TUMORS. CLINICAL SYMPTOMS, DIAGNOSTICS, AND TREATMENT

1. TUMORS.CLINICAL SYMPTOMS, DIAGNOSTICS, AND TREATMENT

2. Tumors are nonconformist cellular populations no longer dedicated to the purposes of the organism as a whole. In contrast with normal cellular populations, ontogenetically grouped to form organs that remain fixedly related to one related to one another and are integratively functional, neoplastic cells do not form organs, are not fixedly related to other cells, and function physiologically as relatively independent uncontrolled elements. They are separated behavioristically into the benign and the malignant types.

3. A benign tumour is one that does not spread or "metastasize" to other parts of the body; a "malignant tumour" is one that does. A benign tumour is caused by cell overgrowth, and thus is different from a cyst or an abscess. Although benign is better news than malignant for biopsy, it does not always mean "harmless", though many are almost harmless. A benign tumour may still grow, and this growth may cause damage to any organs, tissues, or nerves in its vicinity. Hence, a benign tumour can still cause serious illness if it presses on important areas.

4. Etiology. • The primary etiologic factors involved in the inception of tumors in man are still unknown. Presumptively, something happens to the constitution of nuclear material of a cell, rendering it no longer obeisant to regulation of its growth. Although the primary cellular genesis of neoplasia is unknown, it can be induced by a variety of agents, these may be classified as mechanical, infectious, chemical and physical (chiefly, ionizing radiation). • The anthropogenous pollution of external medium in Ukraine is connected to a motor transports (cars in the country haven’t catalysts), metallurgical, power, chemical industry and nuclear power. Ukraine was on 110 place among 122 countries of the world in 2001 behind an index of ecological stability. In northern areas of the country is close six millions population lives in conditions of the raised level of radiation - as result of consequences of failure on Chornobul atomic power station (1986). By the highest oncology case rate Southern and East regions of Ukraine differ, in which there are basic metallurgical, coal and power complexes.

5. GENERAL EVALUATION OF THE ONCOLOGICAL PATIENT Early detection of a malignant tumor is a prefer for its successful treatment. History of the patient usually offers clues that may be suggestive of a malignant process: • the living conditions and habits (e.g. such carcinogenic factors as smoking) • the area of living (e.g. skin cancer is much more common in those living in the South; lung cancer predominates in industrialized areas with excessive air pollution).

6. Cancer is a group of more than 100 different diseases. Cancer occurs when cells become abnormal and keep dividing and forming more cells without order or control. All organs of the body are made up of cells. Normally, cells divide to produce more cells only when the body needs them. If cells divide when new ones are not needed, they form a mass of excess tissue called a tumour. Tumours can be benign (not cancer) or malignant (cancer). The cells in malignant tumours can invade and damage nearby tissues and organs. Cancer cells can also break away from a malignant tumour and travel through the bloodstream or the lymphatic system to form new tumours in other parts of the body. The spread of cancer is called metastasis.

7. The list of conditions in the cancer group includes: Cancer type by severity: • Benign tumour. • Malignant tumour. • Metastatic cancer - spreading of cancer beyond its initial site to lymph nodes and/or other body areas. Cancer type by type of tumour: sarcoma, leukaemia, lymphoma, myeloma, melanoma. Cancer type by common locations: lung cancer, colorectal cancer, brain cancer, throat cancer, oral cancer, liver cancer, bone cancer, pancreatic cancer.

8. At its initial stages a tumor is unlikely to produce any complaints, as the suspicion of a malignancy is sometimes based only on a few indistinct symptoms, the meticulous questioning is mandated. It is therefore necessary to inquire whether there is been any minor change in the patient’s well-being. Of great importance is what is referred to as the syndrome of minor symptoms and signs, i.e. the state of discomfort that may be indicative of a malignancy: fatigability without apparent cause and a reduction in working capability; rejection or unwillingness to eat certain foods; drowsiness; apathy to what used to be of interest; “a foreign body” sensation; abdominal discomfort rather than pain (i.e. a feeling of heaviness); lack of satisfaction after nicturition or defecation, etc.

9. The earlier diagnosis of the malignant tumor has better prognosis. The oncological alertness implies: 1. Physician's knowledge of early and/or atypical symptoms and signs of malignancy and its complications. 2. Physician’s knowledge of the clinical pictures of premalignant conditions and their treatment. 3. The timely referral of patients with supposedly malignant conditions to specialized medical centers. 4. The adequacy of the patient's examination by the physician who was the first to suspect the malignancy irrespective of their specialty.

10. Premalignant conditions include diffuse and focal overgrowth of the epithelium of the skin and mucous membranes, which can be recognized through inspection and endoscopy. The examples might be as follows: - leukoplakia, or “white spots”, i.e. vegetations of the epithelium covering mucous membranes, the changes being undetectable on palpation; - certain benign cutaneous lesions (e.g. papillomas, polyps, birth marks); - different forms of senile dyskeratosis.

