Mesothelioma as cancer was first described in 1870. It is more
common pleural than the peritoneum, with a predominance of right-sided.
Men suffer more than women in a ratio of 8: 1. Mesothelioma can occur at
any age, even in children 2-4 years. In the etiology of mesothelioma
primary importance is the duration of exposure to asbestos and erionite
mineral used in construction practice. Etiological factors of
mesothelioma are genetic predisposition, as well as simian virus SV40.
In
Russia, the epidemiology of this tumor has been overlooked. Meanwhile,
according to the literature, in the United States, where asbestos
professionally exposed to 7-8 million. People, the incidence of
malignant mesothelioma (mesothelioma) is 0.1-0.2 per 100 thousand
inhabitants, and is increasing annually (peritoneum and pleura are
affected equally often ). Since 1976, in France this pathology
attributed to occupational diseases (B. Saillard et al., 1977). The
latency period of malignant mesothelioma is 20-30 years.
The pathogenesis of pleural mesothelioma
The
pathogenesis of pleural mesothelioma has not been studied, however, it
found that asbestos fibers have tropism for serous membrane. Respiratory
they migrate to pleura, which can accumulate in large quantities and
serve as a trigger for the development of tumors. Thanks lymph flow
directed towards the parietal pleura, the tumor cells are implanted in
her and gradually spread over the entire surface. Thus, in the
neoplastic process involves both visceral and parietal pleura, which
leads to disruption of lymph circulation, the rapid accumulation of
fluid in the pleural cavity.
According to the
histological WHO classification (1999), malignant mesothelioma
(mesothelioma) are divided into the following variants (types):
Epithelioid type, constituting 50-70% of all mesothelioma and has the best prognosis (outcome)
Sarcomatoid type (7-20%)
Mixed (20-35%)
The
most frequent adverse is sarcomatoid variant of the tumor. Pleural
effusion occurs in 60-80% of patients, but gradually growing tumor can
cause complete obliteration of the pleural cavity.
Risk factors for malignant mesothelioma
Exposure to asbestos is the major risk factor for mesothelioma. Asbestos is used
in the manufacture of insulation and refractory materials, tiles, brake
pads and so on. After the establishment of the relationship of exposure
to asbestos and the development of mesothelioma is the use of the
substance fell sharply.
The risk of developing mesothelioma
depends on the intensity and duration of exposure to asbestos. Long-term
exposure at a young age greatly increases the risk of mesothelioma. The
period of time from the time of first contact with asbestos before
tumor diagnosis is 20-50 years.
Smoking by itself does not affect
the increase in the incidence of mesothelioma, but the combination of
smoking and asbestos exposure significantly increases the risk of lung
cancer. In smoking men exposed to asbestos, the risk of lung cancer
increased 50-90 times compared to the general population.
For prophylaxis (prevention) of developing mesothelioma is necessary to avoid exposure to asbestos at home and at work.
Mesothelioma Diagnosis
Early
symptoms of mesothelioma are not specific. These patients are often
ignored or taken for acts of ordinary non-neoplastic diseases. Most
patients with mesothelioma symptoms appear within 2-3 months prior to
the detection of tumors.
In some patients the symptoms may persist for 6 months or more.
Approximately
50% of patients with pleural mesothelioma noted pain in the chest on
the side or rear surface. Many patients complain of shortness of breath.
In some cases, there is difficulty swallowing, cough, sweating,
weakness, weight loss and fever.
Other symptoms can point to hoarseness, coughing up blood, swelling of the face and upper limbs.
Patients
with peritoneal mesothelioma can be abdominal pain, nausea, vomiting,
weight loss. Some patients may receive the fluid in the abdomen
(ascites), and / or swelling.
If you suspect that mesothelioma is
an urgent need to see a doctor, who will find out the presence of risk
factors and order tests.
During the examination, the
doctor can detect the presence of fluid in the pleural cavity
(pleurisy), abdomen (ascites) or the pericardium (pericarditis), which
arises as a result of tumor development.
