CA Colon
Colorectal carcinoma is a malignant neoplasm arising from the epithelial lining of the colon or rectum, most commonly as an adenocarcinoma developing through the adenoma-carcinoma sequence.
| Exam domain | One-glance essentials |
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| Epidemiology / risks |
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| Core mechanism |
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| Clinical picture |
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| Investigations |
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References
[1] Lecture slides: Clinical presentation, diagnosis and screening of colorectal cancer_rev1.pdf (clinical presentation, diagnosis, staging and screening sections) [2] Lecture slides: Molecular pathways, route of spread and staging.pdf (adenoma–carcinoma sequence, MSI pathway, spread and TNM staging) [3] Lecture slides: CMB31 Part1 - Systemic therapy in Advanced colorectal cancer - Epidemiology and Therapeutic Targets of Advanced Colorectal Cancer (Professer Thomas Yau) rev3 20250911.pdf (molecular targets and tumour sidedness) [4] Lecture slides: CMB31 Part2 - Systemic therapy in Advanced colorectal cancer - Treatment Options in mCRC (Professer Thomas Yau) rev3 20250911.pdf (systemic therapy by biomarker) [5] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf (large-bowel obstruction and CRC presentation) [6] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer, pp. 102–108) [7] Lecture slides: Professor Chiang Chi Leung - Neoadjuvant and Adjuvant Therapy in Colorectal Cancer_rev2.pdf (rectal neoadjuvant/adjuvant therapy)
CA Colon (Colorectal Cancer)
Colorectal cancer (CRC) refers to malignant neoplasms arising from the epithelial lining (mucosa) of the colon and rectum. The vast majority (~95%) are adenocarcinomas — cancers originating from glandular epithelial cells that line the colonic crypts [1][2].
- "Colorectal" = "colo" (colon, from Greek kolon = large intestine) + "rectal" (rectum, from Latin rectum = straight [intestine])
- The term "CA Colon" in clinical shorthand typically encompasses both colonic and rectal cancers, though rectal cancer has distinct management nuances (especially regarding neoadjuvant therapy and surgical approach)
Key anatomical definitions [3]:
- Rectum:
- Endoscopic definition: up to 15 cm from the anal verge
- Oncological definition: bowel below the peritoneal reflection
- Right-sided tumour: tumour proximal to (before) splenic flexure
- Left-sided tumour: tumour distal to (after) splenic flexure
This right-vs-left distinction matters enormously because they behave differently in terms of embryology, molecular biology, clinical presentation, and response to targeted therapy.
Why does right vs left matter?
The right colon derives from the midgut (supplied by SMA), while the left colon derives from the hindgut (supplied by IMA). They have different embryological origins, different predominant molecular pathways (right-sided → more MSI-high and BRAF mutations; left-sided → more CIN pathway and EGFR-driven), and different clinical presentations. This has direct therapeutic implications: anti-EGFR therapy (cetuximab/panitumumab) works better in left-sided RAS wild-type tumours [4][5].
2. Epidemiology
Colorectal cancer is the most common cancer overall and in males, and the 2nd most common cancer in females in Hong Kong [2][6].
- Incidence: ~74.1 per 100,000 per year (HK data) [2]
- Mortality: ~28.5 per 100,000 per year (2nd most common cause of cancer death in HK, for both males and females) [2][6]
- Male-to-female ratio: approximately 1.6:1 [2]
In 2021, there were 5,899 new cases of CRC in Hong Kong [6]
Stage at diagnosis [2]:
| Stage | Proportion |
|---|---|
| Stage I | 10.6% |
| Stage II | 22.5% |
| Stage III | 25.5% |
| Stage IV | 24.0% |
High Yield – HK Epidemiology
CRC is the number 1 cancer in Hong Kong by incidence. Nearly a quarter of patients present at Stage IV — hence the push for screening. The 5-year overall survival for Stage IV is dismal (~10-15%), versus > 90% for Stage I. This is why early detection through screening is so critical.
- Rare below age 40; peak incidence at 60-70 years [2]
- Positive family history in 10-15% of cases [2]
- Approximately 25% of CRC patients show non-syndromal familial clustering [2]
- Incidence has been rising in Asia (including HK) over recent decades — attributed to the "Westernisation" of diet and lifestyle
- Rectosigmoid is the most common location [2]
- Usually quoted as ~70% left-sided tumours [2]
- However, right-sided tumours are becoming more common [2] — this is a global trend, especially in older patients and in populations with increasing screening uptake (left-sided lesions are detected and removed earlier via sigmoidoscopy/colonoscopy, leaving a relative increase in right-sided detection)
| Location | Approximate % |
|---|---|
| Rectum | ~30% |
| Sigmoid | ~25% |
| Descending colon | ~5% |
| Transverse colon | ~10% |
| Ascending colon/Caecum | ~25% |
| Other | ~5% |
3. Risk Factors
| Risk Factor | Detail & Mechanism |
|---|---|
| Age > 50 | Accumulation of somatic mutations over time (adenoma-carcinoma sequence takes ~10-15 years). The probability of having accumulated enough "hits" (per Knudson's multi-hit hypothesis) increases with age |
| Male sex | M:F = 1.6:1 in HK [2]. Possibly related to hormonal (oestrogen may be protective), lifestyle and metabolic differences |
| Race | Highest in Blacks [2] (in Western data). In HK, Chinese population has high incidence |
| Familial polyposis syndromes | FAP (APC mutation, autosomal dominant, ~1% of all CRC, virtually 100% risk by age 40 without prophylactic colectomy), MAP (MUTYH-associated polyposis, autosomal recessive), Peutz-Jeghers syndrome (PJS), Juvenile polyposis syndrome (JPS) [2][7] |
| Non-polyposis syndromes | HNPCC / Lynch syndrome (~3-5% of all CRC, autosomal dominant, defective mismatch repair genes — MLH1, MSH2, MSH6, PMS2; Amsterdam criteria / revised Bethesda guidelines for diagnosis) [2][7] |
| Personal history of CRC | Metachronous tumours in 1.5-3% within 5 years post-operatively [2] |
| Personal history of colorectal polyps | Especially large (> 2.5 cm), multiple, villous, or dysplastic adenomatous polyps [2][3] |
| IBD-related colitis | 5-15× risk; after 8-10 years in pancolitis, 15-20 years in left-sided colitis [2][8]. Risk is higher with concurrent primary sclerosing cholangitis [8] |
| Acromegaly | 2-14× risk — IGF-1 acts as a growth factor for colonic mucosal cells [2][3] |
| Prior renal transplant | Likely due to chronic immunosuppression [2] |
| Prior cholecystectomy | 1.16× for right-sided CA [2] — likely due to increased bile acid exposure to right colon |
| Ureterocolic anastomoses | Chemical irritation at anastomotic site [2] |
| Coronary artery disease | Shares similar risk factors (metabolic syndrome) [2] |
| Risk Factor | Detail & Mechanism |
|---|---|
| Diet: red and processed meat, animal fat | Heterocyclic amines and polycyclic aromatic hydrocarbons from cooking; haem iron generates free radicals; N-nitroso compounds from processed meat [1][2] |
| Obesity, DM, and insulin resistance | 1.15-1.23× risk [2]. Hyperinsulinaemia → increased IGF-1 → promotes cell proliferation and inhibits apoptosis in colonocytes |
| Central obesity, sedentary lifestyle [3] | Visceral adiposity → chronic low-grade inflammation (adipokines, TNF-α, IL-6) → promotes carcinogenesis |
| Smoking | 1.18× risk, 1.25× mortality [2]. Polycyclic aromatic hydrocarbons and N-nitrosamines cause DNA damage |
| Alcohol | 1.21-1.52× risk depending on intake [2]. Acetaldehyde (ethanol metabolite) is a direct carcinogen; also depletes folate |
| Androgen deprivation therapy | Mechanism not fully elucidated [2] |
| Protective Factor | Detail & Mechanism |
|---|---|
| High fibre diet | Increases stool bulk → dilutes carcinogens, reduces transit time → less mucosal contact time with carcinogens; also promotes beneficial gut microbiome producing butyrate (anti-proliferative short-chain fatty acid) [2] |
| Dietary folate and vitamin B6 | Essential for DNA synthesis and methylation; deficiency → aberrant DNA methylation and impaired DNA repair [2] |
| Calcium, Vitamin D and dairy products | Calcium binds bile acids and fatty acids in the colon lumen, reducing their proliferative effect on colonocytes; Vitamin D has anti-proliferative and pro-apoptotic effects [2] |
| Aspirin and other NSAIDs | Prolonged aspirin/NSAID use is protective [2][3]. Mechanism: COX-2 inhibition → reduced PGE2 → decreased cell proliferation, increased apoptosis, reduced angiogenesis. COX-2 is overexpressed in ~85% of CRC |
| Physical activity | 0.73-0.74× risk [2]. Reduces insulin resistance, visceral fat, and chronic inflammation |
| Combined HRT | Protective effect (oestrogen may promote apoptosis in colonic epithelium) — but effect disappears after stopping [2] |
| Statins | Protective; may inhibit Ras/Rho prenylation (post-translational modification needed for Ras signalling) [2] |
Exam High Yield – Risk Factors Mnemonic
"FAP-Lynch IBD-Age Diet Smoke" — The big-ticket risk factors to always mention:
- Familial syndromes (FAP, Lynch)
- Age > 50
- Polyps (adenomatous)
- IBD (UC > CD)
- Diet (red meat, low fibre)
- Smoking, sedentary, obesity
4. Anatomy and Function
Understanding the anatomy is essential because it determines blood supply (and hence patterns of metastatic spread), lymphatic drainage (surgical margins), clinical presentation (right vs left), and surgical approach.
The large intestine extends from the ileocaecal valve to the anus (~1.5 m):
| Segment | Length | Blood Supply | Venous Drainage | Lymphatic Drainage |
|---|---|---|---|---|
| Caecum & Appendix | ~6 cm | Ileocolic a. (SMA) | SMV → Portal vein | Ileocolic nodes |
| Ascending colon | ~15 cm | Right colic a. (SMA) | SMV | Paracolic → intermediate → principal (SMA) nodes |
| Hepatic flexure | — | Middle colic a. (SMA) | SMV | Middle colic nodes |
| Transverse colon | ~45 cm | Middle colic a. (SMA) | SMV | Middle colic nodes |
| Splenic flexure | — | Left colic a. (IMA) | IMV → Splenic v. | Left colic nodes |
| Descending colon | ~25 cm | Left colic a. (IMA) | IMV | Left colic nodes |
| Sigmoid colon | ~40 cm | Sigmoid aa. (IMA) | IMV | Sigmoid nodes |
| Rectum | ~12-15 cm | Superior rectal a. (IMA), Middle rectal a. (IIA), Inferior rectal a. (internal pudendal) | Superior rectal v. → IMV → Portal; Middle/Inferior rectal vv. → IVC (systemic) | Pararectal → internal iliac nodes |
Key anatomical points:
- The marginal artery of Drummond connects SMA and IMA territories at the splenic flexure [9]
- Watershed areas (Griffiths' point at splenic flexure, Sudeck's point at rectosigmoid) are vulnerable to ischaemia [9]
- The dual venous drainage of the rectum explains why distal rectal tumours can metastasise directly to the lungs (via IVC) without going through the liver first [3]
- The mesorectum (containing perirectal fat, lymph nodes, and vessels enclosed by the mesorectal fascia) is the basis for total mesorectal excision (TME) in rectal cancer surgery
- Mucosa (epithelium + lamina propria + muscularis mucosae) — where adenomas and carcinomas arise
- Submucosa — contains Meissner's plexus; lymphovascular invasion here signifies T1 disease
- Muscularis propria — inner circular, outer longitudinal (condensed into three taeniae coli in the colon); T2 disease involves this layer
- Subserosa / Adventitia — T3 disease extends through muscularis propria into this layer
- Serosa (visceral peritoneum) — T4a disease penetrates the serosa; retroperitoneal segments (ascending, descending colon, posterior rectum) lack serosa → T4b involves invasion of adjacent structures
- Right colon (caecum to transverse): Main function is water and electrolyte absorption. Content is still liquid here. This is why right-sided tumours do not tend to cause obstruction (liquid stool passes around the tumour easily), but they do bleed insidiously → presents with iron deficiency anaemia
- Left colon (descending to sigmoid): Storage and propulsion of increasingly solid stool. Smaller calibre. This is why left-sided tumours tend to cause obstructive symptoms (change in bowel habit, constipation, intestinal obstruction) and haematochezia (frank blood mixed with stool)
- Rectum: Storage reservoir for stool before defecation. Rectal tumours cause tenesmus (sensation of incomplete evacuation due to tumour mass mimicking the sensation of stool in the rectum), mucus discharge, and haematochezia
5. Etiology and Pathophysiology
The central paradigm of CRC carcinogenesis is that most colorectal cancers arise from pre-existing benign adenomatous polyps through a stepwise accumulation of genetic mutations over approximately 10-15 years. This is the adenoma-carcinoma sequence (Vogelstein model) [1][3][10].
