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Cancer
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Cancer

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  • 1. General concepts of cancer <ul><li>Relevance of oncology: </li></ul><ul><li>One-third of all individuals in the U.S.A. Will develop some type of cancer during their lives. </li></ul><ul><li>Is the second cause of death in U.S.A. </li></ul>www.freelivedoctor.com
  • 2. CANCER <ul><li>NEOPLASM: </li></ul><ul><li>SIR RUPERT WILLIS </li></ul><ul><li>ABNORMAL MASS OF TISSUE, THE GROWTH OF WHICH EXCEEDS AND IS UNCOORDINATED WITH THAT OF THE NORMAL TISSUES AND PERSISTS IN THE SAME MANNER AFTER CESSATION OF THE STIMULUS WHICH EVOKED THE CHANGE. </li></ul>www.freelivedoctor.com
  • 3. CANCER IN U.S.A. <ul><li>YEAR 2000 </li></ul><ul><li>1.22 MILLION NEW CASES OF INVASIVE CANCER WERE DIAGNOSED </li></ul><ul><li>552,000 PEOPLE DIED FOR CANCER </li></ul><ul><li>CAUSE 23% OF ALL DEATHS </li></ul><ul><li>(only cardiovascular disease cause more deaths) </li></ul>www.freelivedoctor.com
  • 4. CANCER <ul><li>Gains in the treatment of nonresectable cancer have been gradual and have beeen focused on those malignancies characterized by unusual sensitivity to radiation and chemotherapy. </li></ul><ul><li>Survival rate at 5 years have been increased close to 50% as a result of progress in the early diagnosis and the therapy. </li></ul>www.freelivedoctor.com
  • 5. CANCER <ul><li>The three most common cancers are: </li></ul><ul><li>LUNG </li></ul><ul><li>BREAST </li></ul><ul><li>COLON/RECTUM </li></ul>www.freelivedoctor.com
  • 6. CANCER <ul><li>ECONOMIC BURDEN: More than 10 billion dlls./year </li></ul><ul><li>SOCIAL IMPACT: The number of cases are increasing and are affecting young people every year. </li></ul>www.freelivedoctor.com
  • 7. THE NORMAL CELL CYCLE <ul><li>MITOSIS:Chromatin aligns itself and formed two identical daugther cells </li></ul><ul><li>G1:DNA synthesis ceases (rest period) </li></ul><ul><li>S phase:Unknown signal/ increase of DNA and RNA synthesis </li></ul><ul><li>G2: DNA synthesis stop </li></ul><ul><li>GO: Aditional resting period </li></ul>www.freelivedoctor.com
  • 8. CANCER The relevance of knowing the “cell Cycle” is for a better understanding of the mechanism of action of cancer chemotherapy drugs. www.freelivedoctor.com
  • 9. CANCER <ul><li>Is a Disorder of cellular homeostasis in which there is lost of the normal growth controlling mechanisms. </li></ul>www.freelivedoctor.com
  • 10. The characteristics of cancer cells are: <ul><li>Clonality: Originates from a SINGLE STEM CELL that change in it`s behavior </li></ul><ul><li>Autonomy: The growth rate is unrestricted </li></ul><ul><li>Anaplasia: Lack of normal, coordinated cellular differentiation. </li></ul><ul><li>Metastasis: Dissemination to other parts of the body. </li></ul>www.freelivedoctor.com
