Which is the best mesothelioma book


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Mesotheliomas are soft tissue tumors caused by asbestos. Your prognosis is very bad. There is no causal therapy.


Mesothelioma is, as the name suggests, a diffuse soft tissue tumor emanating from the mesothelium. It is malignant in most of the cases. The main localizations are peritoneal mesothelioma, pleural mesothelioma and pericardial mesothelioma. Of these locations, pleural mesothelioma is the most common. It is triggered by inhaled asbestos fibers and is therefore one of the occupational diseases.


The occurrence of mesothelioma is closely linked to the use of asbestos as a cause. Asbestos has been banned as a useful material since 1990 at the latest. However, due to the long latency, cases are still diagnosed annually. In Germany, a total of 280 women and 1,060 men were newly diagnosed with mesothelioma in 2016. The incidence was thus 0.3 per 100,000 inhabitants for women and 1.5 per 100,000 inhabitants for men. The relative 5-year survival rate was 13% for women and 8% for men. The relative 10-year survival rate for both sexes was 5%. The significantly higher incidence in men compared to women is probably a result of the distribution of work. In the last century, men were exposed to asbestos at work much more frequently and were therefore at a higher risk of inhaling asbestos fibers. If they came home with their work clothes and were cleaned by the wife living in the same household, the wife was also exposed to asbestos and was at increased risk of developing mesothelioma.

There are reliable figures on mesothelioma for Germany. Worldwide, however, the data on the incidence of mesothelioma is very imprecise. This is attributed to poor and missing data collection or a lack of diagnostics. Especially in countries with poor access to health care, the correct diagnoses of mesothelioma are likely to be lower than the actual incidence, since this type of cancer is not so easy to diagnose unless asbestos fibers are found in the biopsy.

However, it should be encouraging that the incidence of mesothelioma will probably decrease worldwide in the next few years. This is due to the fact that asbestos has been banned in most countries since 1990 at the latest because of its carcinogenic properties. The latency period between exposure to asbestos and the onset of the disease is around 40 years, but varies between 15 and 67 years. According to forecasts, the effects of the bans should therefore slowly become visible from around 2020, since the use of asbestos had already been significantly reduced at the time of the ban.


Mesothelioma is triggered in most cases by exposure to asbestos. But there are also isolated mesotheliomas in populations that are not exposed to asbestos. However, these cases are exceptional and could possibly be due to naturally occurring asbestos.

Asbestos itself is an inorganic fiber. There are five different types of fiber, each of which is slightly different in its composition: chrysotile (white asbestos), crocidolite (blue asbestos), amosite (brown asbestos), antophyllite and tremolite. According to some sources, crocidolite is 10 times more dangerous than amoside and amoside is 10 times more dangerous than chrysotile. There is a dose-response relationship between asbestos exposure and the occurrence of mesothelioma. The higher the exposure, the more likely the person will develop mesothelioma in their lifetime. However, it cannot be said from which amount of asbestos a mesothelioma develops and which amounts could possibly be risk-free or low-risk for humans. According to some experts, any exposure is already carcinogenic and inevitably leads to mesothelioma if even a single fiber is inhaled. However, the high carcinogenicity of asbestos fibers is undisputed.

But asbestos might not be the only substance that causes mesothelioma. Other fibers could also possibly be the cause of the disease. Erionite, fluoro-edenite and balangeroite are currently under suspicion, some of which may not be the fiber itself but the contamination with other fibers.

A genetic predisposition is also traded as a possible cause of mesothelioma - the disease has been observed more frequently in some families. In these families there was a mutation in the BRCA1-associated protein (BAP) -1 gene. Another risk factor for mesothelioma is ionizing radiation.


How exactly asbestos can trigger mesothelioma has not yet been fully clarified. The long latency period between exposure to asbestos and the outbreak of disease makes research particularly difficult. One possible explanation is that asbestos fibers exert their cytotoxic effect on the mesothelial cells in particular. In vitro, even small amounts of crocidolite fibers, for example, were sufficient to drive all mesothelial cells in the cell culture to cell death within a week.