Step-by-step explanation:
-
APC gene mutation (chromosome 5q21) — the "gatekeeper":
- APC normally inhibits the Wnt/β-catenin signalling pathway. When APC is functional, it targets β-catenin for proteasomal degradation
- When APC is lost/mutated → β-catenin accumulates in the cytoplasm → translocates to the nucleus → activates transcription of proliferative genes (c-MYC, cyclin D1) → uncontrolled epithelial proliferation
- This is the initiating event in most sporadic CRC and is mutated in ~80% of sporadic CRCs
- In FAP, this mutation is inherited in the germline (first hit present at birth; only needs a somatic "second hit")
-
KRAS oncogene activation (chromosome 12p12):
- KRAS is a GTPase in the RAS-RAF-MEK-ERK signalling cascade
- Normally, KRAS cycles between active (GTP-bound) and inactive (GDP-bound) states
- Activating mutation → KRAS is constitutively "stuck on" → continuous growth signalling
- Found in ~40-50% of CRC
- KRAS mutation status is critical for treatment decisions — anti-EGFR therapies are ineffective if KRAS is mutated (because the signal is activated downstream of EGFR) [4][5]
-
SMAD4 / DCC loss (chromosome 18q21):
- Loss of TGF-β signalling pathway (which normally promotes growth arrest and apoptosis)
- Loss of DCC (Deleted in Colorectal Cancer) — a tumour suppressor
-
TP53 loss (chromosome 17p13):
- p53 is the "guardian of the genome" — it induces cell cycle arrest, DNA repair, or apoptosis in response to DNA damage
- Loss of p53 → cells with DNA damage continue to proliferate → accumulation of further mutations → malignant transformation
5.2 Two Major Molecular Pathways
- The "traditional" adenoma-carcinoma sequence as described above (Vogelstein model)
- Characterised by aneuploidy (abnormal chromosome numbers) and loss of heterozygosity (LOH) at tumour suppressor loci (APC, TP53, SMAD4)
- Higher risk in large (> 2.5 cm), villous, sessile adenomatous polyps [3]
- Predominantly left-sided tumours
- Tends to have KRAS mutations and be microsatellite stable (MSS)
- Caused by defective DNA mismatch repair (MMR) system [1][7][10]
- MMR genes (MLH1, MSH2, MSH6, PMS2) normally correct errors during DNA replication — specifically insertion-deletion loops at microsatellite repeats (short tandem repeat sequences)
- When MMR is defective → errors accumulate at microsatellites → "microsatellite instability"
- Two mechanisms of MMR deficiency:
- Germline mutation in MMR genes → Lynch syndrome (HNPCC) [7]
- Sporadic epigenetic silencing of MLH1 by promoter hypermethylation (CpG island methylator phenotype, CIMP) → accounts for ~12% of sporadic CRC
- Predominantly right-sided tumours
- Often poorly differentiated, mucinous, with dense lymphocytic infiltration (because the high mutation burden generates neoantigens that attract immune cells)
- Better stage-for-stage prognosis than MSS tumours
- MSI-high tumours respond well to immune checkpoint inhibitors (e.g. pembrolizumab/nivolumab) [4][5] — this is because the high neoantigen load makes them immunogenic
- BRAF V600E mutation is common in sporadic MSI-H tumours (but NOT in Lynch syndrome) — this is a useful distinguishing feature [1][4][5]
High Yield – CIN vs MSI Pathways
| Feature | CIN Pathway (85%) | MSI Pathway (15%) |
|---|---|---|
| Mechanism | Chromosomal instability, LOH, aneuploidy | Defective MMR → microsatellite instability |
| Key mutations | APC → KRAS → SMAD4 → TP53 | MMR genes (MLH1, MSH2, MSH6, PMS2) |
| Precursor | Adenomatous polyps (tubular → villous) | Sessile serrated polyps (sporadic MSI-H) or adenomas (Lynch) |
| Side | Predominantly left-sided | Predominantly right-sided |
| Histology | Moderate differentiation | Poorly differentiated, mucinous, lymphocytic infiltrate |
| Prognosis | Standard | Better stage-for-stage |
| Response to immunotherapy | Poor | Excellent (checkpoint inhibitors) |
| Associated syndrome | FAP (germline APC) | Lynch syndrome (germline MMR) |
A third, increasingly recognised pathway:
- Serrated polyps (hyperplastic polyps → sessile serrated lesions → traditional serrated adenomas) can also progress to carcinoma
- Driven by BRAF V600E mutation and CIMP (CpG island methylator phenotype) → epigenetic silencing of tumour suppressors via promoter methylation
- Predominantly right-sided, flat/sessile lesions that are hard to detect endoscopically
- Accounts for a significant proportion of "interval cancers" (cancers diagnosed between screening colonoscopies) because they are flat and easily missed
5.4 Hereditary CRC Syndromes
- Autosomal dominant; germline mutation in APC gene (chromosome 5q21) [7]
- Hundreds to thousands of adenomatous polyps throughout the colon — classically > 100 polyps
- Virtually 100% lifetime risk of CRC if untreated (average age of cancer development ~39 years)
- Extracolonic manifestations: duodenal adenomas (most common extracolonic malignancy), desmoid tumours, osteomas (mandible), congenital hypertrophy of retinal pigment epithelium (CHRPE), epidermoid cysts, supernumerary teeth
- Gardner syndrome: FAP + osteomas + desmoid tumours + epidermoid cysts
- Turcot syndrome: FAP + CNS tumours (medulloblastoma in FAP variant; glioblastoma in Lynch variant)
- Management: prophylactic colectomy (usually proctocolectomy with ileal pouch-anal anastomosis) recommended by age 20-25, or when polyps become numerous
- Attenuated FAP (AFAP): < 100 polyps, later onset, similar genetics but different mutation location on APC gene
- Autosomal dominant; germline mutations in DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2 [7]
- Most common hereditary CRC syndrome (~3-5% of all CRC)
- Lifetime CRC risk: 40-80% (lower than FAP but still very high)
- Right-sided predominance, younger onset (mean age ~45)
- Associated extracolonic cancers: endometrial (most common, 40-60% lifetime risk), ovarian, gastric, urinary tract (renal pelvis/ureter), small bowel, hepatobiliary, brain (Turcot variant), sebaceous skin tumours (Muir-Torre variant)
- Characterised by MSI-high, better prognosis stage-for-stage, responds to immunotherapy
- Clinically identified using Amsterdam II Criteria (3-2-1 rule):
- 3 or more relatives with Lynch-associated cancer
- 2 or more successive generations affected
- 1 or more diagnosed before age 50
- One should be a first-degree relative of the other two
- FAP should be excluded
All newly diagnosed CRC should undergo universal MMR/MSI testing (by IHC for MMR proteins or PCR for MSI) to screen for Lynch syndrome and guide immunotherapy decisions [4][5][7]
- MUTYH-Associated Polyposis (MAP): autosomal recessive, 10-100 adenomatous polyps, resembles attenuated FAP
- Peutz-Jeghers Syndrome (PJS): autosomal dominant, STK11/LKB1 mutation, hamartomatous polyps + mucocutaneous pigmentation (lips, buccal mucosa, fingers), increased risk of GI and extra-GI cancers
- Juvenile Polyposis Syndrome (JPS): hamartomatous polyps, increased CRC risk
- Serrated Polyposis Syndrome: multiple serrated polyps, increased CRC risk
- UC confers a higher risk of CRC than CD [3][8]
- Risk factors for IBD-associated CRC: duration of disease (> 8-10 years), extent of disease (pancolitis > left-sided colitis), severity of inflammation, concurrent primary sclerosing cholangitis (PSC), family history of CRC, presence of dysplasia [8]
- Mechanism: chronic inflammation → oxidative stress → DNA damage → dysplasia → carcinoma (inflammation-dysplasia-carcinoma sequence, different from the adenoma-carcinoma sequence)
- Surveillance colonoscopy is recommended starting 8-10 years after diagnosis of IBD colitis, with chromoendoscopy and multiple biopsies [8]
6. Classification
- Adenocarcinoma (~95%): the overwhelmingly predominant type
- Well-differentiated, moderately differentiated, poorly differentiated
- Mucinous adenocarcinoma (> 50% of tumour is mucin): associated with MSI-H, younger patients, worse prognosis stage-for-stage in MSS tumours but better in MSI-H
- Signet-ring cell carcinoma (> 50% signet-ring cells): very aggressive, poor prognosis
- Neuroendocrine tumours/carcinomas: rare
- Squamous cell carcinoma: extremely rare in colon (more common at anal canal — different entity)
- Lymphoma, sarcoma (GIST), melanoma: rare
- Polypoid/exophytic (fungating): grows into the lumen; more common in right-sided tumours (caecum and ascending colon have larger calibre, so tumours can grow to a large size before causing symptoms)
- Annular/stenosing (apple-core/napkin-ring): grows circumferentially around the bowel wall, constricting the lumen; more common in left-sided tumours → causes obstructive symptoms
- Ulcerative: crater-like ulceration
- Diffusely infiltrating (linitis plastica-type): rare in colon
TNM staging is the most important prognostic factor and guides treatment decisions [1][10]:
T (Primary Tumour):
| Stage | Description |
|---|---|
| Tis | Carcinoma in situ (intramucosal — confined to mucosa, no invasion through muscularis mucosae) |
| T1 | Invades submucosa |
| T2 | Invades muscularis propria |
| T3 | Invades through muscularis propria into pericolorectal tissues (subserosa/pericolic fat) |
| T4a | Penetrates to the surface of the visceral peritoneum (serosa) |
| T4b | Directly invades or is adherent to other organs or structures |
N (Regional Lymph Nodes):
| Stage | Description |
|---|---|
| N0 | No regional LN metastasis |
| N1a | 1 regional LN |
| N1b | 2-3 regional LNs |
| N1c | Tumour deposits in subserosa, mesentery without regional LN involvement |
| N2a | 4-6 regional LNs |
| N2b | ≥7 regional LNs |
A minimum of 12 lymph nodes must be examined for adequate staging [3][10] — this is a quality indicator for surgical resection.
M (Distant Metastasis):
| Stage | Description |
|---|---|
| M0 | No distant metastasis |
| M1a | Metastasis to one organ/site without peritoneal metastasis |
| M1b | Metastasis to ≥2 organs/sites without peritoneal metastasis |
| M1c | Peritoneal metastasis ± other organ involvement |
Stage Grouping:
| Stage | TNM | 5-Year Survival |
|---|---|---|
| I | T1-2, N0, M0 | > 90% |
| IIA | T3, N0, M0 | ~85% |
| IIB | T4a, N0, M0 | ~72% |
| IIC | T4b, N0, M0 | ~60% |
| IIIA | T1-2, N1/N1c, M0 or T1, N2a, M0 | ~83% |
| IIIB | T3-4a, N1/N1c, M0 or T2-3, N2a, M0 or T1-2, N2b, M0 | ~64% |
| IIIC | T4a, N2a, M0 or T3-4a, N2b, M0 or T4b, N1-2, M0 | ~44% |
| IVA | Any T, Any N, M1a | ~10-15% |
| IVB | Any T, Any N, M1b | ~5% |
| IVC | Any T, Any N, M1c | ~5% |
Still sometimes referenced but largely superseded by TNM:
| Dukes | TNM Equivalent | Description |
|---|---|---|
| A | T1-2, N0 | Confined to bowel wall |
| B | T3-4, N0 | Through bowel wall, no LN |
| C | Any T, N+ | LN involvement |
| D | Any T, Any N, M1 | Distant metastasis |
7. Routes of Spread
Understanding routes of spread is essential for staging, surgical planning, and predicting clinical features [3][10]:
- Tumour grows circumferentially (especially left-sided annular lesions) and radially through the bowel wall layers (T staging)
- In rectal cancer, radial spread is particularly important as it determines the circumferential resection margin (CRM) — a positive CRM (tumour within 1 mm of the resection margin) is a strong predictor of local recurrence [3]
- Can invade adjacent organs: bladder (colovesical fistula → pneumaturia), small bowel, uterus, vagina, ureters, sacrum/coccyx
- Follows the lymph nodes along the supplying arteries (epicolic → paracolic → intermediate → principal/apical nodes)
- Virchow's node (left supraclavicular) = Troisier's sign — indicates advanced intra-abdominal malignancy [3]
- This is why adequate lymph node harvest (≥12) during surgery is critical for accurate staging
- Liver is the most common site of distant metastasis [3] — because the colon drains via the portal venous system to the liver
- Lung is the second most common site [3]
- Distal rectal tumour drains via middle and inferior rectal veins → internal iliac veins → IVC → lungs directly (bypassing the liver) [3]
- Other sites: bone, brain, adrenals
- Tumour cells exfoliate from the serosal surface into the peritoneal cavity
- Ovarian metastasis = Krukenberg tumour [3] (classically bilateral, signet-ring cell)
- Pouch of Douglas deposits (detectable on digital rectal examination as a Blumer's shelf) [3]
- Can cause malignant ascites and peritoneal carcinomatosis
- Shedding of tumour cells can implant at distant mucosal sites (e.g. at anastomotic site after surgery — "implantation metastasis")
- This is why the bowel lumen is irrigated during surgery and why anastomotic recurrence can occur
8. Clinical Features
The clinical presentation of CRC depends on the location (right vs left vs rectal), size of the tumour, stage, and presence of complications (obstruction, perforation, bleeding).
Cardinal Teaching Point
Most commonly asymptomatic — detected by screening [3]. This is why screening programmes are so important. When symptoms appear, the cancer is often at a more advanced stage.
8.1 Symptoms
| Feature | Right-Sided (Proximal) — present later | Left-Sided (Distal) — present earlier |
|---|---|---|
| Tumour morphology | Larger calibre lumen, polypoid/fungating lesion | Smaller calibre lumen, annular/constricting lesion |
| Stool consistency at that site | Liquid/semi-solid stool → can bypass the tumour | Solid/formed stool → more likely to be obstructed |
| Predominant presentation | Tend to bleed → iron deficiency anaemia (occult blood loss), dull vague abdominal pain, right-sided abdominal mass | Tend to obstruct → change in bowel habits, haematochezia, intestinal obstruction |
| Change in bowel habits | Not common (liquid stool passes easily) | Common: tenesmus, reduced stool calibre ("pencil-thin stools"), mucoid stool |
| Bleeding | Occult → IDA (tiredness, pallor, dyspnoea on exertion) | Frank haematochezia (bright red or dark red blood mixed with stool) |
Why does the right side present later?
- The caecum and ascending colon have a large diameter (~7.5 cm) and distensible walls → tumours can grow to a large size before causing symptoms
- Stool content is still liquid at the right colon → does not obstruct
- Bleeding is slow and chronic (tumour surface oozes) → iron deficiency develops insidiously → patients present with anaemia symptoms (fatigue, pallor, dyspnoea) rather than obvious bleeding
- Pain is vague and dull (stretching of the visceral peritoneum) — often misdiagnosed as "IBS" or "functional pain"
Why does the left side present earlier?
