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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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Working with asbestos is the most common risk factor for mesothelioma. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.
The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece. In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages—Tuzköy, Karain, and Sarıhıdır. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California. In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as "Metsovo Lung".
The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.
Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.
In the United States, asbestos is considered the major cause of malignant mesothelioma and has been considered "indisputably" associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a “signal” or “sentinel” tumor. A history of asbestos exposure exists in most cases.
Pericardial mesothelioma may not be associated with asbestos exposure.
Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are "not" adequate to prevent or protect against asbestos-related cancers such as mesothelioma. Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma. There appears to be a linear, dose-response relationship, with increasing dose producing increasing risk of disease. Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos. The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer. Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.
The time from first exposure to onset of the disease, is between 25 and 70 years. It is virtually never less than fifteen years and peaks at 30–40 years. The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 1–3 months of exposure.
Asbestos can cause lung cancer that is identical to lung cancer from other causes. Exposure to asbestos is associated with all major histological types of lung carcinoma (adenocarcinoma, squamous cell carcinoma, large-cell carcinoma and small-cell carcinoma). The latency period between exposure and development of lung cancer is 20 to 30 years. It is estimated that 3%-8% of all lung cancers are related to asbestos. The risk of developing lung cancer depends on the level, duration, and frequency of asbestos exposure (cumulative exposure). Smoking and individual susceptibility are other contributing factors towards lung cancer. Smokers who have been exposed to asbestos are at far greater risk of lung cancer. Smoking and asbestos exposure have a multiplicative (synergistic) effect on the risk of lung cancer. Symptoms include chronic cough, chest pain, breathlessness, haemoptysis (coughing up blood), wheezing or hoarseness of the voice, weight loss and fatigue. Treatment involves surgical removal of the cancer, chemotherapy, radiotherapy, or a combination of these (multimodality treatment). Prognosis is generally poor unless the cancer is detected in its early stages. Out of all patients diagnosed with lung cancer, only 15% survive for five years after diagnosis.
Malignant mesothelioma is an aggressive and incurable tumour caused by asbestos arising from mesothelial cells of the pleura, peritoneum (the lining of the abdominal cavity) and rarely elsewhere. Pleural mesothelioma is the most common type of mesothelioma, representing about 75 percent of cases. Peritoneal mesothelioma is the second most common type, consisting of about 10 to 20 percent of cases. Mesothelioma appears from 20 to 50 years after the initial exposure to asbestos. The symptoms include shortness of breath, chronic chest pain, cough, and weight loss. Diagnosing mesothelioma is often difficult and can include physical examination, chest X-ray and lung function tests, followed by CT scan and MRI. A biopsy is needed to confirm a diagnosis of malignant mesothelioma. Mesothelioma has a poor prognosis, with most patients dying within 1 year of diagnosis. The treatment strategies include surgery, radiotherapy, chemotherapy or multimodality treatment. Several tumour biomarkers (soluble mesothelin-related protein (SMRP), osteopontin and fibulin3) have been evaluated for diagnostic purposes to allow early detection of this disease. Novel biomarkers such as volatile organic compounds measured in exhaled breath are also promising.
Pregnancy has been reported to exacerbate LAM in some cases. However, the risk has not been rigorously studied. In a survey of 318 patients who indicated that they had had at least one pregnancy, 163 responded to a second survey focusing on lung collapse. A total of 38 patients reported a pneumothorax with pregnancy, consistent with an incidence of pneumothorax in pregnancy of at least 10% (38 of 318). In one third of patients, the pneumothorax during pregnancy led to the LAM diagnosis. Pneumothoraces were almost twice as frequent on the right as on the left, and four women presented with bilateral spontaneous pneumothorax. Most pneumothoraces took place during the second and third trimesters. This study and others suggest that pregnancy is associated with pleural complications in LAM patients. Few women with a known LAM diagnosis choose to become pregnant and patients in whom LAM is diagnosed during pregnancy rarely have baseline pulmonary function tests available, complicating resolution of this question.
Malignant pleural effusion is a condition in which cancer causes an abnormal amount of fluid to collect between the thin layers of tissue (pleura) lining the outside of the lung and the wall of the chest cavity. Lung cancer and breast cancer account for about 50-65% of malignant pleural effusions. Other common causes include pleural mesothelioma and lymphoma.
