Colon Carcinoma

Epidemiology

• Bailey and Love's Short Practice of Surgery, p. 1380
• Grainger & Allison's Diagnostic Radiology, p. 572

Aetiology and Risk Factors

Dietary and Environmental

• High intake of red and processed meat (haem iron, N-nitroso compounds) is the strongest dietary risk factor worldwide
• Low dietary fibre - increases colonic transit time, prolonging mucosal exposure to carcinogens; emerging evidence also implicates the colonic microbiota in inflammation and gene methylation
• Smoking and alcohol increase risk; obesity is an independent risk factor
• Aspirin/NSAIDs (prostaglandin inhibitors) have substantial epidemiological evidence for protection against CRC
• High magnesium and calcium intake may be protective

Hereditary Risk Factors (~10% of cases)

• Familial Adenomatous Polyposis (FAP): Hundreds to thousands of adenomatous polyps develop; CRC is virtually inevitable without intervention. The accompanying congenital hypertrophy of the retinal pigment epithelium (CHRPE) helps identify at-risk family members. Prophylactic colectomy is advocated.
• Lynch Syndrome (Hereditary Non-Polyposis CRC, HNPCC): Defective DNA mismatch repair genes (MLH1, MSH2, etc.). Associated with right-sided tumours showing microsatellite instability (MSI). Distinguished from sporadic MSI by absence of BRAF V600E mutation.
• Family history: A first-degree relative with CRC before age 50 suggests a familial syndrome.

Chronic Inflammatory Bowel Disease

• Pye's Surgical Handicraft, p. 275
• Bailey and Love's, p. 1380

Pathogenesis: The Adenoma-Carcinoma Sequence

Consensus Molecular Subtypes (CMS)

• CMS1: MSI, right-sided, hypermethylated (Lynch/sporadic)
• CMS2: WNT and MYC signalling activation
• CMS3: Metabolic dysregulation
• CMS4: TGF-beta activation

Evidence for the adenoma-carcinoma sequence:

• Distribution of adenomas mirrors that of cancers (~70% left-sided)
• Larger adenomas are more likely to be dysplastic
• Adenomas found in 1/3 of specimens resected for CRC
• Colonoscopy screening with polypectomy reduces CRC incidence
• Henry's Clinical Diagnosis and Management by Laboratory Methods, p. 1836-1837
• Bailey and Love's, p. 1380

Distribution

• 50-55% of tumours arise in the sigmoid colon and rectum
• The rectum alone accounts for approximately one-third of cases
• Approximately two-thirds of colorectal cancers arise in the colon

Clinical Presentation

• Bailey and Love's, p. 1381

Colonoscopic Appearance

Investigation

Screening

• UK: Faecal Immunochemical Test (FIT) every 2 years for ages 60-74, followed by colonoscopy if positive. Replaced the older guaiac-based FOBT (which showed 15-20% reduction in CRC mortality).
• USA (Goldman-Cecil / USPSTF): Routine screening for adults aged 45-75; options include annual high-sensitivity FOBT/FIT, multitargeted stool DNA (every 1-3 years), CT colonography (every 5 years), or colonoscopy (every 10 years).

Endoscopy

• Flexible sigmoidoscopy: Rapid, no sedation needed; detects up to 70% of cancers; cannot visualise proximal colon. Finding left-sided polyps mandates completion colonoscopy.
• Colonoscopy: Gold standard - provides histological diagnosis AND detects synchronous lesions. Risk of perforation: 1:1000.

Radiology

• CT colonography (virtual colonoscopy): Equivalent sensitivity to colonoscopy for detecting CRC; picks up polyps ≥6 mm. Less invasive but cannot provide biopsy.
• CT chest/abdomen/pelvis: Standard staging for systemic disease. Colon cancer staging.
• MRI pelvis: Essential for local staging in rectal cancer; increasingly being evaluated for locally advanced colon cancer.