- The descending colon and sigmoid have a narrower calibre (~2.5-3 cm)
- Stool is solid and formed → annular constricting lesion narrows the lumen → change in bowel habit (alternating constipation and diarrhoea), tenesmus, and eventually complete obstruction
- Bleeding is frank because solid stool rubs against the tumour surface
- Alternating diarrhoea and constipation [2][11] — the tumour causes partial obstruction; stool accumulates proximally, then is forced through → diarrhoea-like episode
- Reduced stool calibre ("pencil-thin stools") [2][11] — tumour narrows the lumen
- Tenesmus [2][3][11] — sensation of incomplete evacuation; particularly with rectal tumours (tumour mass is perceived as residual stool by stretch receptors in the rectal wall)
- Passage of mucus [2][11] — villous adenomas and mucinous carcinomas can secrete copious mucus → mucus per rectum (sometimes leading to hypokalaemia from potassium-rich mucus loss — "mucus-secreting villous adenoma causing depletion syndrome")
- Urgency/incontinence — especially with low rectal tumours that compromise anal sphincter function
- Haematochezia (fresh blood per rectum) — more common with left-sided and rectal tumours [2][3][11]
- Mechanism: solid stool abrading the tumour surface → mucosal ulceration → bleeding from tumour vasculature
- Blood is typically mixed with stool (cf. haemorrhoids where blood is on the surface or after defecation)
- Occult bleeding — more common with right-sided tumours → detected by faecal immunochemical test (FIT) or presenting as iron deficiency anaemia
- Melaena — rare, only if bleeding is brisk from a right-sided tumour and transit time is slow
- Right-sided: dull, vague, poorly localised aching pain in the right abdomen → visceral pain from distension of the caecum or tumour necrosis [3]
- Left-sided: colicky pain (cramping), worse before defecation → partial obstruction causing increased peristalsis against the obstructing lesion
- Rectal: deep pelvic pain, sacral pain (invasion of sacral nerve plexus) — indicates locally advanced disease
- Jaundice, right upper quadrant discomfort → hepatic metastases [2][11]
- Dyspnoea, cough → pulmonary metastases [2][11]
- Bone pain → skeletal metastases [2][11]
- Ascites → peritoneal carcinomatosis [2][11]
- Irritative urinary symptoms (dysuria, pneumaturia, faecaluria) → colovesical fistula from tumour invading bladder [2][11]
- Intractable pain (sacral nerve invasion) → locally advanced rectal cancer invading presacral plexus [2][11]
- Acute intestinal obstruction: colicky abdominal pain, absolute constipation (no flatus or faeces), abdominal distension, vomiting (late — faeculent vomiting in LBO) [11]
- Perforation: sudden severe abdominal pain, generalised peritonitis, shock → either at the tumour site or at the caecum (closed-loop obstruction if ileocaecal valve is competent → caecal distension → perforation at the weakest point, per Laplace's law)
- Massive haemorrhage: rare but can be life-threatening
8.2 Signs
- Pallor — due to iron deficiency anaemia from chronic occult blood loss (especially right-sided tumours)
- Cachexia/wasting — in advanced disease; loss of temporal fat pads, muscle wasting
- Lymphadenopathy — left supraclavicular node (Virchow's node / Troisier's sign) → indicates advanced intra-abdominal malignancy with spread via the thoracic duct [3]
- Jaundice — liver metastases causing biliary obstruction
- Peripheral oedema — hypoalbuminaemia from cancer cachexia or liver metastases
- Abdominal mass — particularly right-sided tumours which can grow to a large palpable mass before symptoms develop; typically firm, irregular, non-tender (unless complicated), may be fixed or mobile
- Hepatomegaly — irregular, hard, nodular liver edge → liver metastases; may have a hepatic bruit (rarely)
- Ascites — shifting dullness, fluid thrill → peritoneal carcinomatosis or liver metastases with portal hypertension
- Abdominal distension — if large bowel obstruction
- Visible peristalsis — in obstruction, with colicky pain
- Tenderness, guarding, rigidity — if perforation or local peritonitis
DRE is Mandatory
Digital rectal examination (DRE) must NEVER be omitted in any patient with suspected CRC, lower GI symptoms, or iron deficiency anaemia. Up to ~30% of CRC are in the rectum and can be palpated on DRE. You can also assess the tumour's size, position (distance from anal verge), circumferential extent, mobility (fixed = advanced), and relationship to surrounding structures.
- Palpable rectal mass: hard, irregular, friable (bleeds on palpation), may be ulcerated
- Fixed vs mobile: a fixed mass suggests invasion into perirectal tissues or presacral structures
- Blumer's shelf — palpable hard nodule in the pouch of Douglas (peritoneal metastasis)
- Blood/mucus on glove — occult or gross bleeding
- Sphincter tone assessment — low rectal tumours may compromise the external sphincter
- Obstruction: abdominal distension, tympanic percussion, high-pitched tinkling bowel sounds with rushes (early) → absent bowel sounds (late)
- Perforation: peritonism (board-like rigidity, rebound tenderness, absent bowel sounds), tachycardia, hypotension, fever
- Fistula: pneumaturia, faecaluria (colovesical fistula), faeculent vaginal discharge (colovaginal fistula)
- Koilonychia (spoon-shaped nails)
- Angular cheilitis (cracking at corners of mouth)
- Glossitis (smooth, painful tongue)
- Pallor of conjunctivae, palms, nail beds
- Acanthosis nigricans — velvety, dark, thickened skin in axillae and neck folds; associated with GI malignancies
- Dermatomyositis — heliotrope rash, Gottron's papules, proximal muscle weakness; strong association with underlying malignancy (especially in older patients)
- Thrombophilia / Trousseau syndrome — migratory thrombophlebitis; malignancy-associated hypercoagulability (tumour produces tissue factor and mucin → activates coagulation cascade) → DVT, PE [12]
9. Screening for CRC
CRC is an ideal disease for screening because:
- It is common and has high morbidity/mortality
- There is a well-defined precursor lesion (adenomatous polyp) with a long premalignant phase (~10-15 years)
- Detection and removal of polyps (polypectomy) interrupts the adenoma-carcinoma sequence and prevents cancer
- Early-stage CRC (Stage I-II) has excellent survival (> 85-90%) compared to late-stage (Stage IV ~10-15%)
- Effective and acceptable screening tests are available
CRC screening in Hong Kong follows a 2-tier system (Colorectal Cancer Screening Programme, CRCSP):
Tier 1: Faecal Immunochemical Test (FIT) every 2 years, starting from age 50-75 Tier 2: If FIT positive → colonoscopy
- Colonoscopy every 10 years or flexible sigmoidoscopy every 5 years as alternative screening strategies [3]
| Population | Recommendation |
|---|---|
| Average risk | Start screening at age 50 [3] |
| Strong family history | Start at age 40 or 10 years before the age of onset of the affected family member (whichever is earlier) [3] |
| FAP | Sigmoidoscopy/colonoscopy from age 10-12, annually |
| Lynch syndrome | Colonoscopy from age 20-25 (or 2-5 years before youngest case in family), every 1-2 years |
| IBD | Surveillance colonoscopy starting 8-10 years after diagnosis |
| Personal history of CRC/polyps | Colonoscopy — frequency depends on findings |
9.4 Screening Test Modalities [3]
| Test | Details |
|---|---|
| Colonoscopy | Gold standard. Visualises entire colon, allows biopsy and polypectomy. Requires bowel preparation. Risks: perforation (~1/1000), bleeding (post-polypectomy) |
| Flexible sigmoidoscopy | Examines up to splenic flexure. Bowel prep not required (or minimal). Still requires colonoscopy if positive. Right-sided cancer missed (~25%) [3] |
| Test | Details |
|---|---|
| Faecal Immunochemical Test (FIT) | Detects human haemoglobin in stool using antibodies specific to human globin. Not affected by diet or upper GI bleeding (unlike guaiac FOBT, which detects haem and can give false positives with red meat or NSAIDs). Single stool sample. Quantitative. Used in HK CRCSP |
| Guaiac-based FOBT (gFOBT) | Older test; detects haem (not specific to human blood). Affected by diet (red meat, certain vegetables) and drugs (NSAIDs, vitamin C). Largely replaced by FIT |
| CT colonography (virtual colonoscopy) | Bowel prep required. Cannot detect polyps < 5 mm and sessile (flat) polyps [3]. No tissue sampling. Radiation exposure |
| Colon capsule | Bowel prep required [3]. Patient swallows a capsule camera. No tissue sampling |
| Stool DNA testing (e.g. Cologuard) | Combines FIT with molecular markers for methylated genes and KRAS mutations. More sensitive but less specific than FIT alone |
FIT vs gFOBT – Know the Difference
FIT is preferred over gFOBT because it:
- Uses antibodies specific to human globin → no dietary restrictions needed before the test
- Only detects lower GI bleeding (globin from upper GI is degraded by proteases before reaching the colon, so upper GI bleeds don't cause false positives)
- Requires only one stool sample (gFOBT traditionally needs 3)
- Is quantitative (can set a threshold for positivity)
- Has better sensitivity and specificity for CRC and advanced adenomas
While detailed molecular testing guides treatment (covered in management section), the following molecular markers are clinically relevant even at the diagnostic/staging stage:
- CEA (Carcinoembryonic Antigen): not a screening test (low sensitivity and specificity for early-stage disease), but valuable as a baseline before surgery and for post-operative surveillance (rising CEA may indicate recurrence) [1][10]
- MSI/MMR status: determines eligibility for immunotherapy and screens for Lynch syndrome [4][5][7]
- RAS (KRAS/NRAS) mutation status: determines eligibility for anti-EGFR therapy [4][5]
- BRAF V600E mutation: prognostic (worse prognosis if mutated in MSS tumours); helps distinguish sporadic MSI-H from Lynch syndrome [4][5]
High Yield Summary
Definition: CRC = adenocarcinoma arising from colonic/rectal epithelium (~95%); right-sided = proximal to splenic flexure, left-sided = distal to splenic flexure; rectum = below peritoneal reflection or within 15 cm of anal verge.
Epidemiology: #1 cancer in HK by incidence; M:F = 1.6:1; peak 60-70y; ~24% present at Stage IV; rising incidence in Asia.
Risk Factors: Age > 50, male, FHx (25% non-syndromal), FAP/Lynch (10% hereditary), IBD (UC > CD after 8-10y), adenomatous polyps, obesity/DM, red meat, smoking, alcohol. Protective: aspirin/NSAIDs, fibre, calcium/vitamin D, physical activity.
Pathways: CIN (85%) = Vogelstein adenoma-carcinoma sequence (APC → KRAS → SMAD4 → TP53), predominantly left-sided, MSS; MSI (15%) = defective MMR, predominantly right-sided, better prognosis, responds to immunotherapy.
Hereditary Syndromes: FAP (APC, 100% risk, thousands of polyps, prophylactic colectomy); Lynch (MMR genes, 40-80% risk, right-sided, extracolonic cancers — endometrial most common, Amsterdam criteria).
Clinical Features: RIGHT = bleed (IDA, vague pain, mass); LEFT = obstruct (CIBH, haematochezia, pencil stools, tenesmus). Constitutional symptoms, symptoms of metastases (liver > lung > bone > peritoneum). DRE is mandatory.
Spread: Direct (CRM in rectal CA), lymphatic (≥12 LN needed), haematogenous (liver #1 via portal vein; distal rectum → lung via IVC), transcoelomic (Krukenberg, Blumer's shelf).
Screening in HK: FIT every 2 years from age 50 → if positive, colonoscopy. High-risk: start 10 years before youngest affected relative or age 40. FAP: colonoscopy from 10-12y. Lynch: colonoscopy from 20-25y.
Active Recall – CA Colon (Definition, Epidemiology, Risk Factors, Anatomy, Pathophysiology, Clinical Features)
[1] Lecture slides: Hallmarks of cancer and relevance to therapy, carcinogenic factors and cancer prevention.pdf
[2] Senior notes: Ryan Ho GI.pdf (Section 3.3.6 Colorectal Tumours, pp. 163+)
[3] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer, pp. 102+)
[4] Lecture slides: CMB31 Part1 - Systemic therapy in Advanced colorectal cancer - Epidemiology and Therapeutic Targets of Advanced Colorectal Cancer (Professer Thomas Yau) rev3 20250911.pdf
[5] Lecture slides: CMB31 Part2 - Systemic therapy in Advanced colorectal cancer - Treatment Options in mCRC (Professer Thomas Yau) rev3 20250911.pdf
[6] Lecture slides: 2024-2025 Clin Epi colorectal cancer.pdf
[7] Lecture slides: GC 156. Many of my family members have cancers Cancer genetics and cytogenetics (File 1).pdf
[8] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (pp. 32, 41)
[9] Senior notes: Ryan Ho GI.pdf (Section on Ischaemic Colitis, vascular anatomy, p. 146)
[10] Lecture slides: Molecular pathways, route of spread and staging.pdf
[11] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf
[12] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (p. 22)
Differential Diagnosis of CA Colon
The differential diagnosis (DDx) of colorectal cancer must be considered in the context of the presenting complaint, because CRC is a great mimicker — it can present as anaemia, change in bowel habit, PR bleeding, abdominal pain, abdominal mass, intestinal obstruction, or even as a screening finding. You need to think: "What else could produce these same symptoms?"
The approach below is organised by the major presenting clinical scenarios, then synthesised into a unified framework.
The key principle from the GC lecture slides:
Be systematic in problem solving: (1) What is the probability diagnosis? (2) What serious disorders cannot be missed (red flags)? (3) What conditions are often missed (pitfalls)? (4) Could this patient have a "masquerade"? (5) Is this patient trying to tell me something else (hidden agenda)? [13]
CRC can present in many guises, so let's break down the DDx by the chief complaints it commonly mimics.
2. DDx by Chief Complaint
When a patient (especially > 50 years) presents with alternating diarrhoea and constipation, pencil-thin stools, tenesmus, or passage of mucus [2][3][11], you must differentiate CRC from:
| Differential | Key Distinguishing Features | Why it mimics CRC |
|---|---|---|
| Irritable Bowel Syndrome (IBS) | Chronic (> 6 months), fulfils Rome IV criteria. Features AGAINST IBS: weight loss, rectal bleeding, onset in older patients, family history of CA colon or IBD, positive FIT/FOBT, anaemia, raised WBC/ESR, abnormal biochemistry [14]. IBS is a diagnosis of exclusion — no structural abnormality on colonoscopy | Both cause CIBH (alternating diarrhoea/constipation), bloating, and abdominal discomfort. The crucial difference is that IBS is a functional disorder with no alarm features. If you label CRC as IBS and miss it, that is malpractice [14] |
| Inflammatory bowel disease (IBD — UC or Crohn's) | Younger onset (20-40s), diarrhoea (often bloody in UC) is the predominant symptom [15], extra-intestinal manifestations (arthritis, uveitis, erythema nodosum, pyoderma gangrenosum), raised inflammatory markers (CRP, ESR), faecal calprotectin elevated. Colonoscopy + biopsy diagnostic | Both can cause bloody diarrhoea and CIBH. IBD itself is a risk factor for CRC (after 8-10 years of pancolitis) [8] |
| Diverticular disease | Very common in elderly. Symptomatic uncomplicated diverticular disease (SUDD): colicky pain relieved by defecation, CIBH [3]. CT shows diverticulae. CRC can only be excluded with colonoscopy after resolution of acute inflammation [15] | Both cause LLQ pain, CIBH, and even bowel wall thickening on CT. Diverticular stricture can mimic malignant stricture |
| Infectious colitis | Acute onset, fever, travel history (TOCC), diarrhoea rather than abdominal pain is the predominant symptom [15]. Stool culture/PCR positive. Self-limiting in most cases | Bloody diarrhoea may mimic CRC. Important to exclude TB colitis in Hong Kong — can cause strictures and mass lesions that look like CRC on imaging and endoscopy [8] |
| Ischaemic colitis | Elderly female, CVS risk factors, rapid onset of abdominal pain with haematochezia or bloody diarrhoea [9][15]. Affects watershed areas (splenic flexure, rectosigmoid junction). Usually transient and self-limiting | Acute bloody diarrhoea with LLQ pain can mimic complicated left-sided CRC |
Don't Call It IBS Without Ruling Out CRC
In any patient over 50 with new-onset change in bowel habit, you must exclude CRC before labelling it IBS. IBS is a diagnosis of exclusion. The GC lecture slides emphasise: features that should NOT be found in IBS include weight loss, rectal bleeding, onset in older patients, FHx of CA colon/IBD, positive FOBT, anaemia, raised WBC/ESR [14]. If any of these are present, investigate with colonoscopy.
