Surgery chapters
Principles of surgical oncology, diagnostic imaging and tissue/molecular diagnosis
How cancers arise and spread, screening and its biases, grading and TNM staging, the roles of surgery, radiotherapy and chemotherapy, the main imaging methods with their radiation doses, and how tissue is sampled and tested.
- Cancer is graded by how abnormal the cells look and staged by how far it has spread (TNM); staging decides between local treatment (surgery, radiotherapy) and systemic treatment.
- Screening must cut disease-specific mortality; better survival in screen-detected cases may be false because of lead-time, length and selection bias.
- A CT abdomen and pelvis gives roughly the dose of 500 chest X-rays; frozen section gives a rapid answer in theatre, and molecular tests such as HER2 and KRAS now choose targeted drugs.
On this page
Overview
Surgery remains the main curative treatment for most solid tumours, but it works best inside a multidisciplinary team (MDT) with radiologists, pathologists and oncologists. The surgeon needs to know how cancers grow and spread, how they are found and staged, which imaging test to request, and what the pathologist can do with the tissue sent.
Cancer biology in brief
- Cancer cells acquire hallmarks: self-sufficient growth signals, resistance to growth inhibitors, evasion of apoptosis, unlimited replication (telomerase), angiogenesis, invasion and metastasis, altered energy metabolism and escape from immune attack.
- Gompertzian growth: most growth happens before the tumour can be felt or seen. By diagnosis, cells may already have spread, so cancer is often a systemic disease at presentation.
- Seed and soil (Paget): metastases grow only where the "soil" of a distant organ suits the tumour cells.
Inherited cancer syndromes
| Syndrome | Gene | Main tumours | Prevention |
|---|---|---|---|
| FAP | APC | Large bowel cancer (often before 25), duodenal/ampullary, thyroid, desmoids | Prophylactic proctocolectomy |
| Lynch (HNPCC) | Mismatch repair (MLH1, MSH2, MSH6) | Large bowel (40s–50s), endometrial | Colonoscopic surveillance |
| MEN 2A / 2B | RET | Medullary thyroid cancer, phaeochromocytoma | Prophylactic thyroidectomy |
| MEN 1 | Menin | Parathyroid, pancreatic islet, pituitary | Surveillance |
| Li–Fraumeni | p53 | Sarcomas, breast, brain, leukaemia, adrenal | Difficult |
| Familial breast/ovary | BRCA1, BRCA2 | Breast, ovary, prostate | Screening; risk-reducing surgery |
| Peutz–Jeghers | STK11 | Hamartomatous polyps, bowel and breast cancer; lip freckles | Surveillance |
All of these are autosomal dominant.
Environmental causes: tobacco (lung, head and neck, bladder), alcohol (head and neck, oesophagus, liver), HPV (cervix, anus, oropharynx), hepatitis B and C (liver), H. pylori (stomach), EBV (lymphoma, nasopharynx), HIV (Kaposi sarcoma).
Screening
Screening looks for disease in people without symptoms so it can be treated earlier.
| Requirement | Examples |
|---|---|
| The disease | Important and common; recognisable early stage; early treatment better than late |
| The test | Sensitive and specific, safe, cheap and acceptable |
| The programme | Facilities to investigate positives and treat; repeated at intervals; benefit outweighs harm |
Screening biases
| Bias | What happens |
|---|---|
| Lead-time bias | Diagnosis is simply moved earlier, so survival from diagnosis looks longer even if death occurs at the same time |
| Length bias | Slow-growing tumours spend longer in the detectable phase and are picked up more; fast ones appear between rounds |
| Selection bias | People who accept screening are usually healthier than those who refuse |
The only proof that screening works is a fall in disease-specific mortality in the whole population offered screening (randomised comparison), shown for breast and bowel cancer.
Diagnosis, grading and staging
- Tissue diagnosis is almost always needed before major cancer surgery; the wrong operation, however well done, is useless.
- Grade = degree of differentiation (G1 well, G2 moderate, G3 poor). Prostate uses the Gleason score (sum of the two commonest patterns, 2–10; higher = worse).
