Basic biological features of tumors. Etiopathogenesis of stomach cancer and precancerous diseases The role of ionizing radiation and other rays in the occurrence of tumors
Tumor growth is caused by various etiological agents. According to experimental studies, a tumor develops under the influence of ionizing and ultraviolet radiation, various chemicals, DNA viruses of certain classes with horizontal transmission; the tumor may be caused by superinfection of certain RNA viruses, etc.
In medical practice, special attention of the doctor may be attracted to smoking women and men, workers of certain professions associated with potentially carcinogenic substances (aniline dyes, radioactive radiation, asbestos, etc.). Eliminating or reducing the concentration of etiological factors is a real way to reduce the incidence of malignant tumors.
Pathogenesis of cancer. Tumors can be benign or malignant. The former consist mainly of cells of the same type, which do not differ significantly in morphology from normal cells, with little growth potential, and without the ability to invade and metastasize. Many benign tumors retain these features throughout a person’s life, rarely degenerating into the corresponding malignant tumors. For example, subcutaneous tissue lipoma and uterine fibroids transform into sarcoma extremely rarely. However, benign tumors can be a stage in the development of cancer and sarcoma. Thus, diffuse intestinal polyposis develops into cancer throughout life in almost 100% of cases. In many cases, the stage of the tumor maintaining the characteristics of benign tissue growth (precancer) may not be as obvious as with polyposis, but one way or another such a stage, which takes a different period of time, exists. Malignancy is associated with repeated changes in the genetic apparatus of tumor cells, which are prone to mutations significantly more than normal cells. As a result, new cell clones arise, characterized by sharp cellular polymorphism, atypia, germination 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 various localizations uses the most rational methods of diagnosis and treatment of these diseases. We emphasize that the diagnosis - benign or malignant tumor - must be immediate and clear. When establishing a primary diagnosis, an observation method that takes into account the tumor growth rate is a recipe for error. In the pathogenesis of some tumors, genetic factors play an important determining role. In animals, the role of genetic predisposition is obvious (using the example of high- and low-cancer mouse strains). In humans, a tumor can be either the only manifestation of a genome defect or part of various disorders in the genome, leading to multiple malformations and tumors. The doctor should conduct special monitoring of members of such families, discuss with them their professional activities (it is necessary to exclude contact with potential carcinogens) and choose a medical monitoring system (early detection of the tumor). Known genetic tumors include retinoblastoma, nevus basal cell carcinoma, trichoepithelioma, multiple endocrine adenomatosis, pheochromocytoma, medullary thyroid cancer, paraganglioma, and colon polyposis. The development of malignant tumors increases with violations of immunological control (immunodeficiency syndromes - agammaglobulinemia, ataxia-telangiectasia, etc.; long-term use of immunosuppressive drugs in the case of organ transplantation and in certain diseases). Such patients also need more frequent medical monitoring for timely detection of the tumor.
Invasion and metastasis of a malignant tumor determine the course of the disease. Tumor cells grow into neighboring organs and tissues, damaging blood vessels and nerves. Invasion often, for example in skin melanoma, determines the time of development of metastases. Metastasis is one of the main properties of malignant tumors. Although there are isolated examples of metastasis and morphologically benign tumors (for example, adenomas of the thyroid, pancreas, destructive hydatidiform mole); 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 wide variety of organs and tissues. Knowledge of lymph drainage pathways is important when examining patients and planning treatment. In some cases, it is considered mandatory to perform surgery on regional lymph nodes simultaneously with removal of the primary tumor. The same approach is used for radiation therapy, if it is the main method of treatment (irradiation of regional lymph nodes is also planned). Various tumors have features of metastasis to distant organs and tissues. For example, breast cancer more often metastasizes to the bones, testicular cancer, kidney cancer to the lungs, colon cancer to the liver, etc. In most cases, multiple metastases of various sizes occur, preserving the morphological structures and biological characteristics of the primary tumor. The lungs, liver, bones, and brain are most often affected.
It is important to know the features of distant metastasis of each tumor when drawing a conclusion that the tumor is localized. This is necessary when planning surgery and radiation therapy, as well as for dynamic monitoring.
The period of development of metastases may vary. For example, metastases of kidney cancer mainly appear within the first year after diagnosis and surgery, and for breast cancer - within 2-5 years, sometimes even a year later.
Recurrence of tumor growth appears in the same area in the coming months if the operation was non-radical or radiation therapy and/or chemotherapy did not lead to truly complete regression of the tumor. Relapses are similar in morphological structure to the primary tumor, but may have significant differences from it in biological characteristics.
Diagnosis of tumors. Conversation between a doctor and a patient. The doctor pays attention to changes in clinical symptoms in chronic diseases and asks some specific questions. An examination by a doctor can also be preventive - for the active identification of symptoms and examination. In some cases, regular self-examination of people (palpation of the breast, examination of pigmented nevi, etc.) provides significant assistance. A conversation and examination by a doctor provides initial information in formulating a diagnosis.
Cytological method. The diagnosis of a malignant tumor should always be made using cytological and/or histological examination. Materials obtained during tumor puncture, prints, swabs, fluid centrifugates, etc. are subject to cytological examination. After puncture, cytological preparations are immediately fixed and then the necessary stains are used. The role of cytological analysis is important for breast cancer (preoperative tumor puncture), lung cancer (sputum, bronchoscopy materials, transthoracic puncture), early stages of stomach, esophageal, oral cavity, vaginal and other tumors. It is necessary to emphasize the extremely important importance of the cytological method for cancer in situ, when the capabilities of this method are higher than the histological one. The role of cytology for early diagnosis is obvious in cervical cancer. If every woman undergoes regular cytological examination of smears, cervical cancer can be diagnosed at an early stage and cured in 100% of patients.
LECTURE No. 30. Fundamentals of surgical oncology
1. General provisions
Oncology is a science that studies the problems of carcinogenesis (causes and mechanisms of development), diagnosis and treatment, and prevention of tumor diseases. Malignant neoplasms receive close attention in oncology due to their great social and medical significance. Oncological diseases occupy the second place among causes of death (immediately after diseases of the cardiovascular system). Every year, about 10 million people become ill with cancer, and half that number die from these diseases each year. At the present stage, the first place in morbidity and mortality is occupied by lung cancer, which has overtaken stomach cancer in men, and breast cancer in women. In third place is colon cancer. Of all malignant neoplasms, the vast majority are epithelial tumors.
Benign tumors, as the name implies, are not as dangerous as malignant ones. There is no atypia in the tumor tissue. The development of a benign tumor is based on the processes of simple hyperplasia of cellular and tissue elements. The growth of such a tumor is slow; the tumor mass does not grow into the surrounding tissues, but only pushes them aside. In this case, a pseudocapsule is often formed. A benign tumor never metastasizes, no decay processes occur in it, therefore intoxication does not develop with this pathology. Due to all the listed features, a benign tumor (with rare exceptions) does not lead to death. There is such a thing as a relatively benign tumor. This is a neoplasm that grows in a limited cavity, such as the cranial cavity. Naturally, tumor growth leads to increased intracranial pressure, compression of vital structures and, accordingly, death.
Malignant neoplasm is characterized by the following features:
1) cellular and tissue atypia. Tumor cells lose their previous properties and acquire new ones;
2) the ability for autonomous, i.e., uncontrolled by organismal regulatory processes, growth;
3) rapid infiltrating growth, i.e. tumor germination of surrounding tissues;
4) ability to metastasize.
There are also a number of diseases that are precursors and harbingers of tumor diseases. These are the so-called obligate (a tumor necessarily develops as a result of the disease) and facultative (a tumor develops in a large percentage of cases, but not necessarily) precancers. These are chronic inflammatory diseases (chronic atrophic gastritis, sinusitis, fistulas, osteomyelitis), conditions accompanied by tissue proliferation (mastopathy, polyps, papillomas, nevi), cervical erosion, as well as a number of specific diseases.
2. Classification of tumors
Classification by tissue – source of tumor growth.
2. Malignant (cancer):
2. Malignant (sarcomas):
1. Benign (fibroids):
1) leiomyomas (from smooth muscle tissue);
2) rhabdomyomas (from striated muscles).
2. Malignant (myosarcomas).
1. Benign (hemangiomas):
2. Malignant (angioblastomas).
1) acute and chronic;
2) myeloblastic and lymphoblastic.
2) dermoid cysts;
2. Malignant (teratoblastomas).
Pigment cell tumors.
1. Benign (pigmented nevi).
2. Malignant (melanoma).
International clinical classification according to TNM
Letter T (tumor) In this classification, denotes the size and extent of the primary lesion. Each tumor location has its own criteria, but in any case tis(from lat. Tumor in situ- “cancer in situ”) - does not grow into the basement membrane, T1 - the smallest tumor size, T4 - a tumor of significant size with invasion of surrounding tissues and decay.
Letter N (nodulus) reflects the state of the lymphatic system. Nx – the condition of the regional lymph nodes is unknown, there are no distant metastases. N0 – the absence of metastases to the lymph nodes has been verified. N1 – single metastases to regional lymph nodes. N2 – multiple lesions of regional lymph nodes. N3 – metastases to distant lymph nodes.
Letter M (metastasis) reflects the presence of distant metastases. Index 0 – no distant metastases. Index 1 indicates the presence of metastases.