PR bleeding has a broad differential, and CRC must always be excluded in at-risk patients [2][11]:
| Differential | Key Distinguishing Features | Why it mimics CRC |
|---|---|---|
| Haemorrhoids | Blood coating stools or bleeding following defecation. May note perianal prolapsing mass, pruritus (mucus secretion) ± pain (if thrombosed) [2]. Bright red blood, usually painless (unless thrombosed). DRE and proctoscopy diagnostic | Both cause PR bleeding. However, haemorrhoids are extremely common and may coexist with CRC — never assume PR bleeding is "just haemorrhoids" without investigating, especially in patients > 50 |
| Anal fissure | Hx of constipation. Severe sharp pain upon defecation [2]. Visible on inspection (usually posterior midline). Bright red blood on toilet paper | Painful PR bleeding, but the pain pattern and inspection findings are distinctive |
| Diverticular bleeding | Painless, usually profuse haematochezia (not chronic) [2]. Typically self-limiting (75-80% stop spontaneously). Right-sided diverticulae bleed more in Asia | Massive PR bleeding can occur in CRC but is much less common |
| Angiodysplasia | Usually in elderly, may be associated with vascular malformations (e.g. HHT) and aortic stenosis (Heyde's syndrome) [2][16]. Painless, less severe than diverticular but tends to be intermittent [2]. Diagnosis by colonoscopy (cherry-red flat lesions) or CT/conventional angiography | Chronic intermittent PR bleeding causing iron deficiency anaemia — identical to right-sided CRC presentation |
| Inflammatory colitis (UC, Crohn's, infective, ischaemic) | As above | Bloody diarrhoea |
| Radiation colitis/proctitis | Hx of abdominal/pelvic irradiation [2]. Telangiectasiae on colonoscopy | Chronic PR bleeding, especially in patients with prior pelvic radiotherapy for gynaecological or prostate cancers |
| Rectal varices | Portal hypertension (liver cirrhosis). Distinguished from haemorrhoids (haemorrhoidal plexus vs rectal venous plexus) | Massive PR bleeding in a cirrhotic patient |
| Colorectal polyps (adenomatous) | Usually asymptomatic; may cause occult bleeding. Colonoscopic polypectomy is both diagnostic and therapeutic | Precursor lesions of CRC (adenoma-carcinoma sequence); bleeding polyps must be removed and sent for histology |
| Meckel's diverticulum | Younger patients (rule of 2s: 2% prevalence, 2 feet from ileocaecal valve, 2 inches long, presents by age 2). Contains ectopic gastric mucosa → acid secretion → ulceration → painless massive GI bleeding. Diagnosed by Technetium-99m pertechnetate scan (Meckel's scan) | Painless GI bleeding in a young patient |
| Upper GI bleed | Should be considered especially in severe haematochezia (10-15% from UGI source) [2]. Ask about haematemesis, coffee ground vomitus, melaena, NSAID use, liver disease | Brisk UGI bleed can present with haematochezia if bleeding is rapid enough that blood transits the GI tract without being fully digested to melaena |
Any patient with unexplained IDA (especially male or post-menopausal female) must have both upper AND lower GI endoscopy to exclude malignancy [2][17]:
| Differential | Key Distinguishing Features |
|---|---|
| CRC (especially right-sided) | Chronic occult blood loss → IDA. Insidious onset |
| Gastric/oesophageal malignancy | Dysphagia, epigastric pain, early satiety. Upper endoscopy (OGD) diagnostic |
| Peptic ulcer disease | Epigastric pain, NSAID/aspirin use, H. pylori. OGD diagnostic |
| Coeliac disease | Malabsorption (iron, folate, fat-soluble vitamins). Anti-tTG antibodies. Duodenal biopsy shows villous atrophy |
| Dietary insufficiency | Vegan/vegetarian diet, poor intake. Rare as sole cause in developed countries |
| Menstrual blood loss | Pre-menopausal women with heavy menstrual bleeding (menorrhagia) — always ask about menstrual history [17] |
| Angiodysplasia | As above |
| Small bowel tumours | Rare. Capsule endoscopy or CT/MR enterography if upper and lower endoscopy negative |
A right-sided colonic tumour may present as a palpable RIF/right flank mass. The DDx of a right iliac fossa mass includes:
| Differential | Key Features |
|---|---|
| CRC (caecal/ascending colon) | Firm, irregular, non-tender (unless complicated). Associated IDA |
| Appendiceal mass/abscess | Acute onset, fever, leucocytosis, preceded by classical appendicitis pain migration [18] |
| Crohn's disease (ileocaecal) | Young patient, diarrhoea, weight loss, perianal disease. Inflammatory mass |
| TB abdomen (ileocaecal) | Important DDx in Hong Kong. Constitutional symptoms, contact history. Caseating granulomas on biopsy. Can form mass/stricture mimicking CRC |
| Psoas abscess | Psoas sign positive, hip held in flexion. CT shows psoas collection |
| Ovarian mass (right) | Female patients. Pelvic ultrasound diagnostic |
| Lymphoma (mesenteric/ileocaecal) | Constitutional symptoms (B symptoms), massive lymphadenopathy, raised LDH |
| Kidney mass | Ballotable, bimanual palpation positive, resonant anteriorly. Flank pain, haematuria |
CRC is the most common cause of large bowel obstruction (LBO) in adults [11]:
| Differential for LBO | Key Distinguishing Features |
|---|---|
| CRC | Gradual onset of CIBH → acute obstruction. Left-sided predominance (annular lesion). Usually elderly. CT shows "apple-core" lesion |
| Sigmoid volvulus | Elderly, psychiatric patients, chronic constipation, institutionalised. "Coffee-bean" sign on AXR. Massive sigmoid distension |
| Diverticular stricture | History of recurrent diverticulitis. CT shows diverticulae with stricture. Must exclude CRC with colonoscopy after acute episode [15] |
| Pseudo-obstruction (Ogilvie's syndrome) | Post-operative, post-illness, electrolyte imbalance (hypoK, hypoCa, hypoMg). No mechanical obstruction — colonoscopy shows no lesion |
| Hernia (obstructed/strangulated) | Examine hernial orifices! Inguinal, femoral, incisional |
| Faecal impaction | Elderly, immobile patients. DRE reveals faecal loading |
| Differential | Key Features |
|---|---|
| Acute diverticulitis | Clinical triad: lower abdominal pain + fever + leucocytosis [3]. Features suggestive of diverticulitis over CRC on CT: pericolonic and mesenteric inflammation, involvement of > 10 cm of colon, absence of enlarged pericolonic lymph nodes [15]. CRC can only be excluded with colonoscopy after resolution of acute inflammation [15] |
| Appendicitis | Periumbilical pain migrating to RLQ, anorexia, fever, nausea/vomiting [18] |
| IBD | As above |
| Ischaemic colitis | As above |
| Gynaecological causes | Tubo-ovarian abscess, ovarian torsion, ectopic pregnancy [15] — always exclude pregnancy in reproductive-age females |
| Urological causes | Cystitis, nephrolithiasis [15] |
Diverticulitis vs CRC — A Common Exam Trap
Acute diverticulitis and CRC can look very similar on CT (both cause bowel wall thickening, pericolonic fat stranding). The key CT features that favour diverticulitis include: pericolonic/mesenteric inflammation, long segment involvement (> 10 cm), and absence of enlarged pericolonic lymph nodes [15]. However, CRC can only be definitively excluded by colonoscopy after the acute inflammation has resolved (typically 6-8 weeks later) [15]. Up to 10% of patients initially diagnosed with diverticulitis are subsequently found to have CRC.
In the HK context, certain differentials carry extra weight:
| Condition | Why it matters in HK |
|---|---|
| TB colitis (intestinal TB) | TB is endemic in HK. Ileocaecal TB can form strictures, masses, and fistulae that mimic Crohn's disease or CRC. Must biopsy and send for AFB smear/culture + TB PCR. Crucial to rule out TB before starting biologics for IBD [8] |
| Amoebic colitis | Entamoeba histolytica can cause colitis (flask-shaped ulcers) and amoebic liver abscess. Ask about travel history. Stool O&P, serology [8] |
| NPC/gastric CA metastasis | Nasopharyngeal and gastric cancers are common in HK; metastatic disease to the colon/peritoneum is possible |
| Hepatocellular carcinoma (HCC) | High HBV prevalence → HCC is common. A right-sided abdominal mass could be hepatic rather than colonic |
These are the alarm features from the GC lecture slides and senior notes that demand urgent investigation (typically colonoscopy):
Red flags for CRC [2][11][14][17]:
- Age > 50 with new-onset GI symptoms
- Unexplained iron deficiency anaemia (especially in men or post-menopausal women)
- PR bleeding (especially dark blood mixed with stool, not typical haemorrhoidal pattern)
- Change in bowel habit persisting > 6 weeks (new onset)
- Unintentional weight loss
- Palpable abdominal or rectal mass
- Positive FIT/FOBT
- Family history of CRC or adenomatous polyps
- Personal history of IBD, polyps, or prior CRC
| Presenting Complaint | Probability Diagnosis | Serious "Cannot Miss" | Often Missed (Pitfall) |
|---|---|---|---|
| CIBH in elderly | IBS, diverticular disease | CRC, IBD | TB colitis, coeliac disease |
| PR bleeding | Haemorrhoids, anal fissure | CRC, IBD, ischaemic colitis | Angiodysplasia, Meckel's diverticulum |
| IDA (male/postmenopausal) | Dietary, menstrual | CRC, gastric CA | Coeliac disease, angiodysplasia |
| RIF mass | Appendiceal mass | CRC, lymphoma | Crohn's, TB abdomen |
| LBO in elderly | Sigmoid volvulus, adhesions | CRC | Pseudo-obstruction, faecal impaction |
| Acute LLQ pain | Acute diverticulitis | CRC, ischaemic colitis | Ovarian pathology (in females) |
High Yield Summary
Approach: Always consider CRC in any patient > 50 with change in bowel habit, PR bleeding, unexplained IDA, abdominal mass, or intestinal obstruction.
Key DDx by scenario:
- CIBH: IBS (diagnosis of exclusion — no alarm features), IBD, diverticular disease, infectious/TB colitis, ischaemic colitis
- PR bleeding: Haemorrhoids (never assume without investigation), anal fissure, diverticular bleeding, angiodysplasia, IBD, UGI bleed (10-15% of haematochezia)
- IDA: CRC (right-sided), gastric/oesophageal CA, PUD, coeliac disease, angiodysplasia, menstrual loss
- Abdominal mass: CRC, appendiceal mass, Crohn's/TB, ovarian mass, lymphoma
- LBO: CRC (#1 cause), sigmoid volvulus, diverticular stricture, pseudo-obstruction
HK-specific pitfalls: TB colitis (mimics Crohn's and CRC), amoebic colitis. Always rule out TB before biologics.
Critical rule: Diverticulitis and CRC look similar on CT — always follow up with colonoscopy after acute episode resolves. IBS is a diagnosis of exclusion — never diagnose IBS without excluding organic pathology in at-risk patients.
Active Recall – DDx of CA Colon
References
[2] Senior notes: Ryan Ho GI.pdf (Section 3.3.6, pp. 108-109, 163+) [3] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer, pp. 102+; Diverticular disease, pp. 94-95) [8] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (pp. 32, 41) [9] Senior notes: Ryan Ho GI.pdf (Section on Ischaemic Colitis, p. 146) [11] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf [13] Lecture slides: CFB (FM02) Introduction to common problems - Differentiating the normal from the abnormal.pdf (p. 6) [14] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p. 22) [15] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p. 644) [16] Senior notes: Block A - Coffee ground vomitus tarry stool upper GI bleeding.pdf (p. 8) [17] Senior notes: Block A - Pallor_ diagnosis of anaemia; nutritional anaemia; anaemia of systemic diseases.pdf (p. 3) [18] Senior notes: Maksim Surgery Notes.pdf (Acute appendicitis, pp. 88-89)
Diagnostic Criteria, Algorithm and Investigations for CA Colon
Unlike some conditions (e.g. SLE with classification criteria, or IBS with Rome IV criteria), CRC does not have a clinical "diagnostic criteria checklist." The diagnosis is fundamentally histopathological — you need tissue.
The gold standard for CRC diagnosis is colonoscopy with biopsy demonstrating adenocarcinoma on histology [2][3]
That said, the clinical pathway to reaching colonoscopy follows a structured diagnostic algorithm based on the presenting scenario. Think of the diagnostic process in three phases:
- Clinical suspicion (history, examination, alarm features)
- Confirmation (colonoscopy + biopsy = tissue diagnosis)
- Staging (imaging + biomarkers = determine extent of disease)
The approach differs depending on how the patient presents. Let's build the algorithm from first principles:
3. Investigation Modalities — Detailed Breakdown
Investigations for CRC serve three purposes: (A) Diagnosis (confirm the cancer), (B) Staging (determine extent), and (C) Molecular profiling (guide therapy). Let's cover each systematically.
3A. Diagnostic Investigations
"Colonoscopy" = "colon" + "-oscopy" (Greek skopein = to look at) — literally, looking at the colon.
Colonoscopy is the most accurate and versatile diagnostic tool for CRC [2]. It is both diagnostic (visualisation + biopsy) and therapeutic (polypectomy, stenting).