Chest X-ray can detect
thickening of the pleura, the presence of calcifications (mineral
deposits) and pleural fluid in the pleural cavity.
Computed tomography (CT) allows diagnosis of mesothelioma and to determine the prevalence of the process (stage).
Magnetic
resonance imaging (MRI) can help identify lesions diaphragm - the
muscle tissue that separates the chest and abdominal cavity.
Thoracoscopy
(examination of the pleural cavity using a special device) can not only
identify the tumor, and a biopsy (take a piece of tissue for
examination) or to obtain fluid for microscopic examination to confirm
the diagnosis.
Laparoscopy (examination of the abdominal cavity
using a device) you can inspect the abdominal cavity, take a piece of
the tumor or fluid for research.
Stages (prevalence), mesothelioma
Currently only distinguish stages of pleural mesothelioma, as occurs much more often than other sites.
There are 4 stages of pleural mesothelioma.
Stage I - the tumor affects the pleura, left or right, and the lymph nodes are not involved in the process.
Stage II - one-sided defeat of pleura and spread of the tumor on the diaphragm or lung tissue.
Stage
III - one-sided defeat of pleura and distribution process on the
anterior chest wall, or adipose tissue of the mediastinum, or
pericardium, or lymph nodes on the side of mesothelioma.
Stage IV -
mesothelioma involves the process of muscle or ribs, or invades the
diaphragm, or the esophagus, trachea, thymus, large blood vessels, or
spine, or moves to the other side, or spread through the bloodstream to
distant organs.
Treatment of malignant mesothelioma
The
choice of tactics of treatment depends on several factors, including
the stage of the tumor, patient's general condition and his opinion.
Given the rarity of mesothelioma, it is advisable to treat cancer in
specialized institutions that have experience in treating such patients.
Surgical treatment
The
operation can be performed as a palliative and therapeutic purposes.
Under palliative operation meant surgery, that can be used to eliminate
or reduce pain or discomfort caused by tumor growth.
Such operations are used if you can not remove the tumor because of the prevalence of severe or the patient's condition.
Plevroektomiya
/ decortication is usually and palliative surgery involves the removal
of the pleura, which prevents the accumulation of liquids and decrease
pain.
Thoracentesis - a procedure in which a needle is removed fluid from the pleural cavity to facilitate the patient's condition.
The
introduction of talc or antibiotics into the pleural cavity to
temporarily prevent the accumulation of fluid in it is effective in 90%
of patients with pleural mesothelioma.
Puncture the
anterior abdominal wall allows you to remove the accumulated fluid in
the abdomen in patients with peritoneal mesothelioma.
Patients
with pericardial mesothelioma pericardiocentesis execution provides the
ability to remove fluid and improve heart function.
Patients in satisfactory condition with a localized tumor radical operations, ie complete removal of mesothelioma.
It
should be noted that often after the alleged radical operations are
microscopic tumor foci. In this regard, the value of radical surgery in
patients with mesothelioma contested.
Vneplevralnaya
pneumonectomy is the removal of the pleura, diaphragm, pericardium and
lung on the affected side. This extended operation can only be performed
by highly skilled surgeons, oncologists, patients with good general
condition without serious comorbidities.
Patients with
localized mezotelimoy peritoneum may be an attempt to remove the tumor
together with a part of the abdominal wall. Unfortunately, most patients
with mesothelioma peritoneum performance of radical surgery is not
possible due to the prevalence of the process.
In the
case of localized lesions of the pericardium is performed its removal,
and in advanced process - palliative interventions that prevent the
accumulation of fluid.
Radiation therapy
External radiation is used in patients with mesothelioma most often.
With internal radiation radioactive material is applied directly to the tumor.
This
type of radiation therapy is used as the primary method of treatment
for patients in critical condition, when they can not move a serious
operation.
Auxiliary radiotherapy administered after non-radical operation to destroy the remaining cancer cells.
