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Surgical Oncology — Principal Notes

Bailey & Love's Short Practice of Surgery, 28th Edition

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1. WHAT IS CANCER?

• Term 'cancer' credited to Hippocrates (460–370 BCE) — Greek for crab, describing finger-like projections
• Rudolf Virchow: first showed cancer is a disease of cells; omnes cellula e cellula (every cell from a cell)
• Theodor Boveri (1914): importance of chromosomal abnormalities in cancer
• Oswald Avery (1940s): DNA is the genetic material
• Watson & Crick (1953): DNA structure — key to understanding molecular biology of cancer

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2. THE HALLMARKS OF CANCER

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3. CAUSES OF CANCER

Genetic/Inherited

• Tumour suppressor genes (TSGs): TP53, BRCA1/2, RB1, APC, VHL, PTEN, MLH1, MSH2
• Oncogenes: gain-of-function mutations → uncontrolled proliferation
• Inherited syndromes: BRCA1/2 (breast/ovarian), APC (FAP/colorectal), HNPCC/Lynch (colorectal/endometrial), MEN1/2, VHL, Li-Fraumeni, PTEN (Cowden), RB1 (retinoblastoma), NF1/2

Environmental Causes

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4. THE GROWTH OF A CANCER

• Doubling time: the time for a tumour to double its volume
• A tumour becomes clinically detectable (~1 cm³) only after ~30 doublings (10⁹ cells)
• At ~40–45 doublings, the tumour is lethal (~10¹² cells)
• Growth fraction: proportion of cells actively dividing — decreases as tumour enlarges
• Tumour growth is exponential initially, then slows (Gompertzian growth)
• Angiogenesis essential once tumour exceeds ~1–2 mm — VEGF drives this

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5. TUMOUR PATHOLOGY & STAGING

Prognostic Factors for Malignant Tumours

• Tumour size (T stage)
• Nodal status (N stage) — single most important prognostic factor in most solid tumours
• Distant metastases (M stage)
• Histological grade: well / moderately / poorly differentiated (Grade 1–3)
• Histological type: e.g. ductal vs lobular breast carcinoma
• Vascular/lymphatic/perineural invasion
• Resection margin status: R0 (clear), R1 (microscopic), R2 (macroscopic residual)
• Performance status (PS): ECOG/Karnofsky — guides treatment tolerance

TNM Staging System

• T: Primary tumour size/extent
• N: Regional lymph node involvement
• M: Distant metastasis
• Prefix c = clinical staging; p = pathological; y = post-neoadjuvant; r = recurrent

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6. IMAGING IN ONCOLOGY

• RECIST criteria: used to assess radiological response to treatment
• Response categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD)

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7. THE MANAGEMENT OF CANCER

Multidisciplinary Team (MDT)

• Management is more than treatment — requires MDT input
• Core members: surgeon, oncologist (medical & clinical/radiation), radiologist, pathologist, CNS (clinical nurse specialist), palliative care
• All new cancer patients should be discussed at MDT meeting before treatment decisions

Intent of Treatment

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8. SURGERY IN CANCER

Role of Surgery

Curative Surgical Procedures

• Wide local excision (WLE): removal of tumour with adequate margin of normal tissue
• Radical resection: en bloc removal of primary tumour + regional lymph nodes + adjacent involved structures
• Lymphadenectomy: formal removal of regional lymph node basin
• Sentinel lymph node biopsy (SLNB): minimally invasive technique to sample the first draining lymph node(s) without full lymphadenectomy

Oncological Principles of Surgery

1. R0 resection (clear margins) is the goal — R1/R2 resections have significantly worse prognosis
2. En bloc resection: avoid tumour fragmentation/spillage; reduces local recurrence
3. No-touch technique: ligate vascular supply early to prevent haematogenous dissemination
4. Adequate margins: margin distance depends on tumour type (e.g. >1 cm for sarcoma, ≥5 cm for colon cancer)
5. Avoid seeding: minimal tumour manipulation; use protective wound drapes
6. Lymph node harvest: minimum nodes required for accurate staging (e.g. ≥12 nodes for colorectal)

