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Principles of Surgical Oncology Amr Mohsen General Surgery Department Faculty of Medicine Cairo University Principles of Surgical Oncology 1. 2. 3. 4. 5. 6. 7. 8. 9. How cancer arises Aetiology of cancer Stages of cancer development Cancer grading Spread of cancer Diagnosis Treatment Prognosis Hope for the future Contents page 1. How cancer arises Gene mutation Proto-oncogenes >>mutation>> oncogenes >>>> stimulate growth Tumour suppressor genes >>mutation>> defective function Escaping body defense mechanisms Escaping apoptosis Escaping immune system Contents page 1. How cancer arises Examples Oncogenes Tumour suppressor genes Escaping immune system erb-B P53 BRCA1 BRCA2 AIDS & Kaposi Transplant for CA Contents page 2. Aetiology of cancer Initiators that damage genes Chemical agents Viruses Idiopathic (aging) Physical agents Diet Factors enhancing tumour growth Hormones Contents page 3. Stages of cancer development 1. Hyperplasia 2. Metaplasia Contents page 3. Stages of cancer development 3. Dysplasia Contents page 3. Stages of cancer development 4. In situ CA Contents page 3. Stages of cancer development 5. Invasion 6. Mets Contents page 4. Cancer grading Grading is a measure of CA aggression Well-differentiated Moderatelydifferentiated Poorly-differentiated & undifferentiated Contents page 5. Cancer spread Properties that allow metastasis 1. Defective cell adhesion 2. Tumour angiogenesis 3. Escaping apoptosis as they reach distant tissues Contents page 5. Cancer spread Modes of metastasis Local spread 2. Lymphatic spread 3. Blood-born spread 4. Trans-cavitary spread 5. Perineural 1. 6. Contact spread Contents page 5. Cancer spread Contents page 5. Cancer spread Contents page 5. Cancer spread Contents page 5. Cancer spread Contents page 5. Cancer spread Contents page 5. Cancer spread Contents page 5. Cancer spread Stepwise versus explosion concept of metastasis Contents page 5. Cancer spread Contents page 6. Diagnosis Early detection of asymptomatic cases (screening) Mammography PSA colonoscopy for APC Diagnosis of symptomatic cases Clinical Imaging Tumour sampling Tumour markers Endoscopy Contents page 6. Diagnosis Contents page 6. Diagnosis Tumour sampling Types Tissue biopsy – cytology Image-guided – unguided Frozen section – paraffin sections Contents page 6. Diagnosis Tumour sampling Tissue biopsy Needle, endoscopic or operative biopsies Obtains a piece of tissue Diagnosis depends on cellular morphology & tissue architecture (orientation and invasion) Cytology e.g., FNAC & exfoliative cytology Obtains cells Diagnosis depends on cellular morphology only Requires an expert cytologist Contents page 6. Diagnosis Incision Site & direction Contents page 6. Diagnosis Contents page 6. Diagnosis Healthy Cancer Contents page 6. Diagnosis Contents page 6. Diagnosis Tumours markers Help in the diagnosis of certain tumours and in the follow-up of the patients after treatment. •Alpha-feto protein •CEA •PSA •CA 15-3 •CA 19-9 •Thyroglobulin HCC & testicular teratoma GIT, pancreas and breast CA. Prostate CA. Breast CA. GIT & pancreas CA. Thyroid CA. Contents page 7. Treatment Prevention •Smoking •APC •UC with dysplasia or old pancolitis Contents page 7. Treatment Early Late Disease Local Systemic Fate Potentially curable Incurable Aim of ttt Cure Palliation Main ttt Loco-regional Surgery + RT Systemic Chemo + hormo Pain control Adjuvant ttt Chemo + hormo Surg + RT Contents page 7. Treatment Standard modalities A. Surgery B. RT C. Chemotherapy D. Hormone therapy E. Immunotherapy Contents page 7. Treatment A. Surgery Definition of radical surgery Primary tumour Safety margin Lymph nodes •GIT CA •Breast CA •Head & neck & skin Routinely resected Excision or irradiation Treated only if involved Whenever possible lymph nodes are removed in continuity with the primary tumour = block excision. Contents page 7. Treatment A. Surgery Precautions Avoid spillage of malignant cells, local & blood Advantages •Quick •Effective •The largest number of cures •Confirms full ablation of a tumour (clear safety margin). Disadvantages and Limitations •Functional and cosmetic disabilities •Not applied if fixed to a vital structure or with mets. Contents page 7. Treatment B. Radiotherapy May replace surgery or may be given in addition Common indications 1. Cancer of the larynx so as to preserve the voice 2. Early Hodgkin's disease 3. Early prostate cancer 4. As part of conservative therapy for early breast cancer (after surgery) Contents page 7. Treatment B. Radiotherapy Methods Powerful X-rays, gamma rays, electrons, or heavy particles are directed to the tumour by one of two main methods 1. Teletherapy (cobalt & linear accelerator) 2. Brachytherapy (implanted needle) Contents page 7. Treatment B. Radiotherapy Advantages • Preserves surrounding structures • Can destroy microscopic extensions around a tumour that a scalpel might miss • Safer option for old frail patients • Usually does not require hospitalization • SCC is sensitive Disadvantages • Adenocarcinoma is much less sensitive • Burns of the skin or enteritis - difficult to treat • Compared to surgery, radiotherapy is slower • Like surgery, it is not suitable for mets Contents page 7. Treatment C. Chemotherapy Common indications • • Blood & lymphoid CA For solid tumours -Main modality in case of detected metastases -Adjuvant to surgery in early cases where microscopic metastases are possibly present Better results are obtained from combination chemotherapy Contents page 7. Treatment C. Chemotherapy Advantages 1. Can reach malignant cells anywhere in the body 2. Leukaemias, lymphomas and testicular cancer are successfully treated by new combination drugs. Disadvantages 1. Chemotherapy kills the rapidly growing cells of the bone marrow, causes anemia, leucopenia and thrombocytopenia. 2. Other side effects of chemotherapy include diarrhoea, nausea vomiting and hair loss. Contents page 7. Treatment D. Hormone therapy Examples • • • Anti-oestrogens for with ER +ve breast CA Androgen blockade for men with prostate cancer Thyroxin to suppress TSH for papillary thyroid CA Advantages Mild side effects Disadvantages Limited to tissues with hormone receptors Contents page 7. Treatment E. Immune therapy Non-specific BCG TCC of urinary bladder Specific Monoclonal antibodies from a single clone of lymphocytes that have been stimulated by a specific protein of the cancer cells Contents page 7. Treatment Bone marrow transplantation Not a therapy in itself Indications To strengthen depleted bone marrow that is weakened by high, potentially curative doses of RT or chemotherapy Sources •Allogeneic donations •Autologous donations Contents page 8. Prognosis Measures of prognosis Survival Recurrence Usually 5-10 years Contents page 8. Prognosis Patient Tumour Stage most important Grade Site Type Age Debilitating illness Immunosuppression Treatment Early detection Treatment in specialized centres Contents page 8. Prognosis Good prognosis Skin, SCC BCC Leukaemias Lymphomas Testis Bad prognosis Melanoma Oesophagus Stomach Pancreas Contents page 9. Hope for the future •Wider application of early detection programs •Refinement of established modalities of treatment •Gene therapy •Control of angiogenesis •Better targeting of therapy Thanks