CT Staging Image

Staging

TNM System (8th Edition - International Standard)

Dukes' Staging (Simplified, Widely Used)

• A: Invasion into but not breaching muscularis propria
• B: Breaching muscularis propria, no lymph node involvement
• C: Lymph node metastases present
• D: Distant metastases (not originally described by Dukes himself)

Prognostic Factors

• Degree of cellular differentiation (grade)
• Lymphovascular invasion
• Preoperative CEA elevation
• Microsatellite instability status
• Amount of lymphocyte infiltration
• Extent of fibrotic stromal reaction (greater fibrosis = worse outlook)
• Grainger & Allison's, p. 573; Pye's Surgical Handicraft, p. 275; Bailey and Love's, p. 1381

Molecular Biomarkers for Treatment Planning

• Henry's Clinical Diagnosis and Management, p. 1837-1839

Surgical Treatment

Surgical Principles

• Resection of the segment of colon bearing the tumour with its draining locoregional lymph nodes
• Extent of resection governed by the anatomy of the blood supply
• Complete mesocolic excision (CME): Dissection along embryological planes to maximise lymph node harvest - analogous to TME in rectal cancer
• Primary anastomosis where possible; defunctioning stoma if healing is uncertain
• Stapling and hand-suturing techniques have comparable anastomotic leak rates

Specific Operations by Tumour Location

Laparoscopic vs Open Surgery

Liver Metastases

Enhanced Recovery After Surgery (ERAS)

• Bailey and Love's, p. 1382-1384; Pye's Surgical Handicraft, p. 275

Adjuvant and Palliative Therapy

Adjuvant Chemotherapy

• Stage III (Dukes' C): FOLFOX (5-fluorouracil + leucovorin + oxaliplatin) or CAPOX (capecitabine + oxaliplatin) are standard adjuvant regimens
• Stage II: Adjuvant chemotherapy is generally reserved for high-risk features (T4, perineural invasion, obstruction/perforation, <12 lymph nodes examined, poorly differentiated histology)

Metastatic/Palliative (Stage IV)

• Backbone: 5-FU-based regimens (FOLFOX, FOLFIRI)
• Add bevacizumab (anti-VEGF) for KRAS/NRAS/BRAF wild-type
• Add cetuximab or panitumumab (anti-EGFR) only for RAS/BRAF wild-type tumours
• BRAF V600E mutated tumours: targeted therapy with BRAF inhibitor + MEK inhibitor combinations (e.g. encorafenib + binimetinib + cetuximab) now show efficacy per recent network meta-analysis (PMID: 41355781)
• MSI-H/dMMR tumours: pembrolizumab (immune checkpoint inhibitor) is first-line in metastatic setting
• Colonic stenting for obstructing tumours as a bridge to surgery or palliation

Radiotherapy

• More commonly used in rectal cancer due to the pelvic position
• Preoperative chemoradiotherapy reduces local recurrence in stage II-III rectal cancer
• Limited role in colon cancer (mobile, not pelvic-fixed)

Surveillance After Curative Resection

• CEA monitoring every 3-6 months for the first 3 years
• CT chest/abdomen/pelvis annually for 3-5 years
• Colonoscopy at 1 year post-resection, then every 3-5 years to detect metachronous lesions

Key Recent Evidence

CEAP Classification of Chronic Venous Disorders

C - Clinical | E - Etiologic | A - Anatomic | P - Pathophysiologic

C - Clinical Classification

• S (symptomatic): aches, pain, tightness, skin irritation, heaviness, muscle cramps
• A (asymptomatic)

Key additions in the 2020 revision:

• C2r and C6r - explicit recognition of recurrent disease
• C4c (corona phlebectatica) - fan-shaped telangiectasias around the medial/lateral ankle, representing a marker of advanced disease

Example: A symptomatic patient with stasis dermatitis = C4aS

Clinical image of C6 (active venous ulcer):

E - Etiologic Classification

Secondary causes include:

• Intravenous: post-thrombotic syndrome, prior DVT
• Extravenous: extrinsic compression syndromes - May-Thurner syndrome (left common iliac vein compressed by right iliac artery), Nutcracker syndrome (left renal vein compression), trauma, muscle pump dysfunction

A - Anatomic Classification

P - Pathophysiologic Classification

• Skin manifestations are uncommon with AVP <35 mmHg
• Skin manifestations are almost certain with AVP >90 mmHg

How to Write a Complete CEAP Description

Relationship to Other Scoring Systems

• Venous Clinical Severity Score (VCSS): Assesses severity of individual signs and symptoms on a 0-3 scale across 10 domains (pain, varicose veins, oedema, pigmentation, inflammation, induration, ulcers, etc.); useful for longitudinal outcomes research
• Venous Segmental Disease Score (VSDS): Quantifies anatomic extent
• Quality of Life (QoL) instruments: CIVIQ, VEINES-QOL

CEAP is the correct diagnostic label; VCSS and QoL scores are the correct instruments for tracking treatment outcomes over time.

