Mesothelioma

Generality

Mesothelioma is the medical term for a malignant tumor originating in a mesothelial cell.

The mesothelium is the serous membrane that covers the lungs, the heart, some abdominal organs, the testicles in humans, the uterus in women and the cavities in which the organs just mentioned reside.

Tac scan of a patient with pleural mesothelioma. Note the tumor mass indicated by the yellow arrows that compresses the right lung (1). From wikipedia.org

There are various types of mesothelioma; the most known and widespread types are pleural mesothelioma and peritoneal mesothelioma.

The main cause of any mesothelioma in humans is exposure to asbestos or asbestos. Asbestos is a set of minerals that are easily diffusible in the air and inhalable.

The symptoms of mesothelioma depend on the site of origin of the malignant tumor.

For a precise diagnosis, biopsy is essential.

Possible treatments include surgery, radiotherapy and chemotherapy.

What is mesothelioma?

A mesothelioma is any malignant tumor (or cancer) that originates from the cells of the mesothelium .

The mesothelium is a layer of squamous cells, which covers different internal organs (including lungs, heart, some abdominal organs, testicles in men and uterus in women) and the cavities within which these organs reside.

In particular:

• The mesothelium of the lungs and the cavities containing them is called, respectively, a visceral pleura and a parietal pleura .

  The generic term pleura includes both the visceral pleura and the parietal pleura.

• The mesothelium of the heart and of the sac that contains it is known, respectively, as visceral pericardium ( epicardium ) and parietal pericardium .

  The generic term pericardium includes both the visceral pericardium and the parietal pericardium.

• The mesothelium that covers some abdominal organs and the cavity containing these organs is called, respectively, visceral peritoneum and parietal peritoneum .

  The generic term peritoneum includes both the visceral peritoneum and the parietal peritoneum.

• The testicular mesothelium is known as the vaginal cavity of the testicle .
• The mesothelium of the uterus is known as the perimeter (or serous uterine tunic ).

The layer of squamous cells forming the different mesothelium of the human body creates serous membranes .

TYPES OF MESOTHELIOMA

There are various types of mesothelioma. The distinction in different types depends on the mesothelium in which the tumor originates.

The most well-known and widespread types of mesothelioma are:

• Pleural mesothelioma : it is mesothelioma that originates at the level of the pleura. Data in hand, represents, by far, the most common type of mesothelioma in humans.

  It has good infiltrating capacity (it is capable of spreading in neighboring tissues) and can contaminate the nearby pericardium with its cancer cells.

• Peritoneal mesothelium : mesothelioma that occurs at the level of the peritoneum. It represents another good part of the mesotheliomas that can affect the human being, even if decidedly less consistent than the pleural mesothelioma.

  It has poor infiltrating capacity, so it rarely invades adjacent tissues with its cancer cells.

The types of mesothelioma less known and even less common are:

• Pericardial mesothelioma : mesothelioma that originates from the pericardium, ie the mesothelium in which the heart resides.
• Testicular mesothelioma (or mesothelioma of the vaginal tunic of the testicle ): it is mesothelioma which originates from the testicular mesothelium (also known as the vaginal tunic of the testicle).
• Mesothelioma of the perimeter (or mesothelioma of the serous uterine cassock ): it is mesothelioma that originates from the mesothelium of the uterus, also known as uterine serous tunic.

A few more details on pleura and peritoneum

The pleura serves, first of all, to protect the lungs.

Secondly, it produces a lubricating fluid that favors the sliding on the surface of the lungs, so as to allow the latter greater freedom of expansion. Between the visceral pleura and the parietal pleura, there is a virtual space known as the pleural space or pleural cavity.

The peritoneum serves to protect and maintain the abdominal organs that cover it. Like the pleura, it produces a lubricating liquid, which, by interposing itself between the various abdominal organs, favors the mutual sliding.

Causes

For humans, the main cause of mesothelioma is exposure to asbestos or asbestos .

Asbestos is a set of minerals (inosilicates and phyllosilicates), arranged in elongated bodies (the so-called "asbestos fibers") and capable of being easily dispersed in the air (this involves their inhalation).

In order for readers to become aware of the influence of asbestos on the development of a mesothelioma, the following statistical data is reported, relating to the United Kingdom: 9 men out of 10 with mesothelioma and about 8 women out of 10 with mesothelioma are people who have had contact with asbestos in their life.

The effects of asbestos exposure appear after many years: a mesothelioma can arise after 20, if not even 50 years.

Asbestos enters the human body through the respiratory tract . It is for this reason that the most common mesothelioma is pleural mesothelioma.