- Stage = extent of spread, using the TNM system of the UICC (T = primary tumour, N = regional nodes, M = distant metastases), grouped into stages I–IV. Older systems such as Dukes for large bowel cancer map onto TNM.
Grade is about the cells; stage is about the spread. Stage is usually the stronger predictor of outcome.
Stage shift (Will Rogers phenomenon)
Better staging tests find small hidden metastases. Patients move up a stage: the lower stage loses its worst cases and the higher stage gains relatively fit ones. Survival improves in every stage, yet overall survival is unchanged. Always check the pooled result.
Roles of surgery in cancer
| Role | Examples |
|---|---|
| Diagnosis and staging | Biopsy, orchidectomy for testicular tumour, node biopsy for lymphoma, staging laparoscopy (oesophageal, gastric, pancreatic) to find peritoneal deposits and small liver metastases, sentinel node biopsy |
| Removal of the primary | Radical excision with a clear margin and the regional nodes; handle the tumour gently to avoid spillage |
| Removal of metastases | Liver metastases from large bowel cancer (long-term survival in about one-third after complete resection); isolated lung metastases (e.g. renal cancer) |
| Palliation | Bypass for obstruction (ileotransverse anastomosis, biliary bypass), removal of a bleeding primary |
| Prevention | Proctocolectomy in FAP, thyroidectomy in RET carriers, risk-reducing mastectomy in BRCA carriers |
| Reconstruction | Breast reconstruction, flaps |
Sentinel lymph node biopsy
The sentinel node is the first node that drains the tumour. A radiolabelled colloid (often with blue dye) is injected near the primary; a gamma probe or camera finds the "hot" node, which is removed and examined. A negative sentinel node avoids a full nodal clearance. Used in breast cancer and melanoma.
Very radical surgery does not prevent distant metastases (shown by studies of radical versus simpler mastectomy); what matters is clear margins and good local control.
Non-surgical treatment
Radiotherapy
Dose is measured in grays (Gy) and given in small daily fractions so normal tissue can recover.
| The five Rs | Meaning |
|---|---|
| Repair | Normal cells repair damage between fractions (repair half-time a few hours) |
| Reoxygenation | Hypoxic cells resist radiation; as cells die, survivors get more oxygen and become sensitive |
| Repopulation | Surviving tumour cells speed up division, so overall treatment time should be short |
| Redistribution | Cells are most sensitive in late G2 and M phase |
| Radiosensitivity | Tumours differ in intrinsic sensitivity |
Chemotherapy and targeted therapy
- Combination chemotherapy: use effective drugs with different actions and non-overlapping toxicities; radiotherapy reaches "sanctuary" sites such as the brain and testis (spatial cooperation).
- Neoadjuvant treatment is given before surgery to shrink the tumour; adjuvant treatment is given after surgery to kill micrometastases.
- Some cancers are curable without surgery: leukaemia, lymphoma, small cell lung cancer, Wilms tumour and rhabdomyosarcoma (chemotherapy), early laryngeal cancer (radiotherapy).
Tumour markers
Markers are best for monitoring treatment and detecting recurrence, not for screening (they lack specificity).
| Marker | Main use |
|---|---|
| CEA | Large bowel cancer follow-up; also raised in medullary thyroid cancer and mucinous cysts |
| CA 19-9 | Pancreatic cancer, cholangiocarcinoma |
| CA-125 | Epithelial ovarian cancer (non-specific) |
| AFP | Hepatocellular carcinoma; non-seminomatous germ cell tumours |
| hCG | Germ cell tumours, choriocarcinoma |
| PSA | Prostate cancer |
| Thyroglobulin | Follow-up of differentiated thyroid cancer after total thyroidectomy |
| Calcitonin | Medullary thyroid cancer |
Palliative care (symptom control, the WHO analgesic ladder, psychological and family support) runs alongside active treatment, not just at the end.