Debulking / Cytoreductive Surgery

• In some tumours (ovarian cancer, peritoneal metastases), maximal debulking improves survival
• Combined with HIPEC (hyperthermic intraperitoneal chemotherapy) for peritoneal surface malignancy

Palliative Surgery

• Relief of obstruction (bowel/biliary/ureteric)
• Control of bleeding
• Relief of pain (e.g. pathological fracture fixation)
• Decompression (e.g. spinal cord compression)

Reconstructive / Rehabilitative Surgery

• Restore form and function after ablative surgery
• E.g. breast reconstruction after mastectomy, free flap reconstruction after head & neck resection

Prophylactic Surgery

• Total colectomy in FAP or HNPCC
• Risk-reducing mastectomy / salpingo-oophorectomy in BRCA1/2 carriers
• Thyroidectomy in MEN2/familial medullary thyroid carcinoma (RET mutation)

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9. RADIOTHERAPY

Mechanism

• Ionising radiation causes double-strand DNA breaks → cell death (primarily in S/G2 phase)
• Fractionation: dividing total dose into multiple fractions allows normal tissue recovery between fractions while maintaining tumour cell kill

Types

Dose

• Curative (bulky disease): ~70 Gy
• Adjuvant (microscopic residual): ~50 Gy
• Palliative: ~30 Gy (in fewer fractions)

Key Clinical Points

• Cancer sensitivity to RT varies widely
• Late effects can take >20 years to manifest — dissociated from acute effects
• PET used in radiotherapy planning to define nodal disease

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10. ANTI-CANCER DRUGS (SYSTEMIC THERAPY)

Classes

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11. MOLECULAR & GENOMIC ONCOLOGY

Key Concepts

• Tumour mutation burden (TMB): total number of mutations per megabase; high TMB → better response to immunotherapy
• Mismatch repair (MMR) deficiency / MSI-H: Lynch syndrome marker; responds to PD-1 inhibitors
• Liquid biopsy: circulating tumour DNA (ctDNA) in plasma — used for early detection, monitoring, resistance profiling

Immunohistochemistry (IHC)

• Used to identify cell lineage, differentiation, and targetable markers
• E.g. ER/PR/HER2 in breast cancer; CD20 in B-cell lymphoma; EGFR in lung; PD-L1 expression

Examples of Molecular Profiles

Cancer Precision Medicine

• Molecular profiling enables tailored therapy
• Next-generation sequencing (NGS) of tumour tissue identifies actionable mutations
• "Basket trials" treat tumours by molecular signature rather than anatomical site

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12. PAEDIATRIC SURGICAL ONCOLOGY (Summary)

• Paediatric tumours differ biologically from adult cancers
• Common paediatric solid tumours: Wilms' tumour (nephroblastoma), neuroblastoma, hepatoblastoma, medulloblastoma, rhabdomyosarcoma, Ewing sarcoma
• Multimodal therapy (surgery + chemo ± RT) is the norm
• Chemotherapy often more effective in paediatric tumours → less radical surgery possible

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13. KEY SUMMARY BOXES

Summary Box 12.1 — Features of Malignant Transformation

• Establish autonomous lineage
• Resist signals that inhibit growth
• Sustain proliferative signalling
• Obtain replicative immortality
• Evade apoptosis
• Acquire angiogenic competence
• Acquire ability to invade, disseminate, and implant
• Evocation of inflammation
• Evade detection/elimination
• Loss of specialist cell function
• Develop ability to change energy metabolism

Summary Box — Principles of Cancer Surgery

• Curative intent requires R0 resection
• En bloc resection — avoid tumour fragmentation
• Adequate lymph node sampling for staging accuracy
• Margin assessment — intraoperative frozen section when needed
• Reconstructive planning prior to ablative surgery
• Prophylactic surgery in high-risk genetic syndromes
• Minimally invasive approaches (laparoscopic/robotic) do not compromise oncological outcomes in appropriate tumours

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14. INHERITED CANCER SYNDROMES (TABLE 12.1)

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15. ENVIRONMENTAL CAUSES OF CANCER (TABLE 12.2)

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Source: Bailey & Love's Short Practice of Surgery, 28th Edition — Chapters 11 & 12 (Surgical Oncology), pp. 219–240+