RISK FACTORS RELATED TO ASBESTOS

Asbestos

While it was once widely used in industrial plants due to its resistance to fire, acids, micro-organisms and wear, asbestos is no longer in use and many countries of the world have even banned its commercialization, precisely because of its harmful effects on human health. This has greatly reduced the risk of exposure to asbestos and, clearly, also the risk of developing mesothelioma and other related disorders (asbestosis, etc.).

At present, the people still dangerously exposed to asbestos are: those who live near old mining quarries for asbestos, those who live near old buildings presenting parts in asbestos and those who live near rich natural places of those mining components forming asbestos.

It is important to stress this concept: the earlier it begins and the greater the exposure to asbestos during an individual's life, the higher the risk of developing mesothelioma.

Places of greatest exposure to asbestos, before its abolition:

• The cement plants that produced Eternit (Eternit was the commercial name of asbestos).
• The textile industries that produced asbestos-based fabrics, coveralls and gloves.
• Shipyards and railways.
• Building installations.
• Friction materials industries, such as brakes and clutches.
• Mining quarries for the minerals that make up asbestos.

OTHER CAUSES OR ONLY RISK FACTORS

Studying the effects of asbestos on human beings, some research groups have noticed that coming into contact with the SV40 virus, in subjects previously exposed to asbestos, contributes to the onset of mesothelioma. The scientific findings on the subject are still scarce and require further investigation.

According to other researchers, there are other possible causes or risk factors for mesothelioma: radiation exposure from radiation therapy, exposure to thorium dioxide and exposure to a mineral known as erionite, present in Turkey.

Epidemiology

In general, mesothelioma is a very rare malignant tumor. For example, in the United Kingdom, it involves 2, 600 people each year; in Italy, just over 2, 000 individuals a year.

In the past, some studies had shown the existence of a higher incidence of mesothelioma in the male population (NB: the ratio with women was 5 to 1). Most likely, this trend was linked to the fact that asbestos workers - when this substance was still widely in use - were mostly men. It would not be surprising if such research, carried out today, would yield slightly different data and with a lower gap between men and women.

Most people with mesothelioma are over 50 years old (patients aged 70 are by far the most numerous). This particular incidence in the advanced age population is explained by the very slow effects that exposure to asbestos has on human beings.

• Pleural mesothelioma accounts for almost 75% of human mesotheliomas. Thus, about 3 in 4 mesotheliomas are pleural mesotheliomas.
• Peritoneal mesothelioma accounts for almost 25% of human mesotheliomas. Therefore, about one in four mesothelioma is a peritoneal mesothelioma.
• Pericardial mesothelioma and mesotheliomas of the internal reproductive organs of men and women represent the remaining percentage. They are very rare.

Symptoms and Complications

Premise: since pleural mesothelioma and peritoneal mesothelioma are the two most common types of mesothelioma, this chapter will mainly deal with the symptoms of these two malignant mesothelial tumors.

The typical symptoms and signs of pleural mesothelioma are:

• Pain in the chest and sometimes in the lower back region
• Short breath (dyspnea)
• Persistent cough and / or hoarseness
• Pleural effusion
• Hemoptysis (cough with blood)
• Fever above 38 ° C, with sweating, especially at night
• Fatigue and muscle weakness
• Difficulty swallowing
• Unexplained weight loss

The typical symptoms and signs of peritoneal mesothelioma are:

• Abdominal pain
• Abdominal swelling due to fluid accumulation (ascites)
• Sense of nausea and recurrent vomiting
• Loss of appetite
• Inexplicable drop in body weight
• Diarrhea or constipation
• Presence of an abdominal mass, recognizable by touch

PARTICULARITIES OF INITIAL STAGES

Very often, in the early days, both pleural and peritoneal mesotheliomas are asymptomatic, that is, devoid of symptoms and obvious signs.

This peculiarity makes early diagnosis difficult.

COMPLICATIONS OF PLEURIC MESOTHELIOMA

In the most serious cases, pleural mesothelioma can lead to the appearance of different tumors at the thoracic level, the collapse of one or both lungs ( pneumothorax ) and pulmonary embolism .

Furthermore, it is a malignant tumor with metastasizing capacity, therefore it can spread its cancer cells in organs and tissues distant from the place of origin (NB: cells that a malignant tumor disperses in organs and tissues distant from the place of origin are named of metastases ).

COMPLICATIONS OF PERITONEAL MESOTELIOMA

In the most severe cases, peritoneal mesothelioma is responsible for:

• Blood clots inside venous vessels (thrombophlebitis)
• Jaundice
• Hypoglycemia
• A further worsening of ascites
• Metastasis, although it is good to point out that its metastasizing power is lower than that of pleural mesothelioma

SYMPTOMS OF DANGEROUS MESOTHELIOMA

Mesothelioma affecting the pericardium can cause the appearance of: pericarditis, heart failure, pulmonary embolism, cardiac tamponade, chest pain, orthopnea and cough.