Clinical factors predicting the diagnosis of malignant pleural effusions are symptoms lasting more than 1 month and the absence of fever.
Although reliable and comprehensive incidence statistics are nonexistent, LCLC-RP is a rare tumor, with only a few hundred cases described in the scientific literature to date. LCLC's made up about 10% of lung cancers in most historical series, equating to approximately 22,000 cases per year in the U.S. Of these LCLC cases, it is estimated that about 1% will eventually develop the rhabdoid phenotype during tumor evolution and progression. In one large series of 902 surgically resected lung cancers, only 3 cases (0.3%) were diagnosed as LCLC-RP. In another highly selected series of large-cell lung carcinoma cases, only 4 of 45 tumors (9%) were diagnosed as the rhabdoid phenotype using the 10% criterion, but another 10 (22%) had at least some rhabdoid cell formation. It appears likely, therefore, that LCLC-RP probably comprises between 0.1% and 1.0% of all lung malignancies.
Similar to nearly all variants of lung carcinoma, large cell lung carcinoma with rhabdoid phenotype appears to be highly related to tobacco smoking. It also appears to be significantly more common in males than in females.
LAM is almost completely restricted to women. While lung cysts consistent with LAM are reported in some men with tuberous sclerosis, very few of these men develop symptoms. The prevalence of LAM is estimated using data from registries and patient groups and is between 3.4-7.8/million women. The number of new cases each year is between 0.23-0.31/million women/year in the US, UK and Switzerland. The variation between countries and between adjacent states in the US, suggest that a significant number of women with LAM remain either undiagnosed or their symptoms are attributed to other diseases. Adult women with tuberous sclerosis are more likely to develop LAM than women without tuberous sclerosis. Cohorts of patients with tuberous sclerosis have been screened for LAM using CT scanning. In a retrospective study of adults with tuberous sclerosis, CT demonstrated lung cysts in 42% of 95 women and 13% of 91 men. In general, lung cysts were larger and more numerous in women than in men. In a further retrospective study of women with TSC who underwent CT scanning to detect LAM, 25% of those in their 20s had lung cysts whereas 80% of women in their 40s were affected, suggesting that the development of LAM is age dependent at least in tuberous sclerosis-related LAM. Although the prevalence of tuberous sclerosis at 1 in 6000 births is much greater than that of LAM, most pulmonary clinics see more cases of sporadic than tuberous sclerosis-LAM: probably due to a combination of low levels of screening for LAM in tuberous sclerosis and in many, the absence of symptoms.
Female sex and tuberous sclerosis are the only known risk factors. Although use of supplemental estrogen is not associated with development of LAM, one study suggested that use of estrogen-containing contraceptive pills was associated with earlier onset.
It occurs in more than 30% of women with tuberous sclerosis complex (TSC-LAM), a heritable syndrome that is associated with seizures, cognitive impairment and benign tumors in multiple tissues. Most LAM patients who present for medical evaluation have the sporadic form of the disease (S-LAM), however, which is not associated with other manifestations of tuberous sclerosis complex.
Mild cystic changes consistent with LAM have been described in 10–15% of men with TSC, but symptomatic LAM in males is rare. Sporadic LAM occurs exclusively in women, with one published exception to date. Both TSC-LAM and S-LAM are associated with mutations in tuberous sclerosis genes.
Given its rarity, there are no established guidelines for the treatment of peritoneal mesothelioma. The modern approach to malignant peritoneal mesothelioma includes cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy, and intravenous chemotherapy. These are often used in conjunction and in a complementary fashion, and this multifaceted approach has significantly improved outcomes when compared to intravenous chemotherapy alone. For instance, the reported median survival time for patients with stage IV mesothelioma as reported by the American Cancer Society is 12 months; however, with adequate cytoreduction, intraperitoneal, and intravenous chemotherapy combined, some authors report 10-year survival rates projected at nearly 75%.
Multiple factors have been shown to be significant in predicting the outcome and overall survival. Age greater than 60 at surgery, more overall disease burden (defined as a PCI greater than 15), complete cytoreduction (no visible disease), and epitheliod subtype pathology have all been shown to be predictors of both mortality and disease progression. These known predictors notwithstanding, many patients with advanced peritoneal mesothelioma are still surgical candidates, and even patients with the highest possible score on the peritoneal carcinomatosis index (39) can be completely reduced to a PCI of 0 with adequate surgery.
