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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Routine screening of asymptomatic people is not indicated, since the disease is highly curable in its early, symptomatic stages. Instead, women, particularly menopausal women, should be aware of the symptoms and risk factors of endometrial cancer. A cervical screening test, such as a Pap smear, is not a useful diagnostic tool for endometrial cancer because the smear will be normal 50% of the time. A Pap smear can detect disease that has spread to the cervix. Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced. Cervical stenosis, the narrowing of the cervical opening, is a sign of endometrial cancer when pus or blood is found collected in the uterus (pyometra or hematometra).
Women with Lynch syndrome should begin to have annual biopsy screening at the age of 35. Some women with Lynch syndrome elect to have a prophylactic hysterectomy and salpingo-oophorectomy to greatly reduce the risk of endometrial and ovarian cancer.
Transvaginal ultrasound to examine the endometrial thickness in women with postmenopausal bleeding is increasingly being used to aid in the diagnosis of endometrial cancer in the United States. In the United Kingdom, both an endometrial biopsy and a transvaginal ultrasound used in conjunction are the standard of care for diagnosing endometrial cancer. The homogeneity of the tissue visible on transvaginal ultrasound can help to indicate whether the thickness is cancerous. Ultrasound findings alone are not conclusive in cases of endometrial cancer, so another screening method (for example endometrial biopsy) must be used in conjunction. Other imaging studies are of limited use. CT scans are used for preoperative imaging of tumors that appear advanced on physical exam or have a high-risk subtype (at high risk of metastasis). They can also be used to investigate extrapelvic disease. An MRI can be of some use in determining if the cancer has spread to the cervix or if it is an endocervical adenocarcinoma. MRI is also useful for examining the nearby lymph nodes.
Dilation and curettage or an endometrial biopsy are used to obtain a tissue sample for histological examination. Endometrial biopsy is the less invasive option, but it may not give conclusive results every time. Hysteroscopy only shows the gross anatomy of the endometrium, which is often not indicative of cancer, and is therefore not used, unless in conjunction with a biopsy. Hysteroscopy can be used to confirm a diagnosis of cancer. New evidence shows that D&C has a higher false negative rate than endometrial biopsy.
Before treatment is begun, several other investigations are recommended. These include a chest x-ray, liver function tests, kidney function tests, and a test for levels of CA-125, a tumor marker that can be elevated in endometrial cancer.
Prostate cancer screening is an attempt to find unsuspected cancers. Initial screens may lead to more invasive follow-up tests such as a biopsy. Options include the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. Such screening is controversial and, in some people, may lead to unnecessary disruption and possibly harmful consequences. Routine screening with either a DRE or PSA is not supported by the evidence as there is no mortality benefit from screening.
The United States Preventive Services Task Force (USPSTF) recommends against the PSA test for prostate cancer screening in healthy men regardless of age. They concluded that the potential benefit of testing does not outweigh the expected harms. The Centers for Disease Control and Prevention shared that conclusion. The American Society of Clinical Oncology and the American College of Physicians discourages screening for those who are expected to live less than ten to fifteen years, while in those with a greater life expectancy a decision should be made by the person in question based on the potential risks and benefits. In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment." American Urological Association (AUA 2013) guidelines call for weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a ten-year period against the known harms associated with diagnostic tests and treatment. The AUA recommends screening decisions in those 55 to 69 be based on shared decision making, and that if screening is performed it should occur no more often than every two years.
In those who are being regularly screened, 5-alpha-reductase inhibitor (finasteride and dutasteride) reduce the overall risk of being diagnosed with prostate cancer; however, there is insufficient data to determine if they have an effect on the risk of death and may increase the chance of more serious cases.
Checking the cervix by the Papanicolaou test, or Pap test, for cervical cancer has been credited with dramatically reducing the number of cases of and mortality from cervical cancer in developed countries. Pap test screening every three to five years with appropriate follow-up can reduce cervical cancer incidence up to 80%. Abnormal results may suggest the presence of precancerous changes, allowing examination and possible preventive treatment. The treatment of low-grade lesions may adversely affect subsequent fertility and pregnancy. Personal invitations encouraging women to get screened are effective at increasing the likelihood they will do so. Educational materials also help increase the likelihood women will go for screening, but they are not as effective as invitations.
According to the 2010 European guidelines, the age at which to start screening ranges between 20 and 30 years of age, but preferentially not before age 25 or 30 years, and depends on burden of the disease in the population and the available resources.
