Introduction
The human body contains some important spaces or cavities that are lined by thin membranes, namely the pericardial cavity surrounding the heart, the pleural cavities surrounding the lungs, and the peritoneal cavity surrounding the gut. Mesothelioma, also known as malignant mesothelioma, is a type of cancer that arises in the cells forming the membranes that line the serous cavities of the body. This article answer the question “What is mesothelioma?”, and discuss the role of the notorious carcinogen asbestos in its occurrence, mesothelioma of the pleural cavity and of the peritoneal cavity, the symptoms of a patient with mesothelioma, the causes of the tumor, the treatment modalities that can be employed against it, the methods and investigations used to diagnose the disease, as well as the prognosis and the estimated survival rates.
Background
Serous cavities in the human body serve some important functions. The serous membranes lining them are basically like a folded sheet that envelops its specific organ. The organ is thus surrounded by a closed “bag” consisting of two layers, which contain also a thin film of clear fluid in between, which allows the two layers to slide on top of each other when the organ they surround moves. The heart, for example, is constantly beating, and it is therefore helped greatly by the presence of a serous membrane that facilitates its expansions and contractions. Like a well-oiled machine, the heart’s movement becomes smooth and effortless by virtue of its serous membrane, the pericardium.
The lungs, because of the complex process of breathing, have a different situation with regards to their serous cavity, the pleura. At rest, the pleural cavity has a negative pressure, which allows the lungs to remain inflated. When a person starts to inhale, the muscles of breathing, including the diaphragm, the intercostal muscles between the ribs, and the sternocleidomastoid all contract to expand the lungs. When this happens, the pressure within the pleural cavity becomes even more negative, pulling on the lungs and forcing the air sacs (alveoli) to open and take in air. During expiration the chest muscles relax and allow the chest wall to fall back and compress the lungs to push air out of them. In addition, the pleural cavity allows the lungs to expand and contact easily due to the presence of a slick film of fluid between the two layers of the pleura, which effectively functions as a lubricant.
Finally, the mesothelium surrounding the intestines and the other organs in the abdomen is the peritoneum. The peritoneal membrane allows nerves, blood vessels, and lymphatic vessels to reach their intended abdominal organ, and it also helps support and protect the vulnerable abdominal contents.
The mesothelium also plays a role in helping out the immune system of the body, allowing the movement of white blood cells and the synthesis of substances that aid the process of inflammation.
The most common site for the occurrence of mesothelioma in general is the pleura, which lines the lungs. Next is the peritoneum which surrounds the intestines, and then the pericardium around the heart. Very rarely it may affect the covering of the testicles in men. In the United States, the incidence is approximately three thousand patients per year.
Mesothelioma causes
There is one substance in particular that is definitively implicated in the occurrence of mesothelioma, and that is asbestos. Asbestos is a silicate mineral used widely in the past for construction and fireproofing purposes. This was partly due to the fact that it is a good conductor of electricity and that it is highly resistant to heat. Asbestos wasn’t well known in the past, but massive mining operations in the past century put the material under the spotlight because of the appearance of large numbers of miners and construction workers who suffered from diseases caused by prolonged exposure to asbestos dust. Asbestos use was thus eventually outlawed in most countries. The incidence of mesothelioma therefore has predictably been increasing ever since asbestos usage became commonplace. One factor that complicated this point is that people who are exposed to asbestos for a prolonged period do not develop mesothelioma quickly. The time interval between exposure to the carcinogen and developing a mesothelioma is usually measured in decades. This explains the appearance of mesothelioma patients in areas where asbestos use became illegal. They are manifesting the effects of prolonged asbestos exposure years later. This is why one of the first questions a doctor will ask his/her patient is their occupational history to figure out if they had been exposed to a carcinogenic substance like asbestos chronically.
It should also be mentioned that mesothelioma is not the only lung disease that is caused by asbestos. Indeed, it can also cause a non-cancerous condition known as asbestosis.
