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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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Tobacco smoking is the main known contributor to urinary bladder cancer; in most populations, smoking is associated with over half of bladder cancer cases in men and one-third of cases among women, however these proportions have reduced over recent years since there are fewer smokers in Europe and North America. There is an almost linear relationship between smoking duration (in years), pack years and bladder cancer risk. A risk plateau at smoking about 15 cigarettes a day can be observed (meaning that those who smoke 15 cigarettes a day are approximately at the same risk as those smoking 30 cigarettes a day). Quitting smoking reduces the risk, however former smokers will most likely always be at a higher risk of bladder cancer compared to never smokers. Passive smoking has not been proven to be involved.
Thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens such as benzidine. 2-Naphthylamine, which is found in cigarette smoke, has also been shown to increase bladder cancer risk. Occupations at risk are bus drivers, rubber workers, motor mechanics, leather (including shoe) workers, blacksmiths, machine setters, and mechanics. Hairdressers are thought to be at risk as well because of their frequent exposure to permanent hair dyes.
In addition to these major risk factors there are also numerous other modifiable factors that are less strongly (i.e. 10–20% risk increase) associated with bladder cancer, for example, obesity. Although these could be considered as minor effects, risk reduction in the general population could still be achieved by reducing the prevalence of a number of smaller risk factor together.
It has been suggested that mutations at HRAS, KRAS2, RB1, and FGFR3 may be associated in some cases.
Compared to other breeds of dog, Scottish terriers have a much increased risk of developing transitional cell carcinoma.
A 2008 study commissioned by the World Health Organisation concluded that "specific fruit and vegetables may act to reduce the risk of bladder cancer." Fruit and yellow-orange vegetables, particularly carrots and those containing selenium, are probably associated with a moderately reduced risk of bladder cancer. Citrus fruits and cruciferous vegetables were also identified as having a possibly protective effect. However an analysis of 47,909 men in the Health Professionals Follow-Up Study showed little correlation between cancer reduction and high consumption of fruits and vegetables overall, or yellow or green leafy vegetables specifically, compared to the statistically significant reduction among those men who consumed large amounts of cruciferous vegetables.
In a 10-year study involving almost 49,000 men, researchers found that men who drank at least 1,44 L of water (around 6 cups) per day had a significantly reduced incidence of bladder cancer when compared with men who drank less. It was also found that: "the risk of bladder cancer decreased by 7% for every 240 mL of fluid added". The authors proposed that bladder cancer might partly be caused by the bladder directly contacting carcinogens that are excreted in urine, although this has not yet been confirmed in other studies.
Because most bladder cancers are invasive into the bladder wall, surgical removal is usually not possible. The majority of transitional cell carcinomas are treated with either traditional chemotherapy or nonsteroidal anti-inflammatory drugs.
Cancer prevalence in dogs increases with age and certain breeds are more susceptible to specific kinds of cancers. Millions of dogs develop spontaneous tumors each year. Boxers, Boston Terriers and Golden Retrievers are among the breeds that most commonly develop mast cell tumors. Large and giant breeds, like Great Danes, Rottweilers, Greyhound and Saint Bernards, are much more likely to develop bone cancer than smaller breeds. Lymphoma occurs at increased rates in Bernese Mountain dogs, bulldogs, and boxers. It is important for the owner to be familiar with the diseases to which their specific breed of dog might have a breed predisposition.
The prevention of feline cancer mainly depends on the cat's diet and lifestyle, as well as an ability to detect early signs and symptoms of cancer prior to advancement to a further stage. If cancer is detected at an earlier stage, it has a higher chance of being treated, therefore lessening the chances of fatality. Taking domesticated cats for regular checkups to the veterinarian can help spot signs and symptoms of cancer early on and help maintain a healthy lifestyle. Further, due to advancements in research, prevention of certain types of feline illnesses remains possible. A widely known preventative of feline leukemia virus is the vaccine which was created in 1969. Subsequently, an immunofloures-cent antibody (IFA) test for the detection of FeLV in the blood of infected cats was formulated. The IFA test was mainly used to experiment the chances of felines being exposed to cancer. The results showed that 33% of cats who were exposed to FeLV related diseases were at a higher risk for acquiring it, while the cats that were left unexposed were left unaffected. FeLV is either spread through contagion or infection and once infected it is possible for cats to stay that way for the rest of their lives.
Interaction with other Cats
Interaction with other cats with strains or diseases related to FeLV can be a great risk factor for cats attaining FeLV themselves. Therefore, a main factor in prevention is keeping the affected cats in quarantine from the unaffected cats. Stray cats, or indoor/outdoor cats have been shown to be at a greater risk for acquiring FeLV, since they have a greater chance of interacting with other cats. Domesticated cats that are kept indoors are the least vulnerable to susceptible diseases.