  • 11. Abnormalities of cancer cells <ul><ul><li>Abnormal DNA synthesis </li></ul></ul><ul><ul><li>Membrane cells alterations </li></ul></ul><ul><ul><li>Cytoplasmic alterations </li></ul></ul><ul><ul><li>Increase ATP asa activity (Anaerobic shift) </li></ul></ul><ul><ul><li>Increase levels of proteolytic enzymes </li></ul></ul><ul><ul><li>Angiogenesis factor synthesis </li></ul></ul>www.freelivedoctor.com
  • 12. ONCOLOGY DEFINITIONS <ul><li>DIFFERENTIATION: Degree of morphologic and functional resemblance to comparable normal cell. </li></ul><ul><li>ANAPLASIA: Lack of “differentiation”, is a cancer marker. </li></ul><ul><li>ENCAPSULATION: Induction of peripheral fibrosis, characteristic of </li></ul><ul><li>“ benign” neoplasm </li></ul>www.freelivedoctor.com
  • 13. ONCOLOGY DEFINITIONS <ul><li>INVASION/INFILTRATION: Unrestricted permeation into contiguous structures, characteristic of “malignant” neoplasms. </li></ul><ul><li>METASTASES: Remote distant tumor implants from the primary neoplasm. </li></ul><ul><li>LOSS OF GROWTH CONTACT INHIBITION RATE. </li></ul><ul><li>DOUBLING TIME: Time required by the tumor to double in size. </li></ul>www.freelivedoctor.com
  • 14. CANCER <ul><li>Oncogenesis: </li></ul><ul><li>Are those changes induced by oncogenic factors in the normal cellular behavior which lead to the development of malignant/ cancer behavior of cells </li></ul>www.freelivedoctor.com
  • 15. CANCER <ul><li>ETIOLOGY: Cancer incidence vay with age, sex, race and geographic location. Hereditary traits have been obseved, also variations in diet and exposure to chemical and physical agents in the external environment contribute to the development of neoplasia. </li></ul>www.freelivedoctor.com
  • 16. Differences between benign and malignant tumor cells www.freelivedoctor.com
  • 17. Differences between benign and malignant tumor cells www.freelivedoctor.com
  • 18. ETIOLOGIC MECHANISM <ul><li>GENETIC FACTORS </li></ul><ul><li>VIRUS DNA -RNA </li></ul><ul><li>CHEMICAL CARCINOGENS </li></ul><ul><li>PHYSICAL CARCINOGENS </li></ul><ul><li>OTHERS </li></ul>www.freelivedoctor.com
  • 19. GENETIC FACTORS <ul><li>Proposed mechanism are: </li></ul><ul><li>I-Genes which are deregulated and excessively expressed, displaying dominant genetic activity. </li></ul><ul><li>II-Genes which are supressors of tumorigenic genetic activities and are recessive in that both alleles must be lacking for malignacy occur. </li></ul><ul><li>The inheritane patterns are generally autosomal dominant, with varying penetrance. </li></ul>www.freelivedoctor.com
  • 20. CHEMICAL CARCINOGENS <ul><li>Tobacco smoke: (Tar) </li></ul><ul><li>Polycyclic hydrocarbons </li></ul><ul><li>Nitrosamines </li></ul>www.freelivedoctor.com
  • 21. CHEMICAL CARCINOGENS <ul><li>Diethylstilbestrol </li></ul><ul><li>Estrogens </li></ul><ul><li>Alkylating agents </li></ul><ul><li>Azathyoprine </li></ul><ul><li>Methrotexate </li></ul><ul><li>Many others </li></ul>www.freelivedoctor.com
  • 22. CHEMICAL CARCINOGENS www.freelivedoctor.com
  • 23. CHEMICAL CARCINOGENS www.freelivedoctor.com
  • 24. CHEMICAL CARCINOGENS www.freelivedoctor.com
  • 25. PHYSICAL CARCINOGENS <ul><li>ULTRAVIOLET LIGHT </li></ul><ul><li>IONIZING RADIATION </li></ul>www.freelivedoctor.com