Mesothelioma symptoms
When describing the symptoms of any cancerous tumor, they are usually divided into three subdivisions. First, there are the symptoms caused by the tumor at the site where it originally appeared. Second are the manifestations caused by the spread of the tumor to sites other than the original. This ability to spread is called metastasis. Finally, there are symptoms that are caused by the tumor but affect the whole body. This may be because the cancer synthesizes substances that run in the blood stream and spread throughout the circulation.
The symptoms caused by the mesothelium at its original site depend on what that site is. It is to be expected that the presence of a mesothelioma in one serous cavity will affect the organs encased in that particular cavity. For example, if it appears in the lining of the lungs it can cause difficult breathing, chest pain or discomfort, and fluid build-up around the lungs, known medically as pleural effusion. On the other hand, a mesothelioma that arises in the lining of the abdomen (Peritoneal mesothelioma) will usually cause pain or a swelling in the abdomen, and may affect the urinary bladder or intestines.
When it comes to manifestations of metastases, the tumor can spread anywhere through blood or the lymphatic system, and the list of possible symptoms is theoretically endless, which makes it difficult to diagnose metastatic disease without the use of radiological studies. In general though, metastatic disease is not very common in mesothelioma except in late, neglected cases.
Lastly, mesothelioma can cause the patient to spike a fever and appear tired and fatigued for a long time. This may be associated with weight loss and/or a loss of appetite, and excessive sweating at night.
Mesothelioma diagnosis
The diagnosis of any disease takes all the facts into consideration. These vital pieces of info are mainly gleaned from the patient’s history, the physical examination, and the investigations.
In mesothelioma patients, the occupational history is paramount. A patient with difficult breathing and chest pain could have a multitude of problems, but when the physician is informed of the patient’s long exposure to asbestos, the diagnostic choices are narrowed down. The last crucial step in diagnosis is the investigations, which will be discussed in detail below. A suggestive history and complaints alone cannot rule out a possible wildcard.
Firstly, radiological studies are done. An Xray of the chest may show a mass enveloping the pleura, changes in the appearance of the diaphragm, or various other features. This is done by sending electromagnetic waves that penetrate the chest and its structure, and that imprint on a radiographic film that is then looked at by the radiologist.
Another imaging modality that may be used is a CT scan, short for Computed Tomography. This can be thought of as a machine that virtually slices the chest into many sections so that the doctor can see all the structures inside at all planes. This scan is particularly useful in detecting the presence of any metastases. A third imaging technique is the MRI or Magnetic Resonance Imaging. This is the one where the patient lies on their back and is moved into a tunnel-like machine and hears clicking sounds for a while. What really happens is that a powerful magnet is used to collect high quality images from the patient’s body. While something like an Xray will primarily show high density structures such as bone, an MRI shows all structures in exquisite detail. The photos look exactly like what you would see in an anatomy textbook. However MRIs are expensive and take more time to perform than any other imaging modality. One other radiological study that may be employed is the PET (Positron Emission Tomography) scan, which can help rule out metastatic spread to distant body sites.
The single most useful investigation in the diagnosis of a malignant mesothelioma is a tissue biopsy taken with a small tube inserted into the chest. This is called a thoracoscopically guided biopsy. This is termed a “Keyhole surgery”, and is much less invasive than an “open biopsy”, where a surgeon uses a scalpel to cut open the patient’s chest in order to take the tissue sample. Alternatively, a needle may be inserted into the chest under CT guidance to take the specimen.
After the tissue biopsy is extracted, it is cut down to size, stained using one out of a plethora of medicinal stains, and put on a glass slide before being examined under the lens of a microscope by a pathologist. The type of mesothelioma will be determined by what the pathologist sees. Different types of the tumor have different distinguishing features under the microscope, and the type of the mesothelioma will have a very big impact on the treatment modalities used, the prognosis, and the survival rates.
The tissues may be stained by a normal histological stain or may be visualized using antibodies that bind to specific structures within the tumor. This advanced technique is known as immunohistochemistry.