11. Pain is not a characteristic feature of tumor, with the exception of tumors arising from blood vessels and neural tissues, which exert pressure on the tissues. Usually, the pain is related to the distention of the adjacent tissues, infiltration of the nerves or organ insufficiency. Hence, intestinal obstruction resulting from the adluminal growth of a tumor causes spastic pains. In addition, persistent pain suggests either serous involvement or tumorous infiltration of the organ (e.g. tenesmus is a symptom of a rectal tumor).

12. Palpation is one of the major methods used in the physical examination as it provides the physician with vital information of the tumor. The palpation of the tumor is to be gentle and with appropriate pressure, the finger lips being used to feel first the intact adjacent tissue while approaching the tumor itself. It is sometimes performed with both hands, as is the case with feeling the lymph nodes, breast tumors. The size of a tumor measures from millimeters to centimeters. The tumor shape is accounted for by its nature (benign vs. malignant). Modularity of the surface and adherence to the neighboring tissues, coupled with firm consistency, is characteristic of a malignancy, in contrast to a benign overgrowth or a cyst, which has smooth surface and is often round and mobile. It is noted that metastatic nodules on the surface of a malignant tumor are likely to be smooth.

13. The consistency of a tumor appreciably depends on its type: - soft (normally implies a benign nature of the tumor, e.g. lipomas or polyps of mucous membranes; in some cases, however, this can be a finding of an undifferentiated tumor; - hard (associated with an overgrowth of the connective tissue, e.g. fibroma); - firm (firm consistency, together with elasticity without fluctuation, is typical of an encapsulated tumor filled with fluid); - wooden-like without demarcation (provides substantial evidence of a malignant over-growth, i.e. carcinoma).

14. The mobility of a tumor can be either spontaneous (active) or induced (passive). Of special importance is the tumor motility in relationship to the skin or muscles. The tumor can move spontaneously: - when it originates from a mobile organ in the abdominal cavity; - on changing the body position; - on swallowing (goitre); - on muscular contraction (muscle tumor).

15. It is noteworthy that in numerous cases it is the metastases that are identified first. To confirm the diagnosis of a malignant lesion or its metastases, special investigations have to be performed. The following are the examples: • tumors of the umbilicus (sister Josef’s metastases); • tumors of the ovaries (Krukenberg's metastases); • Virchov’s metastases (the metastases to the supraclavicular lymph nodes) suggesting gastric carcinoma with distant metastases; • hepatic enlargement with nodules on its surface in an ascitic patient requires ruling out an abdominal malignant tumor.

16. Similarly, all the lymph nodes have to be thoroughly palpated. Metastatic lymph nodes differ from intact ones in that they are enlarged, round, firm and occasionally nodular and adhered to the surrounding tissues and other lymph nodes. However, unlike inflamed nodes, they commonly lack tenderness. Because the malignancies of numerous organs (e.g. the lung, prostate, breast) produce osseous metastases, a meticulous skeletal investigation is required. The liver may also harbour metastases from various types of tumors, which necessitates its thorough examination. The metastatic liver is enlarged the edges being nodular, firm and non-tender. It is sometimes even possible to palpate separate clear-cut metastatic nodules.

17. To confirm the diagnosis of a malignant lesion of its metastases special investigations have to be performed. • Endoscopy; • Cytology (swabs, aspirates); • Histology (biopsy); • X-ray investigations (roentgenoscopy, roentgenography, tomography, angiography, lymphography); • Radioisotope methods (scanning, scintigraphy); • Ultrasonography; • Computerized axial tomography; • Laboratory tests (blood cell morphology).

18. According to the clinical classification, the four types of pathological overgrowth are identified (in general): • Stage I - tumor is localized, occupies a limited area does not infiltrate into the wall of the organ, metastases are absent. • Stage II - tumor is of a big size, can infiltrate into the organ wall but does not spread beyond the organ, there can be solitary metastases to the regional lymph nodes. • Stage III - tumor is of a big size with degeneration, infiltration into the hollow organ wall; multiple metastases to the regional lymph nodes are present. • Stage IV - is tumor with distant metastases to organs and lymph nodes and with infiltration of surrounding organs.

19. The TNMGP classification may read as follows: T1-4 N0-3 M0-1 G1-4 P1-4. • For vast majority tumors the world classification behind system TNM are used: • T - primary tumor. • T0 - primary tumor not indicated. • Tis - is preinvasive carcinoma (cancer in situ). • T1 - is tumor to 2 cm in diameter, not spreading on surrounding tissues. • T2 - is tumor to 5 cm in diameter, is spreading on surrounding tissues insignificantly. • T3 - is tumor more then 5 cm in diameter and spreading on surrounding tissues. • T4 - is tumor, which spreading of surrounding structures or skin, with restricted mobility.

20. N - regional lymph nodes. N0 - the lymph nodes’ stab are absent. N1 - the metastases in solitary mobility lymph nodes are present. N2 - the metastases in regional lymph nodes, which fixed between it-selves (packet) and neighboring structures are present. N3 - the metastases in more distant lymph nodes are present. Nx - estimation of regional lymph nodes is not enough. M - are distant metastases. M1 - the distant metastases are present. M0 - the distant metastases are absent. Mx - estimation of distant metastases is not enough.