Diagnostic imaging
Radiation safety
Request imaging only if the result will change management, and avoid repeating tests. Use ultrasound or MRI where possible, especially in children and women who may be pregnant. Staff using an image intensifier wear lead aprons, thyroid shields and dose badges.
| Examination | Typical dose (mSv) | Equivalent chest X-rays |
|---|---|---|
| Chest X-ray (PA) | 0.02 | 1 |
| Abdominal X-ray | 1.0 | 50 |
| CT head | 2.3 | 115 |
| Bone scan | 4 | 200 |
| CT chest | 8 | 400 |
| CT abdomen or pelvis | 10 | 500 |
Average natural background radiation in the UK is about 2.2 mSv per year.
CT chest 8 mSv ÷ chest X-ray 0.02 mSv = 400 films
CT abdomen 10 mSv ÷ 0.02 mSv = 500 films
Comparing the modalities
| Modality | Strengths | Weaknesses |
|---|---|---|
| Ultrasound | No radiation, cheap, bedside, dynamic; first-line for liver, gallbladder, kidney; best to tell solid from cystic; Doppler for flow; guides biopsy and drainage | Operator dependent; poor through gas and bone; hard to review later |
| CT | Fast; whole abdomen and chest; excellent for liver, pancreas, kidney, bowel and trauma; 3D reconstruction; CT angiography; guides drainage | High radiation dose; iodinated contrast risks; must lie flat |
| MRI | No ionising radiation; best soft-tissue contrast; best for brain, spine, bone marrow, joints, rectal and pelvic cancer staging; MRCP | Slow; motion artefact; claustrophobia; expensive |
| Nuclear medicine | Shows function; whole body; bone scan very sensitive for metastases | Poor spatial resolution; often non-specific |
| PET-CT | FDG (a glucose analogue) uptake shows active tumour; combines function with CT anatomy; staging and recurrence | Cost; false positives in inflammation |
MRI signals and safety
- T1-weighted: fat, methaemoglobin and mucin are bright; good for anatomy.
- T2-weighted: water (and so most disease: oedema, inflammation, tumour) is bright.
- Cortical bone, air and metal are dark on all sequences.
- Absolute contraindications: cardiac pacemakers/defibrillators (unless MRI-safe), metallic foreign body in the eye, cochlear implants, some intracranial aneurysm clips.
- Relative: first trimester of pregnancy, claustrophobia. Joint replacements are usually safe.
Contrast media
- Iodinated contrast (CT): nephrotoxic when renal function is poor. Check creatinine in diabetics and renal patients, hydrate, use the lowest dose of low-osmolar contrast. Discuss stopping metformin if eGFR is below 60. Observe for about 30 minutes for reactions.
- Gadolinium (MRI): allergy is rare, but in severe renal failure it can cause nephrogenic systemic fibrosis.
Tissue and molecular diagnosis
Types of sample
| Sample | Notes |
|---|---|
| Histology (biopsy: punch, core, mucosal, excision; resection) | Fixed in 10% formalin; shows architecture and invasion; gives grade, margins, nodes and vascular invasion |
| Cytology (FNA, washings, brushings, smears) | Quick, cheap, less invasive, can sample a wide area; cannot show architecture or invasion |
| Fresh tissue | Sent without fixative for frozen section, microbiology or molecular studies |
FNA cytology cannot distinguish follicular adenoma from follicular carcinoma of the thyroid, because that depends on capsular and vascular invasion, which needs histology.
Frozen section
A fresh sample is frozen, cut and stained within minutes while the patient is still on the table.
- Uses: confirm a diagnosis before radical surgery, check margins, confirm that the tissue removed is (for example) parathyroid.
- Drawbacks: poorer quality slides, small samples only, fat is hard to cut, infection risk from fresh tissue, and it is labour intensive.
Why samples fail
Wrong site sampled, too little tissue, necrotic centre, biopsy too superficial, crush or cautery artefact, or samples mixed up or contaminated.