Indications for colonoscopy (in the CRC context) [20]:
- Lower GI symptoms: altered bowel habit, PR bleeding, chronic diarrhoea, abdominal pain
- Positive faecal occult blood (FIT/FOBT)
- Iron deficiency anaemia
- Abnormal imaging (CT finding of colonic wall thickening or mass)
- Screening/surveillance purposes (FAP, Lynch, IBD, post-polypectomy, post-CRC resection)
- Palliative stenting for malignant obstruction
What to look for — Endoscopic appearance [2]:
- Majority are endoluminal masses — exophytic or polypoid — but occasionally can be flat [2]
- May have bleeding (oozing/frank bleeding) in friable, necrotic, or ulcerative masses [2]
- May be circumferential → may obstruct distal scoping [2] (i.e. you cannot pass the scope beyond a tight annular tumour)
- Right-sided: more likely fungating/polypoid
- Left-sided: more likely annular/constricting ("apple-core" morphology)
- Biopsies, brushings, or polypectomy [2]
- Important to tattoo location at polypectomy for future surgical resection if proven to be invasive carcinoma [2] — because after polypectomy, the site heals and becomes indistinguishable from surrounding mucosa; the tattoo (India ink/SPOT) allows the surgeon to localise the site intraoperatively
- Especially important in distal rectal CA as anorectal squamous cell carcinoma (SCC) is treated by upfront chemoradiotherapy instead of surgery [2] — the histological distinction between adenocarcinoma (from rectal mucosa) and SCC (from anal squamous epithelium) fundamentally changes the treatment approach
Histological patterns with prognostic significance [2]:
- Mucinous carcinoma and poorly differentiated carcinoma are associated with poorer prognosis [2]
- Well, moderately, and poorly differentiated adenocarcinoma
- Signet-ring cell component (very aggressive)
Performance [2]:
- Missed CRC rate: only 2-6% [2] — these "missed" cancers are usually flat/sessile lesions (serrated pathway) or in difficult-to-visualise areas (behind folds, at flexures)
- Important to scope the ENTIRE colon [2]
- Incomplete colonoscopy occurs in 11-12% of cases [2] (due to tight stricture, poor bowel preparation, patient intolerance, or tortuous sigmoid)
Complications of colonoscopy:
- Perforation (~1/1,000 diagnostic; ~1/500 with polypectomy)
- Post-polypectomy bleeding (~1-2%)
- Sedation-related complications
- Incomplete procedure
Used when the caecum cannot be reached by colonoscopy, or in patients unfit for colonoscopy.
- Spiral CT with IV contrast, air insufflation, and intraluminal contrast (enema) [2]
- Non-invasive; allows virtual "fly-through" like a colonoscopy [2]
- Requires mechanical bowel preparation (stools can simulate polyps) [2]
- Performance: may be similarly sensitive as colonoscopy for tumours > 1 cm [2][3], but cannot detect polyps < 5 mm and sessile/flat polyps [3]
- Not therapeutic — still requires colonoscopy for biopsy [2][3]
- Provides extraluminal information [3] — can incidentally detect other intra-abdominal pathology (liver metastases, lymphadenopathy, aortic aneurysm)
- Preferred over barium enema where access to colonoscopy is limited [2]
- Examines rectum, sigmoid, descending colon (up to splenic flexure)
- No sedation required — an office procedure [2]
- Considered inadequate for diagnosis due to the gradual worldwide shift towards proximal (right-sided) tumours [2]
- Bowel prep is not required (or minimal) [3]
- If positive, requires full colonoscopy to assess the rest of the colon [3]
- Right-sided cancer missed in ~25% [3]
- Its use followed by barium enema may be considered for patients with major comorbidities [2]
- Largely superseded by CT colonography [3]
- Barium + air [3] — barium coats the mucosa, air distends the lumen, creating a "double contrast" effect on X-ray
- Classical finding: "apple-core" lesion — near-circumferential involvement of bowel walls [3] with shouldering (abrupt transition from normal to abnormal mucosa)
- Risk of barium peritonitis if perforation occurs [3] — this is why it has fallen out of favour
- Limited diagnostic value [2]
High Yield – Diagnostic Investigation Summary
| Modality | Diagnostic Accuracy | Therapeutic? | Key Limitation |
|---|---|---|---|
| Colonoscopy + Bx | Gold standard (miss rate 2-6%) | Yes (polypectomy, stent) | Invasive, incomplete in 11-12%, requires bowel prep + sedation |
| CT colonography | Similar for > 1 cm lesions | No | Cannot detect < 5 mm or flat polyps, radiation, still needs colonoscopy for Bx |
| Flexible sigmoidoscopy | Only sees left colon | Limited | Misses ~25% right-sided cancers |
| DCBE | Superseded | No | Risk of barium peritonitis, limited accuracy |
3B. Staging Investigations
Once CRC is histologically confirmed, staging determines the extent of disease and guides treatment planning. Staging = TNM (covered in prior section). The investigations are designed to determine T, N, and M status.
| Test | Purpose | Key Findings/Interpretation |
|---|---|---|
| CBC with differential | Assess for anaemia | Iron deficiency anaemia (microcytic, hypochromic) — especially right-sided tumours. Leucocytosis if complicated (perforation, abscess) |
| Iron studies (Fe profile) | Confirm iron deficiency | Low ferritin, low serum iron, high TIBC, low transferrin saturation |
| LFT | Screen for liver metastases | Elevated ALP and GGT suggest hepatic metastases (cholestatic pattern). Raised bilirubin if biliary obstruction by hilar metastases. Low albumin reflects poor nutritional status/advanced disease |
| RFT | Baseline renal function | Pre-operative assessment. Also important for chemotherapy dosing (nephrotoxic agents). Ureteric obstruction from locally advanced disease can cause hydronephrosis → elevated creatinine |
| Coagulation (PT/INR) | Pre-operative | Coagulopathy if liver dysfunction from metastases. Also relevant if on anticoagulants |
CEA = "carcino" (cancer) + "embryonic" (found in foetal tissue) + "antigen" — a glycoprotein normally produced during foetal development, but re-expressed by certain cancers.
CEA is an epithelial tumour marker — but NOT a screening or diagnostic test [3].
- Cut-off: < 4.7 ng/mL (some sources use < 5) [3]
- Low diagnostic ability: low sensitivity + low specificity for CRC [3]:
- Elevated in only ~50% of CRC [3] — because CEA may be first-pass metabolised by the liver (i.e. tumours draining via the portal system may have their CEA cleared by hepatic metabolism before it reaches systemic blood; this is why liver metastases often have high CEA — the CEA bypasses hepatic clearance or the liver is too diseased to metabolise it) [3]
- False positives: pregnancy, smoking, TB, IBD, other carcinomas (GI, pancreas, breast) [3]
- Post-operatively: takes 4-6 weeks to return to normal [3]
CEA — Know Its Role
CEA is NOT for screening or diagnosis. Its roles are [3]:
- Prognostication: pre-operative CEA > 5 ng/mL is an independent poor prognostic factor
- Treatment monitoring: serial CEA during chemotherapy tracks response
- Detection of recurrence: post-operative serial CEA measurements (every 3-6 months for 3 years, then every 6 months for 2 years). Even if pre-operative CEA was normal, it can still detect non-portal venous metastases (e.g. lung metastases) that bypass hepatic first-pass metabolism [3]
This is the workhorse staging investigation for all CRC. It assesses:
| What CT Assesses | Details |
|---|---|
| T stage (local extent) | Bowel wall thickening, extramural invasion, invasion of adjacent organs (T4b) |
| N stage (lymph nodes) | Pericolonic, mesenteric, and retroperitoneal lymphadenopathy. Nodes > 10 mm short axis are considered suspicious. Caveat: CT cannot distinguish reactive from metastatic nodes, and cannot detect micrometastases [19] |
| M stage (distant metastases) | Liver metastases (hypodense lesions, may show peripheral enhancement), lung metastases (nodules), peritoneal deposits (ascites, omental caking), bone metastases |
| Complications | Obstruction (dilated bowel loops), perforation (free air, abscess), fistula |
| Surgical planning | Vascular anatomy, relationship to adjacent structures |
Key CT findings in CRC:
- "Apple-core" lesion: irregular annular constriction with shouldering (abrupt edges) — classic for left-sided CRC
- Asymmetric bowel wall thickening with mucosal irregularity
- Pericolonic fat stranding (if tumour extends beyond muscularis propria — T3+)
- "Dirty fat" sign — haziness of pericolic fat indicating extramural tumour spread
MRI provides superior soft tissue resolution compared to CT, making it the modality of choice for local staging of rectal cancer.
MRI pelvis assesses:
- T stage with precision: invasion depth through the rectal wall
- Circumferential resection margin (CRM): the distance from the tumour to the mesorectal fascia. A threatened CRM (tumour ≤ 1 mm from mesorectal fascia) predicts local recurrence and indicates the need for neoadjuvant chemoradiotherapy before surgery [19]
- Extramural venous invasion (EMVI): tumour cells within veins beyond the bowel wall — an independent adverse prognostic factor
- Relationship to sphincter complex: critical for determining whether a sphincter-preserving low anterior resection is feasible, or whether abdominoperineal resection (permanent stoma) is required
- Lymph node assessment: morphological criteria (irregular border, mixed signal intensity) rather than size alone
All patients with rectal cancer should have MRI pelvis for local staging prior to treatment planning [19]
- Alternative to MRI for local T staging of early rectal cancer
- Excellent for distinguishing T1 from T2 lesions (important because T1 tumours may be amenable to local excision / transanal endoscopic microsurgery without radical surgery)
- Operator-dependent; limited by inability to pass the probe beyond obstructing tumours
- Less accurate than MRI for CRM assessment — MRI is preferred in most centres
- 18F-FDG (fluorodeoxyglucose) PET: cancer cells have increased glucose metabolism → increased FDG uptake → "light up" on PET [19]
- Not routinely used for initial staging of CRC [2]
- Indications:
- Evaluating for resectability of isolated liver or lung metastases — to confirm there is no additional occult metastatic disease elsewhere that would make curative metastasectomy futile
- Equivocal findings on CT (e.g. indeterminate pulmonary nodule or liver lesion)
- Rising CEA without identifiable lesion on conventional imaging
- Limitations:
- False positives: inflammation, infection
- False negatives: mucinous tumours (low cellularity, low metabolic activity), small lesions < 1 cm
- Brain metastases are difficult to detect due to high background glucose metabolism [19]
- Quick, cheap baseline assessment for pulmonary metastases
- Low sensitivity compared to CT thorax — largely replaced by CT thorax as part of staging CT
Molecular profiling is now mandatory in all newly diagnosed CRC because it determines prognosis and treatment eligibility [2][3][4][5]:
| Biomarker | Method | Clinical Significance |
|---|---|---|
| MMR/MSI status | IHC for MMR proteins (MLH1, MSH2, MSH6, PMS2) or PCR for MSI | MMR-deficient/MSI-high: (1) Screen for Lynch syndrome (germline testing if IHC shows loss of MLH1/MSH2/MSH6/PMS2); (2) Predicts response to immune checkpoint inhibitors (PD-1 pathway inhibitors — pembrolizumab, nivolumab) [3][4][5]; (3) Better stage-for-stage prognosis; (4) MSI-high Stage II tumours do NOT benefit from 5-FU-based adjuvant chemotherapy — may even be harmed |
| RAS status (KRAS exon 2/3/4, NRAS exon 2/3/4) | PCR or NGS | KRAS/NRAS mutated in ~45% of CRC [3]. Mutant RAS → no response to anti-EGFR therapy (cetuximab/panitumumab) [3][4][5]. Only RAS wild-type patients benefit from anti-EGFR. This is because mutant RAS is constitutively activated downstream of EGFR — blocking EGFR has no effect if the downstream pathway is already permanently "on" |
| BRAF V600E | PCR or IHC | BRAF V600E mutation: (1) Poor prognosis in MSS tumours; (2) In sporadic MSI-H tumours, BRAF V600E is common — its presence essentially excludes Lynch syndrome (because Lynch tumours almost never harbour BRAF mutations) [4][5]; (3) Targeted therapy: BRAF inhibitor (encorafenib) + anti-EGFR (cetuximab) in refractory metastatic CRC |
| HER2 amplification | IHC/FISH | Emerging target for metastatic CRC (trastuzumab + pertuzumab or trastuzumab deruxtecan in HER2+ tumours) |
Universal MMR/MSI Testing — Must Know
All newly diagnosed CRC should undergo universal MMR/MSI testing [4][5][7]. This is not optional — it serves dual purposes:
- Therapeutic: MSI-high tumours respond to immune checkpoint inhibitors (even as first-line in metastatic setting — KEYNOTE-177 showed pembrolizumab superior to chemotherapy as first-line for MSI-H mCRC)
- Genetic screening: identifies Lynch syndrome patients → cascade screening of family members → surveillance colonoscopy → cancer prevention
| Scenario | Investigation | Rationale |
|---|---|---|
| Incomplete colonoscopy | CT colonography [2][3] or post-operative colonoscopy | To assess the proximal colon for synchronous lesions |
| Rectal cancer | MRI pelvis + CT TAP | MRI for local staging (CRM, EMVI); CT for distant staging |
| Isolated hepatic metastasis being considered for resection | MRI liver with hepatocyte-specific contrast (e.g. gadoxetate/Primovist) + PET-CT | MRI liver is more sensitive than CT for detecting small hepatic metastases; PET-CT to exclude extrahepatic disease |
| Suspected peritoneal disease | Diagnostic laparoscopy ± peritoneal cytology | CT has low sensitivity for peritoneal deposits. Laparoscopy directly visualises peritoneal surfaces |
| Emergency obstruction | CT abdomen/pelvis with contrast (before colonoscopy) | Confirms LBO, identifies the transition point, excludes perforation, guides emergency surgery vs stenting decision |
| Suspicion of colovesical fistula | CT with oral/rectal contrast + cystoscopy | Air in bladder on CT, oral contrast in bladder. Cystoscopy shows bullous oedema at fistula site |
| Post-operative surveillance | Serial CEA + CT TAP + colonoscopy at 1 year | Detect recurrence early (CEA Q3-6 months × 3 years; CT Q6-12 months × 3 years; colonoscopy at 1 year post-op, then Q3-5 years) |
Let's synthesise the key investigation findings and their interpretation:
| Finding | Interpretation | Next Step |
|---|---|---|
| Positive FIT | Human haemoglobin in stool → possible CRC or advanced adenoma | Colonoscopy |
| Colonoscopy: mass with biopsy showing adenocarcinoma | Confirmed CRC | Staging CT TAP, CEA, molecular testing. MRI pelvis if rectal |
| Colonoscopy: adenomatous polyp with high-grade dysplasia | Pre-malignant; may contain carcinoma in situ or early invasive CA | Complete polypectomy. If invasive CA on histology → staging |
| CT TAP: liver lesion | Possible hepatic metastasis (M1a) | MRI liver with Primovist for characterisation. PET-CT if considering metastasectomy |
| CT TAP: lung nodule | Possible pulmonary metastasis | PET-CT. If solitary and no other mets → consider metastasectomy |
| MRI pelvis: tumour ≤ 1 mm from mesorectal fascia | Threatened CRM → high local recurrence risk | Neoadjuvant chemoradiotherapy before surgery |
| IHC: loss of MLH1/PMS2 expression | MMR-deficient → likely MSI-high | Check BRAF V600E and MLH1 promoter methylation. If BRAF negative → suspect Lynch syndrome → germline testing |
| KRAS exon 2 mutation | RAS mutant → anti-EGFR therapy will NOT work | Use anti-VEGF-based regimen (bevacizumab) if systemic therapy indicated |
| CEA elevated pre-operatively | Adverse prognostic factor | Baseline for monitoring. Post-op CEA should normalise within 4-6 weeks |
| CEA rising post-operatively | Possible recurrence | CT TAP ± PET-CT to localise recurrence |
| Endoscopic Finding | Significance |
|---|---|
| Polypoid/exophytic mass | Typical right-sided morphology; easier to biopsy |
| Annular constricting lesion | Typical left-sided; may prevent complete colonoscopy; classic "apple-core" on imaging |
| Flat or depressed lesion | Higher risk of submucosal invasion even when small; associated with serrated neoplasia pathway; easily missed |
| Friable, bleeds on contact | Suggests malignancy (tumour neovasculature is fragile) |
| Ulcerated surface | Suggests advanced local disease |
| Second lesion elsewhere in colon | Synchronous tumour (3-5%) or synchronous polyp (30-50%) — changes surgical plan |
| Tattoo marker placed | Important for surgical localisation of small lesions or polypectomy sites |
High Yield Summary
Diagnosis: Gold standard is colonoscopy + biopsy showing adenocarcinoma. CT colonography is the alternative when colonoscopy is incomplete or contraindicated.