For a mesothelioma to develop, the cells - according to the theory - must not die, but have to degenerate. According to another theory, this is where tumor necrosis factor alpha (TNF-alpha) and the signaling molecule NF-kappaB come into play. They seem to be partly responsible for causing an inflammatory reaction in the area around the asbestos fibers. Many mononuclear phagocytes are attracted to this inflammatory response. On site they differentiate into macrophages, absorb the asbestos fibers and release TNF-alpha. As a result of exposure to asbestos, the mesothelial cells simultaneously produce the receptor TNF-R1, which also has a stimulating effect on the release of TNF-alpha. TNF-alpha in turn binds to the associated receptors and thus activates the NF-kappaB signaling pathway. As a result, some of the mesothelial cells survive. Normally they would have to die from exposure to asbestos. If this does not happen, however, a dangerous cycle continues: triggered by the asbestos and with the help of iron-catalyzed free radicals, DNA strand breaks occur in these cells. At the same time, the asbestos fibers ensure that reactive oxygen species and reactive nitrogen species are released. In this way, additional genotoxicity arises. Normally, these cells would now enter into programmed cell death, since they would no longer be tolerable for the body due to their DNA damage. The risk that they degenerate and, as tumor cells, promote the development of cancer is too great. However, since the NF-kappaB signaling pathway was activated by the asbestos reaction, this does not happen and the cells divide instead of entering into programmed cell death. If there are enough damaged cells at some point, a mesothelioma develops.

In addition to TNF-alpha, other growth factors and cytokines are also suspected of being released in response to asbestos exposure. These include the transformation growth factor beta (TGF-beta), the platelet-derived growth factor (PDGF), the insulin-like growth factor (IGF), the interleukins IL-6 and IL-8 as well as the vascular endothelial growth factor (VEGF) and the hepatocyte growth factor (HGF).


At the beginning, mesothelioma is often asymptomatic to asymptomatic. In the course of the disease, localization-specific symptoms increase.

The most common type of mesothelioma is pleural mesothelioma. These patients usually go to the doctor because they suffer from persistent coughing and sputum and are unable to breathe well, or even short of breath. Pain when breathing or coughing up blood (hemoptysis) can also occur. B symptoms with night sweats, fever and unexplained weight loss of more than 10% within the last six months are also reported. Accompanying these specific and non-specific symptoms, patients often suffer from exhaustion, tiredness and exhaustion.

Symptoms specific to this region occur in peritoneal mesothelioma, which occurs very rarely. This includes:

  • Pain in the lower abdomen and pelvis
  • palpable tumors
  • Amenorrhea (lack of menstrual bleeding in women)
  • difficult or painful urination (dysuria)
  • Painful intercourse (dyspareunia)
  • Constipation (constipation)
  • Buildup of fluid in the abdomen (ascites)
  • Weight loss (rather rare)

Pericardial mesothelioma is also very rare. It is associated with cardiac symptoms. These can be, for example:

If the disease has progressed very far, all three forms of mesothelioma can also have other symptoms such as:

  • Pneumothorax or collapsed lungs
  • venous thrombosis causing thrombophlebitis
  • intravascular coagulation with severe internal bleeding
  • Jaundice (jaundice)
  • low blood sugar level (hypoglycaemia)
  • Pleural effusion
  • Pulmonary embolism or blood clots in the pulmonary arteries
  • severe ascites


In addition to the symptoms described above and a history of positive asbestos exposure, the physical examination is already a first indication of mesothelioma. Since not every patient is aware that he or she has been exposed to asbestos in his (professional) life, the anamnesis should also ask about the profession and professional career. Because of the long latency period, exposure may be a long time ago. It can not only have been caused by one's own job, but also, for example, from asbestos fibers brought along on clothes in the household.

In many cases, the initial symptom on physical examination is exudative pleural effusion. This causes fluid to accumulate in the pleural space. This becomes noticeable in auscultation through a muffled breathing noise and a hyposonic knocking sound. In the case of a pericardial effusion, or ascites, also known as ascites or water belly, the symptoms correspond to these clinical pictures, as are the clinical findings on the physical examination. Many patients report pain when breathing and the borders of the lungs can only be moved to a limited extent in the percussion. Therefore, if there is any suspicion, at least the heart, lungs and abdomen should be fully examined. It is advisable to proceed according to the Heidelberg standard examination or a similar structured instruction for carrying out physical examinations in order to cover all organs.


