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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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In the United States screening is typically recommended between the age of 50 and 75 years. For those between 76 and 85 years of age the decision to screen should be individualized. A number of screening methods can be used including stool based tests every 3 years, sigmoidoscopy every 5 years and colonoscopy every 10 years. For those at high risk, screenings usually begin at around 40. It is unclear which of these two methods is better. Colonoscopy may find more cancers in the first part of the colon but is associated with greater cost and more complications. For people with average risk who have had a high-quality colonoscopy with normal results, the American Gastroenterological Association does not recommend any type of screening in the 10 years following the colonoscopy. For people over 75 or those with a life expectancy of less than 10 years, screening is not recommended. It takes about 10 years after screening for one out of a 1000 people to benefit.
In Canada, among those 50 to 75 at normal risk, fecal immunochemical testing or FOBT is recommended every two years or sigmoidoscopy every 10 years. Colonoscopy is less preferred.
Some countries have national colorectal screening programs which offer FOBT screening for all adults within a certain age group, typically starting between age 50 and 60. Examples of countries with organised screening include the United Kingdom, Australia and the Netherlands.
Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk. Aspirin is recommended in those who are 50 to 60 years old, do not have an increased risk of bleeding, and are at risk for cardiovascular disease to prevent colorectal cancer. It is not recommended in those at average risk. There is tentative evidence for calcium supplementation, but it is not sufficient to make a recommendation. Vitamin D intake and blood levels are associated with a lower risk of colon cancer.
While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children..
The two biggest risk factors for ovarian carcinoma are age and family history.
These aggressive tumors are generally diagnosed at advanced stages and survival is generally shorter. The prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. One study suggests that its dismal prognosis seems to be caused by its intrinsic tumor biology, suggesting an area for further research.
Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis.
Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood to distant sites, tissues, or organs.
In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma "in situ", and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas).
In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options.
Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis of the malignancy.
The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon and bladder cancer staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.
The UICC/AJCC TNM systems are most often used. For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used.
Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor and occurs mainly in men ages 38 to 83. However, one such patient treated with a radical cystectomy followed by combined S-1 and Cisplatin adjuvant chemotherapy did demonstrate promising long-term survival of 90 months.
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.
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
An important anatomic landmark in anal cancer is the pectinate line (dentate line), which is located about 1–2 cm from the anal verge (where the anal mucosa of the anal canal becomes skin). Anal cancers located above this line (towards the head) are more likely to be carcinomas, whilst those located below (towards the feet) are more likely to be squamous cell carcinomas that may ulcerate. Anal cancer is strongly associated with ulcerative colitis and the sexually transmissible infections HPV and HIV. Anal cancer may be a cause of constipation or tenesmus, or may be felt as a palpable mass, although it may occasionally present as an ulcerative form.
Anal cancer is investigated by biopsy and may be treated by excision and radiotherapy, or with external beam radiotherapy and adjunctive chemotherapy. The five-year survival rate with the latter procedure is above 70%.
Diet and lifestyle are believed to play a large role in whether colorectal polyps form. Studies show there to be a protective link between consumption of cooked green vegetables, brown rice, legumes, and dried fruit and decreased incidence of colorectal polyps.
Colorectal cancer is a disease of old age: It typically originates in the secretory cells lining the gut, and risk factors include diets low in vegetable fibre and high in fat. If a younger person gets such a cancer, it is often associated with hereditary syndromes like Peutz-Jegher's, hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis. Colorectal cancer can be detected through the bleeding of a polyp, colicky bowel pain, a bowel obstruction or the biopsy of a polyp at a screening colonoscopy. A constant feeling of having to go to the toilet or anemia might also point to this kind of cancer.
Use of a colonoscope can find these cancers, and a biopsy can reveal the extent of the involvement of the bowel wall. Removal of a section of the colon is necessary for treatment, with or without chemotherapy. Colorectal cancer has a comparatively good prognosis when detected early.
Cancer screening uses medical tests to detect disease in large groups of people who have no symptoms. For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life. This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%). High risk people are those age 55–74 who have smoked equivalent amount of a pack of cigarettes daily for 30 years including time within the past 15 years.
CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment. For each true positive scan there are about 19 falsely positives scans. Other concerns include radiation exposure and the cost of testing along with follow up. Research has not found two other available tests—sputum cytology or chest radiograph (CXR) screening tests—to have any benefit.
The United States Preventive Services Task Force (USPSTF) recommends yearly screening using low-dose computed tomography in those who have a total smoking history of 30 pack-years and are between 55 and 80 years old until a person has not been smoking for more than 15 years. Screening should not be done in those with other health problems that would make treatment of lung cancer if found not an option. The English National Health Service was in 2014 re-examining the evidence for screening.
Small carcinoids (<2 cm) without features of malignancy may be treated by appendectomy if complete removal is possible. Other carcinoids and adenocarcinomas may require right hemicolectomy. Note: the term "carcinoids" is outdated: these tumors are now more accurately called "neuroendocrine tumors." For more information, see "appendiceal neuroendocrine tumors."
Pseudomyxoma peritonei treatment includes cytoreductive surgery which includes the removal of visible tumor and affected essential organs within the abdomen and pelvis. The peritoneal cavity is infused with heated chemotherapy known as HIPEC in an attempt to eradicate residual disease. The surgery may or may not be preceded or followed with intravenous chemotherapy or HIPEC.
The prognosis of EMECL is relatively good, and considerably better than most other forms of NSCLC. The skull and dura are possible sites for metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of malignant potential.
The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers:
- Strongly recommends cervical cancer screening in women who are sexually active and have a cervix at least until the age of 65.