Critical colonoscopy principles: Must scope entire colon (synchronous tumours in 3-5%, polyps in 30-50%). Tattoo polypectomy sites. If obstructing tumour prevents complete scope → CT colonography pre-op + mandatory post-op colonoscopy.
Staging: CT TAP with contrast for all CRC. MRI pelvis for all rectal cancer (CRM assessment). PET-CT only if considering curative metastasectomy or equivocal CT findings.
CEA: NOT for screening/diagnosis. Roles: prognostication, treatment monitoring, detection of recurrence. Elevated in only ~50% of CRC. False positives: smoking, pregnancy, TB, IBD. Takes 4-6 weeks to normalise post-op.
Molecular testing (mandatory for all CRC): MMR/MSI (immunotherapy eligibility + Lynch screening), RAS (anti-EGFR eligibility), BRAF V600E (prognosis + Lynch exclusion + targeted therapy).
Key interpretation: MMR-deficient/MSI-H → checkpoint inhibitors work, better prognosis, MSI-H Stage II does NOT benefit from 5-FU chemo. RAS mutant → anti-EGFR will NOT work. BRAF V600E + MSI-H → sporadic (not Lynch).
Active Recall – Diagnosis and Investigations of CA Colon
References
[2] Senior notes: Ryan Ho GI.pdf (Section 3.3.6 Colorectal Tumours, pp. 166+) [3] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer — Investigations, pp. 103+) [4] Lecture slides: CMB31 Part1 - Systemic therapy in Advanced colorectal cancer - Epidemiology and Therapeutic Targets of Advanced Colorectal Cancer (Professor Thomas Yau) rev3 20250911.pdf [5] Lecture slides: CMB31 Part2 - Systemic therapy in Advanced colorectal cancer - Treatment Options in mCRC (Professor Thomas Yau) rev3 20250911.pdf [7] Lecture slides: GC 156. Many of my family members have cancers Cancer genetics and cytogenetics (File 1).pdf [19] Lecture slides: Clinical presentation, diagnosis and screening of colorectal cancer_rev1.pdf [20] Senior notes: Block A - Introduction to GI_Hepatology investigations (LFT, Endoscopy).pdf (p. 26)
Management of CA Colon
The management of CRC is fundamentally multidisciplinary — it requires coordinated input from surgeons, medical oncologists, clinical oncologists (radiation), radiologists, pathologists, and allied health professionals. All cases should be discussed at a multidisciplinary team (MDT) meeting before definitive treatment [3][21][22].
The overarching framework is:
- Curative intent (Stage I–III, and selected Stage IV with resectable oligometastatic disease): surgery ± adjuvant/neoadjuvant therapy
- Palliative intent (unresectable Stage IV): systemic therapy ± local palliative measures
The mainstay of curative treatment for CA colon is surgery. The mainstay of curative treatment for CA rectum adds neoadjuvant chemoradiotherapy in certain cases. [3][21][22]
Management principles by stage [3][21]:
- Stage I: surgery + analysis of ≥ 12 LN
- Stage II: surgery ± adjuvant chemo (consider in high-risk Stage II)
- Stage III: surgery + adjuvant chemo (FOLFOX) ± adjuvant RT (rectal only) ± neoadjuvant chemoRT (in certain rectal only)
- Stage IV: chemo ± surgery for isolated liver metastasis
3. Surgical Management — CA Colon
Surgery is the cornerstone of curative treatment for CA colon [3][22].
Surgical principles (important!) [3]:
- En-bloc resection of primary tumour and locoregional lymph nodes (75% cure rate for resectable disease) [3]
- Adequate resection margins: at least 5 cm proximally and distally [3] — the actual margin depends on the blood supply (you resect the segment supplied by the feeding artery and its lymphatic basin). Why 5 cm? Because microscopic intramural spread rarely extends > 2 cm from the macroscopic tumour edge, and 5 cm provides a comfortable safety margin including the draining lymphovascular territory
- Resect major vascular pedicles and lymphatic drainage basin [3]:
- Excise the colonic mesentery, ligate the arterial supply at its origin, and excise all accompanying lymph nodes [3]
- At least 12 nodes must be harvested for proper N staging [3] — inadequate lymph node harvest might require adjuvant chemotherapy even in otherwise low-risk disease, because you cannot confidently exclude nodal involvement
- Restore bowel continuity whenever possible [3]
The type of colectomy depends on the tumour location, dictated by the vascular supply and lymphatic drainage [3][22]:
| Tumour Site | Surgical Procedure | Vessels Ligated | Rationale |
|---|---|---|---|
| Caecum, Ascending colon | Right hemicolectomy | Ileocolic, right colic, right branch of middle colic artery (all from SMA) | The ileocolic and right colic arteries supply this segment; their accompanying lymph nodes must be removed en bloc |
| Hepatic flexure, Transverse colon, Splenic flexure | Extended right hemicolectomy | Ileocolic, right colic, middle colic artery (SMA) + marginal artery of Drummond | Extends the resection to include the middle colic territory. For splenic flexure tumours, peritumoral subserosal ICG injection can demonstrate lymphatic drainage [3] |
| Splenic flexure, Descending colon | Left hemicolectomy | Left colic artery (IMA) | The left colic artery and its lymphatic basin are resected |
| Sigmoid colon | Sigmoidectomy (high anterior resection) | IMA and left colic artery | IMA ligated at its origin for adequate lymph node clearance |
Elective surgery: laparoscopic/robotic approach is preferred [3]:
- Benefits of minimally invasive surgery: less post-operative pain, shorter hospital stay, faster return to bowel function, lower wound infection rate, equivalent oncological outcomes (same long-term survival and recurrence rates)
- Benefits of robotic surgery: high-quality 3D vision, restoration of eye-hand-target axis [3] — the robot translates the surgeon's hand movements with greater precision and eliminates tremor
Stoma considerations [3]:
- Temporary diverting colostomy/ileostomy is preferred for left-sided anastomosis [3] — the rationale is that left-sided and low colorectal anastomoses have a higher leak rate (the blood supply is more tenuous, and faecal loading is greater); a proximal diverting stoma protects the anastomosis by diverting faecal stream away from the healing anastomotic site
- Right-sided anastomosis (ileocolic) generally does not require a stoma because the blood supply is robust and content is liquid
Emergency surgery is indicated when CRC presents with complications: obstruction, perforation, or haemorrhage [3][23]:
| Scenario | Procedure | Rationale |
|---|---|---|
| Right-sided obstructing lesion | Right hemicolectomy with primary anastomosis ± bowel decompression if stable; temporary ostomy if unstable [3] | The right colon and ileum have robust blood supply; primary anastomosis is usually safe even in emergency. Proximal decompression reduces anastomotic tension |
| Left-sided obstructing lesion | Hartmann's procedure [3] | Hartmann's = resection of the tumour-bearing segment + end colostomy + closure of the rectal stump (Hartmann's pouch). Why not primary anastomosis? In emergency left-sided surgery, the proximal colon is loaded, oedematous, and unprepared → high anastomotic leak risk. Hartmann's is safer in the acute setting. Reversal (re-anastomosis) can be attempted 3-6 months later |
| Alternative to emergency surgery for left-sided obstruction | Endoscopic self-expanding metallic stent (SEMS) as bridge to surgery [23] | Stent relieves obstruction → allows elective surgery 1-2 weeks later with bowel preparation → better outcomes, lower stoma rate. Indications: bridge to surgery (definitive OT 1-2 weeks after stenting) or palliation in unresectable/metastatic disease [23] |
Colonic Stenting — Know the Details
Endoscopic stenting for malignant obstruction [23]:
- Self-expanding metallic stent (SEMS), inserted under endoscopic and/or fluoroscopic guidance
- Contraindications: perforated/strangulated bowel, persistent coagulopathy, distal rectal lesion (≤ 5 cm from anal verge — excruciating pain if stent migrates beyond dentate line) [23]
- Advantages: avoids emergency surgery (mortality > 10%), allows bowel prep for elective surgery, more time for staging, lower stoma rate
- Outcomes: ~92% success rate, median patency 106 days, but 20% re-intervention, 11% migration, 4.5% perforation, 12% re-obstruction [23]
- Less commonly done nowadays in bridge-to-surgery setting due to concerns about perforation risk and potential tumour seeding — but still widely used for palliation
- Malignant polyp (T1 on polypectomy): If the polypectomy is complete with clear margins, favourable histology (well/moderately differentiated, no lymphovascular invasion), and the submucosal invasion is superficial → endoscopic polypectomy alone may be curative (surveillance only). If unfavourable features → formal colectomy
- Synchronous tumours (3-5%): May require extended resection (e.g. subtotal colectomy) if tumours are in different segments
- FAP: Prophylactic total proctocolectomy with ileal pouch-anal anastomosis (IPAA)
4. Management of Rectal Cancer — Additional Considerations
Rectal cancer management differs from colon cancer in several important ways because of the anatomy of the pelvis and the proximity to the anal sphincter [3][22]:
Total mesorectal excision (TME) is the surgical standard:
- The mesorectum (perirectal fat envelope containing lymph nodes, nerves, and vessels, enclosed by the mesorectal fascia) must be excised completely and intact
- TME dramatically reduced local recurrence from ~30% to < 10%
- The quality of the TME specimen (graded as complete, nearly complete, or incomplete by the pathologist) is a key quality indicator
| Tumour Location | Surgical Procedure | Details |
|---|---|---|
| Upper rectum (> 10-12 cm from anal verge) | Anterior resection (AR) | Resect tumour + mesorectum with primary colorectal anastomosis. May not require TME (partial mesorectal excision may suffice if > 5 cm distal margin achievable) |
| Mid rectum (5-10 cm from anal verge) | Low anterior resection (LAR) with TME | Complete TME. Colorectal or coloanal anastomosis. Usually with temporary diverting loop ileostomy to protect the low anastomosis |
| Low rectum (< 5 cm from anal verge) | Ultra-low anterior resection with coloanal anastomosis, or abdominoperineal resection (APR) | If the tumour involves or is very close to the sphincter complex → APR (Miles' operation) = removal of rectum + anus + sphincter complex → permanent end colostomy. If a 1-2 cm distal margin can be achieved above the sphincter → ultra-low AR with coloanal anastomosis |
Neoadjuvant therapy (given BEFORE surgery) is a key component of rectal cancer management, unlike colon cancer where there is no role for neoadjuvant therapy [3][21][22].
Indications for neoadjuvant chemoradiotherapy (chemoRT) in rectal cancer [22]:
- Locally advanced rectal cancer (cT3-4 and/or N+)
- Threatened circumferential resection margin (CRM) on MRI pelvis (tumour ≤ 1 mm from mesorectal fascia)
Rationale — why give treatment BEFORE surgery?
- Tumour downsizing: shrinks the tumour → facilitates R0 resection (complete resection with negative margins)
- Tumour downstaging: may convert an unresectable tumour to a resectable one, or enable sphincter-preserving surgery instead of APR
- Sterilise the mesorectal lymph nodes: reduces nodal disease
- Reduce local recurrence: the pelvis is a confined space with close margins → local recurrence is a major problem; preoperative RT reduces it
- Pathological complete response (pCR): ~15-20% of patients achieve pCR (no residual tumour on histology) after neoadjuvant chemoRT — this is an excellent prognostic sign
Neoadjuvant regimens [22]:
- Long-course chemoRT: 5 weeks of radiotherapy (45-50.4 Gy in 25-28 fractions) + concurrent capecitabine or 5-FU → surgery 6-8 weeks later
- Short-course RT: 5 Gy × 5 fractions (1 week) → surgery within 1 week (or delayed surgery with interval chemotherapy — "total neoadjuvant therapy" / TNT approach)
- Total neoadjuvant therapy (TNT): All systemic chemotherapy + RT given before surgery — emerging as a preferred approach for locally advanced rectal cancer, with higher pCR rates and better compliance
No Neoadjuvant for Colon Cancer
There is no role for neoadjuvant therapy in colon cancer [3]. This is a common exam trap. Neoadjuvant chemoRT is specific to rectal cancer because:
- The pelvis has tight surgical margins → RT helps achieve local control
- Colon cancer does not have the same local recurrence problem (the peritoneal cavity provides space for wide margins)
- RT to the colon would cause excessive toxicity to mobile small bowel loops
5. Adjuvant Chemotherapy — Post-Operative Systemic Therapy
Adjuvant chemotherapy aims to eradicate micrometastatic disease and reduce the risk of recurrence [3][21][24].
