Surgical Management of Malignant Tumors

1. Surgical Management of Malignant Tumors อ. พญ. ทพญ. นุชดา ศรียารัณย ภาควิชาศัลยศาสตร์ช่องปาก คณะทันตแพทยศาสตร์ มหาวิทยาลัยเชียงใหม่

2. Etiology and predisposing factors The exact cause of oral cancer is unknown • Variations in incidence rates : differences in exposure to carcinogenic initiators

3. Risk factors • Genetic predisposition • Atmospheric pollution • Immunosuppression • Viruses • Fungal infection • Diet • Dental sepsis Tobacco Alcohol

4. Tobacco • 24% of all male deaths in developed world • 7% of all female deaths • Smoking is the cause of 45% of all cancer deaths • 95% of all lung cancer deaths • 85% of all oral cancer deaths

5. Tobacco • Carcinogens of tobacco Benzopyrene tobacco specific nitrosamines • Act locally on keratinocyte stem cells • Affecting DNA replication • Causing mutation

6. Alcohol • Pure ethanol is not carcinogenic • Nitrosamines and other impurities • Rising incidence of oral cancer linked to rising alcohol consumption

7. Alcohol • Ethanol increases mucous membrane permeability • Ethanolmetabolised to acetaldehyde locally by bacterial alcohol dehydrogenases and can damage cells – poor oral hygiene • Alcoholic liver disease reduces detoxification of carcinogens • High calorie value suppresses nutrition and leads to nutritional deficiencies

8. Risk factors • Genetic predisposition ? - impaired capacity to metabolise carcinogens - DNA damage repair impaired • Atmospheric pollution - polycyclic aromatic hydrocarbons/nitrosamines/benzenes

9. Risk factors • Immunosuppression - organ transplant patients – lip cancer - no increased risk with AIDS of oral SCC • Viruses -HPV 16 and 18 viral oncogene deactivates p53 inhibit apoptosis

10. Risk factors • HPV and oral cancer • Prevalence 0-100 % in OSCC • But only 40% of head and neck SCC with p53 mutations had high risk HPV • Only 40% of HPV positive tumors showed p53 mutations • HPV infection is pobably an early event • Higher prevalence in younger patients

11. Risk factors • Other viruses Herpes simplex Epstein-Barr virus Hepatitis virus no clear evidence of involvement in oral cancer

12. Risk factors • Fungal infection - candida albicans – potential to promote nitrosation of dietary substrates • Diet -Protective effect of antioxidants Vit A, C, E and trace elements Zinc and selenium • Dental sepsis - poor oral hygiene-socioeconomic status and nitrosating enzyme in plaque

13. Age and sex • older age • ~ 95% occur in over 40 Yrs • The average age at the time of Dx is about 60 Yrs • more frequent in males Male : Female ~ 2 : 1

14. Sites • The Tongue is the most common site for oral cancer • Floor of mouth

15. Histologic types • Carcinoma 96% • Sarcoma 4% • The most common type : squamous cell carcinoma • Major salivary gl. : malignant mixed tumor • Minor salivary gl. : adenoid cystic CA • Lymphoma • Metastatic tumors to oral cavity

16. Diagnosis Examination • Inspection : oral cavity, neck, pharynx • Palpation : neck , oral masses

17. Investigations 1. Surgical biopsy • oral cavity : local anesthesia • Small lesions excisional biopsy • Incisional biopsy is recommended in all cases

18. Surgical biopsy • The biopsy : suspicious area of the lesion and some normal adjacent mucosa • Avoid area of necrosis or gross infection

19. 2. Toluidine blue test • The suspicious area is paint with 1% aqueous solution of toluidine blue for 10 sec. • Rinsed with 1% solution of acetic acid • The toluidine blue binds to DNA present in the superficial cells and resists decoloration by acetic acid

20. Toluidine blue test • Dye binding is proportional to the amount of DNA present and the number and size of superficial nuclei in the tissues • false negatives • guide

21. 3. Fine needle aspiration biopsy • lumps in the neck (suspicious lymph nodes) • percutaneous puncture of the mass with a fine needle and aspiration of material for cytological examination

22. FNAB • The node is fixed between finger and thumb • Puncture by a 21 or 23 gauge needle on a 10 ml syringe • A small amount of air is already in the syringe (2ml) before puncture

23. FNAB • moving the needle around different parts of the node • the plunger is then released and the needle withdrawn through the skin • The tip of the needle must touch the slide • Smear slide