- Recommend that Americans be screened for colorectal cancer via fecal occult blood testing, sigmoidoscopy, or colonoscopy starting at age 50 until age 75.
- Evidence is insufficient to recommend for or against screening for skin cancer, oral cancer, lung cancer, or prostate cancer in men under 75.
- Routine screening is not recommended for bladder cancer, testicular cancer, ovarian cancer, pancreatic cancer, or prostate cancer.
- Recommends mammography for breast cancer screening every two years from ages 50–74, but does not recommend either breast self-examination or clinical breast examination. A 2013 Cochrane review concluded that breast cancer screening by mammography had no effect in reducing mortality because of overdiagnosis and overtreatment.
Screens for gastric cancer using photofluorography due to the high incidence there.
EMECL is staged in the same manner as other non-small cell lung carcinomas, based on the TNM (Tumor-Node-Metastasis) staging system.
This disease is often discovered during surgery for other conditions, e.g., hernia repair, following which an experienced pathologist can confirm the diagnosis. Advanced stages may present as tumors palpable on the abdomen or distention of the belly ("jelly belly" is sometimes used as a slang term for the condition). Due to the rarity of this disease, it is important to obtain an accurate diagnosis so that appropriate treatment may be obtained from a surgical oncologist who specializes in appendix cancer. Diagnostic tests may include CT scans, examination of tissue samples obtained through laparoscopy, and the evaluation of tumor markers. In most cases a colonoscopy is unsuitable as a diagnostic tool because in most cases appendix cancer invades the abdominal cavity but not the colon (however, spread inside the colon is occasionally reported). PET scans may be used to evaluate high-grade mucinous adenocarcinoma, but this test is not reliable for detecting low-grade tumors because those do not take up the dye which shows up on scans. New MRI procedures are being developed for disease monitoring, but standard MRIs are not typically used as a diagnostic tool. Diagnosis is confirmed through pathology.
Monitoring involves the provision of outpatient colonoscopy, and occasionally upper gastric tract esophagogastroduodenoscopy (EGD, to search for premalignant gastric or duodenal tumors), typically once every 1–3 years, and/or a genetic blood test to definitively confirm or deny susceptibility. A small number of polyps can often be excised (removed) during the procedure, if found, but if there are more severe signs or numbers, in patient surgery may be required.
NCBI states that when an individual is identified as having FAP, or the mutations resulting in FAP: "It is appropriate to evaluate the parents of an affected individual (a) with molecular genetic testing of APC if the disease-causing mutation is known in the proband [person first identified with the condition] or (b) for clinical manifestations of APC-associated polyposis conditions".
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.
Because of the way familial polyposis develops, it is possible to have the genetic condition, and therefore be at risk, but have no polyps or issues so far. Therefore, an individual may be diagnosed "at risk of" FAP, and require routine monitoring, but not (yet) actually have FAP (i.e., carries a defective gene but as yet appears not to have any actual medical issue as a result of this). Clinical management can cover several areas:
- Identifying those individuals who could be at risk of FAP: usually from family medical history or genetic testing
- Diagnosis (confirming whether they have FAP)—this can be done either by genetic testing, which is definitive, or by visually checking the intestinal tract itself.
- Screening / monitoring programs involve visually examining the intestinal tract to check its healthy condition. It is undertaken as a routine matter every few years where there is cause for concern, when either (a) a genetic test has confirmed the risk or (b) a genetic test has not been undertaken for any reason so the actual risk is unknown. Screening and monitoring allows polyposis to be detected visually before it can become life-threatening.
- Treatment, typically surgery of some kind, is involved if polyposis has led to a large number of polyps, or a significant risk of cancer, or actual cancer.
Antibodies may be used to determine the expression of protein markers on the surface of cancer cells. Often the expression of these antigens is similar to the tissue that the cancer grew from, so immunohistochemical testing sometimes helps to identify the source of the cancer. Individual tests often do not provide definitive answers, but sometimes patterns may be observed, suggesting a particular site of origin (e.g. lung, colon, etc.). Immunohistochemical testing suggests a single source of cancer origin in about one in four cases of CUP. However, there is a lack of definitive research data showing that treatment guided by information from immunohistochemical testing improves outcomes or long-term prognosis.
Carcinoma "in situ" is, by definition, a localized phenomenon, with no potential for metastasis unless it progresses into cancer. Therefore, its removal eliminates the risk of subsequent progression into a life-threatening condition.
Some forms of CIS (e.g., colon polyps and polypoid tumours of the bladder) can be removed using an endoscope, without conventional surgical resection. Dysplasia of the uterine cervix is removed by excision (cutting it out) or by burning with a laser. Bowen's disease of the skin is removed by excision. Other forms require major surgery, the best known being intraductal carcinoma of the breast (also treated with radiotherapy). One of the most dangerous forms of CIS is the "pneumonic form" of BAC of the lung, which can require extensive surgical removal of large parts of the lung. When too large, it often cannot be completely removed, with eventual disease progression and death of the patient.
Many imaging modalities are used to aid in the diagnosis of primary liver cancer. For HCC these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.
Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders.
Colorectal polyps can be detected using a faecal occult blood test, flexible sigmoidoscopy, colonoscopy, virtual colonoscopy, digital rectal examination, barium enema or a pill camera.
Malignant potential is associated with
- degree of dysplasia
- Type of polyp (e.g. villous adenoma):
- Tubular Adenoma: 5% risk of cancer
- Tubulovillous adenoma: 20% risk of cancer
- Villous adenoma: 40% risk of cancer
- Size of polyp:
- <1 cm =<1% risk of cancer
- 1 cm=10% risk of cancer
- 2 cm=15% risk of cancer
Normally an adenoma which is greater than 0.5 cm is treated