Treatment of neoplastic diseases

Etiology of cancer. Tumor growth is caused by various etiological agents. According to experimental studies, the tumor develops under the influence of ionizing and ultraviolet irradiation, various chemicals, DNA viruses of some classes with horizontal transmission; The tumor can be caused by superinfection of some RNA viruses, etc. A variety of etiological factors is also characteristic of a person.

In medical practice, a special attention of a doctor may be attracted by smoking women and men, workers of some professions related to potentially carcinogenic substances (aniline dyes, radioactive radiation, asbestos, etc.). Elimination or reduction of the concentration of etiological factors is a real way to reduce the incidence of malignant tumors.

Pathogenesis of cancer. Tumors can be benign and malignant. The first consist mainly of the same type of cells that do not differ significantly in morphology from normal cells, with little potency to growth, without the ability to invade and metastasize. Many benign tumors retain these traits throughout the life of a person, rarely degenerating into the corresponding malignant tumors. For example, lipoma of the subcutaneous tissue, uterine fibroids are transformed into sarcoma very rarely. However, benign tumors can be a stage in the development of cancer and sarcoma. So, the diffuse polyposis of the intestine during lifetime almost in 100% of cases passes into a cancer. In many cases, the stage of tumor preservation of the characteristics of benign tissue proliferation (precancer) may not be as obvious as in polyposis, but somehow this stage, occupying a different period of time, exists. Malignancy is associated with repeated changes in the genetic apparatus of tumor cells, which are prone to mutations substantially larger than normal cells. As a result, new clones of cells appear that are characterized by sharp cellular polymorphism, atypia, sprouting into adjacent organs and the ability to grow into metastatic foci in other organs and tissues.

A doctor who knows the clinical patterns, features of the development of symptomatology of benign and malignant tumors of different localization, uses the most rational methods of diagnosis and treatment of these diseases. We emphasize that the diagnosis of a tumor-benign or malignant-must be immediate and clear. When establishing the primary diagnosis, the method of observation, taking into account the growth rate of the tumor, is the path to error.

In the pathogenesis of certain tumors, genetic factors are important. In animals, the role of the genetic predisposition is obvious (on the example of high- and low-growth lines of mice). In humans, a tumor can be either the only manifestation of a genome defect or some of the various disorders in the genome that lead to multiple malformations and tumors. The doctor should conduct special monitoring of members of such families, discuss with them their professional activities (contact with potential carcinogens should be excluded) and choose a medical control system (early detection of the tumor). Among the known Âgenetic tumors are retinoblastoma, an uncontested basal cell carcinoma, trichoepithelioma, multiple endocrine adenomatosis, pheochromocytoma, medullary thyroid cancer, paraganglioma, and polyposis of the large intestine.

The development of malignant tumors becomes more frequent in cases of immunological disorders (immunodeficiency syndromes - agammaglobulinemia, ataxia-telangiectasia, etc., prolonged use of immunosuppressive agents in case of organ transplantation and in some diseases). Such patients also need more frequent medical monitoring for the timely detection of a tumor.

The invasion and metastasis of a malignant tumor determine the course of the disease. Tumor cells germinate into neighboring organs and tissues, damage vessels and nerves. Invasion often, for example, with melanoma of the skin, determines the time of development of metastases. Metastasis is one of the main properties of precisely malignant tumors. Although there are isolated examples of metastasis and morphologically benign tumors (for example, adenomas of the thyroid, pancreas, destructive bladder skidding); This is a rare exception. Benign tumors, as a rule, do not metastasize.

Metastases of malignant tumors are found in regional lymph nodes, as well as in a variety of organs and tissues. Knowing the ways of lymph drainage is important when conducting a patient survey and planning treatment. In a number of cases, it is considered necessary to perform an operation at the regional lymph nodes simultaneously with the removal of the primary tumor. The same approach is used in radiation therapy, if it is the main method of treatment (regional lymph nodes are also planned to be irradiated). Different tumors have features of metastasis in distant organs and tissues. For example, breast cancer more often produces bone metastases, testicular cancer, kidneys into the lungs, colon cancer to the liver, etc. In most cases, multiple metastases of different sizes occur that preserve the morphological structures and biological characteristics of the primary tumor. The most commonly affected lungs, liver, bones, brain. Features of distant metastasis of each tumor are important to know when drawing conclusions that the tumor is localized. This is necessary in the planning of surgery and radiotherapy, as well as for dynamic observation.