Features of malignancy on histology
Metastasis (definitive), invasion (of surrounding tissue, vessels, nerves), loss of normal architecture, necrosis, many and atypical mitoses, and nuclear changes: pleomorphism, enlargement, hyperchromasia, raised nuclear–cytoplasmic ratio, prominent nucleoli.
Further tests
| Special stain | Shows |
|---|---|
| PAS | Glycogen, fungi (diastase-PAS: mucin) |
| Perls Prussian blue | Iron |
| Congo red | Amyloid |
| Ziehl–Neelsen | Acid-fast bacilli (mycobacteria) |
| Van Gieson; reticulin | Collagen; reticulin fibres |
| Immunohistochemistry marker | Points to |
|---|---|
| Cytokeratins | Carcinoma (epithelial) |
| CD45 (CD20 B cell, CD3 T cell) | Lymphoma |
| S100, HMB45, Melan A | Melanoma |
| Synaptophysin, chromogranin | Neuroendocrine tumour |
| CD117 (KIT), DOG-1 | GIST |
| TTF-1 | Lung (and thyroid) |
| PSA; thyroglobulin | Prostate; thyroid |
| CK20, CDX2 | Large bowel |
Molecular pathology
Techniques: FISH (gene amplification, translocations), PCR and sequencing.
| Test | Clinical use |
|---|---|
| HER2 (IHC, then FISH if equivocal) | Breast and gastric cancer → trastuzumab if over-expressed |
| KRAS/NRAS | Metastatic large bowel cancer: mutation predicts no benefit from cetuximab/panitumumab (anti-EGFR) |
| EGFR mutation; ALK rearrangement | Lung cancer → gefitinib; crizotinib |
| BRAF V600E | Melanoma → vemurafenib |
| KIT / PDGFRA | GIST diagnosis; response to imatinib |
| Mismatch repair loss (IHC) / microsatellite instability | Screens for Lynch syndrome; predicts better prognosis in large bowel cancer |
| Clonal gene rearrangement | Favours lymphoma over reactive lymphoid tissue |
Using a tumour's molecular profile to choose a drug is called theranostics or precision medicine.
Expect: screening criteria and lead-time/length bias, grade versus stage, TNM and stage migration, roles of surgery including prophylactic operations and resecting large bowel liver metastases, sentinel node biopsy, the five Rs of radiotherapy and hypoxic radioresistance, neoadjuvant versus adjuvant, tumour markers, radiation dose of CT in chest X-ray equivalents, ultrasound for cystic versus solid, MRI T1/T2 and contraindications, contrast nephropathy and gadolinium, frozen section pros and cons, FNA limits, special stains, IHC markers and HER2/KRAS testing.
Quick revision
- Grade = differentiation; stage = spread (TNM); stage matters more.
- Screening proof = lower disease-specific mortality; beware lead-time and length bias.
- Sentinel node = first draining node; breast and melanoma.
- Prophylactic surgery: FAP (colectomy), RET (thyroidectomy), BRCA (mastectomy).
- Hypoxia makes tumours radioresistant; fractionation exploits repair and reoxygenation.
- CT chest about 400 and CT abdomen about 500 chest X-rays.
- MRI: water bright on T2; pacemaker and eye metal are contraindications.
- FNA cannot show invasion; frozen section is fast but lower quality.
- HER2 → trastuzumab; KRAS mutant → no anti-EGFR; KIT → imatinib.
Written by The House Job from standard references (Bailey & Love).
FAQ
What is lead-time bias?
Finding a cancer earlier makes survival measured from diagnosis look longer even when the patient dies at the same time as they would have without screening.
Why is a sentinel node biopsy done?
To check the first draining node for tumour; if it is clear, the rest of the nodal basin is very likely clear and a full node dissection can be avoided.
Which test best tells a solid from a cystic lump?
Ultrasound. It is quick, uses no radiation and can also guide aspiration or biopsy.
What are the drawbacks of frozen section?
The slides are of lower quality than routine sections, only small pieces can be handled, fatty tissue is hard to cut, fresh tissue is an infection risk and the process disrupts the laboratory.