  • 26. ONCOGENIC VIRUSES <ul><li>Viruses have been implicated as the direct cause of only one human cancer. </li></ul><ul><li>The HTLV-I (human T-lymphotrophic virus can lead to adult T-cell leukemia. </li></ul><ul><li>Several others are closely associated but have to be taken only as cofactors in oncogenesis. </li></ul>www.freelivedoctor.com
  • 27. ONCOGENIC VIRUSES <ul><li>DNA VIRUS: </li></ul><ul><li>PAPILOMA VIRUS (WARTS, C.U. Ca., Anogenital cancer) </li></ul><ul><li>HERPES SIMPLEX (C.U. Carcinoma) </li></ul><ul><li>EPSTEIN-BARR (Burkitt`s Lymphoma, Nasopharyngeal carcinoma) </li></ul><ul><li>Hepatitis B (Hepatocellular carcinoma) </li></ul>www.freelivedoctor.com
  • 28. ONCOGENIC VIRUSES <ul><li>RNA virus: Mainly transcriptase reverse virus </li></ul><ul><li>AIDS virus (Kaposy`s sarcoma, primary C.N.S. Lymphoma) </li></ul><ul><li>HTLV-I and II (T leukemia) </li></ul>www.freelivedoctor.com
  • 29. GENERAL AND LOCAL EFFECTS OF CANCER <ul><li>Cancer can kill the patien by: </li></ul><ul><li>Local effects </li></ul><ul><li>Systemic effects </li></ul>www.freelivedoctor.com
  • 30. LOCAL EFFECTS OF CANCER ON HOST <ul><li>Occlusion </li></ul><ul><li>Destruction of critical structures </li></ul><ul><li>Ulceration </li></ul><ul><li>Tumor infarction </li></ul><ul><li>Abscess formation </li></ul>www.freelivedoctor.com
  • 31. LOCAL EFFECTS <ul><li>Occlusion at the level of: </li></ul><ul><li>Airways </li></ul><ul><li>Gastrointestinal tract </li></ul><ul><li>Blood vessels </li></ul><ul><li>Lymphatic channels </li></ul><ul><li>Urinary tract </li></ul><ul><li>Biliary tract </li></ul><ul><li>Heart (valves/pericardium) </li></ul><ul><li>Cerebro-spinal fluid system </li></ul>www.freelivedoctor.com
  • 32. LOCAL EFFECTS <ul><li>DESTRUCTION OF CRITICAL STRUCTURES: </li></ul><ul><li>Large blood vessels (aorta, carotid, etc.) </li></ul><ul><li>Pituitary gland </li></ul><ul><li>C.N.S. </li></ul><ul><li>Skull </li></ul><ul><li>Bones </li></ul>www.freelivedoctor.com
  • 33. SYSTEMIC EFFECTS OF CANCER ON HOST <ul><li>Cachexia </li></ul><ul><li>Hormone and hormone-like production </li></ul><ul><li>Paraneoplastic syndromes </li></ul>www.freelivedoctor.com
  • 34. PARANEOPLASTIC SYNDROMES <ul><li>Paraneoplastic syndromes are related to “remote” effects of cancer cells on the host, whic are not attributable to functions of the original normal tissue </li></ul>www.freelivedoctor.com
  • 35. PARANEOPLASTIC SYNDROMES <ul><li>Paraneoplastic syndromes resembles other clinical endocrine, neurologic and coagulation clinical syndromes, but, by definition the clinical abnormalities are due to systemic effects produced by the cancer cells. </li></ul>www.freelivedoctor.com
  • 36. PARANEOPLASTIC SYNDROMES <ul><li>Relevance of paraneoplastic syndromes remains on two facts: </li></ul><ul><li>1.- As explained before, these syndromes have a different etiology and sometimes different mechanisms of production, by then, treatment of the clinical abnormalities have to be different also. </li></ul>www.freelivedoctor.com
