment of ovarian torsion includes laparoscopy to uncoil the torsed ovary and possibly oophoropexy to fixate the ovary which is likely to twist again. In severe cases, where blood flow is cut off to the ovary for an extended period of time, necrosis of the ovary can occur. In these cases the ovary must be surgically removed.
Gynecologic ultrasonography is the imaging modality of choice. Use of doppler ultrasound in the diagnosis has been suggested. However, doppler flow is not always absent in torsion – the definitive diagnosis is often made in the operating room.
Lack of ovarian blood flow on doppler sonography seems to be a good predictor of ovarian torsion. Women with pathologically low flow are more likely to have OT (77% vs. 29% in a study). The sensitivity and specificity of abnormal ovarian flow for OT are 44% and 92%, respectively, with a positive and negative predictive value of 78% and 71%, respectively. Specific flow features on Doppler sonography include:
- Little or no intra-ovarian venous flow. This is commonly seen in ovarian torsion.
- Absent arterial flow. This is a less common finding in ovarian torsion
- Absent or reversed diastolic flow
Normal vascularity does not exclude intermittent torsion. There may occasionally be normal Doppler flow because of the ovary's dual blood supply from both the ovarian arteries and uterine arteries.
Other ultrasonographic features include:
- Enlarged hypoechogenic or hyperechogenic ovary
- Peripherally displaced ovarian follicles
- Free pelvic fluid. This may be seen in more than 80% of cases
- "Whirlpool sign" of twisted vascular pedicle
- Underlying ovarian lesion can often be found
- Uterus may be slightly deviated towards the torted ovary.
Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks' gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier.
In the United States, most obstetricians prefer universal screening with a screening glucose challenge test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the woman is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening.
Some pregnant women and careproviders choose to forgo routine screening due to the absence of risk factors, however this is not advised due to the large proportion of women who develop gestational diabetes despite having no risk factors present and the dangers to the mother and baby if gestational diabetes remains untreated.
Hydatidiform moles should be treated by evacuating the uterus by uterine suction or by surgical curettage as soon as possible after diagnosis, in order to avoid the risks of choriocarcinoma. Patients are followed up until their serum human chorionic gonadotrophin (hCG) level has fallen to an undetectable level. Invasive or metastatic moles (cancer) may require chemotherapy and often respond well to methotrexate. As they contain paternal antigens, the response to treatment is nearly 100%. Patients are advised not to conceive for half a year after hCG levels have normalized. The chances of having another molar pregnancy are approximately 1%.
Management is more complicated when the mole occurs together with one or more normal fetuses.
Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed. Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first 2 trimesters is only around 10% and the positive predictive value is around 20%.
After removal, the testicle is fixed with Bouin's solution because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. In broad terms, testicular cancer is staged as follows:
- Stage I: the cancer remains localized to the testis.
- Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm).
- Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.
Further information on the detailed staging system is available on the website of the American Cancer Society.
Between 5 and 10 percent of women with POF may become pregnant. Currently no fertility treatment has officially been found to effectively increase fertility in women with POF, and the use of donor eggs with in-vitro fertilization (IVF) and adoption are popular as a means of achieving parenthood for women with POF. Some women with POF choose to live child-free. (See impaired ovarian reserve for a summary of recent randomized clinical trials and treatment methods.)
Currently New York fertility researchers are investigating the use of a mild hormone called dehydroepiandrosterone (DHEA) in women with POF to increase spontaneous pregnancy rates. Published results from studies conducted on DHEA have indicated that DHEA may increase spontaneously conceived pregnancies, decrease spontaneous miscarriage rates and improve IVF success rates in women with POF.
Additionally, over the last five years a Greek research team has successfully implemented the use of dehydroepiandrosterone (DHEA) for the fertility treatment of women suffering with POF.The majority of the patients were referred for donor eggs or surrogacy, however after a few months of DHEA administration, some succeeded in getting pregnant through IVF, IUI, IUTPI or natural conception. Many babies have been born after treatment with DHEA.
Ovarian tissue cryopreservation can be performed on prepubertal girls at risk for premature ovarian failure, and this procedure is as feasible and safe as comparable operative procedures in children.