Vaccines
Vaccines help the immune system fight off disease causing organisms, which is another key to prevention. However, vaccines can also cause tumors if not given properly. Vaccines should be given in the right rear leg to ease tumor removal process. Vaccines given in the neck or in between the shoulder blades are most likely to cause tumors and are difficult to remove, which can be fatal to cats. Reducing the number of vaccinations given to a cat may also decrease the risk for it developing a tumor.
Spaying and Neutering
Spaying and neutering holds many advantages to cats, including lowering the risk for developing cancer. Neutering male cats makes them less subjected to testicular cancer, FeLV, and FIV. Spaying female cats lowers the risk for mammary cancer, ovarian, or uterine cancer, as it prevents them from going into heat. Female cats should be spayed before their first heat, as each cycle of heat creates a greater risk for mammary cancer. Spaying a female cat requires the removal of the ovaries and uterus, which would eliminate their chances of developing cancer in these areas.
Exposure to Sun
The risk of skin cancer increases when a cat is exposed to direct sunlight for prolonged periods. White cats, or cats with white faces and ears, should not be allowed out on sunny days. Between the hours of 10:00 am to 4:00 pm, it is recommended to keep domesticated cats indoors, as the sun is at its highest peak between these times. Sun block is also available for cats, which can help prevent skin irritation, and a veterinarian should be contacted to find out which brands are appropriate and to use on cats.
Exposure to Secondhand Smoke
Cats living in a smoker’s household are three times more likely to develop lymphoma. Compared to living in a smoke-free environment, cats exposed to secondhand smoke also have a greater chance of developing squamous cell carcinoma or mouth cancer. Cancer is also developed mostly due to the cat's grooming habits. As cats lick themselves while they groom, they increase chances of taking in the toxic, cancer-causing carcinogens that gather on their fur, which are then exposed to their mucus membranes.
Lifestyle
Providing a cat with the healthiest lifestyle possible is the key to prevention. Decreasing the amount of toxins, including household cleaning products, providing fresh and whole foods, clean and purified water, and reducing the amount of indoor pollution can help cats live a longer and healthier life. To lessen susceptibility to diseases, domesticated cats should be kept inside the household for most of their lives to reduce the risk of interacting with other stray cats that could be infected with diseases.
When cancer is determined as the illness affecting the cat, an important part of the healing process is determining the type of cancerous tumor present. This is helpful in selecting the best therapeutic approach and increases chances of recovery.
Breeds that may be more commonly affected include the English Cocker Spaniel, German Shepherd Dog, Alaskan Malamute, Dachshund, and Springer Spaniel. It is a disease of middle-age to older dogs and even though early reports described spayed females as more commonly affected, multiple recents studies have shown no gender overrepresentation.
Cancer is a complex, multifactorial disease. Carcinogenesis is linked with DNA mutations, chromosomal translocations, chocolate, dysfunctional proteins, and aberrant cell cycle regulators. Cancer alters the DNA of cells and the mutated genetic material is passed on to daughter cells, resulting in neoplasms. The mutated DNA effects genes involved with the cell cycle, classified as either oncogenes or tumor suppressor genes. Oncogenes are responsible for cell proliferation and differentiation. Oncogenes responsible for cell growth are overexpressed in cancerous cells. Tumor suppressor genes prevent cells with erroneous cell cycles from replicating. Cancer cells ignore cell cycle regulators that control cell growth, division, and death.
The histology of spontaneous tumorigenesis in canines is attributed to the multiplicity and complexity of the disease. The heterogeneity of its development encompasses inherited, epigenetic, and environmental factors.
The selective breeding techniques used with domestic dogs causes certain breeds to be at high risk for specific cancers. Selection for specific phenotypes in dog breeding causes long-range linkage disequilibrium in their DNA. Certain areas of alleles have the tendency to separate less frequently than normal random segregation, which leads to long ranges of repeated DNA sequences. These repeated sequences caused by decreased genetic diversity within breeds, can lead to a high prevalence of certain diseases and especially cancer in breeds.
Aggressive surgical removal of the tumor and any enlarged sublumbar lymph nodes is essential for treatment of the tumor and associated hypercalcaemia. There is a high recurrence rate, although removal of lymph nodes with metastasis may improve survival time. Radiation therapy and chemotherapy may be helpful in treatment. Severe hypercalcaemia is treated with aggressive IV fluid therapy using sodium chloride and medications such as loop diuretics (increased kidney excretion of calcium) and aminobisphosphonates (decreased calcium release from bones). A poorer prognosis is associated with large tumor size (greater than 10 cm), hypercalcaemia, and distante metastasis. Early, incidental diagnosis of small anal sac masses may lead to a better prognosis with surgery alone (ongoing study).