LCLC-RP are considered to be especially aggressive tumors with a dismal prognosis. Many published cases have shown short survival times after diagnosis. Some studies suggest that, as the proportion of rhabdoid cells in the tumor increases, the prognosis tends to worsen, although this is most pronounced when the proportion of rhabdoid cells exceeds 5%. With regard to "parent" neoplasms other than LCLC, adenocarcinomas with rhabdoid features have been reported to have worse prognoses than adenocarcinomas without rhabdoid features, although an "adenocarcinoma with rhabdoid phenotype" tumor variant has not been specifically recognized as a distinct entity under the WHO-2004 classification system.
Interestingly, there are case reports of rhabdoid carcinomas recurring after unusually long periods, which is unusual for a fast-growing, aggressive tumor type. One report described a very early stage patient whose tumor recurred 6 years after initial treatment. Although rapidly progressive, fulminant courses seem to be the rule in this entity, long-term survival has also been noted, even post-metastectomy in late stage, distant metastatic disease.
Asbestos is a known cause of peritoneal mesothelioma in humans.
A 1975 study of three small villages in central Cappadocia, Turkey—Tuzköy, Karain and Sarıhıdır—found that peritoneal mesothelioma was causing 50% of all deaths. Initially, this was attributed to erionite, a zeolite mineral with similar properties to asbestos, but detailed epidemiological investigation demonstrated that the substance causes the disease mostly in families with a genetic predisposition to mineral fiber carcinogenesis. The studies are being extended to other parts of the region.
An estimated 48,000 cancers are diagnosed yearly in the US that come from occupational causes; this represents approximately 4-10% of total cancer in the United States. It is estimated that 19% of cancers globally are attributed to environmental exposures (including work-related exposures).
According to a recent study, the main risk factors for RA-ILD are advancing age, male sex, greater RA disease activity, rheumatoid factor (RF) positivity, and elevated titers of anticitrullinated protein antibodies such as anticyclic citrullinated peptide. Cigarette smoking also appears to increase risk of RA-ILD, especially in patients with human leukocyte antigen DRB1.
A recently published retrospective study by a team from Beijing Chao-Yang Hospital in Beijing, China, supported three of the risk factors listed for RA-ILD and identified an additional risk factor. In that study of 550 RA patients, logistic regression analysis of data collected on the 237 (43%) with ILD revealed that age, smoking, RF positivity, and elevated lactate dehydrogenase closely correlated with ILD.
Recent studies have identified risk factors for disease progression and mortality. A retrospective study of 167 patients with RA-ILD determined that the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) was a risk factor for progression, as were severe disease upon diagnosis and rate of change in pulmonary function test results in the first 6 months after diagnosis.
A study of 59 RA-ILD patients found no median survival difference between those with the UIP pattern and those without it. But the UIP group had more deaths, hospital admissions, need for supplemental oxygen, and decline in lung function.
"Lung tumors" are neoplastic tumors of the lung These include:
Primary tumors of the lung/pulmonary system:
- Bronchial leiomyoma, a rare, benign tumor
- Lung cancer, the term commonly used to refer to "carcinoma of the lung"
- Pulmonary carcinoid tumor
- Pleuropulmonary blastoma
- Neuroendocrine tumors of the lung
- Lymphomas of the lung.
- Sarcomas of the lung.
- Some rare vascular tumors of the lung
Non-lung tumors which may grow into the lungs:
- Mediastinal tumors
- Pleural tumors
Metastasis or secondary tumors/neoplasms with other origin:
- Metastasis to the lung
Colorectal cancer patients with peritoneal involvement can be treated with Oxaliplatin or Irinotecan based chemotherapy. Such treatment is not expected to be curative, but can extend the lives of patients. . Some patients may be cured through Hyperthermic intraperitoneal chemotherapy but the procedure entails a high degree of risk for morbidity or death.
Many occupational cancers are preventable. Personal protective gear, workplace controls, and worker education can prevent exposure to carcinogens in the workplace. Tobacco smoking has also been shown to increase the risk of work-related cancers; decreasing or abstaining from smoking can decrease cancer risk.
Agencies like the US Food and Drug Administration, Environmental Protection Agency, and Occupational Safety and Health Administration have developed safety standards and limits for chemical and radiation exposure.
When a pleural effusion has been determined to be exudative, additional evaluation is needed to determine its cause, and amylase, glucose, pH and cell counts should be measured.