Adequate imaging will follow the physical exam. For example, chest x-rays in two planes are ideal. If an X-ray is taken, a mostly unilateral pleural effusion or a pleural thickening are noticeable. However, the gold standard in mesothelioma imaging is not the X-ray image, but computed tomography (CT) with contrast agent. It provides more precise data and is superior to x-rays in terms of diagnosis. Computed tomography can detect diffuse or nodular pleural thickening. Even more precise images are provided by a multi-line spiral CT machine, or MSCT for short, which helps to assess how far the tumor has already penetrated into the chest wall, diaphragm, peritoneum or mediastinum.

As an alternative to computed tomography, PET-CT can be used to better identify pleural lesions. However, it is not part of the routine diagnosis of suspected mesothelioma. Magnetic resonance imaging (MRI) as additional imaging is considered to be potentially helpful in diagnostics. However, their superiority over CT has not yet been confirmed.

In addition to the diagnostic component, imaging is also relevant in order to be able to carry out the decisive step in diagnostics: the biopsy. Only it brings the final diagnosis of a mesothelioma. The areas to be biopsied cannot be precisely determined without prior imaging. To avoid flying blind, the biopsy is usually performed with imaging.


The biopsy is considered the gold standard in mesothelioma diagnosis. It is usually performed under local anesthesia. Different types of biopsy are possible. In Germany, the thoracoscopic biopsy is the most common in the diagnostic literature. She has a 20% risk of causing vaccine metastases. These are metastases that arise in the biopsy canal because individual tumor cells were drawn into this canal during removal and grow into metastases there. Nevertheless, it achieves particularly high sensitivity and specificity values ​​in diagnostics and can secure more meaningful material than most other methods.

The thoracoscopic biopsy can be performed, for example, by means of video-assisted thoracoscopy (video-assisted thoracosopic surgery [VATS]). The advantage of this method is that at the same time possible symptoms can be alleviated or remedied by doing a pleurodesis. A percutaneous needle biopsy or a radiologically guided percutaneous pleural biopsy give significantly poorer results. Even with image-guided implementation, significantly fewer mesotheliomas are correctly diagnosed here.

The biopsy sample is then examined both histologically / microscopically and immunohistochemically. This is important to differentiate mesothelioma from adenocarcinoma, for example. The former is often positive for mesothelin, calretinin, cytokeratin 5/6 and vimentin.


Mesothelioma is classified according to the WHO classification and the mesothelioma interest group. On the basis of the leading histological tumor type, it is divided into diffuse malignant mesotheliomas and localized malignant mesotheliomas with the respective subtypes: In diffuse malignant mesothelioma there are epithelioid, sarcomatoid, desmoplastic and biphasic, in localized malignant mesothelioma the epithelioid, sarcomatoid , well-differentiated papillary mesothelioma, and adenomatoid tumors. However, the classification is usually not sufficient as it does not include cases in which a diagnosis cannot be made clearly.

The European Mesothelioma Panel (Commission of the European Communities, C.E.C.) therefore recommends classifying mesothelioma as follows:

  • Mesothelioma A sure mesothelioma, no doubt about the histological diagnosis
  • Mesothelioma B probable mesothelioma (insufficient tissue size, poor quality, lack of differentiation, lack of certain histological details)
  • Mesothelioma C possible mesothelioma (lack of sufficient evidence for a positive diagnosis)
  • Mesothelioma D probably not a mesothelioma
  • Mesothelioma E certainly not a mesothelioma, specific diagnosis of another tumor should be given.

In staging, the TNM classification with T for tumor, N for lymph node involvement and M for distant metastases is used. This results in stages I to IV with the respective subdivisions.

Imaging is particularly important for staging of spread. This is the only way to detect distant metastases in particular. For this purpose, an abdominal sonography, a bone scintigraphy or an MRI of the neurocranium can also be performed. The latter is particularly suitable for finding remote settlements of mesothelioma scattered through the bloodstream - an MRI of the neurocranium is particularly sensitive for this.