  • 37. PARANEOPLASTIC SYNDROMES <ul><li>2.- Some paraneoplastic syndromes dissapear completely after removal of the cancer, while some of the resembled clinical syndromes have not cure. This fact, makes more important the differential diagnosis between them. </li></ul>www.freelivedoctor.com
  • 38. PATHOPHYSIOLOGY <ul><li>The pathophysiology of paraneoplastic syndromes remains unclear, but some proposed mechanisms are: </li></ul><ul><li>1.- Hormone & hormone “like” synthesis </li></ul><ul><li>2.- Synthesis of identifiable chemical mediators </li></ul><ul><li>3.- Production of auto-inmune responses </li></ul><ul><li>4.- Activation of factors of the coagulation system </li></ul>www.freelivedoctor.com
  • 39. 1.- HORMONE & HORMONE “LIKE” SYNTHESIS( ectopic hormone secretion) <ul><li>Gene derepression </li></ul><ul><li>Cellular dedifferentiation </li></ul><ul><li>Cellular arrested differentiation </li></ul>www.freelivedoctor.com
  • 40. 2.- SYNTHESIS OF IDENTIFIABLE CHEMICAL MEDIATORS <ul><li>Prostaglandins </li></ul><ul><li>Interleukins </li></ul><ul><li>Tumor necrosis factor </li></ul><ul><li>Neurotransmitters / Neurohormones </li></ul>www.freelivedoctor.com
  • 41. 3.-PRODUCTION OF AUTOIMMUNE RESPONSES <ul><li>Auto-antibodies </li></ul><ul><li>Cross reactions </li></ul>www.freelivedoctor.com
  • 42. 4.- ACTIVATION OF COAGULATION SYSTEM FACTORS <ul><li>Increased Coagulation </li></ul><ul><li>Increased Fibrinolysis </li></ul>www.freelivedoctor.com
  • 43. ECTOPIC HORMONE SYNDROMES IN NON-ENDOCRINE TUMORS <ul><li>Hypercortisolism (Cushing`s sd.) </li></ul><ul><li>A.C.T.H. Synthesis </li></ul><ul><li>C.R.H. Synthesis </li></ul><ul><li>Etiology: </li></ul><ul><li>Lung cancer (small cell type) 50% </li></ul><ul><ul><li>Carcinoid tumor </li></ul></ul><ul><ul><li>Thymoma </li></ul></ul><ul><ul><li>Bronchial adenoma (Benign neoplasia) </li></ul></ul><ul><ul><li>Medullary thyroid carcinoma </li></ul></ul>www.freelivedoctor.com
  • 44. Hypercalcemia <ul><li>Without bone metastasis: </li></ul><ul><li>Prostaglandin synthesis (PGE2) </li></ul><ul><li>Interleukin 2-Osteoclast activating factor </li></ul><ul><li>P.T.H. secretion </li></ul>www.freelivedoctor.com
  • 45. HYPERCALCEMIA ETIOLOGY <ul><li>Multiple myeloma </li></ul><ul><li>Solitary plasmocytoma </li></ul><ul><li>Lung cancer </li></ul><ul><li>Leukemia </li></ul><ul><li>Lymphoma (Hodgkin and Non-hodgkin) </li></ul><ul><li>Breast cancer </li></ul><ul><li>Renal carcinoma </li></ul>www.freelivedoctor.com
  • 46. INAPPROPIATE SECRETION OF ANTIDIURETIC HORMONE <ul><li>This particular syndrome “could be”associated with neoplasias and some pulmonary infections. </li></ul><ul><li>Etiology: </li></ul><ul><li>Small cell carcinoma of the lung </li></ul><ul><li>Carcinoid tumor </li></ul><ul><li>Pulmonary tuberculosis </li></ul><ul><li>Pneumonia ( Bacterial and viral) </li></ul>www.freelivedoctor.com