| Stage | Adjuvant Chemotherapy? | Details |
|---|---|---|
| Stage I | No | Excellent prognosis with surgery alone (> 90% 5-year survival) |
| Stage II (low-risk) | Generally not recommended | Low absolute benefit (~3-5%). Observation preferred. But consider if MSS (see below) |
| Stage II (high-risk) | Consider adjuvant chemotherapy [3][21][24] | High-risk features: T4 tumour, lymphovascular invasion (LVI), perineural invasion (PNI), poorly differentiated histology, inadequate LN dissection (< 12 nodes), positive resection margin, bowel obstruction or perforation at presentation [24] |
| Stage III | Yes — standard of care [3][21][24] | All Stage III (node-positive) patients should receive adjuvant chemotherapy |
High Yield – MSI-H and Stage II Chemotherapy
MSI-high Stage II tumours do NOT benefit from 5-FU-based adjuvant chemotherapy — and may even be harmed [4][5]. This is because:
- MSI-H tumours have a better prognosis stage-for-stage (the immune infiltrate provides anti-tumour surveillance)
- 5-FU may paradoxically impair the immune response
- Therefore: if Stage II is MSI-H → observation, NOT adjuvant chemotherapy (even if other high-risk features are present — this is debated but generally favours omission of 5-FU monotherapy)
Cytotoxic chemotherapy backbone [3][21][24]:
| Regimen | Components | Duration | Indication |
|---|---|---|---|
| FOLFOX | Folinic acid (leucovorin) + 5-Fluorouracil (5-FU) + Oxaliplatin | 6 months (12 cycles Q2W) | Standard for Stage III and high-risk Stage II [3] |
| XELOX (CapeOx) | Capecitabine + Oxaliplatin | 3 months (if lower risk: T1-3, N1) or 6 months [3] | Alternative to FOLFOX. Capecitabine is oral (convenient) |
| Capecitabine monotherapy | Capecitabine alone | 6 months | For patients unfit for oxaliplatin (e.g. pre-existing neuropathy, elderly, comorbid) |
| 5-FU/LV monotherapy | 5-FU + leucovorin | 6 months | Alternative to capecitabine monotherapy |
Understanding the drugs — from first principles [3][21][24]:
| Drug | Class | Mechanism of Action | Key Side Effects |
|---|---|---|---|
| 5-Fluorouracil (5-FU) | Anti-metabolite (pyrimidine analogue) | "Fluoro" = fluorine atom substituted into uracil. 5-FU inhibits thymidylate synthase → blocks conversion of dUMP to dTMP → impairs DNA synthesis → cell death. Given IV as continuous infusion | Mucositis, diarrhoea, myelosuppression, hand-foot syndrome [24] |
| Capecitabine | Anti-metabolite (pyrimidine analogue) — oral prodrug of 5-FU | "Cape-cita-bine" — an oral prodrug that is converted to 5-FU preferentially in tumour tissue (by thymidine phosphorylase, which is overexpressed in tumour cells). Convenient oral alternative to IV 5-FU | Hand-foot syndrome (especially capecitabine), diarrhoea, mucositis [24] |
| Oxaliplatin | Alkylating agent (platinum compound) | "Oxa" = oxalate ligand + "platin" = platinum. Forms platinum-DNA adducts → cross-links DNA → blocks replication and transcription → apoptosis. 3rd-generation platinum (after cisplatin, carboplatin) | Peripheral neuropathy (dose-limiting — cumulative, cold-triggered: acute cold dysaesthesia + chronic sensory neuropathy), myelosuppression |
| Leucovorin (folinic acid) | Biochemical modulator | Not cytotoxic itself. Enhances 5-FU efficacy by stabilising the ternary complex of thymidylate synthase + 5-FU + folate → more potent enzyme inhibition | Well tolerated |
| Irinotecan | Topoisomerase I inhibitor | "Irino-tecan" — inhibits topoisomerase I → prevents religation of DNA single-strand breaks → DNA damage → cell death. Used more in the metastatic setting (FOLFIRI) | Diarrhoea (early cholinergic — treat with atropine; late secretory — treat with loperamide), myelosuppression |
IDEA trial (2018): For low-risk Stage III (T1-3, N1), 3 months of XELOX/CapeOx is non-inferior to 6 months → standard practice to use 3 months in this group (less neurotoxicity). For high-risk Stage III (T4 or N2), 6 months remains standard.
6. Systemic Therapy for Metastatic CRC (Stage IV)
The goal of systemic therapy in metastatic CRC (mCRC) is to prolong survival, palliate symptoms, and maintain quality of life [4][5][21][24].
Upfront chemotherapy for mCRC: doublet therapy [21]:
- Oxaliplatin or irinotecan + fluoropyrimidine (5-FU/leucovorin or capecitabine)
- FOLFOX: 5-FU/LV + oxaliplatin
- FOLFIRI: 5-FU/LV + irinotecan
- XELOX: capecitabine + oxaliplatin
Triplet chemotherapy (FOLFOXIRI) may be used in fit patients with aggressive disease or where maximal tumour shrinkage is needed (e.g. potentially convertible to resectable) — higher response rate but more toxicity
6.2 Targeted Therapy — Guided by Molecular Profile
The choice of targeted therapy is determined by molecular testing (RAS, BRAF, MSI status) and tumour sidedness [4][5][21][24]:
| Drug | Target | Mechanism | Indication |
|---|---|---|---|
| Bevacizumab | VEGF-A | Monoclonal antibody that binds and neutralises VEGF-A → inhibits angiogenesis (tumour neovasculature). Without blood supply, the tumour cannot grow beyond ~2 mm | Added to chemotherapy backbone in mCRC, particularly for patients with KRAS/NRAS/BRAF mutations when anti-EGFR is contraindicated [21][24] |
| Aflibercept | VEGF-A, VEGF-B, PlGF | Soluble decoy receptor (VEGF Trap) — binds VEGF ligands with higher affinity than bevacizumab | Second-line mCRC (with FOLFIRI) [21] |
| Regorafenib | Multi-kinase inhibitor (VEGFR, PDGFR, BRAF, etc.) | Oral small-molecule inhibitor of multiple kinases involved in angiogenesis and tumour growth | Refractory mCRC (after failure of standard chemotherapy) [21] |
Anti-VEGF contraindications [24] (understand these by thinking about what VEGF does — it promotes angiogenesis, wound healing, and vascular integrity):
- Haemorrhage — VEGF inhibition impairs vascular integrity → bleeding risk
- Impaired wound healing — must stop bevacizumab ≥ 4-6 weeks before surgery and not restart until wound healed
- Arterial thromboembolic diseases — paradoxically, anti-VEGF increases thrombotic risk (endothelial dysfunction, loss of PGI2/NO production)
- Other: hypertension, proteinuria, GI perforation (especially if tumour is in situ)
ONLY indicated in Stage IV (metastatic) disease. There is NO evidence to support use of targeted therapy in the adjuvant setting [24]
| Drug | Target | Mechanism | Prerequisites |
|---|---|---|---|
| Cetuximab | EGFR (ErbB1/HER1) | Chimeric monoclonal antibody that binds EGFR extracellular domain → blocks ligand binding → inhibits downstream RAS-RAF-MEK-ERK signalling → reduces proliferation | Only in RAS wild-type (KRAS + NRAS WT) tumours [4][5][24] |
| Panitumumab | EGFR | Fully human monoclonal antibody (less immunogenic than cetuximab) with same mechanism | Only in RAS wild-type tumours [4][5][24] |
Why does RAS mutation status matter? [4][5][24]:
- EGFR sits at the top of the RAS-RAF-MEK-ERK signalling cascade
- If RAS (KRAS or NRAS) is mutated → the pathway is constitutively active regardless of whether EGFR is blocked → anti-EGFR has no effect
- KRAS mutation results in constitutive activation of the RAS-RAF-ERK pathway leading to resistance to anti-EGFR therapy [24]
- Mutant KRAS will NOT benefit from cetuximab or panitumumab and leads to unnecessary adverse events [24]
- KRAS and BRAF mutations are mutually exclusive [24]
- Mutant BRAF is also unlikely to benefit from cetuximab or panitumumab [24]
Anti-EGFR side effects: cutaneous reactions (acneiform rash, pruritus, nail changes — the rash actually correlates with efficacy!), headache, diarrhoea, infection, hypomagnesaemia, infusion reactions [24]
Tumour sidedness and anti-EGFR [4][5]:
- Anti-EGFR works better in LEFT-sided tumours than right-sided, even if RAS wild-type
- This is because right-sided tumours more frequently harbour alternative oncogenic drivers (BRAF, MSI-H, serrated pathway) that bypass EGFR dependence
- Current practice: anti-EGFR (cetuximab/panitumumab) preferred for left-sided RAS WT mCRC; anti-VEGF (bevacizumab) preferred for right-sided or RAS mutant mCRC [4][5]
| Drug | Target | Indication |
|---|---|---|
| Pembrolizumab | PD-1 | First-line for MSI-H/dMMR metastatic CRC (KEYNOTE-177: superior PFS vs chemotherapy) [4][5] |
| Nivolumab ± Ipilimumab | PD-1 ± CTLA-4 | MSI-H/dMMR mCRC (CheckMate 142) [4][5] |
Why do checkpoint inhibitors work in MSI-H tumours? [4][5]:
- MSI-H tumours have defective DNA mismatch repair → accumulate thousands of somatic mutations → generate abundant neoantigens (abnormal proteins displayed on cell surface by MHC)
- These neoantigens are "seen" by T cells → strong anti-tumour immune response
- BUT the tumour upregulates PD-L1 to evade this immune attack (PD-L1 binds PD-1 on T cells → "turns off" the T cell)
- PD-1 inhibitors (pembrolizumab, nivolumab) block PD-1 → "release the brakes" on T cells → restore anti-tumour immunity
- MSS tumours have low mutation burden → few neoantigens → checkpoint inhibitors are ineffective
- Encorafenib (BRAF inhibitor) + cetuximab (anti-EGFR) for BRAF V600E-mutant mCRC after failure of prior therapy (BEACON trial)
- Rationale: BRAF V600E constitutively activates the RAF-MEK-ERK pathway. But in CRC (unlike melanoma), single-agent BRAF inhibitor causes feedback activation of EGFR → combination with anti-EGFR is needed to block this escape route
Isolated liver metastases are potentially curable with surgery (hepatic metastasectomy) [3][21]:
- ~20-25% of mCRC patients have liver-only metastases
- 5-year survival after liver metastasectomy: 25-50% (compared to < 5% with chemotherapy alone)
- Criteria for resectability: technically feasible R0 resection with adequate future liver remnant (FLR > 20-30%), no unresectable extrahepatic disease, patient fit for surgery
- Perioperative chemotherapy: FOLFOX for 3 months pre-op + 3 months post-op (EPOC trial) to downsize liver metastases and treat micrometastatic disease
- PET-CT before metastasectomy to exclude occult extrahepatic disease [2]
- MRI liver with Primovist to detect additional small hepatic metastases missed on CT
For patients with unresectable Stage IV or those unfit for systemic therapy:
| Modality | Indication |
|---|---|
| Colonic stenting | Malignant large bowel obstruction — palliation [23] |
| Palliative colectomy/diversion | If stenting fails or is contraindicated; bypass or defunctioning stoma |
| Palliative radiotherapy | Symptomatic bone/brain metastases, bleeding rectal tumours |
| Best supportive care | Pain management (WHO analgesic ladder), nutritional support, psychosocial support, end-of-life care |
Surveillance aims to detect recurrence early when it is still amenable to curative re-intervention (especially isolated liver or lung recurrence):
| Modality | Frequency |
|---|---|
| Clinical review + CEA | Every 3-6 months for 3 years, then every 6-12 months for 2 more years |
| CT thorax + abdomen + pelvis | Every 6-12 months for 3 years (higher risk) |
| Colonoscopy | At 1 year post-op → if normal, repeat at 3 years → then every 5 years (to detect metachronous tumours) |
- Bowel preparation: mechanical bowel prep + oral antibiotics (reduces surgical site infection)
- Prophylactic antibiotics: indicated for clean-contaminated procedures [25] — colorectal surgery is clean-contaminated (entry into GI lumen). Typically a single dose of IV cefuroxime + metronidazole at induction
- DVT prophylaxis: LMWH + pneumatic compression devices (CRC patients are at high thrombotic risk — Trousseau syndrome)
- Enhanced Recovery After Surgery (ERAS) protocol: early oral feeding, early mobilisation, multimodal analgesia (minimise opioids), avoid routine NG tube, avoid excessive IV fluids → faster recovery, shorter hospital stay
- Nutritional support: if malnourished or anticipated prolonged fasting > 5-7 days post-operatively → perioperative nutritional support [26]. Enteral feeding is ALWAYS first choice if GI tract can be used safely [26]. If GI tract non-functional → parenteral nutrition (TPN) [26]
High Yield Summary
Stage I: Surgery alone. Stage II: Surgery ± adjuvant chemo (if high-risk features: T4, LVI, PNI, poor differentiation, < 12 LN, positive margin, obstruction/perforation). MSI-H Stage II: do NOT give 5-FU chemo. Stage III: Surgery + adjuvant chemo (FOLFOX 3-6 months; 3 months XELOX if low-risk T1-3 N1). Stage IV: Molecular-guided systemic therapy ± curative metastasectomy if resectable oligometastatic.
Surgery: En-bloc resection + ≥ 12 LN. Right hemicolectomy for right-sided; left hemicolectomy/sigmoidectomy for left-sided. Laparoscopic preferred. Emergency: right → primary anastomosis; left → Hartmann's or stent as bridge.
Rectal cancer: MRI pelvis staging. Neoadjuvant chemoRT for cT3-4/N+/threatened CRM. TME standard. No neoadjuvant for colon cancer.
Metastatic CRC systemic therapy: MSI-H → checkpoint inhibitors first-line. MSS + RAS WT + left-sided → chemo + anti-EGFR. RAS mutant or right-sided → chemo + anti-VEGF. BRAF V600E → encorafenib + cetuximab.
Anti-VEGF (bevacizumab): contraindicated in haemorrhage, impaired wound healing, arterial thromboembolism. Stage IV only — no adjuvant role.
Anti-EGFR (cetuximab/panitumumab): ONLY for RAS wild-type. RAS mutant → constitutive pathway activation → anti-EGFR useless. BRAF mutant also unlikely to benefit.
Active Recall – Management of CA Colon
References
[2] Senior notes: Ryan Ho GI.pdf (Section 3.3.6 Colorectal Tumours, pp. 166+) [3] Senior notes: Maksim Surgery Notes.pdf (Management of colon cancer, pp. 104-105) [4] Lecture slides: CMB31 Part1 - Systemic therapy in Advanced colorectal cancer - Epidemiology and Therapeutic Targets of Advanced Colorectal Cancer (Professor Thomas Yau) rev3 20250911.pdf [5] Lecture slides: CMB31 Part2 - Systemic therapy in Advanced colorectal cancer - Treatment Options in mCRC (Professor Thomas Yau) rev3 20250911.pdf [21] Senior notes: Maksim Medicine Notes.pdf (Clinical oncology — Colorectal cancer, p. 54) [22] Lecture slides: Professor Chiang Chi Leung - Neoadjuvant and Adjuvant Therapy in Colorectal Cancer_rev2.pdf [23] Senior notes: Ryan Ho GI.pdf (Large Bowel Obstruction — Endoscopic stenting, p. 139) [24] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Treatment — Medical, pp. 896+); MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 693+) [25] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (Prophylactic antibiotics, p. 12) [26] Senior notes: Ryan Ho Fluids and Nutrition.pdf (Perioperative nutritional support, pp. 8-11)
Complications of CA Colon
Complications of CRC can be broadly divided into three categories: (A) Complications of the disease itself (i.e., what the tumour does to you), (B) Complications of treatment (surgery, chemotherapy, radiotherapy), and (C) Complications of metastatic disease. Understanding each complication from first principles — why it happens — is essential for both exams and clinical practice.