The time of development of metastases can be different. For example, metastases of kidney cancer are mainly manifested during the first year after diagnosis and surgery, and for breast cancer - for 2-5 years, sometimes 10-15 years.

Recurrence of tumor growth appears in the same zone in the coming months if the operation was non-radical or radiotherapy and / or chemotherapy did not lead to a truly complete regression of the tumor. Relapses along the morphological structure are similar to the primary tumor, but may have significant differences from it on biological characteristics.

Diagnosis of tumors. The doctor's conversation with the patient. The doctor pays attention to the change in clinical symptoms in chronic diseases, asks some specific questions. A doctor's examination can be preventative, for active detection of symptoms and examination. In some cases, regular self-examination of people (palpation of the breast, examination of pigment nevuses, etc.) is of considerable help. Conversation and examination of the doctor make initial information in the formulation of the diagnosis.

Cytological method. The diagnosis of a malignant tumor should always be established using a cytological and / or histological examination. Cytological examination includes materials obtained with puncture of the tumor, prints, flushes, liquid centrifuges, etc. After puncture, cytological preparations are immediately fixed and then the necessary stains are used. Important role of cytological analysis in breast cancer (preoperative puncture of the tumor), lung cancer (sputum, bronchoscopy materials, transthoracic puncture), early stages of cancer of the stomach, esophagus, oral cavity, vagina and other tumors. It is necessary to emphasize the extremely important importance of the cytological method in cancer in situ, when the possibilities of this method are higher than the histological. The role of cytological research for early diagnosis is evident in cervical cancer. If every woman regularly carries out a cytological examination of smears, cervical cancer can be diagnosed at an early stage and cured in 100% of patients.

The histological method gives the most complete picture of the disease. The material for the study is obtained by biopsy and after removal of the tumor. Establish the morphological type and variant of the tumor, the degree of invasion, the level of differentiation, the accompanying tissue reactions, etc. In-depth study (electron microscopy, immunomorfologicheskie, histochemical methods) makes it possible to deepen the characteristics of the tumor.

Endoscopic methods of investigation are important for the diagnosis of certain tumors, as well as when determining the extent of their spread. Apply endoscopic examination of the nasopharynx, larynx, trachea and bronchi, esophagus, stomach, duodenum, colon and rectum, bladder, pleural and abdominal cavity, etc.

X-ray methods remain important in the diagnosis of tumor diseases of the breast, lung, kidney, gastrointestinal tract, etc. In recent years, computer tomography (CT) has been used successfully. Its informativity is high when a small tumor size is detected in the thyroid gland, kidney, liver, lung, pancreas, etc. A smaller diagnostic value of CT is for stomach cancer, intestine and some other tumors. During CT examination, a targeted tumor puncture can be performed.

Ultrasonic tomography is a highly informative method of investigation; It is used for the diagnosis of tumors of the abdominal cavity and retroperitoneal space, soft tissues of the trunk and so on. During the study, the tumor can also be targeted. Radionuclidean methods are very promising (meaning the creation of tumor-specific labeled antibodies). At present, for diagnosis, scintigraphy of the bones of the skeleton, brain, lungs is used; To characterize the functional state - scintigraphy of the kidneys, liver.

Biochemical methods of research provide useful information when examining cancer patients. Specific biochemical changes in the body of cancer patients have not been established. Some tumors show some changes: in disseminated prostate cancer, a high level of acid phosphatase is found in 75% of patients (however, with localized cancer - less than 20%); In pancreatic cancer - an increase in amylase (25%), with liver cancer - an increase in the liver fraction of alkaline phosphatase. Of great practical importance is the detection of a high level of fetoprotein in liver, testicle, various teratocarcinomas; Carcinoembryonic antigen - in colon cancer; Chorionic gonadotropin - in the chorioepithelioma of the uterus and testicle. Biochemical tests can detect endocrine secretion of the tumor and explain many clinical syndromes caused by tissue-specific or paraneoplastic endocrine activity. A high level of ACTR, antidiuretic, parathyroid, thyroid stimulating, follicle-stimulating, luteotropic, melanostimulating hormone, erythropoietin is detected; Cortisol, adrenaline, noradrenaline, insulin, gastrin, serotonin, etc.