  • 47. Hypoglicemia <ul><li>Ectopic insulin production </li></ul><ul><li>Insulin “like” hormone production (somatomedins). </li></ul><ul><li>Etiology: </li></ul><ul><li>Gastric carcinoma </li></ul><ul><li>Uterine fibroma </li></ul><ul><li>Uterine fibrosarcoma </li></ul><ul><li>Retroperitoneal fibrosarcoma </li></ul><ul><li>Neuroma </li></ul>www.freelivedoctor.com
  • 48. SECRETION OF CHORIONIC GONADOTROPIN <ul><li>Clinical features: </li></ul><ul><li>Male: Female: </li></ul><ul><ul><li>Gynecomastia *Amenorrhea </li></ul></ul><ul><ul><li>Infertility *Menstrual disorders </li></ul></ul><ul><ul><li>Impotence (hyper-hypo) </li></ul></ul><ul><ul><li>False (+) pregnancy test *Infertility </li></ul></ul><ul><ul><ul><ul><ul><li>*False (+) pregnancy test </li></ul></ul></ul></ul></ul>www.freelivedoctor.com
  • 49. SECRETION OF CHORIONIC GONADOTROPIN <ul><li>Etiology: </li></ul><ul><li>Lung carcinoma </li></ul><ul><li>Gastric carcinoma </li></ul><ul><li>Ovarian carcinoma </li></ul><ul><li>Pancreatic carcinoma </li></ul><ul><li>Hepatoma </li></ul>www.freelivedoctor.com
  • 50. OTHER HORMONE RELATED SYNDROMES <ul><li>T.S.H. Production </li></ul><ul><li>Prolactin </li></ul><ul><li>Growth hormone </li></ul><ul><li>V.I.P. (Vasoactive intestinal polipeptide) </li></ul><ul><li>Gastrin </li></ul><ul><li>Bombesin </li></ul><ul><li>Glucagon </li></ul><ul><li>Erythropoietin </li></ul>www.freelivedoctor.com
  • 51. NEUROMUSCULAR PARANEOPLASTIC SYNDROMES <ul><li>Myasthenia gravis: Thymoma </li></ul><ul><li>Mechanism: Auto-antibodies against the acetilcholine receptor at the “motor end” plate. </li></ul><ul><li>Myasthenic syndrome (Lambert eaton syndrome) </li></ul><ul><li>Etiology: Small cell carcinoma of the lung </li></ul><ul><li>Mechanism: Auto-antibodies against the calcium channels on the motor nerve terminals, which interfere with the Ach release. </li></ul>www.freelivedoctor.com
  • 52. CANCER ASSOCIATED RETINOPATHY <ul><li>Etiology: Small cell carcinoma of the lung </li></ul><ul><li>Mechanism: Immunoglobulins against several polypeptide or protein antigens in the retinal and tumor cells. (Cross reaction) </li></ul><ul><li>Clinical picture: Proggressive loss of visual acuity </li></ul>www.freelivedoctor.com
  • 53. CEREBELLAR DEGENERATION <ul><li>Etiology: Small cell carcinoma of the lung </li></ul><ul><ul><ul><ul><ul><li>Ovarian cancer </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Mechanism: </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>1.-Immunoglobulins that react selectively with cerebellar purkinje cells. </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>2.-Associated viral c.n.s. Infections </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>3.-Side effects of chemotherapy </li></ul></ul></ul></ul></ul>www.freelivedoctor.com
  • 54. PERIPHERAL NEUROPATHY <ul><li>( 15% of all cancer patients) </li></ul><ul><li>Sensory neuropathy </li></ul><ul><ul><li>Motor neuropathy </li></ul></ul><ul><ul><li>Mixed </li></ul></ul><ul><ul><li>MECHANISM: </li></ul></ul><ul><ul><li>*Unknown </li></ul></ul><ul><ul><li>*Auto-antibodies against axonal components </li></ul></ul><ul><ul><li>*Side effects of chemotherapy </li></ul></ul>www.freelivedoctor.com