There are also special letter designations that are placed after pathohistological examination (it is impossible to set them clinically).
Letter R (penetration) reflects the depth of tumor invasion into the wall of a hollow organ.
Letter G (generation) in this classification reflects the degree of differentiation of tumor cells. The higher the index, the less differentiated the tumor and the worse the prognosis.
Clinical staging of cancer according to Trapeznikov
Stage I. Tumor within the organ, absence of metastases to regional lymph nodes.
Stage II. The tumor does not invade surrounding tissues, but there are single metastases to regional lymph nodes.
Stage III. The tumor grows into surrounding tissues and there are metastases to the lymph nodes. The resectability of the tumor at this stage is already doubtful. It is not possible to completely remove tumor cells surgically.
Stage IV. There are distant tumor metastases. Although it is believed that only symptomatic treatment is possible at this stage, resection of the primary tumor site and solitary metastases can be performed.
3. Etiology, pathogenesis of tumors. Diagnosis of tumor disease
To explain the etiology of tumors, a large number of theories have been put forward (chemical and viral carcinogenesis, disembryogenesis). According to modern concepts, malignant neoplasms arise as a result of the action of numerous factors of both the external and internal environment of the body. The most important environmental factors are chemicals - carcinogens, which enter the human body with food, air and water. In any case, the carcinogen causes damage to the genetic apparatus of the cell and its mutation. The cell becomes potentially immortal. If the body's immune defense fails, the damaged cell continues to multiply and its properties change (with each new generation, the cells become more malignant and autonomous). A very important role in the development of tumor disease is played by disruption of cytotoxic immune reactions. Every day, about 10 thousand potentially tumor cells appear in the body, which are destroyed by killer lymphocytes.
After approximately 800 divisions of the initial cell, the tumor acquires a clinically detectable size (about 1 cm in diameter). The entire period of the preclinical course of a tumor disease takes 10-15 years. From the moment when a tumor can be detected, 1.5-2 years remain until death (without treatment).
Atypical cells are characterized not only by morphological, but also by metabolic atypia. Due to the distortion of metabolic processes, tumor tissue becomes a trap for the body's energy and plastic substrates, releases a large amount of under-oxidized metabolic products and quickly leads to exhaustion of the patient and the development of intoxication. In the tissue of a malignant tumor, due to its rapid growth, an adequate microvasculature does not have time to form (vessels do not have time to grow behind the tumor), as a result, metabolic processes and tissue respiration are disrupted, necrobiotic processes develop, which leads to the appearance of foci of tumor decay that form and maintain state of intoxication.
In order to detect an oncological disease on time, the doctor must have an oncological alertness, i.e., during the examination it is necessary to suspect the presence of a tumor, based only on small signs. Establishing a diagnosis based on obvious clinical signs (bleeding, sharp pain, tumor disintegration, perforation into the abdominal cavity, etc.) is already late, since the tumor clinically manifests itself at stages II-III. For the patient, it is important that the neoplasm is detected as early as possible, at stage I, then the probability that the patient will live for 5 years after treatment is 80-90%. In this regard, screening examinations, which can be carried out during preventive examinations, become important. In our conditions, the available screening methods are fluorographic examination and visual detection of cancer in external locations (skin, oral cavity, rectum, breast, external genitalia).
The examination of a cancer patient must be completed with a pathohistological examination of a suspicious formation. The diagnosis of a malignant neoplasm is untenable without morphological confirmation. This must always be remembered.
4. Treatment of cancer
Treatment should be comprehensive and include both conservative measures and surgical treatment. The decision on the scope of future treatment for a cancer patient is made by a council consisting of an oncologist, a surgeon, a chemotherapist, a radiologist, and an immunologist.
Surgical treatment may precede or follow conservative measures, but complete recovery from a malignant neoplasm without removal of the primary lesion is doubtful (excluding tumor diseases of the blood, which are treated conservatively).
Surgery for cancer can be:
Radical operations imply complete removal of the pathological focus from the body. This is possible by following the following principles:
1) ablastics. During the operation, it is necessary to strictly observe ablastics, as well as asepsis. Ablasticity of the operation is to prevent the spread of tumor cells to healthy tissues. For this purpose, the tumor is resected within healthy tissue without affecting the tumor. In order to check ablasticity after resection, an emergency cytological examination of a smear-imprint from the surface remaining after resection is carried out. If tumor cells are detected, the extent of resection is increased;
2) zonality. This is the removal of nearby tissue and regional lymph nodes. The volume of lymph node dissection is determined depending on the extent of the process, but one must always remember that radical removal of lymph nodes leads to the occurrence of lymphostasis after surgery;
3) antiblastics. This is the destruction of locally spread tumor cells, which in any case are dispersed during surgery. This is achieved by injecting the circumference of the pathological focus with antitumor drugs and regional perfusion with them.
Palliative surgery is performed if it is impossible to carry out radical surgery in full. In this case, part of the tumor tissue is removed.
Symptomatic operations are performed to correct emerging disturbances in the functioning of organs and systems associated with the presence of a tumor node, for example, the application of an enterostomy or bypass anastomosis for a tumor obstructing the gastric outlet. Palliative and symptomatic operations cannot save the patient.
Surgical treatment of tumors is usually combined with other treatment methods, such as radiation therapy, chemotherapy, hormonal therapy and immunotherapy. But these types of treatments can also be used independently (in hematology, radiation treatment of skin cancer). Radiation treatment and chemotherapy can be used in the preoperative period in order to reduce the volume of the tumor, relieve perifocal inflammation and infiltration of surrounding tissues. As a rule, the course of preoperative treatment is not long, since these methods have many side effects and can lead to complications in the postoperative period. The bulk of these therapeutic measures are carried out in the postoperative period. If a patient has stages II-III of the process, surgical treatment must necessarily be supplemented by a systemic effect on the body (chemotherapy) in order to suppress possible micrometastases. Special schemes have been developed to achieve the maximum possible removal of tumor cells from the body without causing a toxic effect on the body. Hormone therapy is used for some tumors of the reproductive system.
Etiology of cancer
Precancerous diseases of the red border of the lips and oral mucosa. Classification. Etiology, pathogenesis, clinical picture, diagnosis.
Currently, more than 10 million people in the world get cancer every year, and about 7 million people die (WHO data - 2003). Cancer is a disease of genes.
Etiology of cancer:
1. The theory of embryonic dystopia (Yu. Kongeim, 1882)
2. Theory of chronic nonspecific irritation (R. Vikhrov, 1885)
3. Theory of chemical carcinogenesis (P. Pott, 1775; L. Shabad, 1981)
4. Theory of infectious viral carcinogenesis (L. Zilber, 1946)
Exogenous factors: smoking (79%) – t°, toxins; chronic diseases; exposure to carcinogens; radioactive substances, destruction of immunotransmitters; chronic injuries (9%); PR hygiene (47%): theory of immune surveillance, associated with the endocrine and nervous system (herpes-candidiasis-poor hygiene > distracted immunity > precancer); galvanosis - the damaging effect of various metals on epithelial cells (the same charge of Ni, Co, W and other metal ions - the occurrence of repulsive forces), the first manifestations are redness, burning, dryness; then a precancer condition is possible.
Cell division: healthy (:50) and cancerous (: an infinite number of times). Apoptosis.
Carcinogenic substances. Currently, more than 1200 of them are known. Sources of carcinogens. Oncoviruses - about 60 of them are known, easily trigger the cancer process.
In most patients, cancer is preceded by certain diseases of the oral mucosa and red border of the lips, which are called precancerous. The precancer condition is microscopic multicentrically occurring multiple foci of non-inflammatory atypical growth of immature epithelium with a tendency to infiltrative growth - “dormant cells”. Their occurrence is primarily promoted by injuries, especially chronic ones, including smoking and chewing tobacco, betel nut, drinking nas, and alcohol. Injuries are considered as external factors of carcinogenesis. Cancer is often preceded by proliferative processes, benign tumors, and chronic inflammatory diseases accompanied by erosions and ulcers. A precancerous disease exists for a long time (from several months to tens of years), then it can (but not necessarily) turn into cancer. Timely detection and treatment of precancerous diseases eliminates the threat of cancer or allows for timely, more effective and harmless treatment.
Pathogenesis of tumor growth:
– initiation – transformation of normal cells into tumor cells (due to a virus or carcinogenic substance);
Characteristic states of the immune system for phases.
Every cancer has its own precancer, but not every precancer has its own cancer.
Directions of precancer: progression; growth without progress, regression, without change.
Depending on the degree of likelihood of malignancy, obligate and facultative pretumor processes are distinguished. Without treatment, obligate precancers inevitably lead to the development of cancer over various periods. In most cases they are already cancer in situ from the very beginning. Optional precancers do not always lead to cancer. We have adopted the classification of precancers proposed by A.L. Mashkilleyson in 1970 and approved with minor amendments in 1976 by the Committee for the Study of Head and Neck Tumors of the All-Union Scientific Medical Society of Oncologists.
Classification of pretumor processes of the oral mucosa
A. With a high frequency of malignancy (obligate): 1) Bowen's disease.
B. With a low incidence of malignancy (optional): 1) verrucous and erosive leukoplakia; 2) papillomatosis; 3) erosive-ulcerative and hyperkeratotic forms of lupus erythematosus and lichen planus; 4) post-radiation stomatitis.
