1. 1 Clinical Effect, Prevention & Treatment of Tumor Dr. Yupa Min Pathology Unit

2. 2 EFFECTS OF TUMOR ON HOST Tumor-Host interactions are a two way street. Both Benign & Malignant tumors can cause adverse effects on the host. Malignant tumors have more lethal & harmful effects. Tumors evoke both humoral & cell mediated immune responses on the host

3. EFFECTS OF BENIGN TUMOR ON HOST (1) Location & impingement on adjacent structures (2) Functional activity such as hormone production (3) Bleeding & Secondary infection (4) Malignant transformation 3

4. 4 1.Location & impingement on adjacent structure e.g. benign tumor of gut  as they enlarge  compress intestine  intestinal obstruction pituitary tumor A small (1-cm) pituitary adenoma can compress & destroy the surrounding normal gland & thus lead to serious hypopituitarism. This adenoma can also compress the optic chiasma leading to blindness.

5. 5 2.Functional activity such as hormone production benign tumor of endocrine organ may produce sufficient hormone to cause clinical signs & symptoms. e.g.  cell adenoma of pancreas  increased insulin  fatal hypoglycemia Pituitary adenoma  increased growth hormone secretion  Gigantism, Acromegaly

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7. 7 3.Bleeding & Secondary infection a). bleeding & ulceration e.g. benign tumor of natural surfaces such as skin or mucosa of gut  ulceration, Secondary infections, bleeding. ( melena in GIT, hematuria in urinary tract) b). torsion, rupture, infarction Pedunculated benign tumor or benign tumor of mobile organ  torsion  hemorrhagic infarction causing acute pain. e.g Dermoid cyst of ovary

8. 8 4.Malignant transformation Benign tumor rarely become malignant, but some tumor undergo malignant transformation. e.g. 1) Villous adenoma of colon  CA colon 2) Multiple polyposis of colon  CA colon 3) Adenoma of stomach  CA stomach

9. EFFECTS OF MALIGNANT TUMOR ON HOST (1) Location & impingement on adjacent structure (2) Erosion, invasion & destruction of local tissue (3) Metastasis to vital organ (4) Hormonal effects (5) Cachexia 9

10. 10 1.Location & impingement on adjacent structures - More pronounced & complete than that of benign tumor e.g CA head of pancreas  compress common bile duct  obstructive jaundice

11. 11 2.Erosion, invasion & destruction of local tissue e.g. Cancers arising within or metastasis to endocrine gland  destruction of gland  endocrine insufficiency CA cervix  invade/compress ureter  obstructive uropathy  uremia  death Erosive destructive growth of tumor  ulceration, secondary infection & bleeding. e.g. CA of gut  melena

12. 12 3.Metastasis to vital organ such as Brain, Bone Marrow, liver, lung  death 4. Hormonal effects Non endocrine tumours can produce endocrinopathies due to production of ectopic hormones &peptides. “PARANEOPLASTIC SYNDROME”

13. 13 The endocrinopathies are frequently encountered paraneoplastic syndromes. Because the cancer cells are not of endocrine origin, the functional activity is referred to as ectopic hormone production. Cushing syndrome is the most common endocrinopathy. Approximately 50% of individuals with this endocrinopathy have carcinoma of the lung.

14. 14 PARANEOPLASTIC SYNDROME DEFINITION : Symptom complexes in cancer bearing patients that cannot readily be explained, either by local or distant spread of tumor or by the elaboration of hormone indigenous to the tissue from which the tumor arose.

15. 15 It is important to recognize because 1.They may represent earliest manifestation of an occult neoplasm. 2.They may represent significant clinical problems & may lethal. 3.They may mimic metastatic disease & confuse treatment. -found in 10% of patients with malignant disease

16. 16 CLINICAL SYNDROMESUNDERLYING CANCERCAUSAL MECHANISM ENDOCRINOPATHIES Cushing $ SIADH (Syndrome of inappropriate ADH secretion ) Hypercalcemia Carcinoma lung carcinoma lung Intracranial neoplasms carcinoma lung Breast carcinoma Renal carcinoma ACTH or ACTH like substance ADH or ADH like substance PTH like peptide

17. 17 CLINICAL SYNDROMESUNDERLYING CANCERCAUSAL MECHANISM Hypoglycemia Carcinoid Syndrome Polycythemia Hepatocellular carcinoma Carcinoma lung Pancreatic carcinoma Gastric carcinoma RCC, HCC, Insulin or insulin like substance Serotonin, histamine, bradykinin Erythropoietin

18. 18 CLINICAL SYNDROMESUNDERLYING CANCERCAUSAL MECHANISM NERVE & MUSCLE $ Myasthenia, Polymyositis, Peripheral neuropathy, Cortico-cerebellar Degeneration. DERMATOLOGIC DISORDER Acanthosis nigricans Carcinoma Lung Breast carcinoma Gastric carcinoma Carcinoma Lung Antibodies against tumor cells may cross react with neuronal cells.  Immunologic  secretion of EGF

19. 19 CLINICAL SYNDROMESUNDERLYING CANCERCAUSAL MECHANISM OSSEUS, HPOA [ Hypertrophic Pulmonary OsteoArthropathy] -Periosteal new bone frormation at the distal end of long bones, metatarsals, metacarpals & proximal phalanges -Arthritis of adjacent joints -Clubbing of digits ARTICULAR & SOFT TISSUE Bronchogenic carcinoma (Carcinoma Lung ) CHANGES Unknown

20. 20 HPOA

21. 21 CLINICAL SYNDROMESUNDERLYING CANCERCAUSAL MECHANISM VASCULAR & Venous thrombosis ( Trousseau phenomenon ) Anemia HEMATOLOGIC CHANGES Bronchogenic carcinoma Pancreatic carcinoma Thymic neoplasms Tumor products ( mucins that activate clotting ) Unknown (due to depression of bone marrow and chronic bleeding)

22. 22 Acanthosis nigricans is characterized by gray-black patches of verrucous hyperkeratosis on the skin. in about 50% of the cases, particularly in those over age 40, the appearance of such lesions is associated with some form of cancer. Sometimes the skin changes appear before discovery of the cancer.