One of the manifestations of mesothelioma is the accumulation of fluid inside the pleural cavity surrounding the lungs. This fluid build-up may compress the lungs and make it harder to breathe, but for diagnostic purposes we can aspirate some of this liquid and examine the cells floating within. This technique alone isn’t enough to diagnose the cancer but can contribute to the diagnostic process, in addition to relieving some pressure from the patient’s lungs. The same procedure is carried out if the fluid accumulates around the heart in the pericardial cavity or in the abdomen inside the peritoneal cavity.
Prevention of mesothelioma
Since exposure to large amounts of asbestos for prolonged periods is the most important risk factor for the development of this disease, it follows that the best preventive measure is to avoid any and all interactions with the carcinogen.
When it comes to early detection of mesothelioma in a person who had been exposed to asbestos, no single test has been considered definitive, but research is being done on the efficacy of measuring serum levels of osteopontin and using the Mesomark assay to detect molecules released into the blood by the tumor cells.
Mesothelioma treatment
As previously mentioned, the most important factor in determining the appropriate treatment modality and the prognosis of this disease is the histopathological type. It should also be emphasized that the earlier the tumor is diagnosed, the more likely it is that it can be treated successfully.
The three main categories of treatment methods in any tumor are surgery, chemotherapy, and radiotherapy. The physician usually mixes and matches multiple methods depending on the susceptibility of the tumor to each.
1) Chemotherapy
Chemotherapy means the usage of powerful drugs given to the patient by mouth or by injection, which are toxic to the tumor cells and cause their destruction. These chemicals are so strong that they may affect the normal cells of the body, leading to various side effects, including but not limited to nausea, vomiting, and diarrhea. The doctor can prescribe one or more of these drugs after taking into account which is most effective against the specific tumor type the patient has and while trying to minimize the side effects. Currently, cisplatin is considered a first-line drug, and it may or may not be combined with other chemotherapeutic drugs such as pemetrexed, raltitrexed, gemcitabine, and adriamycin among others.
One novel twist on the standard chemotherapy regimen is what is known as Hyperthermic chemotherapy. Here, the surgeon removes as much tumor tissue as possible and then, instead of administering the drugs orally or into the blood stream, the chemotherapeutic cocktail is heated up and administered directly into the affected serous cavity. This allows the usage of high concentrations of drugs without having severe side effects as they aren’t circulating in the blood stream, and the additional heat allows the materials to penetrate deeply into the tissues and damage the cancer cells more effectively.
2) Radiotherapy
on the other hand, is the practice of using a powerful type of radiation called ionizing radiation to kill the cancer cells. The rays are aimed only at the part of the body where the tumor resides to minimize unwanted side effects. When it comes to the treatment of mesothelioma with this modality, radiotherapy is usually employed after surgical resection of the tumor to ensure the destruction of all cancer cells and to decrease the chances of it growing back. In patients who cannot tolerate a surgical operation, whether due to advanced age or severe disease, radiotherapy can be used as a palliative treatment to reduce the size of the tumor and thus decrease the symptoms caused by it to some extent.
3) Immunotherapy
This line of treatment is based on the idea of injecting certain substances into the body that stimulate the immune system more than normal, allowing it to attack the cancer cells more fiercely. However, it is still only a subject of research regarding mesothelioma treatment and no specific substances have been deemed both safe and effective enough to standardise.
4) Surgery
Surgical treatment of mesothelioma is an important treatment modality, although it isn’t always necessarily successful in curing the disease. The two operations most commonly used in this tumor are pleurectomy with decortication and extrapleural pneumonectomy. Before either of these is carried out the patient’s health must be thoroughly assessed to determine if he/she will be able to tolerate the procedure. It should also be restated that an early diagnosis increases the chances of a successful treatment, especially with surgery. A tumor that is discovered late may very well have metastasized to other bodily organs, rendering surgery less useful. The two surgical procedures will be described in some detail below.
