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Surg onco MB6.pptx
- 1. SURGICAL ONCOLOGY Dr Winston Makanga, M.B.Ch.B, M.MEd (Surg) Consultant General and Laparoscopic Surgeon
- 2. Objectives of the lecture • Epidemiology • Definition of relevant terms • Carcinogenesis and biology • Etiology • Work-up for cancer (screening, diagnosis, staging) • Treatment • Palliation
- 4. Global
- 5. Definitions • Neoplasia: • Benign vs malignant • Dysplasia and carcinoma in situ • Malignancy: Primary vs secondary
- 6. Cancer biology • Defining features of malignant cells • Autonomy/Self sufficiency • Immortality • Angiogenesis • Invasiveness • Dissemination, implantation and inflammation • Evasiveness • Reprograming of metabolism • Subversion
- 7. Pathogenesis • Cancer initiation, promotion and progression • Oncogenes and tumor suppressor genes • Metastasis and routes of spread
- 8. Oncogenes & TSGs Gene Function HER-2 Membrane mitosis signal receptor p53 Prevents the accumulation of oncogenic mutations kRas Intracellular signaling for mitosis and response to growth inhibitors C-myc master regulator of cellular metabolism and proliferation Bcl 2 Mediates apoptosis MMRs Repair mismatched neuclotides (leads to MSI*)
- 9. Etiology • Hereditary cancers (BRCA, APC, rb1, MEN) • Inherited germline genetic error (translocation, deletion, inversion, silencing) • Chemical carcinogens • Genotoxins, cocarcinogens & promoters • Physical carcinogens • FB, chronic wounds, parasites • Viral carcinogens • EBV, HHV, HBV, HCV, HTLV, HPV, HIV • Radiation • Ionizing vs non-ionizing (UV) Somatic mutation (genetic or epigenetic)
- 10. Screening • Risk stratification • Gail model for ca breast: age,(menarche, first live birth), relatives with ca breast, previous biopsy , atypical ductal hyperplasia) • Mammography • PSA/DRE • FOBT or FIT • Pap smear • UGI and LGI scope
- 11. Diagnosis • History and physical examination • Definitive diagnosis by tissue biopsy • Endoscopic, incisional, punch, excisional, core(image guided)*, ?FNA • Enables grading and histochemistry • Ensure consistency between histology and clinical picture • Excisional Bx is aimed at curative intent • Orient incision to allow for later scar excision if necessary • Direct access to tumor to preserve planes and limit spread • Lymph nodes should be excised whole to allow architectural assessment *risk of sampling error ~20%
- 12. Tumor markers • Present in high amounts in certain cancers: predictive vs prognostic • Can be in the serum or in the tissue • Serum markers: • PSA • CEA - colon • AFP - liver • Cancer Antigens (CA) 19-9 (colon, pancreas), 15-3 (breast), 27-29(breast,colon,stomach) • Tissue markers • HER-2, E2, P2, Ki67, p23, p53, oncotype DX
- 13. Staging • Assesses anatomical extent – can be clinical cTNM • Assists in: Prognostication, evaluation of treatments, exchange of information, treatment selection • Incorporates pre-op radiological assessment of lesion, nodes & distant organs rTNM • US, XR, CT, MRI, PET, Bone scan • Post excisional assessment gives a pathological staging pTNM • Distant staging for patients at high risk for mets • T evaluates size/extent of primary tumor, N – nodal mets*, M - distant
- 15. Surgical treatment • Goal is to achieve cure – wide negative margins, removal of draining nodes • Optimal margins varies among tumors • Role of sentinel node biopsy to determine LND • Patient performance status/fitness for surgery • Operability MUST be determined pre-op • Multiple distant metastases • Bulky disease with extensive nodal spread • Encasement of vital structures preventing en bloc resection • Role of palliative resections • Metastasectomy
- 16. Chemotherapy • Adjuvant vs neoadjuvant • Goals • Eradication of micrometastatic disease • Decrease local/distance recurrence • Achieve/improve operability • Reduce (or eradicate) disease burden and prolong survival • Assessment of response • Complete • Partial • Stable • Progression • Choice and combination of CTA Shrink tumor for better/lesser surgery Treatment of micromets without delay of post op recovery Assess effectiveness of CTA
- 17. Classification
- 18. Administration/combination • Systemic IV or enteral vs direct delivery (e.g. TACE) • Intermittent vs continuous administration • Anticipate toxicity and mitigate • Pulsing or reduce dose • Combination of agents • Coadminister cytoprotectants, CSF, EPO • Combination • Maximum cell kill within toxicity range for each drug • Broader range of coverage • Prevents or delays the emergence of drug-resistance
- 19. Radiotherapy • External beam or internal (probes/implants/liquid isotope) • Mostly for primary post-op clearance of remnant micro mets • Can be used for isolated distant mets • Used in combination with chemo in neo-adjuvant setting • Fractionation is used to minimize toxicity (Total Gy/# sessions) • Operate within the limits of • Repair • Reoxygenation • Repopulation • Redistribution • Radiosensitivity (and role of radiosensitizers)
- 20. Other therapy • Hormonal therapy • For hormone dependent malignancies: breast, prostate • Tamoxifen, leuprolide, DES • Targeted therapy • Inhibits angiogenesis or points of aggressiveness • Anti VEGF (Bevacizumab), anti HER2 (Trastuzumab), anti c-kit (Imatinib) • Immunotherapy • Potentiate inherent antitumor immunity • Gene therapy • Aims to replace/repair mutated TSG
- 21. Follow-up and tumor markers • Outcome measures • Overall survival • Progression/Disease free survival • Interval of follow ups • Indicators of recurrence • Signs and symptoms • Radiology/scope • Tumor markers; PSA, CEA, Ca 125, 19-9, 13-3
- 22. Palliation • Relieving symptoms without aim of cure • In metastatic or bulky unresectable disease • Low performance score (for the type of surgery) • Ideally should be as minimally invasive as possible • Analgesics • Cytoreductive chemo to reduce mass effect • Palliative recanalization of blocked lumens (stents, lasers, cryoablation) • Palliative interventions to control mass effect, bleeding (APC, embolization) • Palliative bypasses, resections for infection or bleeding, decompression
- 23. Review • Epidemiology • Definition of relevant terms • Carcinogenesis and biology • Etiology • Work-up for cancer (screening, diagnosis, staging) • Treatment • Palliation