24. FNAB • Wet fixed material: an alcoholic ‘spray fixed’ immediately, 10 min • Thinner film : air dry • after the aspiration, aspirate 2ml of 95% ethanol as fixative into the same syringe

25. FNAB • fast , almost painless, needs no specialised equipment and without complication • The technique depends on 2 aspects: - successful puncture of the node - transfer of cells and stroma onto slide

26. FNAB • Frable and Young: 94.5% accuracy with head and neck lesions • may avoid the need for open biopsy • Risk of spreading malignant cells into the surrounding tissues (Tumor implantation into the needle track, when large gauge needle has been used)

27. 4. Radiography • Limited value • 50% of calcified component of bone must be lost before any radiographic change • Panthomography alveolar and antral involvement • lungs and skeleton

28. 5. Computerised tomography Great benefit in head and neck • Primary tumor and lymph node metastasis • Value in the investigation of metastasis in the lungs, liver and skeleton

29. 6. Radionuclide studies • Technetium pertechnetate bone scans • Not specific (increased uptake : increased metabolic activity in the bone) • Detecting distant metastases

30. 7. Magnetic resonance imaging (MRI) • Highly contrasted image for soft tissue lesion • Bone is not imaged • only the marrow being directly visualized

31. 8. Ultrasound Noninvasive, readily available and cost effective • Abdominal ultrasound : liver metastases • intra-oral tumors : high degree of accuracy, demonstrating bone invasion (early stage) • Regional LN

32. Precancerous lesion • Leukoplakia • Erythroplakia

33. Location of leukoplakia/erythroplakia Occurrence probability of dysplasia 1. Buccal mucosa1. Floor of mouth 2. Mandibular vestibule2. Tongue 3. Maxillary gingiva3. Lower lip 4. Mandibular gingiva4. mandibular gingiva 5. Tongue5. Buccal mucosa 6. Floor of mouth6. Mandibular vestibule 7. Lower lip7. Maxillary gingiva

34. Leukoplakia Dysplasia 1. Mild Dysplasia 2. Moderate Dysplasia 3. Severe Dysplasia

35. Leukoplakia Mangement • Looking for etiology factors - stop smoking immediately • non/mild dysplasia - total excision - F/U 3-6 mo. when non total excision

36. Leukoplakia • Moderate dysplasia - total excision - F/U 4-8 wk. when non total excision • Severe dysplasia - total excision - F/U every 4wk.

37. Erythroleukoplakia Moderate dysplasia Management - total excision with 1 cm margin , extend in submucosa - F/U every 4wk.

38. Erythroplakia Management - total excision with 1 cm margin , extend in submucosa - F/U every 4wk.

39. Spread of tumor • Local extension • Lymphatic spread - stepwise spread • Hematogenous spread

40. Biology of metastasis • SCC : most to regional LN sometimes through blood (lung, brain, bone)

41. Biology of metastasis • Steps 1. Invasion through basement membrane, between endothelial cell or blood vessel (collagenase, heparanase, stromelysin) 2. Entrance into lymphatics or blood vessel form tumor embolus 3. Survival of cancer cell in lymphatics or blood vessel

42. Biology of metastasis 4. Escape from circulation into new tissue (collagenase, heparanase, stromelysin) 5. Implantation in new tissue area with cloning require : angiogenic factors, GF to recruit blood supply, stimulate self-replication, down regulate host cells, activate host cell (osteoclast)

43. Incidence of LN metastases Depend on : - size - site - histological type of primary tumor

44. LN metastases • most commonly in the upper deep cervical and submandibular nodes on the same side of the primary tumor • lower deep cervical nodes : rare • Contralateral node metastases : rare

45. Incidence of LN metastases Site : - more posterior lesion in the mouth the more likely LN metastases Retromolar trigone : 45% Tongue : 35% Floor of mouth = lower alveolus : 30% buccal mucosa and hard palate, lower lip : 10-15%

46. Incidence of LN metastases Histology SCC : The better differentiated, the less metas. verrucous CA : low well diff. SCC : 26% moderated diff. SCC :33% poorly diff. SCC : 50%

47. Diagnosis of LN metastases • Clinical examination • Imaging • Cytology • Histology

48. Imaging CT - sensitivity similar to clinical exam. sensitivity > 90% Node above 1 cm suspicious of malinancy

49. Diagnosis of LN metastases Ultrasound - simple, relative cheap - used to guide FNAB of impalpable nodes

50. Diagnosis of LN metastases Cytology (FNAB) - useful confirmatory test - accuracy is high - false-negative results open biopsy