21. G - is level of differentiation. G1 - is high level of differentiation. G2 - is middle level of differentiation. G3 - is low level of differentiation. G4 - is notdiffential tumor. P - penetration. P1 - is tumor in mucous membrane. P2 - the tumor to grow in sub mucous membrane. P3 - the tumor to grow in layer of muscles. P4 - the tumor to grow through serous membrane and to leave of organ.

22. GENERAL PRINCIPLES OF TUMOUR TREATMENT The malignant diseases call for immediate therapy, whereas benign masses require treatment if they • cause dysfunction of the organ affected; • result in cosmetic defects; • are found premalignant; • are suspected of transforming into malignant ones.

23. The therapeutic methods for malignant disease include surgery, radiation, chemo- and/or hormone therapy. Surgery is the main method of treatment of malignant tumors and it is often combined with radiation or chemotherapy. This is referred to as combined therapy (for example, in breast cancer, cancer of the uterus, ovaries, etc.). The radiation therapy can be either employed pre- or postoperatively. This can also accompany chemotherapy, as is the case, for example, in myeloma or Hodgkin’s lymphoma. When the tumor has advanced so far that successful surgery in view of a metastatic spread is very unlikely, the case is considered inoperable. Operating on patients with malignant tumors, the surgeon should follow the principle of ablasty, which implies the prevention of spread of tumor cells during the surgery by means of removing the mass within the intact tissues. To avoid damaging the tumor, it is necessary to ligate the veins as early and excise the tumor, fat tissues and lymph nodes en bloc.

24. The principle of antiblasty involves: 1) the measures aimed at destroying the cancer cells in the operation site (in the wound, in the lymph vessels and veins using electrocautery, laser or plasmatic scalpels; 2) cleansing the wound after excision of the tumor with 70% alcohol solution; 3) infusions of chemotherapeutic drugs. As the tumor cells can spread beyond the organ affected to the lymphatic vessels, lymph nodes and surrounding tissues, it is recommended that a large portion or the entire organ involved be removed together with the surrounding tissues and fasciae. This is known as the principle of vines. An operation for breast cancer serves as an illustration, in which case the breast with the fatty tissues, fasciae and the subclaviсuгal, axillary lymph nodes as well as the pectoralis minor muscles is removed en bloc.

25. The radical operation involves the removal of the entire organ (e.g. the breast, uterus) or its large portion (the stomach, bowel) together with the regional lymph nodes. The combined surgery during which the organ affected is excised with part of or the entire organ into which the tumor has spread is also regarded radical. Palliative operations are performed to remove part or the entire organ if the metastases are not liable to ablation. They are indicated when complications of the malignancy are found (e.g. tumor decay with bleeding, perforation of gastric or colon cancer). Symptomatic operations are aimed at eliminating complications caused by the enlarged tumor without removing the tumor itself (e. g. gastrostomy in oesophageal cancer; inter-intestinal anastomosis in bowel cancers complicated by intestinal obstruction, tracheostomy in cancer of the larynx).

26. Radiation therapy. Above half of the patients with malignant tumors are exposed to radiotherapy. It can either be used as an independent method for early stages of the disease (e.g. cancer of the lower lip, cervix of the uterus and the skin) or is included in the combined therapy. Radiation therapy commonly coupled with surgery and undertaken either pre- or postoperatively. In addition, radiotherapy can be combined with chemo- or hormone therapy. The curative effect on the tumor and its metastases is achieved through external, intra-cavitary or interstitial radiation. External radiation involves g-therapy with radioisotopes (60Co, 137Cs. etc.).

27. Chemotherapy. Chemotherapy – this is using of drugs by synthetic or natural origin with purpose of firm to stop of malignant cells’ development. Chemotherapy uses chemical agents to destroy cancer cells throughout the body Hence, the use of chemotherapy in combination with other methods of treatment. If combined with surgery, chemotherapy is employed to treat, for instance, ovarian cancer. Also, it is of great importance for the treatment of systemic oncological diseases (e.g. leukaemia, Hodgkin's lymphoma). At the early stage of malignancy, i.e. when the tumor can be removed surgically, chemotherapy alone should not be attempted.

28. The following main groups of chemotherapeutic preparations are used; • Cytostatics (novembihin, cyclophosphan, TEPA [triethylenethiophospharamide], dopan, vinblastin, vincristin, etc.) hamper the growth of tumor cells, affecting cellular mitosis. • Antimetabolites after the metabolism of cancer cells by: • suppressing the synthesis of purins (mercaptopurine); • acting on the enzyme systems (fluoruracil) or on the transformation of folic acid (methotrexate); • Anti-cancer antibiotics are a group of commands produced by fungi or microorganisms: actynomycine D, bruneomycin, mytomycin.

29. Hormone therapy. Hormones are the treatment of hormone receptor-positive tumors. These medications supplement the combined therapeutic methods of surgery, radiotherapy and chemotherapy. The preparations of the male sex hormone - androgen (testosterone propionate. methyltestosterone) are indicated in breast cancer, whereas those of female sex steroid - estradiol (synestrol and diethylstilboestrol) are known to be effective in cancer of the prostate. Hormone therapy of tumors also includes surgeries on the endocrine glands e.g. surgical castration of women with breast cancer.