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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
Adult survivors of childhood cancer have some physical, psychological, and social difficulties.
Premature heart disease is a major long-term complication in adult survivors of childhood cancer. Adult survivors are eight times more likely to die of heart disease than other people, and more than half of children treated for cancer develop some type of cardiac abnormality, although this may be asymptomatic or too mild to qualify for a clinical diagnosis of heart disease.
Familial and genetic factors are identified in 5-15% of childhood cancer cases. In <5-10% of cases, there are known environmental exposures and exogenous factors, such as prenatal exposure to tobacco, X-rays, or certain medications. For the remaining 75-90% of cases, however, the individual causes remain unknown. In most cases, as in carcinogenesis in general, the cancers are assumed to involve multiple risk factors and variables.
Aspects that make the risk factors of childhood cancer different from those seen in adult cancers include:
- Different, and sometimes unique, exposures to environmental hazards. Children must often rely on adults to protect them from toxic environmental agents.
- Immature physiological systems to clear or metabolize environmental substances
- The growth and development of children in phases known as "developmental windows" result in certain "critical windows of vulnerability".
Also, a longer life expectancy in children avails for a longer time to manifest cancer processes with long latency periods, increasing the risk of developing some cancer types later in life.
There are preventable causes of childhood malignancy, such as delivery overuse and misuse of ionizing radiation through computed tomography scans when the test is not indicated or when adult protocols are used.
The environmental exposures that contribute to emergence of ALL is contentious and a subject of ongoing debate.
High levels of radiation exposure from nuclear fallout is a known risk factor for developing leukemia. Evidence whether less radiation, as from x-ray imaging during pregnancy, increases risk of disease remains inconclusive. Studies that have identified an association between x-ray imaging during pregnancy and ALL found only a slightly increased risk. Exposure to strong electromagnetic radiation from power lines has also been associated with a slightly increased risk of ALL. This result is questioned as no causal mechanism linking electromagnetic radiation with cancer is known.
High birth weight (greater than 4000g or 8.8lbs) is also associated with a small increased risk. The mechanism connecting high birth weight to ALL is also not known.
Evidence suggests that secondary leukemia can develop in individuals treated with certain types of chemotherapy, such as epipodophyllotoxins and cyclophosphamide.
A neuroectodermal tumor is a tumor of the central or peripheral nervous system.
Hemangioblastomas can cause polycythemia due to ectopic production of erythropoietin as a paraneoplastic syndrome.
Of all cancers involving the same class of blood cell, 2.3% of cases are Burkitt lymphoma. Epstein-Barr virus infection is strongly correlated with this cancer.
The majority of patients with neurocutaneous melanosis are asymptomatic and therefore have a good prognosis with few complications. Most are not diagnosed, so definitive data in not available. For symptomatic patients, the prognosis is far worse. In patients without the presence of melanoma, more than 50% die within 3 years of displaying symptoms. While those with malignancy have a mortality rate of 77% with most patients displaying symptoms before the age of 2.
The presence of a Dandy-Walker malformation along with neurocutaneous melanosis, as occurs in 10% of symptomatic patients, further deteriorates prognosis. The median survival time for these patients is 6.5 months after becoming symptomatic.
Papillary tumors of pineal region are extremely rare, constituting 0.4-1% of all central nervous system tumors. These tumors most commonly occur in adults with the mean age being 31.5. There have been cases reported for people between the ages 5 to 66 years. There is a slight predominance of females who have these tumors.
Taken together, haematological malignancies account for 9.5% of new cancer diagnoses in the United States and 30,000 patients in the UK are diagnosed each year. Within this category, lymphomas are more common than leukemias.
Tumors of the hematopoietic and lymphoid tissues or haematopoietic and lymphoid malignancies are tumors that affect the blood, bone marrow, lymph, and lymphatic system. As those elements are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation (and thus the leukemias and the lymphomas) closely related and often overlapping problems.
While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of haematological malignancies.
Haematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "Haematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all haematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
Hematological malignancies may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.
A subgroup of them are more severe and are known as haematological malignancies (American spelling hematological malignancies) or blood cancer. They may also be referred to as liquid tumors.
Papillary tumors of the pineal region (PTPR) were first described by A. Jouvet et al. in 2003 and were introduced in the World Health Organization (WHO) classification of Central Nervous System (CNS) in 2007. Papillary Tumors of the Pineal Region are located on the pineal gland which is located in the center of the brain. The pineal gland is located on roof of the diencephalon. It is a cone shaped structure dorsal to the midbrain tectum. The tumor appears to be derived from the specialized ependymal cells of the subcommissural organ. Papillary tumors of the central nervous system and particularly of the pineal region are very rare and so diagnosing them is extremely difficult.
Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. How it is handled depends primarily on the type of leukemia. Nearly all leukemias appearing in pregnant women are acute leukemias. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester. Chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with Interferon-alpha hormones. Treatment for chronic lymphocytic leukemias, which are rare in pregnant women, can often be postponed until after the end of the pregnancy.
Common inherited risk factors include mutations in "ARID5B", "CDKN2A/2B", "CEBPE", "IKZF1", "GATA3", "PIP4K2A" and, more rarely, "TP53". These genes play important roles in cellular development, proliferation, and differentiation. Individually, most of these mutations are low risk for ALL. Significant risk of disease occurs when a person inherits several of these mutations together.
The uneven distribution of genetic risk factors may help explain differences in disease rate among ethnic groups. For instance, the "ARID5B" mutation is less common in ethnic African populations.