Biochemical methods allow to determine the content of receptors of some hormones in tumor tissue (estradiol, progesterone, testosterone, corticosteroids). Such an analysis is performed by biopsy or by removal of a tumor with rapid freezing of tissue; The result of the study is useful in the development of therapeutic tactics (for example, in breast cancer, etc.).

The listed methods for diagnosing malignant tumors are most informative if applied in a rational combination. As a result of the survey, a well-founded diagnosis of a malignant tumor is established and the disease is classified according to the international TNM classification (T is the size of the primary tumor, N is the state of the regional lymph nodes, M is the absence or presence of distant metastases). After the operation, the classification of the disease is specified. For most tumors, TNM criteria have been developed.

Treatment of malignant tumors. In the treatment of patients with malignant tumors, a variety of problems arise, the solution of which requires the participation not only of oncologists, but also of qualified physicians of other specialties who must clearly understand the features of the main medical methods used in oncology and the possibilities for subsequent rehabilitation of patients. The main methods of treatment: surgical intervention, radiation therapy, chemotherapy, biotherapy. Radical surgery is performed mainly in the early stages of the disease, as well as with locally advanced tumors after previous effective radiation or chemotherapy. Palliative surgery is aimed at reducing the mass of the tumor, which increases the effectiveness of therapeutic effects. Such operations significantly alleviate the condition of patients (for example, with intestinal obstruction, bleeding, etc.). A variant of surgical treatment may be cryogenic destruction of the tumor, performed as a radical or palliative action.

Radiation therapy is used for radiation-sensitive tumors (small cell lung cancer, breast cancer, nasopharynx, larynx, other head and neck tumors, Ewing's sarcoma, cervical cancer, etc.) alone or in combination with surgery, chemotherapy. Various methods of radiotherapy (remote gamma-therapy, intracavitary radiation therapy, neutrons, protons, radioactive isotopes, etc.) are used. Chemotherapy is now becoming the most important treatment for malignant tumors. Chemotherapy is prescribed to reduce the mass of the tumor with an inoperable tumor, after surgery to prevent the development of metastases (adjuvant chemotherapy) or in the presence of metastases. Recently, chemotherapy has also been used for surgical tumors, followed by continued treatment (with sensitivity) after surgery (neoadjuvant chemotherapy). In some diseases, modern chemotherapy, being the main component of treatment, provides a cure for a significant number of patients (malignant seminoma and non-seminiferous testicular tumors, uterine chorionic epithelium, localized forms of osteogenic sarcoma, breast cancer, Ewing's sarcoma, nephroblastoma in children, etc.). More often chemotherapy leads to complete or partial regression of a tumor with different duration of remission (disseminated breast cancer, ovary, melanoma, small cell lung cancer, etc.), which increases the life expectancy of patients and reduces the clinical manifestations of the disease. Chemotherapy is also used for cancer of the stomach, colon, prostate, bladder, kidney, etc.

In modern clinical chemotherapy, various antitumor drugs (antimetabolites, antibiotics, alkylating and various others) are used. Antitumor drugs are used alone or as part of medicinal combinations, which makes it possible to achieve the greatest effectiveness of treatment. The basis of chemotherapy is the difference in the response of normal and tumor cells to the cytostatic effect. The most significant successes of chemotherapy are observed with sensitive tumors of small dimensions, the mass of which rapidly increases and has the greatest sensitivity to the drug. Later on, in large tumor nodes, the tumor doubling time increases, the growth fraction falls, and the effectiveness of chemotherapy decreases. Other biological characteristics of the tumor, the pharmacokinetics of the preparations, etc., are also important.