In the United States, screening is recommended to begin at age 21, regardless of age at which a woman began having sex or other risk factors. Pap tests should be done every three years between the ages of 21 and 65. In women over the age of 65, screening may be discontinued if no abnormal screening results were seen within the previous 10 years and no history of CIN 2 or higher exists. HPV vaccination status does not change screening rates. Screening can occur every 5 years between ages 30 and 65 when a combination of cervical cytology screening and HPV testing is used and this is preferred. However, it is acceptable to screen this age group with a Pap test alone every three years. Screening is not beneficial before age 25 as the rate of disease is low. Screening is not beneficial in women older than 60 years if they have a history of negative results. The American Society of Clinical Oncology (ASCO) guideline has recommend for different levels of resource availability.
Liquid-based cytology is another potential screening method. Although it was probably intended to improve on the accuracy of the Pap test, its main advantage has been to reduce the number of inadequate smears from around 9% to around 1%. This reduces the need to recall women for a further smear. The United States Preventive Services Task Force supports screening every 5 years in those who are between 30 and 65 years when cytology is used in combination with HPV testing.
Pap tests have not been as effective in developing countries. This is in part because many of these countries have an impoverished health care infrastructure, too few trained and skilled professionals to obtain and interepret Pap tests, uninformed women who get lost to follow-up, and a lengthy turn-around time to get results. These realities have resulted in the investigation of cervical screening approaches that use fewer resources and offer rapid results such as visual inspection with acetic acid or HPV DNA testing.
The tumor marker CA-125 is frequently elevated in endometrial cancer and can be used to monitor response to treatment, particularly in serous cell cancer or advanced disease. Periodic MRIs or CT scans may be recommended in advanced disease and women with a history of endometrial cancer should receive more frequent pelvic examinations for the five years following treatment. Examinations conducted every three to four months are recommended for the first two years following treatment, and every six months for the next three years.
Women with endometrial cancer should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival, and because it has its own costs and side effects. If a recurrence is suspected, PET/CT scanning is recommended.
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.
Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination, rather than surgical findings. It allows only these diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical conization.
For many patients with stage I cancer, adjuvant (preventative) therapy following surgery may not be appropriate and patients will undergo surveillance instead. The form this surveillance takes, e.g. the type and frequency of investigations and the length time it should continue, will depend on the type of cancer (non-seminoma or seminoma), but the aim is to avoid unnecessary treatments in the many patients who are cured by their surgery, and ensure that any relapses with metastases (secondary cancers) are detected early and cured. This approach ensures that chemotherapy and or radiotherapy is only given to the patients that need it. The number of patients ultimately cured is the same using surveillance as post-operative “adjuvant” treatments, but the patients have to be prepared to follow a prolonged series of visits and tests.
For both non-seminomas and seminomas, surveillance tests generally include physical examination, blood tests for tumor markers, chest x-rays and CT scanning. However, the requirements of a surveillance program differ according to the type of disease since, for seminoma patients, relapses can occur later and blood tests are not as good at indicating relapse.
CT scans are performed on the abdomen (and sometimes the pelvis) and also the chest in some hospitals. Chest x-rays are increasingly preferred for the lungs as they give sufficient detail combined with a lower false-positive rate and significantly smaller radiation dose than CT.
The frequency of CT scans during surveillance should ensure that relapses are detected at an early stage while minimizing the radiation exposure.
For patients treated for stage I non-seminoma, a randomised trial (Medical Research Council TE08) showed that, when combined with the standard surveillance tests described above, 2 CT scans at 3 and 12 months were as good as 5 over 2 years in detecting relapse at an early stage.
For patients treated for stage I seminoma who choose surveillance rather than undergoing adjuvant therapy, there have been no randomized trials to determine the optimum frequency of scans and visits, and the schedules vary very widely across the world, and within individual countries. In the UK there is an ongoing clinical trial called TRISST. This is assessing how often scans should take place and whether magnetic resonance imaging (MRI) can be used instead of CT scans. MRI is being investigated because it does not expose the patient to radiation and so, if it is shown to be as good at detecting relapses, it may be preferable to CT.
For more advanced stages of testicular cancer, and for those cases in which radiation therapy or chemotherapy was administered, the extent of monitoring (tests) after treatment will vary on the basis of the circumstances, but normally should be done for five years in uncomplicated cases and for longer in those with higher risks of relapse.
The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.
A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.
Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, even though the unit treated more men with the worst prognosis.
Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers
Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy. In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.
Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).