Palliative
irradiation is used to relieve symptoms caused by tumor growth:
shortness of breath, pain, bleeding and difficulty swallowing.
Radiation
therapy can cause adverse reactions and complications in the form of
skin burns, weakness, nausea, vomiting, loose stools, damage lung
tissue, difficulty breathing.
The majority of adverse events being held after completion of the irradiation.
You should know that radiation therapy may aggravate side effects of chemotherapy.
Chemotherapy
In
the treatment of patients with malignant mesothelioma chemotherapy can
be administered not only intravenously, but intrapleural and
intraperitoneally (into the abdominal cavity).
Depending on the
stage of the tumor, chemotherapy may be as basic and auxiliary
treatment. Moreover, chemotherapy is used only as a palliative, giving
only a temporary effect.
Of the anticancer drugs used: doxorubicin, cisplatin, methotrexate, vinorelbine, et al. In various combinations.
Adverse
reactions of chemotherapy include: nausea, vomiting, loss of appetite,
hair loss, sores in the mouth, increased susceptibility to infections,
bleeding.
The majority of adverse events being held after completion of treatment.
Surgical
treatment in the volume or plevrektomii plevropnevmonektomii are rare
in localized forms, only in 7-10% of patients. After plevropnevmonektomy
operative mortality reaches 14-15%, significantly higher than the
(minimum) plevrektomy mortality. Life expectancy after these operations
do not differ: the median survival corresponds to 9-21 months .; 2-year
survival rate is 11-45% (Giaccone G., 2002; Rahman M. et al., 2003).
Improving long-term results of surgical treatment (primarily
plevropnevmonektomy) associated with adjuvant chemotherapy.
Experience
of surgical, combined treatment (surgery + chemotherapy + radiotherapy)
* allowed to develop the following recommendations for pleural
mesothelioma:
1. Extrapleural pneumonectomy Execution
(plevropnevmonektomii), holding 4-6 weeks up to 6 cycles of chemotherapy
with the appointment of platinum, followed by radiotherapy in the area
of remote lungs and mediastinum. Direct mortality in different
comparison groups was 5-22%, median - 21 months., 2-5-year survival rate
- 45 and 22%, respectively. The factors most favorable prognosis are
the type of epithelial tumors, as well as the absence of metastases.
2.
Radiotherapy (ODS to 50 Gy.) Reduces the pain, but does not prolong
life (increased dose, as well as a combination of radiation and
chemotherapy did not improve survival).
3. The efficiency of
modern chemotherapy for pleural mesothelioma rarely exceeds 20%. Marked
tumor regression and objective improvement in the application of
cisplatin, cycloplatam, mitomycin, raltitreksida (tomudeksa), etoposide,
carboplatin, ifosfamide, vinorelbine, gemcitabine (Gemzar), pemetrexed
(Alimta).
4. Combination chemotherapy is performed by the
schemes: doxorubicin + cyclophosphamide, doxorubicin, ifosfamide,
doxorubicin and cisplatin + - mitomycin C, cisplatin kampto + mitomycin
C, gemcitabine and cisplatin (carboplatin), gemcitabine + Alimta, Alimta
and cisplatin (carboplatin). Last 3 schemes are considered the standard
treatment of pleural mesothelioma.
In the presence of
pleural effusion may intrapleural administration of cytostatic drugs or
biotherapy to stop or slow down the accumulation of fluid. For this
purpose, cisplatin, bleomycin, and - interferon and interleukin-2.
Possibilities of photodynamic therapy investigated.
In
addition, in clinical trials targeted drugs: Avastin, Iressa, Gleevec,
thalidomide, et al., Which can increase the survival rate. Among the
targeted therapies should pay attention to inhibitors of vascular
endothelial growth factor. It is noted that pleural mesothelioma high
level expression of vascular endothelial growth factor correlates with
increased capillary density and low survival. In this regard, with
mesothelioma studied semaksanib, bevacizumab (Avastin) and thalidomide.