Several genetic syndrome also carry increased risk of ALL. These include: Down syndrome, Fanconi anemia, Bloom syndrome, X-linked agammaglobulinemia, severe combined immunodeficiency, Shwachman-Diamond syndrome, Kostmann syndrome, neurofibromatosis type 1, ataxia-telangiectasia, paroxysmal nocturnal hemoglobinuria, and Li-Fraumeni syndrome. Fewer than 5% of cases are associated with a known genetic syndrome.
Rare mutations in "ETV6" and "PAX5" are associated with a familial form of ALL with autosomal dominant patterns of inheritance.
The disease is believed to be induced by a combination of Epstein Barr virus infection and immunosuppression through; immunosuppressive drugs (with case reports of methotrexate and azathioprine), infections such as HIV or chronic viral hepatitis or endogenous T-cell defects.
For low-grade tumors, the prognosis is somewhat more optimistic. Patients diagnosed with a low-grade glioma are 17 times as likely to die as matched patients in the general population.
The age-standardized 10-year relative survival rate was 47%. One study reported that low-grade oligodendroglioma patients have a median survival of 11.6 years; another reported a median survival of 16.7 years.
Lymphomatoid granulomatosis (LYG or LG) is a very rare lymphoproliferative disorder first characterized in 1972 with lymphomatoid meaning lymphoma-like and granulomatosis denoting one of its microscopic characteristics, polymorphic lymphoid infiltrates and focal necrosis within it. While most commonly found in middle age patients, it has been observed in young people with a study identifying 47 cases of patients aged 0–18 years in the literature. Males are found to be affected twice as often as females.
This group comprises anaplastic astrocytomas and glioblastoma multiforme. Whereas the median overall survival of anaplastic (WHO grade III) gliomas is approximately 3 years, glioblastoma multiforme has a poor median overall survival of ~15 months.
Hemangioblastoma are among the rarest central nervous system tumors, accounting for less than 2%. Hemangioblastomas usually occur in adults, yet tumors may appear in VHL syndrome at much younger ages. Men and women are approximately at the same risk. Although they can occur in any section of the central nervous system, they usually occur in either side of the cerebellum, the brain stem or the spinal cord.
Primary cerebral lymphoma (or "primary central nervous system lymphoma") is a form of NHL. It is very rare in immunocompetent people, with an incidence of 5–30 cases per million person-years. However the incidence in immunocompromised individuals is greatly increased, up to 100 per million person-years.
Primary cerebral lymphoma is strongly associated with Epstein–Barr virus (EBV). The presence of EBV DNA in cerebrospinal fluid is highly suggestive of primary cerebral lymphoma.
Treatment of AIDS patients with antiretroviral drugs reduces the incidence of primary cerebral lymphoma.
Mammary analogue secretory carcinoma (MASC) (also termed MASC; the "SG" subscript indicates salivary gland)) is a salivary gland neoplasm that shares a genetic mutation with certain types of breast cancer. MASC was first described by Skálová et al. in 2010. The authors of this report found a chromosome translocation in certain salivary gland tumors that was identical to the (12;15)(p13;q25) fusion gene mutation found previously in secretory carcinoma, a subtype of invasive ductal carcinoma of the breast.
Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies. The affected people may have a single gene or multiple genes in common. In some cases, families tend to develop the same kinds of leukemia as other members; in other families, affected people may develop different forms of leukemia or related blood cancers.
In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia. For example, people with Down syndrome have a significantly increased risk of developing forms of acute leukemia (especially acute myeloid leukemia), and Fanconi anemia is a risk factor for developing acute myeloid leukemia. Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia.
Chronic myelogenous leukemia is associated with a genetic abnormality called the Philadelphia translocation; 95% of people with CML carry the Philadelphia mutation, although this is not exclusive to CML and can be observed in people with other types of leukemia.
Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome associated with a broad variety of tumors including lung cancer, ovarian cancer, breast cancer, Hodgkin’s lymphoma and others. PCD is a rare condition that occurs in less than 1% of cancer patients.
As is the case with other paraneoplastic syndromes, PCD is believed to be due to an autoimmune reaction targeted against components of the central nervous system, mostly to Purkinje cells.
It is thought to be triggered when tumor cells (in PCD, most commonly ovarian or breast cancer) ectopically express proteins normally expressed in the cerebellum. This is believed to trigger an anti-tumor immune response that may be clinically significant, but also an anti-neural immune response. A broad spectrum of neuronal and glial proteins has been identified as target antigens in PCD.
Neurological symptoms may include, among others, dysarthria, truncal, limb and gait ataxia and nystagmus. Symptoms often develop subacutely and progress rapidly over a period of weeks or months to a plateau period that can last for months to years and which often reflects complete loss of Purkinje cells.
Of particular note, PCD symptoms precede the diagnosis of the underlying cancer in the majority of cases, and often present insidiously and progress rapidly for weeks to months to a severely disabled state followed by a variable plateau period that can last for months to years. Therefore, newly developing cerebellar ataxia should always prompt proper diagnostic measures to exclude PCD.
Tumor removal is still the therapeutic mainstay with very early treatment being essential to prevent irreversible neuronal loss. Immunosuppressive or immunomodulatory treatments are often ineffective. There may be a role for high-dose gammaglobulin therapy in the treatment PCD, but due to the rare occurrence of this disease, controlled trials of this therapy may be difficult.
Treatment with dose-adjusted EPOCH with rituximab has shown promising initial results in a small series of patients (n=17), with a 100% response rate, and 100% overall survival and progression-free survival at 28 months (median follow-up).
In order to remove it completely, surgery may be an option.It relieves the hydrocephalus (excess water in the brain) about half of the time.
Another treatment is chemotherapy, recommended for patients with severe problem.
The incidence of Hodgkin's disease in the general population is about 10–30 per million person-years. This increases to 170 per million person-years in HIV positive patients.