People with Barrett's esophagus (a change in the cells lining the lower esophagus) are at much higher risk, and may receive regular endoscopic screening for the early signs of cancer. Because the benefit of screening for adenocarcinoma in people without symptoms is unclear, it is not recommended in the United States. Some areas of the world with high rates of squamous-carcinoma have screening programs.
Inhibin, a hormone, has been used as tumor marker for granulosa cell tumor.
Staging is based on the TNM staging system, which classifies the amount of tumor invasion (T), involvement of lymph nodes (N), and distant metastasis (M). The currently preferred classification is the 2010 AJCC staging system for cancer of the esophagus and the esophagogastric junction. To help guide clinical decision making, this system also incorporates information on cell type (ESCC, EAC, etc.), grade (degree of differentiation – an indication of the biological aggressiveness of the cancer cells), and tumor location (upper, middle, lower, or junctional).
Estrogens are produced by "functioning" tumours, and the clinical presentation depends on the patient's age and sex.
- Female
- If the patient is postmenopausal, she usually presents with abnormal uterine bleeding, and in some cases hemoperitoneum.
- If the patient is of reproductive age, she would present with menometrorrhagia. However, in some cases she may stop ovulating altogether.
- If the patient has not undergone puberty, early onset of puberty may be seen.
- these tumors tend to have late recurrencies ( even after 30 years )
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.
An area of research is the search for endometriosis markers.
In 2010 essentially all proposed biomarkers for endometriosis were of unclear medical use, although some appear to be promising. The one biomarker that has been in use over the last 20 years is CA-125. A 2016 review found that in those with symptoms of endometriosis and once ovarian cancer has been ruled out, a positive CA-125 may confirm the diagnosis. Its performance in ruling out endometriosis; however, is low. CA-125 levels appear to fall during endometriosis treatment, but has not shown a correlation with disease response.
Another review in 2011 identified several putative biomarkers upon biopsy, including findings of small sensory nerve fibers or defectively expressed β3 integrin subunit. It has been postulated a future diagnostic tool for endometriosis will consist of a panel of several specific and sensitive biomarkers, including both substance concentrations and genetic predisposition.
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.
Surgically, endometriosis can be staged I–IV by the revised classification of the American Society of Reproductive Medicine from 1997. The process is a complex point system that assesses lesions and adhesions in the pelvic organs, but it is important to note staging assesses physical disease only, not the level of pain or infertility. A person with Stage I endometriosis may have a little disease and severe pain, while a person with Stage IV endometriosis may have severe disease and no pain or vice versa. In principle the various stages show these findings:
- Stage I (Minimal)
- Stage II (Mild)
- Stage III (Moderate)
- Stage IV (Severe)
The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:
"Amsterdam Criteria (all bullet points must be fulfilled):"
- Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two
- Two successive affected generations
- One or more colon cancers diagnosed under age 50 years
- Familial adenomatous polyposis (FAP) has been excluded
"Amsterdam Criteria II (all bullet points must be fulfilled):"
- Three or more family members with HNPCC-related cancers, one of whom is a first-degree relative of the other two
- Two successive affected generations
- One or more of the HNPCC-related cancers diagnosed under age 50 years
- Familial adenomatous polyposis (FAP) has been excluded
Genetic testing for mutations in DNA mismatch repair genes is expensive and time-consuming, so researchers have proposed techniques for identifying cancer patients who are most likely to be HNPCC carriers as ideal candidates for genetic testing. The Amsterdam Criteria (see below) are useful, but do not identify up to 30% of potential Lynch syndrome carriers. In colon cancer patients, pathologists can measure microsatellite instability in colon tumor specimens, which is a surrogate marker for DNA mismatch repair gene dysfunction. If there is microsatellite instability identified, there is a higher likelihood for a Lynch syndrome diagnosis. Recently, researchers combined microsatellite instability (MSI) profiling and immunohistochemistry testing for DNA mismatch repair gene expression and identified an extra 32% of Lynch syndrome carriers who would have been missed on MSI profiling alone. Currently, this combined immunohistochemistry and MSI profiling strategy is the most advanced way of identifying candidates for genetic testing for the Lynch syndrome.
Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.
Adenomyosis can vary widely in the extent and location of its invasion within the uterus. As a result, there are no established pathognomonic features to allow for a definitive diagnosis of adenomyosis through non-invasive imaging. Nevertheless, non-invasive imaging techniques such as transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) can both be used to strongly suggest the diagnosis of adenomyosis, guide treatment options, and monitor response to treatment. Indeed, TVUS and MRI are the only two practical means available to establish a pre-surgical diagnosis.