Classification of pre-tumor processes of the red border of the lips
A. With a high incidence of malignancy (obligate):
1) warty precancer; 2) limited precancerous hyperkeratosis; 3) abrasive precancrosis cheilitis of Manganotti.
B. With a low incidence of malignancy (optional): 1) leukoplakia; 2) keratoacanthoma; 3) cutaneous horn; 4) papilloma with keratinization; 5) erosive-ulcerative and hyperkeratotic forms of lupus erythematosus and lichen planus; 6) post-radiation cheilitis.
Observations - Cancer loves the right side.
Below is information about obligate and some optional precancers of the mucous membrane and red border of the lips.
Bowen's disease (morbus Bowen)
This disease was first described by Bowen in 1912. It is a cancer in situ from the very beginning. Etiology: chronic trauma to the oral mucosa.
Clinical picture. The posterior part of the oral cavity (palate, arches) is most often affected. The lesion is usually single, most often looks like a hyperemic bright red spot, smooth or with a velvety surface due to small papillary growths. The central area is similar to leukoplakia with a finely tuberous surface or lichen planus with foci of keratinization on a hyperemic background. Due to atrophy of the mucous membrane, the lesion sinks somewhat in comparison with the surrounding areas, and in some places easily bleeding erosions appear on it. The size of the lesion is from 1-2 mm to 5-6 cm, its outlines are uneven and quite clear. The compaction at the base is not detected. When localized on the tongue, the papillae of the tongue at the site of the lesion disappear. Regional lymph nodes are usually not palpable. Subjective sensations are insignificant, but with erosions pain can be expressed. The clinical picture of Bowen's disease on the oral mucosa is not always clearly expressed. The disease may manifest itself only as a small area of hyperemia or resemble leukoplakia without significant inflammation.
The disease continues indefinitely; in some cases, invasive growth quickly occurs, and trauma accelerates this process; in others, it remains in the cancer in situ stage for years. The diagnosis must be confirmed by histological examination.
Histologically, Bowen's disease reveals a picture of intraepithelial spinocellular cancer: polymorphism of cells of the spinous layer up to atypia, an increase in the number of mitoses, their irregularity, giant cells, multinucleated cells, acanthosis, in some cases hyperkeratosis and parakeratosis. The basement membrane and basal layer are preserved. In the upper part of the stroma there is a small infiltrate of lymphocytes and plasma cells.
Differential diagnosis is carried out with leukoplakia, lichen planus, chronic traumatic lesions, lupus erythematosus, syphilis.
Treatment. Excision of the lesion within healthy tissue with mandatory histological examination, consultation with an oncologist.
Warty precancer (praecancer verrucosus)
Described by A. L. Mashkilleyson in 1965. Etiology: trauma, increased insolation.
It occurs almost exclusively on the lower lip and looks like a painless hemispherical nodule with a warty surface with a diameter of mm. The color of the lesion ranges from almost normal red border to stagnant red. On top, the nodule is covered with gray scales that are difficult to remove and is located on an unchanged red border or against the background of slight hyperemia.
At histological The study reveals a pronounced limited proliferation of the epithelium due to the expansion of the styloid layer, in some cases hyperkeratosis and parakeratosis, polymorphism of the cells of the spinous layer of varying degrees of severity, up to severe. The basement membrane is preserved. The transition to an invasive form of cancer occurs quickly - within 1-2 months from the onset of the disease.
Differential diagnosis should be carried out primarily with papilloma and warts. But a papilloma has a stalk, and a wart has a hypertrophic stratum corneum along the periphery. Malignancy may occur within 1-2 months. The diagnosis is clarified after histological examination.
Treatment: surgical only (excision of the lesion followed by histological examination) together with an oncologist.
Limited precancerous hyperkeratosis of the red border of the lips (hyperkeratosis praecancrosa circumscripta)
Etiology: trauma, increased insolation.
Clinical picture: Men over 30 are more likely to get sick. A polygonal area of keratinization measuring more than 2 mm appears on the lateral surface of the red border of the lower lip. The lesion in most patients seems to be immersed in the mucous membrane, often slightly sunken, but may be somewhat elevated, with a smooth surface covered with thin, tightly packed scales. When scraped, it cannot be removed. Palpation reveals a superficial lamellar compaction. There are no background changes; less often, this form of precancer occurs against the background of nonspecific inflammation.
At histological The study reveals a limited area of acanthosis, often the phenomenon of cell dislocation and polymorphism, and hyperkeratosis on the surface.
Differential diagnosis carried out with lupus erythematosus, leukoplakia and lichen planus. Malignancy occurs after several months or years.
Treatment: together with an oncologist, surgical excision of the lesion followed by histological examination.
Abrasive precancrotic cheilitis Manganotti (cheilitis abra - siva praecancrosa Manganotti)
This form was isolated and described by Manganotti in 1933. It occurs predominantly in men over 50 years of age. Contributors to the occurrence of this disease are herpetic infection, increased insolation, mechanical trauma, glandular and meteorological cheilitis, hypovitaminosis, and diseases of the gastrointestinal tract.
Clinical picture. Against the background of mild, limited or diffuse chronic catarrhal inflammation of the lower lip, one or, rarely, several red erosions with a smooth surface appear, which is sometimes covered with a dense bloody or serous crust. It is difficult to remove, and slight bleeding occurs. Erosion that is not covered with a crust does not tend to bleed. There is no seal at the base. Erosions are characterized by a sluggish course and are resistant to all kinds of treatment with ointments and applications. Existing for a long time, they can epithelialize, but then reappear in the same or other places.
At histological examination an epithelial defect is detected, and inflammatory infiltration is detected in the underlying connective tissue. The epithelium at the edges of the erosion is in a state of acanthosis or atrophic. Epithelial strands extend from it deep into the stroma. The spinous cells are in some places in varying degrees of dislocation and atypia. Cytological examination can detect the phenomena of dyskaryosis of epithelial cells, elements of inflammation, but more often only inflammation.
The process lasts from 1-2 months to many years, without treatment it leads to malignancy. Clinically, this is manifested by compaction at the base and around the erosion, the appearance of papillary growths on the surface of the erosion, its easy bleeding, and keratinization around the erosion. The diagnosis is confirmed by the presence of atypical cells in scrapings from the lesion or the results of histological examination.
Differential diagnosis should be carried out with erosive forms of leukoplakia, lichen planus, lupus erythematosus, pemphigus, erythema multiforme, actinic cheilitis, secondary syphilis, herpetic erosions.
Treatment. It is necessary to carefully remove local irritants, then carry out sanitation of the oral cavity, including full prosthetics, strictly prohibit smoking and eating irritating foods, and recommend eliminating insolation. It is necessary to identify and treat concomitant diseases of other organs and systems. Vitamin A is prescribed orally (a solution of retinol acetate in oil 3.44% or a solution of retinol palmitate in oil 5.5%) 10 drops 2-3 times a day, multivitamins. Local applications with an oil solution of vitamin A are prescribed, and for background inflammation, ointments with corticosteroids and antibiotics are prescribed. Conservative therapy should not be carried out for more than 1 month. The best results are obtained by surgical removal of the lesion. within healthy tissues.
Only with Manganotti cheilitis is it permissible to attempt conservative treatment. Treatment of all types of obligate precancer is surgical - complete excision of the lesion within healthy tissue, followed by urgent histological examination. The excised tissue is examined by preparing serial sections. The operation should be preceded by sanitation of the oral cavity and elimination of irritants. If surgery is not possible, radiation therapy is indicated.
Prevention: healing the body, proper nutrition, eliminating adverse effects and bad habits.
Cutaneous horn (cornu cutaneum)
Cutaneous horn is a limited hyperplasia of the epithelium with severe hyperkeratosis, resembling a horn in appearance and density. Etiology unknown.
It occurs on the red border of the lip, most often the lower lip, in people over 60 years of age, and is painless. A slowly growing, painless, limited lesion appears, up to 1 cm in diameter, from the base of which extends a cone-shaped horn of a dirty gray color, dense, fused to the base. Cutaneous horn is a long-term (years) disease. Its malignancy is indicated by the appearance of inflammation and compaction around the base of the horn, increased keratinization. The diagnosis is clarified after removal of the lesion and its histological examination. Treatment surgical followed by histological examination.
Keratoacanthoma is a benign epidermal tumor that quickly develops and spontaneously regresses. The etiology is unknown; it is assumed that immune disorders and hereditary factors contribute to the occurrence of keratoacanthoma.
The disease is localized on the red border of the lip, very rarely on the tongue. Keratoacanthoma appears as a grayish-red dense nodule with a funnel-shaped depression in the center, filled with fairly easily removable horny masses. The tumor grows quickly and within a month reaches its maximum size (2.5X1 cm). Keratoacanthoma is painless, mobile, and not fused with surrounding tissues. After 6-8 months, the tumor either spontaneously regresses and disappears, leaving a scar, or becomes malignant, turning into cancer. Keratoacanthoma should be distinguished from warty precancer and cancer. Cancer has a denser consistency, a dense base, and after removal of the horny masses, bleeding appears. Keratoacanthoma differentiate with cutaneous horn, basal cell carcinoma, squamous cell carcinoma.
Treatment: carried out jointly with an oncologist, surgical excision of the lesion or its diathermocoagulation, cryotherapy, close-focus radiotherapy.
