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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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
This type of cancer occurs most often in Caucasians between 60 and 80 years of age, and its rate of incidence is about twice as high in males as in females. There are roughly 1,500 new cases of MCC diagnosed each year in the United States, as compared to around 60,000 new cases of melanoma and over 1 million new cases of nonmelanoma skin cancer. MCC is sometimes mistaken for other histological types of cancer, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, and small cell carcinoma, or as a benign cyst. Researchers believe that exposure to sunlight or ultraviolet light (such as in a tanning bed) may increase the risk of developing this disease. Similar to melanoma, the incidence of MCC in the US is increasing rapidly.
Immunosuppression can profoundly increase the odds of developing Merkel-cell carcinoma. Merkel-cell carcinoma occurs 30 times more often in people with chronic lymphocytic leukemia and 13.4 times more often in people with advanced HIV as compared to the general population; solid organ transplant recipients have a 10-fold increased risk compared to the general population.
The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013. Risk factors for squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 60 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair Celtic skin and chronically exposed to UV radiation. Squamous cell carcinoma of the skin is the most common among all sites of the body. Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.
People who have received solid organ transplants are at a significantly increased risk of developing squamous cell carcinoma due to the use of chronic immunosuppressive medication. While the risk of developing all skin cancers increases with these medications, this effect is particularly severe for SCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma. The incidence of SCC development increases with time posttransplant. Heart and lung transplant recipients are at the highest risk of developing SCC due to more intensive immunosuppressive medications used. Squamous cell cancers of the skin in individuals on immunotherapy or suffering from lymphoproliferative disorders (i.e. leukemia) tend to be much more aggressive, regardless of their location. The risk of SCC, and non-melanoma skin cancers generally, varies with the immunosuppressive drug regimen chosen. The risk is greatest with calcineurin inhibitors like cyclosporine and tacrolimus, and least with mTOR inhibitors, such as sirolimus and everolimus. The antimetabolites azathioprine and mycophenolic acid have an intermediate risk profile.
Other associations include exposure to smoking, pesticides, and working in petroleum refining or rubber manufacturing.
Glioblastoma has been associated with the viruses SV40, HHV-6, and cytomegalovirus.
Use of the kangri pot has been correlated with the risk of Kangri cancer. The pot holds hot wood and charcoal, and as a unit, the pot is put in direct contact with the skin of the abdomen and the thigh areas as a way to keep warm during winters in north India. Elements that are believed to contribute to the development of Kangri cancer are heat, burning wood particles, smoke, soot, and tar of burnt chinar leaves that could also be used as a fuel source for burning in the production of heat.
In one study, researchers noted kangri pot usage patterns and found that Kangri cancer “patients gave the history of using the Kangri especially for 3-4 winter months [...] every year for 5-6 hours daily.”
Tobacco smoking is by far the main contributor to lung cancer. Cigarette smoke contains at least 73 known carcinogens, including benzo["a"]pyrene, NNK, 1,3-butadiene and a radioactive isotope of polonium, polonium-210. Across the developed world, 90% of lung cancer deaths in men during the year 2000 were attributed to smoking (70% for women). Smoking accounts for about 85% of lung cancer cases.
Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be defined as someone living or working with a smoker. Studies from the US, Europe and the UK have consistently shown a significantly increased risk among those exposed to passive smoke. Those who live with someone who smokes have a 20–30% increase in risk while those who work in an environment with secondhand smoke have a 16–19% increase in risk. Investigations of sidestream smoke suggest it is more dangerous than direct smoke. Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.
Marijuana smoke contains many of the same carcinogens as those in tobacco smoke. However, the effect of smoking cannabis on lung cancer risk is not clear. A 2013 review did not find an increased risk from light to moderate use. A 2014 review found that smoking cannabis doubled the risk of lung cancer.
Beyond the behavioral risk factor of prolonged usage of Kangri pots, researchers have begun to look at genetic mutations that may make some people more predisposed to develop Kangri cancer.