  • 55. HEMATOLOGIC PARANEOPLASTIC SYNDROMES <ul><li>Polycytemia </li></ul><ul><li>Hemolytic anemia </li></ul><ul><li>Thrombocytopenic purpura </li></ul><ul><li>Coagulopathy </li></ul>www.freelivedoctor.com
  • 56. POLYCYTEMIA ( ERYTHROCYTOSIS) <ul><li>Etiology: </li></ul><ul><li>Cerebellar hemangioblastoma </li></ul><ul><li>Uterine benign fibroma </li></ul><ul><li>Pheochromocytoma </li></ul><ul><li>Adrenocortical carcinoma </li></ul><ul><li>Hepatoma / carcinoma </li></ul><ul><li>Ovarian cancer </li></ul><ul><li>Mechanism: Ectopic production of erythropoietin </li></ul>www.freelivedoctor.com
  • 57. HEMOLYTIC ANEMIA <ul><li>Etiology: </li></ul><ul><li>Lymphoid malignancies </li></ul><ul><li>Lung carcinoma </li></ul><ul><li>Breast cancer </li></ul><ul><li>G.I. Carcinoma </li></ul><ul><li>Mechanism: Immune mediated hemolysis (cross-reaction) </li></ul>www.freelivedoctor.com
  • 58. PARANEOPLASTIC COAGULOPATHIES <ul><li>Hypercoagulability (thrombosis Prone) </li></ul><ul><li>Etiology: Pancreatic carcinoma </li></ul>www.freelivedoctor.com
  • 59. DISSEMINATED INTRAVASCULAR COAGULATION (D.I.C.) <ul><li>Mucin producing adenocarcinomas (G.I. Tract) </li></ul><ul><li>Prostatic carcinoma </li></ul><ul><li>Acute myeloblastic leukemia type IV </li></ul>www.freelivedoctor.com
  • 60. BLEEDING TENDENCY (CLOTTING FACTOR DEFFICIENCIES) <ul><li>Lymphomas : Antibodies against clotting factors </li></ul><ul><li>Amiloid deposit: Factor “X” defficiency </li></ul><ul><li>Hepatic carcinoma : Deffective fibrinogen </li></ul>www.freelivedoctor.com
  • 61. CAQUEXIA / MALNUTRITION <ul><li>There are several mechanism proposed to explain the severe emaciation of patients with cancer. </li></ul><ul><li>Direct effect at G.I. Tract </li></ul><ul><li>Obstruction of the lumen (dysphagia) </li></ul><ul><li><Gastric emptying with a fullness sensation </li></ul><ul><li><Gastric secretion /digestion </li></ul><ul><li><Small intestine digestion /absorption </li></ul><ul><li>Increase Motility / secretion (GIP-VIP) </li></ul><ul><li>Parasitic effect of the tumor </li></ul>www.freelivedoctor.com
  • 62. ANOREXIA OF CANCER PATIENTS <ul><li>Proposed mechanism are alterations in: </li></ul><ul><li>Smell and taste, by altered glucose & A.A. Metabolism </li></ul><ul><li>Secretion of inhibitory peptides </li></ul><ul><li>Cachectin substance </li></ul><ul><li>Cancer treatment: Chemotherapy-Radiotherapy-Surgery-Morphine </li></ul>www.freelivedoctor.com
  • 63. FUNCTIONAL BEHAVIOR OF NEOPLASM <ul><li>Functional tumors </li></ul><ul><li>Ectopic hormone syndromes </li></ul><ul><li>Paraneoplastic syndromes </li></ul>www.freelivedoctor.com
  • 64. HORMONE AND HORMONE-LIKE PRODUCTION <ul><li>Thyroid Ca. Hypo /hyperthyroidism </li></ul><ul><li>Adrenal Ca. Hypo/Hypercortisolism </li></ul><ul><li>Pituitary tumors Prolactin, growth h. </li></ul><ul><li>Pancreatic Ca. Insulinoma, Gastrinoma VIPoma </li></ul><ul><li>Ovarian Ca. Hypo/Hyperestrogen. </li></ul><ul><li>Testicular cancer Hyperandrogenism, Precocious puberty </li></ul>www.freelivedoctor.com

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