Diagnosis

In general, the diagnostic procedure that leads to the identification of a mesothelioma begins with an accurate physical examination and a careful medical history ( clinical history ). Thus, it continues with some imaging tests, including X-rays, CT scans, nuclear magnetic resonance and PET .

Finally, it ends with a biopsy, the most indicative exam and one that confirms any suspicion born during previous assessments.

IMPORTANCE OF THE ANAMNESIS

As mentioned, mesothelioma affects almost exclusively people exposed to asbestos.

This characteristic makes the anamnesis a fundamental point of the diagnostic path, since an individual who has never had contact with asbestos in life, even if he presents a suspicious symptomatology, most likely suffers from a disorder other than mesothelioma.

In this regard, it is worth pointing out that the clinical manifestations of mesotheliomas are very similar to those of other morbid conditions. To cite an example, pleural mesothelioma presents symptoms and signs that reflect the symptoms and signs of lung cancer or pulmonary fibrosis.

DIAGNOSTICS FOR IMAGES

Diagnostic imaging tests allow the doctor to identify the exact location of the tumor mass or masses and to see if they have invaded other organs or tissues, or if they have had particular effects (pleural effusion, ascites, etc.).

BIOPSY

The biopsy consists in the collection of a sample of cells from the tumor mass and in the laboratory analysis of this sample.

Through the analysis of tumor cells, the doctor is able to understand the type of cell that gave rise to the malignant tumor: if it turns out that the process of formation of the tumor mass began at the level of a mesothelial cell (ie of a mesothelium), then the aforementioned tumor mass is a mesothelioma.

Furthermore, biopsy is useful because it allows to detect two important features of a malignant tumor: staging and grade .

In the case of pleural mesothelioma, the collection of the cell sample for biopsy is performed by thoracoscopy or thoracotomy procedures .

In the case of peritoneal mesothelioma, the sample of cells for biopsy is taken by a laparoscopy procedure .

What are staging and the degree of a malignant tumor?

The staging of a malignant tumor includes all that information, collected during biopsy, which concerns the size of the tumor mass, its infiltrating power and its metastasizing capacities.

The degree of a malignant tumor, on the other hand, includes all those data that emerged during the biopsy, which concern the extent of transformation of malignant tumor cells, compared to their healthy counterparts.

Treatment

The choice of which treatment to adopt in the case of mesothelioma depends on various factors, including: staging and degree of malignant tumor (presence of metastases, progression of the disease, etc.), the general state of health of the patient (patients are generally elderly with other ailments) and the affected body regions.

Currently, the options for treating a mesothelioma are surgery, radiotherapy and chemotherapy.

SURGERY

The goal of surgery is the removal of the tumor mass that constitutes mesothelioma. For less severe mesotheliomas, surgical removal surgery can also provide good results. However, in general, mesotheliomas lend themselves little to resection (ie elimination by surgery).

To further complicate matters, then, it can be the uncomfortable site of the malignant tumor: if the latter, in fact, originates in an area that is difficult to reach with surgical instrumentation, the removal operation is even more complex.

RADIOTHERAPY

In the case of mesothelioma, radiotherapy can be an alternative to surgery - if this is not practicable - or a form of adjuvant treatment, to be performed after surgical removal of the tumor mass ( adjuvant radiotherapy ).

When radiation therapy has an adjuvant value, it serves to destroy the cancer cells that the surgeon was unable to remove.

CHEMOTHERAPY

Chemotherapy consists of the administration of one or more antitumor drugs, systemically, intrapleural (ie directly into the thoracic cavity) or intraperitoneal (ie directly into the abdominal cavity).

Depending on the characteristics of mesothelioma present, the attending physician can decide whether to opt for pre-surgical chemotherapy (also called neoadjuvant chemotherapy ) or for post-surgical chemotherapy (also known as adjuvant chemotherapy ).

The goal of neoadjuvant chemotherapy is to reduce the tumor mass, so as to make subsequent surgical removal easier.

The goal of adjuvant chemotherapy, on the other hand, is to eliminate the tumor cells that the surgeon, through the resection procedure, was unable to remove.

POSSIBLE CARE OF THE FUTURE

Recently, doctors and researchers are experimenting with the effects of some particular medicines, belonging to the category of monoclonal antibodies and also known as biological drugs .

Among the biological drugs that seem to have therapeutic effects against mesothelioma, the tremelimumab deserves special mention .

Prognosis

Mesothelioma almost always has a negative prognosis, as its diagnosis occurs, very often, too late, when the situation is already severely compromised.

The average survival rate in pleural or peritoneal mesothelioma is 12 months. However, it is worth pointing out that some patients can survive for up to 3 years (obviously with the most appropriate therapies).

The average survival rate in pericardial mesothelioma is 10 months.