- In one study, compared to a control group, people with Kangri cancer were found to be approximately twice as likely to have a mutation in the TP53 gene (codon 72 polymorphism). Patients with higher grade tumors exhibited more proline amino acid mutations at this site.
- Another study confirmed this association of Kangri Cancer and TP53 mutations, specifically substitutions and insertions, in 40% of the Kangri cancer patients who were studied. The researchers observed a significant correlation with mutation status and age as well as with the presence of lymph nodes in patients. TP53 may, in the future, serve as “potential molecular marker and prognostic tool” for Kangri cancer. Furthermore, PTEN mutations were found in two of thirty patients studied; though due to the small sample size, no useful conclusions could be postulated.
- Two polymorphisms of the HSP70 gene were discovered to be correlated with “poor prognosis” of Kangri cancer; the “Hsp70-2 A/G or G/G and Hsp70homC/C genotypes” could potentially be utilized to measure risk of Kangri cancer development as well as to predict prognosis.
No links have been found with the consumption of cured meat or electromagnetic fields, such as from cell phones and electrical wiring within homes.
Links that are unclear include those with formaldehyde and radiation exposure from medical imaging.
Outdoor air pollutants, especially chemicals released from the burning of fossil fuels, increase the risk of lung cancer. Fine particulates (PM) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk. For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is estimated to account for 1–2% of lung cancers.
Tentative evidence supports an increased risk of lung cancer from indoor air pollution related to the burning of wood, charcoal, dung or crop residue for cooking and heating. Women who are exposed to indoor coal smoke have about twice the risk and a number of the by-products of burning biomass are known or suspected carcinogens. This risk affects about 2.4 billion people globally, and is believed to account for 1.5% of lung cancer deaths.
The overall 5-year survival rate of anaplastic thyroid cancer has been given as 7% or 14%, although the latter has been criticized as being overestimated.
Treatment of anaplastic-type carcinoma is generally palliative in its intent for a disease that is rarely cured and almost always fatal, with worse prognosis associated with large tumours, distant metastases, acute obstructive symptoms, and leukocytosis. Death is attributable to upper airway obstruction and suffocation in half of patients, and to a combination of complications of local and distant disease, or therapy, or both in the remainder.
Anaplastic thyroid cancer is extremely aggressive; in most cases death occurs in less than 1 year as a result of aggressive local growth and compromise of vital structures in the neck. ATC in most series has a median survival of 4 to 5 months from the time of diagnosis, with rare long-term survivors.
Basal-cell cancer is a very common skin cancer. It is much more common in fair-skinned individuals with a family history of basal-cell cancer and increases in incidence closer to the equator or at higher altitude. There are approximately 800,000 new cases yearly in the United States alone. Up to 30% of Caucasians develop basal-cell carcinomas in their lifetime. In Canada, the most common skin cancer is basal cell carcinoma (as much as one third of all cancer diagnoses), affecting 1 in 7 individuals over a lifetime.
In the United States approximately 3 out of 10 caucasians develop a basal cell carcinoma during their lifetime. This tumor accounts for approximately 70% of non-melanoma skin cancers. In 80 percent of all cases, basal cell carcinoma affects the skin of head and neck. Furthermore, there appears to be an increase in the incidence of basal-cell cancer of the trunk in recent years.
Most sporadic BCC arises in small numbers on sun-exposed skin of people over age 50, although younger people may also be affected. The development of multiple basal-cell cancer at an early age could be indicative of nevoid basal-cell carcinoma syndrome, also known as Gorlin's Syndrome.
In the 1960s, the incidence 5 years after a radical mastectomy varied from 0.07% to 0.45%.
Today, it occurs in 0.03% of patients surviving 10 or more years after radical mastectomy.