Pleurectomy with decortication is an operation consisting of two parts. Before starting, the patient is put under general anesthesia, and is positioned on his/her side to allow the surgeon to reach the tumor with the least amount of difficulty. The surgeon makes an incision called a thoracotomy, which is a long incision that extends from the back of the patient then curves along the ribs. The scalpel cuts through the skin, subcutaneous tissue and chest muscles to reach the pleural cavity. Once there, the surgeon removes the outer layer of pleura, called the parietal pleura. This is the first step of the procedure and is what we call a pleurectomy. It may or may not be combined with the removal of other structures, such as the diaphragm or the serous sac covering the heart, which is called the pericardium. Then, the surgeon removes as much tumor tissue as possible from the lungs and chest area. This is the second step of the operation, which is called a decortication.
The other surgical operation that can be used in the treatment of a malignant mesothelioma is what is known as an extrapleural pneumonectomy. Here again the patient is put under general anesthesia and laid down on his/her side which is the optimal position for this surgery. The surgeon makes a long incision similar to the one used in a pleurectomy with decortication but when the lungs are reached, a much more extensive dissection is done. Not only is the pleura and pericardium removed, but the patient’s entire diseased lung is excised. Part of the diaphragm (the horizontal muscular structure below the lungs) may also be removed. This advanced degree of dissection makes an extrapleural pneumonectomy more risky and thus less commonly carried out in comparison to a pleurectomy with decortication. However, some patients may need an extrapleural pneumonectomy to control an advanced, invasive malignant mesothelioma that wouldn’t have been controlled by the less rigorous pleurectomy with decortication.
As more and more advances are made in medical tech, the surgeries can more easily be performed not by huge incisions but by using small cameras and tubes called laparoscopes. This severly cuts down on the recovery time and reduces the risk of accidentally injuring a structure in the chest cavity that shouldn’t have been involved in the operation.
A mesothelioma affecting the abdominal cavity can be treated by removing the peritoneal lining. Likewise, a mesothelioma around the heart can be managed by a surgical removal of the pericardial sac.
5) Multimodality therapy
As the name suggests, multimodality therapy is the practice of combining surgery, radiotherapy, and chemotherapy to treat a patient who has mesothelioma. However, not all patients are indicated for this line of treatment, and with a larger treatment regimen come more severe side effects.
Follow up
Malignant mesothelioma is a difficult disease to treat, so it is no surprise that the treatment lines available to manage this disease are very tiring for the patient. Therefore, a patient who has underwent surgery or radiotherapy or taken chemotherapy medications should follow up with a nutritionist to figure out a suitable diet that helps him/her heal. They should also visit a pulmonologist to undergo some pulmonary physiotherapy to regain some of the lost lung function and to make breathing easier. Physical activity should also be started as soon an possible as well.
Prognosis and survival rates of mesothelioma
Prognosis depends heavily on the histopathological type of the tumor, and as with all cancers the earlier the diagnosis the more promising the prognosis. However, even with all the advances in the fields of surgery, the novel techniques being used with chemotherapy, and the new technologies being used in radiotherapy, the prognosis of malignant mesothelioma is unfortunately poor. The tumor usually grows insidiously, causing little distress. It is then able to spread covertly to other parts of the body and thus become virtually incurable. The goal of treatment then changes from trying to cure the disease to relieving the patient’s symptoms.
Mesothelioma prognosis is improved with certain histological types, in younger individuals, and in female patients. Older individuals usually have a less promising prognosis.
The average life expectancy after surgery is about 12 to 21 months. Patients who are diagnosed late and are thus not candidates for surgery have an average life expectancy of about 15 months.
The life expectancy for pericardial mesothelioma is about ten months.
Mesothelioma survival rates are as follows:
- Pleural mesothelioma:
- One year survival rate is 73%
- Five year survival rate is 12%
- Peritoneal mesothelioma:
- One year survival rate is 92%
- Five year survival rate is 52%