Papillomatosis is an accumulation of many papillomas on the skin and mucous membranes.
Etiology: trauma, chronic inflammation.
Clinical picture: Borovsky E.V. (1984) identifies the following types of papillomatosis:
Reactive papillomatosis of various natures:
inflammatory papillary hyperplasia of the mucous membrane of the hard palate and alveolar processes;
traumatic papillomatosis of the mucous membranes of the cheeks, lips, tongue;
rhomboid papillomatosis of the tongue.
Papillomatosis of non-plastic nature.
Papillomas have a round or mushroom-shaped shape, are located on a stalk or on a wide base, their consistency is soft, sizes range from 1-2 mm to 1-2 cm, palpation is painless. Reactive papillomas stop growing after the stimulus stops.
Papillomatoses of a non-plastic nature often become malignant. The appearance of increased keratinization, bleeding, dense infiltration at the base, ulceration, and rapid growth indicates malignancy.
Treatment: surgical followed by histological examination.
Lichen planus
They assume the autoimmune nature of the disease with a violation of local immune mechanisms that develop against the background of estrogen deficiency; a psycho-emotional factor is always present.
Prevalence: women and older women get sick more often.
Forms: typical, exudative-hyperemic, erosive-ulcerative, hyperkeratotic, bullous, atypical, infiltrative.
Factors contributing to aggravation of the clinical picture: trauma, galvanism, candidiasis, diabetes mellitus, hypertension, errors in diet.
Localization: in the oral cavity – mucous membrane of the cheeks, tongue, lips; on the skin - forearms, shins.
Symptoms: the course is often asymptomatic, sometimes there is roughness of the mucous membrane; sometimes sensitivity, burning, pain.
Clinical picture: in the oral cavity there is a white lace pattern consisting of individual small papules, sometimes merging into a solid white spot that rises above the surface of the mucous membrane. On the skin - bluish-red, with a waxy sheen, flat, itchy papules from 0.2 to 1 cm in diameter.
Diagnostics: based on clinical data and examination of the oral mucosa.
Histological picture: the epithelium is keratinized, a diffuse lymphocytic infiltrate is detected in the papillary layer, the basement membrane is edematous.
antihistamines (suprastin, diazolin, bicarfen, fenkarol)
psychotropic therapy (valerian, peony, motherwort, seduxen, phenazepam)
vitamin therapy (vit.A, provitamin A-vetoron-T, vit.PP)
glucocorticoids (prednisolone, dexamethosone, triamcion)
histoglobulin - as a histamine release blocker
painkillers (1% pyromecaine solution, 5% pyromecaine solution, methyluracil ointment, 10% lidocaine aerosol, panthenol)
antiseptics (hydrogen peroxide solution, potassium permanganate solution, furatsilin)
epithelializing agents (solcoseryl, oil solution Vit. A and E)
corticosteroid ointments (celistoderm, advantan)
Principles of patient management :
elimination of traumatic factors
oral sanitation
blood test for sugar and estrogens
Lichen planus (erosive-ulcerative form)
Symptoms: painful, long-term non-healing erosions on the oral mucosa.
Clinical picture: erosions of irregular shape, covered with fibrinous plaque with papular elements.
epithelializing and regenerating agents
requires long-term treatment and changes in medications
Prognosis: Favorable, however, erosions are not prone to epithelialization for a long time.
Erosive-ulcerative and hyperkeratotic forms of lichen planus are an optional precancer; the likelihood of malignancy increases in older people with numerous risk factors.
An autoimmune disease in which neutrophils in the blood and the basement membrane of the skin become foreign to the body.
Prevalence: women and older women get sick more often.
Localization: skin and red border of the lips, oral mucosa.
Forms: on the red border of the lips - a typical, erosive-ulcerative, deep form of Irganga-Kaposi. On the mucous membrane - typical, exudative-hyperemic, erosive-ulcerative.
Symptoms: dryness and tightening of the red border of the lips, asymptomatic course (in the deep form), pain when eating in all forms on the oral mucosa.
Diagnostics: rashes on the oral mucosa are always combined with characteristic changes on the skin of the face.
Histological picture: parakeratosis alternating with hyperkeratosis, vacuolar degeneration of cells of the basal layer of the epithelium, dense infiltrate in the connective tissue of lymphocytes, degeneration of collagen fibers.
synthetic antimalarials: delagil, plaquenil, hingamin
Long-term lesions of lupus erythematosus may become malignant if left untreated.
Leukoplakia (“white plaque”)
Develops as a response of the mucous membrane to long-term trauma, often chemical (smoking), mechanical.
Prevalence: more often in men years.
Forms: flat, verrucous, erosive; a combination of different forms is possible.
Symptoms: asymptomatic, sometimes a feeling of roughness of the mucous membrane.
Clinical picture: a limited area of white color, irregular shape, not elevated or raised above the surface of the mucosa, may have cracks and erosions. The surface of the lesion is rough or smooth.
Localization: mucous membrane of the lips, cheeks, corners of the mouth, along the line where the teeth meet.
Diagnostics: a section of the mucous membrane that cannot be removed when scraped.
for verucous and erosive forms: total excision within a wide range.
for flat forms: inside – aevit, pyridoxine; Locally – applications of oil solution Vit.A, 10% linimet dibunol.
Principles of patient management:
tobacco smoking ban
oral sanitation
elimination of traumatic agents
protection of the red border of the lips from direct sunlight (photoprotective ointments)
endocrinological examination (prescription of testosterone blockers)
The occurrence is associated with the activation of the Epstein-Barr virus.
Prevalence: Occurs only in AIDS patients.
Localization: lateral surfaces of the tongue.
Symptoms: asymptomatic.
Clinic: a limited area of thickening of the mucous membrane of an opal-white color with unclear boundaries.
Diagnostics: based on serological studies confirming HIV infection. Treatment: underlying disease.
Forecast: bad (malignant).
Verrucous and erosive forms of leukoplakia are optional precancers with a high degree of malignancy.
Chronic cracked lip
lip pain that gets worse when smiling or eating
The long-term existence of a chronic lip fissure is considered as a background disease capable of malignancy (6%), with thickening of the edges and base, keratinization in the circumference, and possible small papillomatous growths in the depths of the fissure.
severe headaches
paroxysmal pain radiating along the trunk of the affected nerve
burning and paresthesia of the innervated area
Clinical picture: on the mucous membrane of the oral cavity and skin, strictly in the zone of innervation of 2 or 3 branches of the trigeminal nerve, erosions appear, covered with fibrinous plaque, and are sharply painful. Intraepidermal vesicles on the skin are filled with transparent serous contents; the appearance of vesicles is characterized by stages.
cytological data
analgesics and non-steroidal anti-inflammatory drugs
anti-inflammatory and painkillers
Recurrences of herpes zoster indicate a significant decrease in immunity - it is necessary to exclude HIV infection, malignant neoplasm, and leukemia.
The autoimmune mechanism of the disease has been proven.
Clinical picture: on the skin there are blisters from 0.5-5 cm with a flaccid tire - bright red erosion; there is erosion on the mucous membrane with fragments of the bladder covering at the edges. On the red border of the lips: erosions are covered with yellowish-brown or hemorrhagic crusts
Treatment: carried out by a dermatologist. Corticosteroids and cytostatics are prescribed.
Forecast: relatively favorable with early diagnosis and timely treatment; poor without treatment (before the era of corticosteroids, more than 50% were fatal).
Malignant epithelial neoplasm (cancer)
asymptomatic or mild pain
enlargement of regional lymph nodes
results of cytological examination
radical surgery on cervical lymph nodes affected by tumor metastases
Forecast: depends on the location, size, type of tumor, age and health of the patient.
Squamous cell keratinizing carcinoma
Prevalence: more often in mature men.
Localization: mucous membrane of the lips, tongue, floor of the mouth, cheeks.
Clinical picture: white spot, flat or raised above the mucous membrane; cracks, erosions; Later, a dense infiltrate and enlarged cervical lymph nodes are determined.
Diagnostics: based on histological examination of the lesion after wide surgical excision.
Treatment: wide excision, possibly radiation therapy.
Prognosis: favorable for lips affected; bad if the floor of the mouth or base of the tongue is affected.
Dentists, like doctors of any other profile, must exercise oncological vigilance when examining a patient. No matter what complaints the patient comes with, examination of the entire oral cavity and the red border of the lips is the law for the doctor. Any deviation from the norm should attract his close attention. Early manifestations of cancer may go unnoticed by the patient, and it is the doctor’s duty to identify them in a timely manner as early as possible. The concept of “oncological alertness” is, first of all, the sum of specific knowledge of oncology, allowing the doctor to conduct an early or timely diagnosis of cancer. This concept also includes knowledge of precancerous diseases and their treatment, knowledge of the organization of oncological care, a network of oncological treatment institutions, and the rapid referral of the patient to his destination. In difficult diagnostic cases, one should think about the possibility of growth of a malignant tumor and make a diagnosis as soon as possible. Treatment without diagnosis should not last more than 7 days. Local irritants should be eliminated and agents that promote tumor growth should not be used (cauterization, physiotherapy, etc.). In difficult cases, the doctor is obliged to involve more experienced specialists in examining the patient.