23. 23 CACHEXIA Constellation of progressive weakness, malaise, anemia, loss of appetite and wasting Progressive loss of body fat & lean body mass. Very common in terminal stages of advanced cancer

24. 24 May result from action of Cytokines. eg: TNF produced by macrophages in response to tumor cells or by the tumor cells themselves mediates cachexia. TNF  causing a catabolic state with decreased synthesis, storage & increased mobilization & utilization of body fat. Other cytokines such as IL1, IFN  synergize with TNF . Protein mobilization may also be involved.

25. 25 Additionally, other soluble factors produced by tumors, such as proteolysis- inducing factor and a lipid-mobilizing factor, increase the catabolism of muscle and adipose tissue These factors reduce protein synthesis - by decreasing m-RNA translation and - by stimulating protein catabolism through the activation of the ATP-dependent ubiquitin-proteasome pathway. Also attributed by grief & anxiety.

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27. 27 Tumor Grading Histologic estimate of malignancy of a tumour Criteria depends on Degree of differentiation Nuclear pleomorphism & hyperchromasia Number of mitoses Cancers are classified as Grade I to IV with increasing anaplasia. Well,Moderate,Poorly Differentiated. E.g. GLEASON’s Grading System for CA prostate BLOOM & RICHARDSON’s Grading System for CA breast

28. 28 Tumour Staging Clinical estimate of extent of tumour spread TNM staging T = size of primary tumour N = extent of regional lymph node spread M= presence of metastases Ann Arbor Staging - lymphoma Duke’s /Astler Coller’s Staging - CA colon Stages 0 to IV (including size, nodal spread, metastases) Staging is a better predictor of prognosis than tumor grade.

29. 29 Treatment of Cancer Treated by surgery chemotherapy radiation therapy immunotherapy monoclonal antibody therapy or other methods

30. 30 Choice of Therapy depends upon tissue responsiveness to a modality the location the grade of the tumor the stage of the disease the general state of the patient (performance status)

31. 31 Palliation - Symptom control is control of pain, nausea, vomiting Diarrhea hemorrhage other common problems is an important determinant of the quality of life of cancer patients, plays an important role in the decision if the patient can undergo other treatments

32. 32 Prevention of tumors (a)Vaccination E.g., HPV(human papilloma virus) vaccination decreases the risk of CA cervix because it is one of the major causative agents in CA cervix. HBV(hepatitis B virus) vaccination reduces the risk of Hepatocellular carcinoma (HCC)

33. 33 (b)Personal habit E.g. Avoidance of smoking reduces the risk of CA Lung. Avoidance of smoked & preserved foods decreases the risk of CA stomach. Fiber diet decreases the risk of CA Colon.

34. 34 (c)Screening: : -Cancer cells have lowered cohesion and are easily exfoliated. These shed cells are evaluated for features of dysplasia and anaplasia. Cytologic smear is first founded by George Papanicoleau in 1928 (PAP smear). It is used as a Gynae cytology smear in 1943 for detection of CA Cervix & Endometrium. -Pap smear in women of reproductive age  early detection of cervical cancer & early treatment  can prevent complications & progression. Some types of cancer have a prognosis that is substantially better than nonmalignant diseases such as heart failure and stroke.

35. 35 (1) Those that prevent the mutagenic initiation of the carcinogenic process – “blocking agents” (2) Those that prevent the further promotion or progression of lesions that have already been established – “suppressing agents”

36. 36 natural and synthetic analogues of retinol – vitamin A Retinoids –arrest or reverse the process of carcinogenesis –prevent the development of invasive carcinoma in experimental animals effective when used in combination with other preventive agents, especially tamoxifen

37. 37 a selective estrogen receptor modulator (SERM) is a non-steroidal derivative that binds to the oestrogen receptor has both estrogenic and anti-estrogenic actions, depending on the target tissue anti-estrogenic on mammary epithelium & proestrogenic on uterine epithelium

38. 38 a 5 a-reductase antagonist, is now in widespread used to treat benign prostatic hypertrophy (BPH) being evaluated for chemoprevention of prostate carcinogenesis in a large clinical trial

39. 39 DFMO prevents carcinogenesis in animal models of colon, bladder, breast, liver, skin, and stomach cancers. further clinical trials are planned.

40. 40 All the inhibitors of prostaglandin synthesis have been shown to be active in animal models for the suppression of carcinogenesis, especially colon carcinogenesis A large number of NSAIDs – aspirin, ibuprofen, sulindac, and piroxicam – have shown potent chemopreventive activity

41. 41 can block the mutagenic activity of a variety of carcinogens by preventing their binding to DNA Both agents are active in animal test systems for the prevention of cancer, and both are in clinical trial

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