Most mammary tumors in rats are benign fibroadenomas, which are also the most common tumor in the rat. Less than 10 percent are adenocarcinomas. They occur in male and female rats. The tumors can be large and occur anywhere on the trunk. There is a good prognosis with surgery. Spayed rats have a decreased risk of developing mammary tumors.
Mammary tumors are the third most common neoplasia in cats, following lymphoid and skin cancers. The incidence of mammary tumors in cats is reduced by 91 percent in cats spayed prior to six months of age and by 86 percent in cats spayed prior to one year, according to one study. Siamese cats and Japanese breeds seem to have increased risk, and obesity also appears to be a factor in tumor development. Malignant tumors make up 80 to 96 percent of mammary tumors in cats, almost all adenocarcinomas. Male cats may also develop mammary adenocarcinoma, albeit rarely, and the clinical course is similar to female cats. As in dogs, tumor size is an important prognostic factor, although for tumors less than three centimeters the individual size is less predictive. According to one study, cats with tumors less than three cm had an average survival time of 21 months, and cats with tumors greater than three cm had an average survival of 12 months. About 10 percent of cat mammary tumors have estrogen receptors, so spaying at the time of surgery has little effect on recurrence or survival time. Metastasis tends to be to the lungs and lymph nodes, and rarely to bone. Diagnosis and treatment is similar to the dog. There is a better prognosis with bilateral radical surgery (removing the both mammary chains) than with more conservative surgery. Doxorubicin has shown some promise in treatment.
Surgical treatment remains the treatment of choice for cats and dogs diagnosed with intestinal tumors who are in otherwise good health.
The average age at which intestinal tumors are diagnosed ranges between 10–12 years for cats and 6 to 9 years for dogs. There are many different types of intestinal tumors, including lymphoma, adenocarcinoma, mast cell tumor, and leiomyosarcoma.
Many types of skin tumors, both benign (noncancerous) and malignant (cancerous), exist. Approximately 20-40% of primary skin tumors are malignant in dogs and 50-65%
are malignant in cats. Not all forms of skin cancer in cats and dogs are caused by sun exposure, but it can happen occasionally. On dogs, the nose and pads of the feet contain sensitive skin and no fur to protect from the sun. Also, cats and dogs with thin or light-colored coats are at a higher risk of sun damage over their entire bodies.
Tumors that develop within the liver may be either benign (noncancerous) or malignant (cancerous). Tumors can start in the liver, or spread to the liver from another cancer in the body. Malignant liver tumors have been reported to metastasize to other organs such as regional lymph nodes, lungs, kidneys, pancreas, spleen and others.
New vaccine protocols have been put forth by the American Association of Feline Practitioners that limit type and frequency of vaccinations given to cats. Specifically, the vaccine for feline leukemia virus should only be given to kittens and high risk cats. Feline rhinotracheitis/panleukopenia/calicivirus vaccines should be given as kittens, a year later and then every three years. Also, vaccines should be given in areas making removal of VAS easier, namely: as close as possible to the tip of the right rear paw for rabies, the tip of the left rear paw for feline leukemia (unless combined with rabies), and on the right shoulder—being careful to avoid the midline or interscapular space—for other vaccines (such as FVRCP). There have been no specific associations between development of VAS and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment.
There are no known risk factors that have been identified specific to the disease. The tumor appears to arise from the primitive cells of childhood, and is considered a childhood cancer.
Research has indicated that there is a chimeric relationship between desmoplastic small-round-cell tumor (DSRCT) and Wilms' tumor and Ewing's sarcoma. Together with neuroblastoma and non-Hodgkin's lymphoma, they form the small cell tumors.
DSRCT is associated with a unique chromosomal translocation t(11;22)(p13:q12) resulting in an EWS/WT1 transcript that is diagnostic of this tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth.
The EWS/WT1 translocation product targets ENT4. ENT4 is also known as PMAT.
A perianal gland tumor is a type of tumor found near the anus in dogs that arises from specialized glandular tissue found in the perineum. Perianal glands do not exist in cats. It is also known as a hepatoid tumor because of the similarity in cell shape to hepatocytes (liver cells). It is most commonly seen in intact (not neutered) dogs and is the third most common tumor type in intact male dogs. There are two types of perianal gland tumors, perianal gland adenomas, which are benign, and perianal gland adenocarcinomas, which are malignant. Both have receptors for testosterone. Perianal gland adenomas are three times more likely to be found in intact male dogs than females, and perianal gland adenocarcinomas are ten times more common in male dogs than females. The most commonly affected breeds for adenomas are the Siberian Husky, Cocker Spaniel, Pekingese, and Samoyed; for adenocarcinomas the most commonly affected breeds are the Siberian Husky, Bulldog, and Alaskan Malamute.