- Red blood cell counts are elevated in cases of bloody effusions (for example after heart surgery or hemothorax from incomplete evacuation of blood).
- Amylase levels are elevated in cases of esophageal rupture, pancreatic pleural effusion, or cancer.
- Glucose is decreased with cancer, bacterial infections, or rheumatoid pleuritis.
- pH is low in empyema (<7.2) and may be low in cancer.
- If cancer is suspected, the pleural fluid is sent for cytology. If cytology is negative, and cancer is still suspected, either a thoracoscopy, or needle biopsy of the pleura may be performed.
- Gram staining and culture should also be done.
- If tuberculosis is possible, examination for "Mycobacterium tuberculosis" (either a Ziehl–Neelsen or Kinyoun stain, and mycobacterial cultures) should be done. A polymerase chain reaction for tuberculous DNA may be done, or adenosine deaminase or interferon gamma levels may also be checked.
The most common causes of exudative pleural effusions are bacterial pneumonia, cancer (with lung cancer, breast cancer, and lymphoma causing approximately 75% of all malignant pleural effusions), viral infection, and pulmonary embolism.
Another common cause is after heart surgery, when incompletely drained blood can lead to an inflammatory response that causes exudative pleural fluid.
Conditions associated with exudative pleural effusions:
- Parapneumonic effusion due to pneumonia
- Malignancy (either lung cancer or metastases to the pleura from elsewhere)
- Infection (empyema due to bacterial pneumonia)
- Trauma
- Pulmonary infarction
- Pulmonary embolism
- Autoimmune disorders
- Pancreatitis
- Ruptured esophagus (Boerhaave's syndrome)
- Rheumatoid pleurisy
- Drug-induced lupus
The meningeal covering of the central nervous system may be the site of tumor growth. Breast cancer, lung cancer and melanoma are the most common tumors.
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.
Tumor-like disorders of the lung pleura are a group of conditions that on initial radiological studies might be confused with malignant lesions. Radiologists must be aware of these conditions in order to avoid misdiagnosing patients. Examples of such lesions are: pleural plaques, thoracic splenosis, catamenial pneumothorax, pleural pseudotumor, diffuse pleural thickening, diffuse pulmonary lymphangiomatosis and Erdheim-Chester Disease.
The most common causes of transudative pleural effusions in the United States are heart failure and cirrhosis. Nephrotic syndrome, leading to the loss of large amounts of albumin in urine and resultant low albumin levels in the blood and reduced colloid osmotic pressure, is another less common cause of pleural effusion. Pulmonary emboli were once thought to cause transudative effusions, but have been recently shown to be exudative.
The mechanism for the exudative pleural effusion in pulmonary thromboembolism is probably related to increased permeability of the capillaries in the lung, which results from the release of cytokines or inflammatory mediators (e.g. vascular endothelial growth factor) from the platelet-rich blood clots. The excessive interstitial lung fluid traverses the visceral pleura and accumulates in the pleural space.
Conditions associated with transudative pleural effusions include:
- Congestive heart failure
- Liver cirrhosis
- Severe hypoalbuminemia
- Nephrotic syndrome
- Acute atelectasis
- Myxedema
- Peritoneal dialysis
- Meigs' syndrome
- Obstructive uropathy
- End-stage kidney disease
Tobacco smoke is a known carcinogen. Workers in the hospitality industry may be exposed to tobacco smoke in the workplace, especially in environments like casinos and bars/restaurants.
Ectopic endometrial tissue reaches the pleural space of the lung or the right hemi-diaphragmatic region and erodes the visceral pleura, causing the formation of a spontaneous pneumothorax. The condition is often cyclical, due to its associations with the beginning of the menstrual cycle.
Affected persons usually present with recurrent spontaneous pneumothorax associated with the onset of the menstrual cycle. Additionally, chest/scapular pain and/or evidence of endometriosis in the abdominopelvic cavity are other manifestations.
On radiological studies, pneumothorax is visualized using conventional chest x-rays and CT scans. In 90% of the cases, the pneumothorax is located on the right side. In some cases, small nodules can be seen in the pleura using CT scans. Confirmation can be done using video assisted thoracoscopic surgery (VATS).
Treatment for the pneumothorax is with chest tube placement. As for the ectopic endometrial tissue, therapy with gonadotropin-releasing–hormone or resection of the lesions can improve symptoms.