Treatment is carried out by oncologists. After treatment for cancer or precancerous diseases, patients should undergo clinical observation. The clinical picture of severe forms of cancer of various localizations is presented in the course of surgical dentistry.
Cancer of the oral mucosa and red border of the lips
In most cases, keratinizing squamous cell carcinoma develops on the red border of the lips and in the mucous membrane of the oral cavity, less often non-keratinizing. This is almost always spinocellular carcinoma, arising from the cells of the styloid layer, and very rarely basal cell carcinoma (usually on the red border of the lower lip).
The clinical course of early forms of cancer depends on previous precancerous diseases, on the nature of growth (exophytic, endophytic, mixed forms). Cancer may initially be painless, but in the tongue it is usually accompanied by pain, often severe and radiating. Based on the appearance at the onset of the disease, papillary, infiltrative and ulcerative forms are distinguished.
Papillary form. At the beginning, a limited compaction appears in the form of a warty outgrowth on a broad base or on a stalk. Its surface is covered with papillary growths and often horny masses. Upon palpation, shallow infiltration around and at the base is determined. The tumor grows in breadth and depth, disintegrates quite quickly in the center and turns into an ulcerative form.
The infiltrative form of cancer is the most unfavorable. At the beginning of the disease, a painless compaction appears, often located under the mucous membrane. The infiltrate grows, disintegrates in the center, and a typical cancerous ulcer appears.
The ulcerative form is the most common, since in most cases the tumor begins to disintegrate early and looks like erosion and then like an ulcer. With the onset of invasive growth, it is typical for cancer to have a compaction around the ulcer in the form of a roller and at the base, determined by palpation. In the initial stage, the compaction is insignificant or not clinically detectable at all, then, due to the rapid growth of the tumor, it increases, sometimes reaching a rocky density. In the later stages, the difference in forms is not determined; the pattern of ulcerative-infiltrative growth predominates. The ulcer usually has raised, everted, dense edges, an uneven granular bottom, in the oral cavity covered with a gray-yellow coating or gray necrotic coating; on the red border of the lip, the ulcer is covered with a dense gray coating or, if bleeding, with bloody-gray crusts. Inflammatory phenomena in the tissues surrounding the cancer are pronounced or clinically absent.
Tumor growth is accelerated by injuries with sharp edges of teeth, dentures, eating hot food, smoking, cauterization, etc. Cauterizing agents cannot be used for ulcers of any etiology, but this is especially dangerous for malignant tumors. After cancer metastasizes to the lymph nodes, the latter become denser, enlarge, and then fuse with the surrounding tissues. Tongue cancer metastasizes especially early, which is apparently due to its greater mobility.
Cancer of the oral cavity and red border of the lips is a cancer of visual localization, which facilitates its diagnosis and allows inspection and palpation of the lesion without special equipment. With the help of a stomatoscope, earlier morphological changes can be seen. The clinical diagnosis must be confirmed by morphological studies - cytological or histological methods.
The cytological method of research allows making the correct diagnosis in 90-95% of cases. In such cases, the material is taken by scraping or puncture.
The main features that distinguish a cancer cell from a non-cancerous cell are the following: 1) the vicious structure of the cell membrane and intracellular membranes, as a result of which cancer cells are more easily separated from the main tissue, lose their cytoplasm, and “naked” nuclei appear; 2) morphological and chemical anaplasia of nuclei, their sizes are different (usually larger than normal), polychromatophilia, uneven chromatin arrangement, giant cells, multinucleated cells, tubercular nuclei, mitoses, etc.; 3) anaplasia of nucleoli, an increase in their number; 4) in the cytoplasm and nucleus there are additional inclusions, signs of degeneration, phagocytosis. It is not always possible to obtain sufficient quantities of material for cytological examination. “Soft”, low-differentiated crayfish give abundant scraping, while “dense”, scirrhous crayfish receive scanty scraping, which is not always sufficient.
Differential diagnosis of cancer must be carried out with leukoplakia, benign tumors, traumatic and trophic ulcers, specific lesions (tuberculosis, syphilis, leprosy), ulcers with lichen planus and other chronic inflammatory processes.
In each specific case of cancer, as a rule, it is impossible to establish what was its immediate etiological cause. Nevertheless, it is obvious that it is always based on DNA damage caused by one or another factor in the environmental or internal environment of the body (“cancer is a disease of genes”).
Carcinogens damage DNA accidentally (i.e., they are nonspecific with respect to its nucleotide sequences), but with an increase in the dose of carcinogenic exposure, the probability of damage in one of the tens of trillions of cells of the body increases to those genes that “orchestrate” cellular reproduction (proto-oncogenes and suppressor genes, genes DNA repair and programmed cell death).
Viral carcinogenesis. There are many known viruses that cause tumors in animals - DNA-containing (for example, monkey virus SV40) and RNA-containing, or retroviruses (for example, Rous sarcoma virus). Evidence of viral etiology has been obtained for a number of human tumors: Burkitt's lymphoma, nasopharyngeal cancer (DNA-containing Epstein-Barr virus), cervical cancer (papilloma virus), as well as T-cell leukemia of adults (retrovirus HTLV-1) and some others . In general, viruses appear to be “responsible” for a relatively small group of human cancers.
Chemical carcinogenesis. There are approximately 20 known chemical carcinogens (industrial, medicinal and natural) that can cause tumors in humans. Benzo(a)pyrene (BP), the main representative of a large group of polycyclic aromatic hydrocarbons (PAHs), formed both as a result of human activity and natural phenomena (in particular, volcanic activity), has been established to be widely distributed in the environment. PAHs include methylcholanthrene, dimethylbenz(a)anthracene, etc. As noted above, tobacco smoking is the most dangerous in terms of carcinogenicity (100 cigarettes contain 1.1-1.6 μg of BP). In addition, tobacco smoke (consisting of the gas phase and solid particles) contains dibenz(a)anthracene and nickel, which are carcinogenic to humans. Mortality from lung cancer is directly proportional to the number of cigarettes smoked per day: people who smoke 16-25 cigarettes per day have a 30 times higher risk of developing lung cancer than non-smokers.
Carcinogenic nitroso compounds (nitrosomethyl and nitrosoethyl ureas, nitrosodimethylamines) cause tumors in all animal species studied. Particular attention paid to this class of compounds is due to the possibility of their endogenous synthesis in the body from nitrites (nitrates) and secondary amines contained in food. Secondary amines can also be formed in the colon with the participation of bacterial flora.
Chemical carcinogens are divided into procacarcinogens (they make up the absolute majority) and direct carcinogens. Procarcinogens 304
turn into true, ultimate carcinogens as a result of metabolic transformations catalyzed by tissue enzymes (nonspecific oxidases). The latter are localized mainly in the endoplasmic reticulum. PAUTipabenz(a)pyrene or dimethylbenz(a)anthracene, as well as procarcinogens, become final carcinogens, turning into the corresponding epoxides, as well as as a result of spontaneous reactions.
Direct carcinogens (nitrosamines, p-propionlactone, dimethylcarbamyl chloride, etc.) act without preliminary metabolic modification.
Chemical carcinogens interact with cellular DNA; By covalently joining it, they form various adducts and also induce single- and double-strand breaks.
Radiation carcinogenesis. The carcinogenic effect of ionizing radiation became known soon after the discovery of natural radioactivity (the first case of radiation-induced skin cancer was described in 1902). Ionizing radiation can cause tumors of almost all organs, but most often - tumors of the skin and bones, leukemia, as well as endocrine-dependent tumors (breast and ovarian cancer). The frequency and types of malignant neoplasms induced by ionizing radiation depend on many factors, in particular on the penetrating ability of radiation, the nature of the impact (external or internal), the organotropy of radionuclides and the distribution of the dose over time - acute, chronic, fractional irradiation, etc.
Ultraviolet carcinogenesis. Long-term exposure to sunlight (their ultraviolet spectrum) is the main inducer of melanomas on open areas of the skin (head, neck, arms). In this regard, blondes with light skin and hair are the most sensitive.
DNA damage is the basis of all types of carcinogenesis.
Types of carcinogenesis differ in the nature of the directly acting genotoxic factor.
Multistage carcinogenesis. Carcinogenesis is a long multi-stage process of accumulation of genetic damage. Latent period, i.e. the period from initial changes in the cell to the first clinical manifestations of tumor growth can be 10-20 years. Tumors are of clonal origin, i.e. Each primary tumor focus consists of a clone of cells, descendants of one maternal transformed cell, which have inherited its main property - unregulated reproduction. The normal cells surrounding the tumor are not involved in the process of malignant growth.
In the later stages of the tumor process, metastases often occur - secondary foci in distant tissues, which means the tumor spreads throughout the body. Metastases are not independently formed tumors, but descendants of the same primary transformed
cells. Primary multiple tumors (several independently occurring tumors in one patient) should be distinguished from metastases. In these cases, a genetic predisposition to malignant neoplasms is most often possible.
In the process of carcinogenesis, there are three main stages - initiation, promotion and progression.
Initiation - primary damage to the cell - consists of the occurrence of a mutation under the influence of various chemical and physical factors (see above) in one of the genes that regulate cell reproduction. The cell becomes “initiated”, i.e. potentially capable of unlimited division, but requiring a number of additional conditions for the manifestation of this ability.