Diagnostic Investigation

• Detects venous obstruction (absence of flow, echogenic thrombus, non-compressibility)
• Detects venous reflux (prolonged reversal of flow on Valsalva or compression-release manoeuvre)
• Establishes the E, A, and P descriptors

Clinical Application and Treatment by CEAP Stage

Benign Breast Disease (BBD)

Nomenclature and Concept

ANDI - Aberrations of Normal Development and Involution

• Bailey and Love's Short Practice of Surgery 28th Ed., p. 940
• Schwartz's Principles of Surgery 11th Ed.

ANDI Classification

• Schwartz's Principles of Surgery, Table 17-2

Pathological Classification (Page's System) and Cancer Risk

Group 1 - Nonproliferative Lesions (No increased cancer risk)

• Cysts (micro and macro) and apocrine metaplasia
• Duct ectasia
• Mild ductal epithelial hyperplasia (<4 cell layers, not crossing the lumen)
• Calcifications (epithelial-related)
• Simple fibroadenoma
• Mastitis, fibrosis, squamous/apocrine metaplasia
• Columnar cell lesions, fat necrosis

Group 2 - Proliferative Lesions Without Atypia (RR 1.5-2.0×)

• Moderate/florid ductal hyperplasia (>4 cell layers, crosses lumen, RR 1.8)
• Sclerosing adenosis (RR 1.7-2.1)
• Radial scar (RR 1.8; upstaging rate 3-40% - requires biopsy)
• Complex sclerosing lesion (RR 2.6; surgical excision recommended)
• Intraductal papilloma - solitary (RR 2.1); peripheral papillomatosis (RR 3.0-3.5)
• Complex fibroadenoma (RR 1.2-2.2)

Group 3 - Proliferative Lesions With Atypia (RR 4-5×)

• Atypical Ductal Hyperplasia (ADH) - RR 4-fold; if extensive (>2 ducts or >2 mm): RR 7-fold
• Atypical Lobular Hyperplasia (ALH) - RR 4-fold
• LCIS - RR 10-fold (marker lesion, not a direct precursor)
• DCIS - RR 10-fold (true precursor, requires treatment)

Key distinction: ADH is defined as features of low-grade DCIS involving fewer than two ducts or measuring <2 mm. When two or more ducts are involved or the lesion exceeds 2 mm, the lesion is reclassified as DCIS.

Cancer Risk Table (Dupont & Page, NEJM 1985)

Histology of Fibrocystic Changes

Individual Conditions

1. Mastalgia (Breast Pain)

• Affects 50-70% of women presenting to a breast clinic
• Classified as:

• Begins around day 14, peaks at days 27-28, relieved by menses
• Both breasts involved; upper outer quadrant predominance
• Severity measured on Visual Analogue Scale (VAS 0-10)
• Severe forms disrupt sleep and daily activities

• No relation to menstrual cycle; may be unilateral, localised
• Often associated with duct ectasia or periductal mastitis
• Must exclude referred pain: musculoskeletal (Tietze syndrome), cervical spondylosis, oesophageal reflux, cardiac pain

2. Fibroadenoma

• Most common discrete breast lump in women under 30; peak incidence 15-25 years
• Arises from aberrant lobular development; oestrogen-dependent
• Clinical features: smooth, firm, rubbery, highly mobile ("breast mouse"), well-circumscribed, non-tender
• Histology: biphasic tumour - epithelial (glandular) and stromal (fibrous) components; two patterns:
  • Intracanalicular: stroma compresses ducts into slits
  • Pericanalicular: stroma surrounds open, round ducts
• Giant fibroadenoma: >5 cm; common in adolescents and in African women
• Risk: simple fibroadenoma carries no significant increased cancer risk; complex fibroadenoma RR 1.2-2.2×

• Young women (<25 yrs): ultrasound + reassurance if confident diagnosis; biopsy may not be needed if ultrasound features pathognomonic
• Core-needle biopsy for confirmation in older women
• Options: observation (many regress spontaneously, especially <2 cm), cryoablation, ultrasound-guided vacuum-assisted biopsy, or surgical excision
• Lesions >3 cm are generally best excised