A newly discovered virus called Merkel cell polyomavirus (MCV) likely contributes to the development of the majority of MCC. Approximately 80% of MCC have this virus integrated in a monoclonal pattern, indicating that the infection was present in a precursor cell before it became cancerous. At least 20% of MCC tumors are not infected with MCV, suggesting that MCC may have other causes as well.
Polyomaviruses have been known to be oncogenic (cancer-causing) viruses in animals since the 1950s, but MCV is the first polyomavirus strongly suspected to cause tumors in humans. Like other tumor viruses, most people who are infected with MCV probably do not develop MCC. It is currently unknown what other steps or co-factors are required for MCC-type cancers to develop. MCC can also occur together with other sun exposure-related skin cancers that are not infected with MCV (i.e. basal cell carcinoma, squamous cell carcinoma, melanoma). Intriguingly, most MCV viruses obtained so far from tumors have specific mutations that render the virus uninfectious. It is unknown whether these particular mutations result from sun exposure. MCC also occurs more frequently than would otherwise be expected among immunosuppressed patients, such as transplant patients, AIDS patients, and the elderly persons, suggesting that the initiation and progression of the disease is modulated by the immune system.
While infection with MCV is common in humans, MCC patients whose tumors contain MCV have higher antibody levels against the virus than similarly infected healthy adults. A recent study of a large patient registry from Finland suggests that individuals with MCV-positive MCC's have better prognoses than do MCC patients without MCV infection. While MCV-positive MCC may be a less aggressive form of the disease, the results of the aforementioned study may instead be due to significant differences in other confounding factors, including tumor stage at the time of diagnosis, the age of the patient, or the location of the tumor rather than any intrinsic difference in disease aggressiveness or response to therapy.
Micrometastasis is a form of metastasis (the spread of a cancer from its original location to other sites in the body) in which the newly formed tumors are too minuscule to be detected.
Adjuvant chemotherapy and adjuvant radiotherapy are directed at killing any micrometastases, thus preventing relapse (regrowth of the cancer) and the (likely) death of the patient. Early detection of micrometastases could identify the patients who are most (and least) likely to benefit from adjuvant therapy.
Basal-cell carcinoma is a common skin cancer and occurs mainly in fair-skinned patients with a family history of this cancer. Sunlight is a factor in about two-thirds of these cancers; therefore, doctors recommend sunscreens with at least SPF 30. One-third occur in non-sun-exposed areas; thus, the pathogenesis is more complex than UV exposure as "the" cause.
The use of a chemotherapeutic agent such as 5-Fluorouracil or imiquimod, can prevent development of skin cancer. It is usually recommended to individuals with extensive sun damage, history of multiple skin cancers, or rudimentary forms of cancer (i.e., solar keratosis). It is often repeated every 2 to 3 years to further decrease the risk of skin cancer.
Unlike its differentiated counterparts, anaplastic thyroid cancer is highly unlikely to be curable either by surgery or by any other treatment modality, and is in fact usually unresectable due to its high propensity for invading surrounding tissues.
Palliative treatment consists of radiation therapy usually combined with chemotherapy.
New drugs, such as fosbretabulin (a type of combretastatin), bortezomib and TNF-Related Apoptosis Induced Ligand (TRAIL), are however being under investigation "in vitro" and in human clinical studies. Based on encouraging Phase I and II clinical trial results with fosbretabulin, a type of drug that selectively destroys tumor blood vessels, a large, multi-national clinical trial is being undertaken to determine whether the drug can extend the survival of patients with ATC.