Promotion. There are many chemical substances, so-called promoters (in particular, phorbol esters), which do not damage DNA and are not carcinogens, but whose chronic exposure to initiated cells leads to the appearance of a tumor. The main thing in promotion, apparently, is the effect of stimulating cell division, due to which a critical mass of initiated cells appears. This in turn contributes, firstly, to the release of initiated cells from tissue control and, secondly, to the mutation process.
Progression. The once-existing idea that tumor growth is only a quantitative increase in the number of homogeneous cells is absolutely wrong. In fact, along with a quantitative increase in tumor mass, it constantly undergoes qualitative changes and acquires new properties - increasing autonomy from the regulatory influences of the body, destructive growth, invasiveness, the ability to form metastases (usually absent in the early stages) and, finally, its amazing adaptability to changing conditions. Signs of tumor malignancy arise and evolve independently of each other. This is the fundamental difference between tumor progression, which can never be considered complete, and normal tissue differentiation, which is always strictly programmed until the final structure is formed.
The basis of progression is the clonal heterogeneity of the tumor. A transformed cell, as a result of repeated division, produces a clone of cells similar to itself - with the same genotype and phenotype at first. However, due to the inherent instability of the genome of tumor cells - this is their fundamental feature and the driving force of all subsequent metamorphoses (in which defects of the p53 gene apparently play a key role), more and more new clones appear, differing geno- and phenotypically.
The development of mammary gland cancer in animals is also observed as a result of impaired ovarian function during unilateral castration, resection and irradiation of the ovaries, etc. As a result of these effects, follicular cysts develop in the ovaries, causing hyperestrogenization, and later changes occur in the mammary glands (fibroadenoma, mastopathy , cancer and tumors of the ovaries) and endometrium.
The opinion about dishormonal influences and, first of all, about an increase in estrogenic activity as one of the main reasons for the development of mastopathy and breast cancer is shared by many scientists. It has been established that endocrine influences that have a stimulating effect on the processes of epithelial proliferation in the mammary glands depend on the complex interaction of ovarian hormones (follicular and luteal), hormones of the adrenal cortex and gonadotropic hormones of the pituitary gland, primarily on follicle-stimulating hormone (FSH). The correlative production of these hormones is carried out due to influences coming from the hypothalamic
areas and cerebral cortex. With various dishormonal disorders, the function of not only the ovaries, but also the adrenal glands, pituitary gland or hypothalamus (due to general diseases such as intoxications) may be primarily affected. It is impossible to take into account all these harmful effects that occurred in the past in patients with mastopathy and breast cancer in each case. The ovaries are the most vulnerable and susceptible to various harsh external influences (chronic and acute inflammatory processes); Apparently, their dysfunction is most often the basis of the pathogenesis of pretumor diseases and breast cancer in women.
According to M. N. Zhaktaev and O. V. Svyatukhina (1972), based on a study of ovarian-menstrual function and the condition of the genital organs in 500 patients with mastopathy, 500 patients with breast cancer and 1000 healthy women (see p. 617), It was revealed that various menstrual dysfunctions were found in 81.3, respectively; 73 and 15.2%, and a history of gynecological diseases in 52.2, 58.6 p 34.4 "/o (at the time of examination, gynecological diseases were found in 33.4, 36.8 and 5.5%, respectively) .
These data indicate a more frequent and longer period of pathological conditions, and therefore pathogenetic influences from the ovaries on the mammary glands of women suffering from mastopathy and breast cancer. In my opinion, timely complete recovery from inflammatory processes of the appendages and uterus can protect against the development of pathological conditions in the mammary glands.
The viral nature of human breast cancer has not been proven. Only in mice of pure lines was a milk factor identified, called the Bitner virus. However, the origin of this virus has not yet been clarified. Some authors consider the Bittner virus to be exogenous, while others consider it an endogenous factor, developing due to changes in endogenous proteins (L. L. Zplber, 1946; L. M. Shabad, 1947; Bittner, 1939, etc.). There are studies indicating the presence of a large amount of milk factor in males, but mammary gland cancer does not occur in them. If estrogens are administered to males, then they develop mammary gland cancer (E. E. Pogosyants; Shimkin, etc.). However, the presence of milk factor is not enough to cause breast cancer. Only with changes in endocrine status can the incidence of tumor development in experimental animals be increased or sharply decreased. The milk factor in other animal species and in humans has not yet been established.
The significance of the hereditary factor for the development of breast cancer has not been sufficiently studied. There are reports that among close relatives of patients this type of malignant tumors is more common than others. According to S. A. Holdin (1962), E. B. Polevoy (1975), Winder, McMahon (1962) and others, breast cancer sometimes occurs in several sisters, mother and daughters, etc. The causes of these factors are unknown . E. B. Polevaya reports that the daughters of women. Breast cancer (BC) is a malignant lesion of breast tissue, usually its ducts and lobules.
Epidemiology.
Benign breast tumors are the most common cancer after skin cancer and account for 16% of all cancers among the female population. Over the past 25 years in Russia there has been a significant increase in this pathology, in different regions - from 150 to 200% and higher, from the indicators before 1985. Breast cancer also occurs in men, but not in comparable numbers than in women. Women over 50 are at greatest risk of developing breast cancer, accounting for 80% of all cases of this disease.
Etiology and pathogenesis.
Despite the fact that the reasons for the development of breast tumors are not fully known, there is an opinion in scientific circles that this type of cancer can occur due to the combined effect of several risk factors, including:
Age. The risk of cancer in one or both breasts increases with age. The disease very rarely occurs in women under 35 years of age, and 8 out of 10 cases occur in women aged 50 years or older.
The patient has a history of cancer and some other breast pathologies. The risk of developing breast cancer increases 3-4 times if a woman has had one of the following diseases, disorders and conditions in the past:
Precancer of the breast, including ductal carcinoma (DCIS);
Local carcinoma (LCIS);
Atypical ductal hyperplasia;
Treatment with radiation therapy for Hodgkin's lymphoma at a young age;
Dense breast tissue (when the breasts are composed primarily of glandular and connective tissue with very little fatty tissue).
Hormonal factors. The risk of breast cancer increases if you:
Are over 50 and have been taking estrogen- or progesterone-based hormone replacement therapy for more than 10 years;
Do not have children or gave birth after 30 years;
Did not breastfeed at all or breastfed for less than a year after the birth of the child;
Have menarche before 12 years or late menopause (after 50);
Are you taking birth control pills?
Lifestyle factors.
Alcohol abuse. Long-term use of alcohol-containing products usually leads to liver damage. This directly increases the risk of developing a malignant breast tumor, since the liver helps control estrogen levels. Excess weight. After menopause, body fat is the main source of estrogen. If a woman is overweight, the level of these hormones in the body can increase significantly, which, in turn, increases the risk of breast cancer. Smoking. Genetic factors (familial anemia). Only 5-10% of breast cancers are associated with the inherited oncogene BRCA1 or BRCA2. Provided that several blood relatives have cancer of the female genital area or breast, inheritance of a genetic defect can be suspected. Classification: Breast cancer is described according to four classification schemes, each of which considers different criteria and serves different purposes: - histological description; - degree of differentiation (low, high and middle classes); - status of proteins and gene expression; - tumor stage according to TNM grading. Currently, breast cancer must be classified primarily by histological type.
1.1 Locally advanced (non-invasive) types of tumor (precancer).
Ductal carcinoma in situ; - lobular carcinoma in situ. 1.2 Invasive types (cancer itself). - ductal invasive tumor (occurs in 80% of cases); - lobular invasive tumor (in 10%). 1.3 Rare types of breast cancer. - inflammatory; - triple negative. 1.4 Extremely rare types of breast cancer. - Paget's cancer (affects the areola and nipple); - tubular; - mucinous; - medullary.
Clinic and symptoms.
There are practically no subjective symptoms in the initial stages of breast cancer; most often, the tumor is discovered by chance by the woman herself or her partner in the form of an atypical lump. It is precisely because of the absence of obvious signs of the disease that women after menopause are recommended to undergo routine mammography once a year. Any of the following signs may indicate the presence of a malignant tumor: - swelling of the entire breast or some part of it; - skin rashes on the mammary gland, similar to irritation; - soreness of the nipple or change in its position from normal to retracted; - redness, peeling or roughening of the breast/nipple skin; - nipple discharge not associated with lactation; - an unexplained change in the shape of the mammary gland (deformation); - a dense, inactive compaction in the form of a lump in the armpit area. These symptoms can also be signs of less serious diseases, such as a cyst or infection, but, in any case, if abnormalities appear in the mammary glands, you should immediately seek medical help.
Diagnosis.
One of the important preventive measures for breast cancer is early diagnosis. Methods of early diagnosis, depending on age:
Women over 20 years of age should conduct self-examinations once a month, 3-5 days after the end of the regimen. Each mammary gland and armpit should be examined and carefully palpated; if any changes are found, you should visit a gynecologist. If there are no changes, you must undergo a medical examination every 3 years.
Women over 40 should visit a gynecologist for a checkup once a year and also have a screening mammogram once a year.
When visiting a specialist, the patient is interviewed and examined. If necessary, a referral is given for mammography or ultrasound examination of the mammary glands, depending on the results of which a biopsy may be prescribed. The collected material is examined for the presence of atypical cells; if they are found, their histological features are assessed. Also, to determine the characteristics of the tumor (its location, extent, size), clarifying diagnostic methods are prescribed - ultrasound, magnetic resonance or computed tomography.