3. Breast Cysts

• Most common nonproliferative breast lesion; peak incidence 35-50 years
• Arise from TDLU when fluid accumulates due to distension and obstruction of efferent ductule
• Three types on ultrasound:
  • Simple: anechoic, well-circumscribed, posterior acoustic enhancement - no malignant potential
  • Complicated: homogeneous internal echoes, no solid component
  • Complex: solid component or thick internal septations - may harbour malignancy; requires biopsy

• Fine-needle aspiration (21G needle, 10 mL syringe): typical cyst volume 5-75 mL
• If fluid is non-bloodstained and no residual mass: discard fluid (cytology not cost-effective)
• If fluid is bloodstained or residual mass remains: send for cytology; core biopsy; pneumocystogram may help assess cyst wall
• Aspiration now usually performed under ultrasound guidance

4. Sclerosing Adenosis

• Disorder of both proliferative and involutional phases
• Mimics carcinoma on clinical examination, mammography, and gross pathology
• Histologically: distorted, compressed lobular units with increased acini and dense fibrous stroma
• No increased cancer risk per Schwartz; RR 1.7-2.1 per Fischer's
• Management: excisional biopsy often necessary to exclude carcinoma

5. Duct Ectasia and Periductal Mastitis

• Duct ectasia: dilatation of the major subareolar ducts with periductal fibrosis; common in women >50 years; may cause thick, green/brown nipple discharge, nipple retraction
• Periductal mastitis: inflammation around ducts; associated with smoking (nicotine damages subareolar duct epithelium); more common in younger women
• May present as: subareolar mass/abscess, nipple discharge, nipple retraction, mammary duct fistula
• Periductal mastitis is not a puerperal (lactational) abscess - it occurs in non-lactating women and is more prone to recurrence and fistula formation

• Antibiotics covering anaerobes (polymicrobial); combination therapy
• Ultrasound-guided aspiration of abscess if present
• Surgery: for recurrent/non-resolving cases; total duct excision (Hadfield's procedure) is definitive; duct fistula requires fistulotomy or excision of fistulous tract

6. Intraductal Papilloma

• Benign papillary growth within a lactiferous duct; composed of fibrovascular core with epithelial and myoepithelial lining
• Solitary papilloma: usually in a major subareolar duct; presents with serosanguineous or bloodstained nipple discharge from a single duct orifice; RR 1.5-2.0 (some sources: 2.1)
• Papillomatosis: 5+ papillomas in multiple peripheral ducts; bilateral distribution; RR 3.0-3.5; surgical excision recommended
• Juvenile papillomatosis ("Swiss cheese disease"): multiple firm palpable nodules in young women; contains papillomas, apocrine cysts, ductal hyperplasia; positive family history of breast cancer increases lifetime cancer risk
• Management: microdochectomy (excision of the involved duct) for solitary papilloma; total duct excision for papillomatosis or multiple duct involvement

7. Radial Scar / Complex Sclerosing Lesion

• Radial scar: stellate lesion with a fibroelastic core and entrapped ducts/lobules; mimics carcinoma on mammography (spiculated mass)
• RR 1.8; upstaging to cancer on excision: 3-40%
• Complex sclerosing lesion (>1 cm): RR 2.6; surgical excision recommended
• Management: vacuum-assisted core biopsy or open surgical excision

8. Phyllodes Tumour

• Rare fibroepithelial tumour similar to fibroadenoma but with more cellular stroma
• Spectrum: benign - borderline - malignant
• Distinguished from fibroadenoma by stromal hypercellularity, mitotic activity, and leaf-like architecture on histology
• Benign phyllodes: no increased cancer risk but wide local excision is required (clear margins) due to risk of local recurrence; not amenable to observation alone

Risk Stratification and Surveillance Summary (Fischer's Mastery of Surgery)

Triple Assessment

1. Clinical examination - character of lump, axillary nodes, skin changes
2. Imaging - ultrasound (preferred <35 yrs); mammography (preferred ≥35 yrs); MRI for high-risk women
3. Pathology - fine-needle aspiration cytology (FNAC) or core-needle biopsy (CNB) - CNB preferred as it gives histological architecture and receptor status