Differential diagnoses


The prognosis for mesothelioma is usually very bad. It is often only recognized when complications have already occurred and therapy is only possible to a limited extent. Intervention can either be surgically, radiotherapy, chemotherapy or immunotherapy. However, none of the therapies has so far achieved a breakthrough in the therapy of mesothelioma. The mean survival is still around one year after the initial diagnosis.

Patients with mesothelioma should be treated in specialized centers, including palliative and pain therapy approaches. Individual therapies or multimodal therapies can be offered. The choice of therapy depends on the patient and the individual risk factors. So far, no curative therapy has been established.


Pleurodesis can already be performed during a diagnostic VATS to reduce symptomatic pleural effusions and relieve pain for the patient. Recurring pleural effusions can also be treated at this point using talc pleurodesis. VATS is considered to be the therapy of first choice to alleviate symptoms. Like other surgical therapies, however, it does not prolong survival.

A surgical R0 resection of a mesothelioma is usually not possible. An attempt can be made to completely remove the tumor surgically viewed macroscopically. A possible option here is a pleurectomy or decortication. In this method, the parietal pleura and the visceral pleura are removed in one piece. If a patient does not benefit from pleurodesis, pleurectomy can be the method of choice to prevent recurring pleural effusions. However, the patient should be informed in advance that the pleurectomy will create a "tied lung" and that this will be restricted in its function. Whether this can be reconciled with the quality of life desired by the patient must be discussed with the patient himself.To date, pleurectomy has had no significant effect on long-term survival.

Another surgical intervention option would be extrapleural pleuropneumectomy. Here the pleura, the lungs as well as parts of the pericardium and diaphragm are removed. Since this operation is associated with a high morbidity rate and is more often fatal than pleurectomy, it should only be performed in very experienced and highly specialized centers. This therapy also has no influence on overall survival.


Chemotherapy, too, has so far shown only very limited success. Nevertheless, it is recommended as an (adjuvant) first-line therapy. For example, cisplatin and pemetrexed plus folic acid and vitamin B12 are used as supplements. Fit patients should receive them as early as possible. Ideally, it is administered before functional clinical limitations occur. Whether patients are fit enough for chemotherapy can be determined using the Karnofsky index, for example. It should be above 60% for chemotherapy to be considered. If the patient is too unfit for chemotherapy, symptom-relieving radiation therapy can be considered.


Research is currently being carried out into radiotherapy for mesothelioma. It can be used to relieve pain, especially in pain caused by infiltrative tumors. The entire tumor cannot be irradiated because the damage to the heart and lungs would be too great. The puncture canals, etc. are suitable for radiotherapy.


A combination therapy of chemotherapy and bevacizumab as first-line therapy has shown good results in studies. The progression-free time could be extended by two months and the overall survival could also be increased somewhat. In Europe and the USA, however, the antibody is not yet approved for widespread use in mesothelioma. Nonetheless, a combination therapy is recommended for fit patients, but not for those with a complete macroscopic resection, as the study situation is insufficient here.


Follow-ups are performed every three to six months to measure the status of the disease. As part of this monitoring, control CTs of the thorax and abdomen are performed. The overall monitoring, however, is based on the severity of symptoms and the progression of the disease. If the patient is worse off, the monitoring intervals can be shortened.


The prognosis for mesothelioma is usually poor. Often, curative therapy is no longer possible once the disease is diagnosed. The mean survival time is around one year. Only about 12% of patients with negative prognostic factors live longer than the first year.

The prognosis is influenced by factors such as age, gender, tumor subtype and tumor stage. Epithelioid tumor subtypes have a more favorable prognosis.


The best prevention of mesothelioma is to avoid asbestos. In the context of occupational safety, asbestos removal and disposal may only be carried out under sufficiently high protective measures.

If people have had contact with asbestos, they should also remember that fibers can hang in clothing. As a result, not only are they at risk, but also their colleagues and household members if the laundry is removed and cleaned at home. Here, too, precaution can be taken.


  • Mesothelioma is in most cases an occupational disease.
  • Relatives of people who have been exposed to asbestos at work can also have an increased risk of mesothelioma. Asbestos fibers can be brought home with clothing.
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