Treatment.
Depending on the characteristics of the tumor, as well as the general condition of the patient, one of the main treatment methods or a combination of them is selected: - surgery - radiotherapy - chemotherapy - hormonal therapy - biological therapy (targeted). Surgery. Most patients with breast cancer undergo surgery to remove the tumor. In the early stages of some types of cancer, it is possible to perform surgery to remove only the cancer focus and preserve the breast (organ-preserving surgery):
Lumpectomy: the tumor itself and part of the healthy tissue around it are removed at the same time;
Partial (segmental) mastectomy: an operation to remove part of the gland, tumor and some normal tissue around the lesion. For more serious indications, a simple mastectomy is performed - surgical removal of the entire mammary gland and part of the lymph nodes from the armpit area. Modified radical mastectomy - removal of the entire gland, more axillary lymph nodes and part of the chest muscles. If necessary, neoadjuvant therapy is indicated - chemotherapy treatment before surgery to reduce the size of the tumor. To reduce the risk of relapse and kill those cancer cells that could remain in the body, adjuvant therapy (radiation, hormonal or chemotherapy) is prescribed after surgery. Radiation therapy. This method uses high-energy X-rays or other types of radiation to destroy cancer cells or stop their growth. External and internal (sealed needles, catheters, etc.) radiation sources are used. Chemotherapy.
The tumor is treated with cytostatics. The advantage of this method is that it acts systemically and destroys atypical cells anywhere in the body. The above listed treatment methods are locally targeted. Hormonal therapy. Allows you to block certain hormones that have a positive effect on the development of tumors. For certain types of breast cancer (early stages, metastatic), tamoxifen is prescribed. A side effect of this drug is the growth of the endometrium, so the patient is recommended to undergo an ultrasound of the uterus once a year and, in case of atypical bleeding, immediately consult a doctor. For the treatment of early stages of breast cancer, some aromatose inhibitors can be used as adjuvant therapy instead of tamoxifen or as a replacement after 2 years of taking it. To treat metastatic cancer, it is chosen which of the two drugs is more effective in a particular case. Targeted therapy. Unlike chemotherapy drugs, biological drugs (Lapatinib, Trastuzumab) act not on the atypical cells themselves, but on proteins (HER2) that promote tumor growth. They can be used either independently or in combination with other types of treatment.
Prevention.
It is obvious that the risk of developing breast cancer is directly related to a woman’s reproductive behavior and her lifestyle. As preventive measures, regular physical activity is recommended (it will reduce the risk by 15-25%), giving up bad habits and returning to previous norms associated with the birth and feeding of children.
Breast cancer. Epidemiology. Etiology. Pathogenesis. Clinic. Breast cancer is a malignant neoplasm that develops from epithelial cells of the ducts and/or lobules of the gland parenchyma.
Epid-i. Breast cancer ranks 1st in the structure of cancer incidence in women. Ranked 2nd in the world. In 5th place in Bel. The highest rates are in the USA. The lowest incidence is recorded in African countries. The incidence of breast cancer increases with age, starting at 40 and reaching a peak in early adulthood. For women aged 70 years, the annual risk of breast cancer is 3 times higher than for women aged 40 years, and the annual risk of death from breast cancer is 5 times higher than for women aged 40 years.
Etiol-i. A hereditary predisposition to breast cancer has been proven. Based on this, we distinguish:
Sporadic cancer (about 68%); no cases of breast cancer in both parents in 2 generations;
Familial breast cancer (about 23%). Cases of breast cancer in one or more blood relatives;
Genetic predisposition to cancer as a result of the presence of mutations in the BRCA1/BRCA2 genes (about 9%). There are cases of breast cancer in blood relatives, as well as associated cancer (primary multiplicity - damage to the ovaries, colon).
Risk groups for breast cancer depend on the following etiological factors:
1. Hormonal factors:
a) endogenous - hyperestrogenemia as a result of:
Features of the menstrual cycle (early menarche before 12 years; late menopause after 55 years)
Childbearing function (nulliparous women, first birth after 30 years; abortions before 18 years and after 30 years)
Features of lactation (hypo- and agalactia)
Features of sexual life (its absence, late onset, frigidity, mechanical methods of contraception)
Hormone replacement therapy in pre- and postmenopausal women for more than 5 years.
Long-term use of combined oral contraceptives: more than 4 years before the first birth, more than 15 years at any age.
2. Lifestyle and environmental factors
- geographical location and nutrition (high-calorie diet, excess consumption of animal fats, low physical activity)
Alcohol abuse (increases risk by 30%)
Smoking (under 16 years of age – doubles the risk)
Radiation (exposure) and breast injuries
3. endocrine and metabolic disorders. obesity, atherosclerosis, adrenal and thyroid diseases
4. individual history:
Age over 40
Previous history of breast or ovarian cancer
5. Pre-existing breast diseases
- atypical mammary hyperplasia
6. Family history: genetic factors:
- close relatives have breast cancer, ovarian cancer, colorectal cancer
Association with hereditary syndromes (Cowden, BLOOM)
- BRCA-1 gene mutations; BRCA-2
Pathogenesis. Due to the influence of factors - activation of proliferative processes, increase in FSH production. follicle - enlarged estrogens - proliferation of the uterine mucosa, epithelium of the gland ducts. Protective factors: early pregnancy, first child is a boy, debt. feeding. Clinical manifestations of breast cancer.
1) a painless dense formation of various sizes, round or irregular in shape, with a bumpy surface, slight limitation of mobility (if it does not grow into the chest wall). The mammary gland is often deformed (enlarged or reduced, has local bulging, cut contour).
2) skin symptoms. a) symptom of wrinkling - the skin over the tumor is gathered into a wide fold with the index and thumb, the wrinkles that appear are normally located parallel; with cancer, the parallelism of wrinkles is disrupted, they converge to one area (a positive symptom of “wrinkling”)
b) platform symptom - when administered in a manner similar to the previous one, a flattened area of fixed skin appears
c) symptom of retraction (umbilication) – when taking the same method as the previous one, a slight retraction appears
d) lemon peel symptom – lymphatic edema of the skin, visible visually
e) thickened fold of the areola (Krause's sign)
f) change in skin color over the tumor
g) cancerous ulcer - not deep, denser than the surrounding tissues, has undermined edges protruding above the surface of the skin and an uneven bottom covered with a dirty coating
3) nipple symptoms. changes in the shape and position of the nipple, retraction of the nipple and limitation of its mobility up to complete fixation (Pribram's symptom - displacement of the tumor along with the nipple - the result of tumor germination of the excretory ducts of the gland), hemorrhagic discharge from the nipple
4) Enlarged axillary lymph nodes.
5) Isolated edema.
Secondary symptoms. ulceration of the skin, bleeding, secondary infection, metastases to the bones (spine, pelvis, hip, ribs), metastases to the liver, lungs, pleura.
Physical examination: asymmetry, increase in volume, different levels of nipples, nipple discharge, skin changes, palpation while standing and lying down, symptoms see above.
Inspection. Examination of the mammary glands should be carried out in sufficient lighting, at some distance from the patient, standing first with her hands down, and then with her hands raised up.
Examination reveals local or total hyperemia of the skin of the mammary gland; hyperemia can spread to the skin of the chest or abdominal wall, upper limb. In most cases, it is combined with local or total swelling of the mammary gland, which is referred to as the “lemon peel” symptom. The presence of skin ulcerations, nodular seals, crusts, fistulas, and tissue decay are also inherent in the tumor process. During palpation the following is examined:
1) dimensions (diameter) - it is customary to mark up to 1 cm, up to 2 cm, from 2 to 5 cm, over 5 cm; measurements are usually made using a ruler or compass;
2) anatomical form - nodular, locally widespread, or locally infiltrative, diffusely infiltrative (occupying either most or the entire mammary gland);
3) consistency - dense, densely elastic, lumpy;
4) localization - central, external quadrants (upper and lower), internal quadrants (upper and lower).
When palpating regional l. u. in the axillary, subclavian and supraclavicular areas it is important to establish:
a) absence of compacted and enlarged l.u.;
b) the presence of enlarged or compacted l.u.;
c) location of enlarged l.u. in the form of a chain or conglomerate of nodes welded together;
d) the presence or absence of edema of the upper limb.
The combination of anamnestic information, examination and palpation data is a condition for determining the clinical form of breast cancer: nodular, local infiltrative, diffuse infiltrative or complicated (infiltrative-edematous, infiltrative-lymphangitic, ulcerative).
The so-called “occult” form of breast cancer, which is characterized by a combination of a microscopic primary tumor with large metastatic lesions of regional lymph nodes, most often axillary, is considered separately.
Of particular interest is Paget's cancer, a unique form of breast cancer that affects the nipple and areola. Based on the predominance of certain clinical symptoms in Paget's cancer, they distinguish between eczema-like (nodular, weeping rashes on the skin of the areola), psoriasis-like (presence of scales and plaques in the area of the nipple and areola), ulcerative (crater-like ulcer with dense edges) and tumor (presence of tumor-like formations in subareolar zone or in the nipple area) shape.