The greatest effectiveness of antitumor drugs is achieved through their use in rational combinations. Information on the synergy of drugs is obtained as a result of preclinical studies. At various malignant tumors of a person, there are recommendations for the most effective chemotherapy - the so-called first line, and also for further treatment with insufficient effect (second and third lines). The question of rational regimens of treatment is urgent. The principle of achieving maximum therapeutic effect in a short time is shared by most oncologists. Serious criticism is the practice of "curing" drugs with little activity or simply available to the doctor at a given time. Such inadequate treatment not only does not help, but significantly reduces the therapeutic result of subsequent rational chemotherapy. It is explained by the property of tumor cells to develop resistance to cytostatic drugs in a short time.

Drug resistance of a tumor is the most difficult problem of modern chemotherapy, and irrational treatment of patients deepens it. Among the reasons for tumor resistance are the activation of the gene for multiple drug resistance, insufficient drug delivery to the cell, insufficient activation of the drug, increased inactivation, increased binding enzyme concentration, the emergence of alternative metabolic pathways, rapid recovery after injury,

Rational chemotherapy involves the use of different regimens depending on the treatment task. The treatment regimen can be intense, causing significant side effects, moderately toxic or simply non-toxic. It is mandatory to hold repeat courses. The intervals between the courses are determined by the task of treatment and by the characteristic of the side effects of the drugs. The therapeutic effect of antitumor drugs is evaluated after each course of treatment, usually after 2-4 weeks. With measurable tumors, a centimeter or a compass is used to determine the largest diameter and the maximum second diameter perpendicular to the first. These data are compared before and after treatment. In the presence of multiple foci, 3-5 foci of different size are chosen for observation. When metastases to the lungs make radiographs, carefully describe the location and size of the tumor.

In some tumors, ultrasound and computed tomography, hagiography, other radiographic methods, and detection of tumor markers are important. The manifestations of indistinctly measurable and unmeasurable tumors are also recorded. It is important to emphasize the need for a thorough description of all identified signs of the disease before and after treatment. Complete regression - disappearance of all manifestations of the disease; Significant partial regression - reduction of the size of tumor foci S 50%; A slight objective improvement - a decrease in the size of the tumor by 25-49%. Stabilization of the disease is a long (for up to 6 months) absence of dynamics associated with the chemotherapy.

Practitioners should also know the side effects of cytotoxic drugs. The introduction of maximum therapeutic doses of drugs, i.e., therapeutic tactics, involves the development of side effects of varying degrees. They can be observed directly (nausea, vomiting, allergic reactions, etc.), in the near future (leukopenia, thrombocytopenia, diarrhea, stomatitis, etc.) or in the distant period as a result of prolonged use of drugs (nephro-, cardio- , Neuro-, ototoxicity, etc.). Side effects should be carefully recorded, which is important when planning further chemotherapy.

In addition to cytotoxic drugs, chemotherapy includes the use of endocrine drugs. Most often they are used for hormone-dependent tumors (cancer of the breast, thyroid, endometrium, prostate, etc.). Rational therapy involves a preliminary analysis of the content of estrogen, progesterone, androgen receptors in the tumor tissue. Receptors are defined in a distant tumor or with a biopsy. Typically, the primary tumor and its multiple metastases have similar characteristics at the levels of the hormone receptors. Apply antiestrogens, androgens, corticosteroids, progestins - for breast cancer, endometrial cancer, estrogens - for prostate cancer, etc. Improving the effectiveness of treatment is achieved by removing hormonal glands (ovaries, testicles), turning off the function of the pituitary gland (irradiation, removal, administration Releasing hormones of the pituitary gland). Endocrine therapy can be the main method of treatment (for example, with breast cancer and the uterus body in deep menopause with a high level of estrogen and / or progesterone receptors). Often cytostatic and endocrine drugs are used together, which increases the effectiveness of treatment.

Biotherapy includes the use of various natural biologically active agents (interferons, interleukins, etc.), immunotherapy with vaccines, activated lymphocytes, immunomodulating pharmacological drugs, etc. This is a new promising area of ​​medicine, the development of which is closely related to the improvement Testing of immunological reactions in humans, obtaining recombinant and principally new pharmaceutical preparations, as well as with the achievements of experimental immunology. The use of biotherapy in oncology practice is just beginning. T-activin, leacadin, reaferon have been put into practice. It is necessary to accumulate scientific information and more significant practical experience for clarifying the role of biotherapeutic influences in the general system of modern treatment of patients with malignant tumors.