Perianal gland tumors are located most commonly in the skin around the anus, but can also be found on the tail or groin. Adenomas are more common, making up 91 percent of perianal gland tumors in one study. Adenomas and adenocarcinomas look alike, both being round, pink and usually less than three centimeters in width. Adenocarcinomas are more likely to be multiple and invasive into the underlying tissue, and they can metastasize to the lymph nodes, liver, and lungs.
Both types should be removed and sent to a pathologist for identification. However, 95 percent of perianal gland adenomas will disappear after neutering the dog. Removing the tumor and neutering the dog at the same time will help prevent recurrence. Dogs with perianal gland adenocarcinomas should be treated with aggressive surgery and the radiation therapy and chemotherapy if necessary.
Surgical treatment is recommended for cats and dogs diagnosed with primary liver tumors but not metastasis to the liver. There are not many treatment options for animals who have multiple liver lobes affected.
Desmoplastic small-round-cell tumor is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones.
The tumor is classified as a soft tissue sarcoma. It is considered a childhood cancer that predominantly strikes boys and young adults. The disease rarely occurs in females, but when it does the tumors can be mistaken for ovarian cancer.
In dogs, mast cell tumors are the most frequent round cell tumor.
The specific treatment will depend on the tumor's type, location, size, and whether the cancer has spread to other organs. Surgical removal of the tumor remains the standard treatment of choice, but additional forms of therapy such as radiation therapy, chemotherapy, or immunotherapy exist.
When detected early, skin cancer in cats and dogs can often be treated successfully. In many cases, a biopsy can remove the whole tumor, as long as the healthy tissues removed from just outside the tumor area do not contain any cancer cells.
Inflammation in the subcutis following vaccination is considered to be a risk factor in the development of VAS, and vaccines containing aluminum were found to produce more inflammation. Furthermore, particles of aluminum adjuvant have been discovered in tumor macrophages. In addition, individual genetic characteristics can also contribute to these injection-site sarcomas. The incidence of VAS is between 1 in 1,000 to 1 in 10,000 vaccinated cats and has been found to be dose-dependent. The time from vaccination to tumor formation varies from three months to eleven years. Fibrosarcoma is the most common VAS; other types include rhabdomyosarcoma, myxosarcoma, chondrosarcoma, malignant fibrous histiocytoma, and undifferentiated sarcoma.
Similar examples of sarcomas developing secondary to inflammation include tumors associated with metallic implants and foreign body material in humans, and sarcomas of the esophagus associated with "Spirocerca lupi" infection in dogs and ocular sarcomas in cats following trauma. Cats may be the predominant species to develop VAS because they have an increased susceptibility to oxidative injury, as evidenced also by an increased risk of Heinz body anemia and acetaminophen toxicity.
Two types of mast cell tumors have been identified in cats, a mast cell type similar to dogs and a histiocytic type that appears as subcutaneous nodules and may resolve spontaneously. Young Siamese cats are at an increased risk for the histiocytic type, although the mast cell type is the most common in all cats and is considered to be benign when confined to the skin.
Mast cell tumors of the skin are usually located on the head or trunk. Gastrointestinal and splenic involvement is more common in cats than in dogs; 50 percent of cases in dogs primarily involved the spleen or intestines. Gastrointestinal mast cell tumors are most commonly found in the muscularis layer of the small intestine, but can also be found in the large intestine. It is the third most common intestinal tumor in cats, after lymphoma and adenocarcinoma.
Diagnosis and treatment are similar to that of the dog. Cases involving difficult to remove or multiple tumors have responded well to strontium-90 radiotherapy as an alternative to surgery. The prognosis for solitary skin tumors is good, but guarded for tumors in other organs. Histological grading of tumors has little bearing on prognosis.
Mast cell tumors mainly occur in older adult dogs, but have been known to occur on rare occasions in puppies. The following breeds are commonly affected by mast cell tumors:
- Boxer
- Staffordshire bull terrier
- Bulldog
- Basset hound
- Weimaraner
- Boston terrier
- Great Dane
- Golden retriever
- Labrador retriever
- Beagle
- German shorthaired pointer
- Scottish terrier
- Pug
- Shar pei
- Rhodesian ridgeback