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More than 90% of stomach tumors are malignant. Gastric adenocarcinoma accounts for 95% of their total number. Every year about 1 million people around the world get sick with stomach cancer. The incidence rate in different countries varies quite widely. The highest rates are recorded in Japan, China, Belarus and Russia, and the lowest in the USA. In the vast majority of countries, this malignant tumor occurs in men 2 times more often than in women. In Russia, the mortality rate from stomach cancer during the first year after diagnosis reaches 55%, second in this indicator only to malignant neoplasms of the lung and esophagus.
Currently, malignant tumors are considered as a disease of the genome with many common molecular pathways. Changes in the genome are determined by both congenital pathology and external influences, among which physical, chemical agents and viruses can be distinguished. The common feature of these factors is the ability to change DNA. Malignant transformation of a normal cell occurs with the accumulation of oncogenes encoding proteins that are involved in the processes of cell division and differentiation, in combination with the inactivation of suppressor genes responsible for the synthesis of proteins that inhibit cell division and induction of apoptosis (the process of programmed cell death, allowing the body to get rid of defective structures).
In mammalian cells, the cellular response to damaging factors is carried out by the p53 gene, which is called the “guardian of the genome.” Having received information about DNA damage, it induces repair or, if the damage is significant and irreversible, sends the cell along the path of apoptosis to prevent the proliferation of cells with an extended mutation. Functional inactivation of THIS gene by oncovirus proteins in normal cells causes disruption of cell cycle control and accumulation of genetic abnormalities that activate oncogenes and inactivate tumor suppressor genes. Approximately 50% of primary human tumors carry mutations in the p53 gene. These tumors are clinically more aggressive.
Currently, it is impossible to identify any one cause of stomach cancer. The malignant process develops under the influence of several factors. Heredity plays a certain role in the occurrence of gastric adenocarcinoma, although its significance has not been fully determined. The environmental impact seems to be stronger.
In the late 60s of the 20th century, the carcinogenic properties of nitrosamines were discovered. A number of these compounds, such as dimethylnitrosamines, are constantly detected in the air of rubber, leather and other industries. Particularly alarming are the data on the spontaneous synthesis of nitroso compounds in the human body due to nitrates, which are so rich in food products. An important role in the development of stomach cancer is played by the consumption of canned food, smoked meats and canned foods. Many emulsifiers that are used as food preservatives are not only harmful, but also carcinogenic.
Consuming large amounts of salt is also a risk factor, and the presence of fresh fruits and vegetables in the diet has a protective effect. Vitamin C and other antioxidants, contained in significant quantities in “green” vegetables (lettuce, cabbage) and fruits, prevent the conversion of nitrites into mutagenic substances. The most clear example of the role of diet in the development of stomach cancer is demonstrated by the United States, where over the past 70 years the promotion of rational nutrition has significantly reduced the incidence of stomach cancer in the population. It is important to note that the incidence of stomach cancer among first-generation emigrants from Japan permanently residing in the United States decreased by 3 times.
Colonization of the achlorhydric stomach by bacteria also promotes the conversion of dietary nitrates to nitrites and the conversion of dietary amines in the presence of nitrates into carcinogenic nitrosamines. Recently, when determining the cause of gastric cancer, great attention has been paid to the role of Helicobacter pylori, which is recognized as leading in the etiology of chronic non-immune antral gastritis. In 1994, the International Agency for Research on Cancer listed this organism as a clear carcinogen, consistently causing superficial gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, carcinoma in situ, and ultimately invasive carcinoma. The proportion of stomach cancer cases associated with the presence of this bacterium is estimated at 42%. Severe dysplasia indicates imminent or existing gastric cancer and should be an indication for gastrectomy.
Stomach cancer occurs with increased frequency in certain diseases of the stomach, which are considered as background. These include chronic atrophic gastritis, intestinal metaplasia and hyperplastic gastropathy.
The risk of developing stomach cancer is increased in patients with adenomatous polyps of the stomach. Unlike hyperplastic polyps, which contain a proliferation of histologically normal gastric epithelium (they make up 80% of their total number), adenomatous polyps transform into cancer in 10-20% of cases. Especially often multiple adenomatous polyps, as well as those whose diameter exceeds 2 cm, undergo malignant degeneration.
In patients suffering from pernicious anemia for over 5 years, the risk of developing stomach cancer increases by 2 times.
Long-standing stomach ulcers increase the risk of cancer by 1.8 times. It has been noted that patients who have undergone gastric resection for a benign disease have an increased risk of developing cancer in the organ stump. Within 15 years after such an operation, the risk does not increase, and only 25 years after gastrectomy it increases 3 times. At the same time, duodenal ulcer and achlorhydria caused by the use of H2 receptor antagonists and gastric proton pump inhibitors do not increase the incidence of gastric cancer.
Savelyev V.S.
Surgical diseases
In 1908-1911 it was installed viral nature of leukemia and sarcomas of chickens. In subsequent decades, the viral etiology of a number of lymphoid and epithelial tumors in birds and mammals was proven. It is now known that under natural conditions, for example, leukemia is caused by viruses in chickens, cats, cattle, mice, and gibbon monkeys.
Opened in recent years first viral pathogen, which causes the development of leukemia in humans, is ATLV (adult T-cell leukemia virus - adult T-cell leukemia virus). T-cell leukemia of adults is an endemic disease found in two regions of the globe - the islands of Klushi and Shihoku in the Sea of Japan and black population of the Caribbean countries. Patients with this lymphoma are found sporadically in other regions, but many of them have some connection with endemic areas.
This disease occurs usually in people over 50 years of age, occurs with skin lesions, hepatomegaly, splenomegaly, lymphadenopathy and has a poor prognosis ATLV or HTLV virus is exogenous to humans, differs from other known animal retroviruses, is transmitted horizontally to T cells from mother to child, from husband to wife (but not vice versa), during blood circulation, is not detected in any other forms of human leukemia or lymphoma. Thus, adult T-cell leukemia is a typical infectious disease (vertical transmission of the virus through germ cells has been excluded by special studies). In endemic areas, more than 20% of practically healthy people, mainly relatives of patients, are carriers of the virus.
In other parts globe antibodies to the virus rarely found. It is believed that 1 in 2,000 infected people will become ill. A virus indistinguishable from ATLV was found in a monkey in Africa. In addition to lymphoma (leukemia), this virus can cause AIDS, in which T-cell immunity is impaired.
Viral etiology also suspected in relation to some other human tumors. Epstein-Barr virus (EBV), part of the group of herpes viruses, is a very likely etiological factor in Burkitt's lymphoma. EBV DNA is routinely detected in cells of this lymphoma in endemic foci in Africa. However, Burkitt's lymphoma occurs outside Africa, but EBV DNA is found in only a minority of such cases. Common to EBV-positive and EBV-negative tumors are characteristic chromosome rearrangements (translocation between chromosomes 8 and 14), which is considered as evidence of a common etiology of these tumors.
DNA This virus is found in the genome of undifferentiated nasopharyngeal carcinoma cells, but not in nasopharyngeal tumors of other histogenesis. In patients with these tumors, a high titer of antibodies to various components of EBV is noted, significantly exceeding these indicators in the population - EBV is widespread, and antibodies to it are found in 80-90% of healthy people. A high titer of antibodies was found in patients with lymphogranulomatosis. Suppression of immunity and activation of EBV are, according to some authors, the main cause of the development of lymphomas and immunoblastic sarcomas in patients with transplanted kidneys exposed to immunosuppressive agents; This is supported by the high titer of antibodies to EBV and the detection of EBV DNA in the genome of tumor cells.
There is evidence to suggest an infectious (viral) etiology. cervical cancer the incidence of this cancer is higher with early onset of sexual activity with frequent changes of partners; it is increased in the second wives of men whose first wives also suffered from the same disease. Based on seroepidemiological data, they think about the role of the herpes virus type II as an initiator; Condyloma virus is also suspected.
In areas with high frequency occurrence of viral hepatitis B The incidence of hepatocellular cancer has also increased. On the other hand, patients with this tumor are more likely to be seropositive for the hepatitis B virus than healthy individuals; but there are also seronegative cases of cancer. Tumor cell lines containing viral DNA and producing its antigen were obtained. In general, the role of hepatitis B virus in the induction of hepatocellular carcinoma remains unclear.
From human warts(verrucae vulgaris) several types of papilloma viruses have been isolated, which are believed to cause only benign tumors that are not prone to malignancy. Only one of these viruses (type 5) was isolated from papillomas that develop in hereditary epidermodysplasia verruciformis and tend to malignize.
Initially tumor viruses were considered as infectious agents that induce cells to reproduce unregulatedly. In contrast, L.A. Zilber (1945) developed a theory according to which the genome of a tumor-derived virus integrates into the genome of a normal cell, turning it into a tumor cell, i.e., tumor-derived viruses are fundamentally different in their action from infectious ones. In the 70s, genes necessary for the transformation of a normal cell into a tumor cell were discovered in tumor-derived RNA-containing viruses - transforming genes or oncogenes (v-onc - viral oncogenes). Subsequently, copies or analogues of oncogenes were identified in normal cells of various animals and humans (c-ops - “cellular” cellular oncogenes), then the ability of the oncogene to be integrated into the genome of the virus was proven.
Oncogenes today identified, their chemical structure and localization in chromosomes were determined. Proteins, the products of the activity of these genes, have also been identified; each of them synthesizes its own specific protein.