Esthesioneuroblastoma is a slow developing but malignant tumor with high reoccurrence rates because of its anatomical position. The tumor composition, location and metastatic characteristics as well as the treatment plan determine prognosis. Common clinical classification systems for esthesioneuroblastoma include the Kadish classification and the Dulguerov classfictation. Histopathological characteristics on top of Kadish classification can further determine cancer prognosis. In severe, Kadish class C tumors, Haym's grades of pathology are important for prognosis. Patients with low grade Kadish class C tumors have a 10-year survival rate of 86 percent compared to patients with high grade class C tumors who have a survival rate of 28 percent. Surgically treated patients with high grade tumors are more likely to experience leptomeningeal metastases or involvement of the cerebral spinal fluid unlike patients with low grade tumors who usually only see local recurrence. Survival rates for treated esthesioneuroblastoma are best for surgery with radiotherapy (65%), then for radiotherapy and chemotherapy (51%), just surgery (48%), surgery, radiotherapy and chemotherapy (47) and finally just radiotherapy (37%). From the literature, radiotherapy and surgery seem to boast the best outcome for patients. However, it is important to understand that to some degree, prognosis is related to tumor severity. More progressed, higher grade tumors would result in chemotherapy or radiotherapy as the only treatment. It is no surprise that the prognosis would be worse in these cases.
15% of lung cancers in the US are of this type. Small cell lung cancer occurs almost exclusively in smokers; most commonly in heavy smokers and rarely in non-smokers.
All in all, small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.
In "limited-stage" disease, median survival with treatment is 14–20 months, and about 20% of patients with limited-stage small-cell lung carcinoma live 5 years or longer. Because of its predisposition for early metastasis, the prognosis of SCLC is poor, with only 10% to 15% of patients surviving 3 years.
The prognosis is far more grim in "extensive-stage" small-cell lung carcinoma; with treatment, median survival is 8–13 months; only 1–5% of patients with extensive-stage small-cell lung carcinoma treated with chemotherapy live 5 years or longer.
Early detection is key. Untreated patients usually live 5 to 8 months after diagnosis.
Sarcomas are quite rare with only 15,000 new cases per year in the United States. Sarcomas therefore represent about one percent of the 1.5 million new cancer diagnoses in that country each year.
Sarcomas affect people of all ages. Approximately 50% of bone sarcomas and 20% of soft tissue sarcomas are diagnosed in people under the age of 35. Some sarcomas, such as leiomyosarcoma, chondrosarcoma, and gastrointestinal stromal tumor (GIST), are more common in adults than in children. Most high-grade bone sarcomas, including Ewing's sarcoma and osteosarcoma, are much more common in children and young adults.
Radiation burns are caused by exposure to high levels of radiation. Levels high enough to cause burn are generally lethal if received as a whole-body dose, whereas they may be treatable if received as a shallow or local dose.
Esthesioneuroblastoma accounts for 2% of all intranasal tumors with an incidence of 0.4 cases per million people. Fewer than 700 cases of esthesioneuroblastoma have been seen in the US since 1988. Fewer than 400 unique cases have been reported globally. Esthesioneuroblastoma can occur at any time, with peak occurrence reported in the second and sixth decade of life.
Fluoroscopy may cause burns if performed repeatedly or for too long.
Similarly, Computed Tomography and traditional Projectional Radiography have the potential to cause radiation burns if the exposure factors and exposure time are not appropriately controlled by the operator.
A study of radiation induced skin injuries has been performed by the Food and Drug Administration (FDA) based on results from 1994, followed by an advisory to minimize further fluoroscopy-induced injuries. The problem of radiation injuries due to fluoroscopy has been further investigated in review articles in 2000, 2001, 2009 and 2010.
In addition to being named based on the tissue of origin, sarcomas are also assigned a grade (low, intermediate, or high) based on the presence and frequency of certain cellular and subcellular characteristics associated with malignant biological behavior. Low grade sarcomas are usually treated surgically, although sometimes radiation therapy or chemotherapy are used. Intermediate and high grade sarcomas are more frequently treated with a combination of surgery, chemotherapy and/or radiation therapy. Since higher grade tumors are more likely to undergo metastasis (invasion and spread to locoregional and distant sites), they are treated more aggressively. The recognition that many sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long-term survival for patients with localized osteosarcoma was only approximately 20%, but now has risen to 60–70%.