1. Complications of the Disease (Untreated / At Presentation)
These are the ways CRC presents as an emergency or causes morbidity before treatment. They arise from the tumour's local growth and its systemic effects.
CRC is the most common cause of large bowel obstruction (LBO) in adults [11][27].
Pathophysiology: As the tumour grows circumferentially (especially left-sided annular/stenosing lesions in the narrower descending and sigmoid colon), it progressively narrows the lumen. Initially partial obstruction produces change in bowel habit (alternating diarrhoea and constipation). Eventually complete obstruction occurs — the hallmark presentation of complicated left-sided CRC.
- Clinical features of LBO: colicky abdominal pain (peristalsis against the obstructing lesion), progressive abdominal distension, absolute constipation (no flatus or faeces), and late vomiting (faeculent vomiting — because LBO vomiting occurs late due to the long distance for retrograde peristalsis)
- Closed-loop obstruction: If the ileocaecal valve is competent (which it is in ~60-70% of people), the colon becomes a closed loop between the ileocaecal valve and the obstructing tumour. The caecum distends progressively (it is the widest-diameter segment of the colon → by Laplace's law, wall tension = pressure × radius, so the caecum experiences the greatest wall tension → highest risk of perforation). Caecal diameter > 12 cm on imaging is at imminent risk of perforation [11][27]
- Management: as discussed in the previous section — emergency Hartmann's procedure, endoscopic stenting as bridge to surgery, or right hemicolectomy with primary anastomosis (right-sided lesions)
High Yield – Closed-Loop Obstruction and Laplace's Law
If the ileocaecal valve is competent, an obstructing left-sided CRC creates a closed-loop obstruction. The caecum (largest diameter) bears the greatest wall tension (T = P × r by Laplace's law) and is at highest risk of perforation. A competent ileocaecal valve prevents retrograde decompression into the ileum → the colon is a pressurised, closed system. This is a surgical emergency.
Pathophysiology: Perforation can occur via two mechanisms:
- At the tumour site: the tumour itself ulcerates and necroses through the full thickness of the bowel wall → localised or free perforation
- At the caecum (diastatic perforation): as described above, in closed-loop obstruction, the caecum perforates due to maximal wall tension → this can be distant from the tumour itself
- Clinical features: sudden severe abdominal pain, generalised peritonitis (board-like rigidity, rebound tenderness, absent bowel sounds), tachycardia, hypotension, fever. CXR or CT shows free air under the diaphragm (pneumoperitoneum)
- Consequences: faecal peritonitis → sepsis → multiorgan failure → death if untreated. Mortality is high (> 20% in perforated CRC)
- Perforation with peritonitis is associated with high mortality [27][28]
- Management: emergency laparotomy, resection of the tumour-bearing segment (Hartmann's procedure most commonly), peritoneal lavage, broad-spectrum IV antibiotics
Pathophysiology: tumour neovasculature is fragile and abnormal (lacks normal vessel architecture — this is one of the hallmarks of cancer, sustained angiogenesis [1]). The tumour surface ulcerates and bleeds.
- Chronic occult bleeding: insidious, leads to iron deficiency anaemia (IDA) — this is the classic presentation of right-sided CRC. The patient is often unaware of the blood loss. IDA develops gradually: fatigue → exertional dyspnoea → high-output cardiac failure in severe cases
- Acute massive haemorrhage: rare but can occur (haematochezia or melaena). More commonly associated with left-sided or rectal tumours
- CRC presenting with obstruction, perforation, or haemorrhage — these complications are often independent predictors of poor prognosis [2]
Pathophysiology: locally advanced tumour invades adjacent organs, and the necrotic tumour centre creates an abnormal communication (fistula) between the colon and the neighbouring structure.
| Fistula Type | Adjacent Organ | Clinical Features | Mechanism |
|---|---|---|---|
| Colovesical fistula | Bladder | Pneumaturia (air in urine), faecaluria (faecal matter in urine), recurrent UTIs | Tumour (usually sigmoid) erodes into the dome of the bladder. Gas and faeces enter the bladder |
| Colovaginal fistula | Vagina | Faeculent vaginal discharge, passage of air per vagina | Usually occurs after hysterectomy (vaginal cuff is adjacent to sigmoid/rectum) |
| Coloenteric fistula | Small bowel | Diarrhoea (bypassing absorptive surface) | Tumour invades adjacent small bowel loops |
| Enterocutaneous fistula | Skin (abdominal wall) | Faecal discharge from abdominal wall | Tumour invades anteriorly through the abdominal wall (rare, very advanced disease) |
Pathophysiology: tumour perforation that is contained (walled off by omentum and adjacent structures) → pericolonic or intra-abdominal abscess. Presents with persistent fever, localized tenderness, palpable mass, raised WBC/CRP despite antibiotics.
- Management: CT-guided percutaneous drainage + IV antibiotics, followed by definitive surgical resection
Already discussed extensively, but worth re-emphasising as a "complication" of the disease:
- Chronic occult blood loss → depletion of iron stores → microcytic hypochromic anaemia
- Any male or post-menopausal female with unexplained IDA must have both upper and lower GI endoscopy to rule out malignancy
Pathophysiology: CRC (like many solid tumours, especially mucin-secreting adenocarcinomas) produces procoagulant substances:
- Tissue factor expressed by tumour cells → activates the extrinsic coagulation cascade
- Mucin from mucinous CRC → activates platelets and coagulation factors
- Cancer-associated inflammation → elevated acute-phase reactants (fibrinogen, factor VIII)
- Result: hypercoagulable state → DVT, PE, migratory superficial thrombophlebitis (Trousseau's sign)
This is why DVT prophylaxis is essential in all CRC surgical patients and why unexplained VTE should prompt investigation for occult malignancy [12]
2. Complications of Treatment
2A. Post-Operative Complications (Surgical)
| Complication | Details | Mechanism / Why It Happens |
|---|---|---|
| Massive bleeding | Requiring conversion from laparoscopic to open surgery (< 10%) [3] | Injury to major vessels during dissection (mesenteric vessels, iliac vessels) |
| Injury to neighbouring structures [3][29]: | Due to anatomical proximity and adhesions | |
| — Left ureter and gonadal vessels | Especially during left-sided colectomy / sigmoid resection | The left ureter crosses under the IMA at its origin and runs along the pelvic brim — easily injured during IMA ligation |
| — Iliac artery | Vascular injury during pelvic dissection | Close proximity in the pelvis |
| — Gallbladder, Duodenum (D2) | Right hemicolectomy | The hepatic flexure is in close proximity to the gallbladder and D2 |
| — Seminal vesicles | Low anterior resection | Posterior to the prostate/seminal vesicles in males |
| — Spleen | Splenic flexure mobilisation in TME [3] | Traction on the splenocolic ligament during mobilisation of the splenic flexure → splenic capsular tear |
| — Autonomic nerve injury | Especially in rectal surgery [3] | The pelvic autonomic nerves (hypogastric nerves, pelvic splanchnic nerves) run in close proximity to the mesorectum. Sympathetic injury → urinary incontinence, impaired ejaculation. Parasympathetic injury → urinary retention, erectile dysfunction [3] |
High tie vs low tie of IMA [3]: High tie (at IMA origin) provides better lymph node clearance and reduces anastomotic tension, but low tie (distal to left colic artery origin) avoids damage to the hypogastric nerve and carries a lower risk of autonomic dysfunction [3]
| Complication | Details | Mechanism |
|---|---|---|
| Surgical site infection (SSI) [29] | Wound infection (superficial or deep), intra-abdominal abscess | Colorectal surgery is clean-contaminated (entry into bowel lumen). Despite prophylactic antibiotics and bowel preparation, bacterial contamination is inevitable |
| Post-operative ileus [29] | Delayed return of bowel function (> 3-5 days). Abdominal distension, nausea, inability to tolerate oral feeding | Reflex inhibition of GI motility due to surgical handling of bowel, anaesthesia, opioid analgesics, electrolyte imbalance (hypokalaemia). Distinguished from mechanical obstruction by absence of transition point on imaging |
| Anastomotic bleeding [29] | Bleeding from the staple/suture line into the bowel lumen. Presents as PR bleeding post-operatively | Management: transfusion + correct coagulopathy. Usually self-limiting. Colonoscopic haemostasis if persistent |
| Anastomotic leakage [29] | The most feared early complication | See below — expanded section |
Anastomotic Leak — Must Know in Detail
Anastomotic leakage is the most serious early post-operative complication of colorectal surgery [29]:
- Incidence: 3-6% for colonic anastomoses; up to 10-15% for low rectal anastomoses (which is why diverting stomas are used)
- Timing: Becomes apparent 5-7 days post-operatively [29] — this is typically when you expect an anastomosis to be healing (collagen deposition at day 5-7); if healing fails, leakage occurs
- Why does it happen?: Poor blood supply to anastomotic site, tension on the anastomosis, inadequate technique, malnutrition, corticosteroid use, distal rectal location (the blood supply is more tenuous distally)
- Clinical signs: pain (new or worsening), fever, tachycardia, feculent or purulent drainage [29]
- Radiological signs: fluid- or gas-containing collections on CT [29]
- Management: fluid resuscitation + broad-spectrum IV antibiotics + bowel rest + image-guided percutaneous drainage of abscess, temporary fecal diversion, or resection of the anastomosis [29]
- This can lead to faecal peritonitis, sepsis, multiorgan failure, and death if not recognised and managed promptly
| Complication | Details | Mechanism / Management |
|---|---|---|
| Anastomotic stricture [3][29] | Narrowing at the anastomotic site → obstructive symptoms (CIBH, colicky pain, subacute obstruction) | Excessive scar formation/fibrosis at the anastomosis. Majority do not require intervention. Those requiring it can be treated with finger dilatation (low anastomosis) or endoscopic balloon dilatation (high anastomosis) [29] |
| Fistula [29] | Enterocutaneous (colocutaneous), rectovaginal (colovaginal), and rectourinary fistula | Due to anastomotic leak, local recurrence, or radiation injury. Enterocutaneous fistula can be managed conservatively since most will close spontaneously. Rectovaginal or rectourinary fistula should be managed with proximal fecal diversion [29] |
| Adhesions / Adhesive small bowel obstruction [2] | Post-operative intra-abdominal adhesions → SBO | Any abdominal surgery causes adhesions. SBO from adhesions is the most common cause of SBO overall |
| Incisional hernia | Herniation through the surgical wound/port site | Wound healing impairment, obesity, smoking, increased intra-abdominal pressure |
| Perineal hernia [3] | After abdominoperineal resection (APR) | The pelvic floor defect created by removing the rectum and anus allows herniation of pelvic contents through the perineal wound |
| Low Anterior Resection (LAR) Syndrome [3][29] | See below | |
| Tumour recurrence [2][3] | Local (anastomotic or pelvic) or distant (liver, lung) recurrence | Residual microscopic disease. Recurrence occurs in ~40% of CRC patients [3]. Local recurrence in ~3-12% (higher in rectal CA) [2]. This is why surveillance is critical |
| Chronic diarrhoea [2] | Especially after right hemicolectomy (loss of absorptive surface for water and bile salts) | Bile salt malabsorption → osmotic diarrhoea in the remaining colon. Managed with cholestyramine (bile acid sequestrant) |
| Impotence [2] | 15-50% of males after rectal surgery | Damage to pelvic autonomic nerves during TME |
Low anterior resection (LAR) syndrome is a highly clinically relevant late complication of rectal cancer surgery [3][29]:
- Symptoms: change in bowel movement persisting ≥ 1 month after surgery, ranging from constipation to faecal urgency, faecal incontinence, clustering of bowel openings, and evacuation dysfunction [3]
- Pathophysiology: multifactorial [3]:
- Colonic dysmotility: loss of the rectal reservoir and colonic denervation alter transit
- Neorectal reservoir dysfunction: the surgically created "neorectum" has reduced capacity and compliance compared to the native rectum
- Anal sphincter dysfunction: stretch injury from the circular stapler, radiation damage, autonomic nerve injury
- Prevention: post-operative pelvic floor muscle exercises, antegrade colonic irrigation via stoma or enema, fecal diversion [3]
- Management: antidiarrhoeal agents (loperamide), transanal irrigation, pelvic floor rehabilitation, sacral nerve stimulation [3]
If a stoma (colostomy or ileostomy) is created during surgery, it carries its own set of complications [3][29]:
Early (< 30 days) [29]:
- Stomal bleeding: usually minor, from mucocutaneous junction
- Stomal necrosis: ischaemia of the exteriorised bowel segment (compromised mesenteric blood supply during stoma creation). The stoma appears dusky, dark, or black. May require revision if necrosis extends below fascial level
- Stomal retraction: the stoma sinks below skin level → difficulty with appliance adherence → leakage and skin irritation. Due to tension on the mesentery or inadequate bowel mobilisation
- Mucocutaneous separation: dehiscence at the junction of stoma and skin. Usually heals by secondary intention
- Skin irritation and dermatitis: Most common in end and loop ileostomy due to high-output and high alkaline enzymatic effluent [29] — the proteolytic enzymes in ileal output (which have not yet been neutralised by colonic bacteria) are very caustic to skin
Late (> 30 days) [29]:
- Parastomal hernia: most common late stoma complication. Herniation of bowel through the fascial defect around the stoma. May cause obstruction or incarceration. Often requires surgical repair with mesh
- Stomal prolapse: the bowel telescopes outward through the stoma. More common with loop colostomy
- Stomal stenosis: narrowing of the stoma at skin or fascial level → difficulty passing stool, thin ribbon-like output. May require revision
Adverse effects of chemotherapy [24]:
| Drug | Key Side Effects | Mechanism |
|---|---|---|
| 5-FU / Capecitabine | Mucositis (inflammation of mucous membranes — mouth ulcers, oesophagitis, diarrhoea), nausea/vomiting, diarrhoea, febrile neutropenia, alopecia, hand-foot syndrome (palmar-plantar erythrodysaesthesia — especially capecitabine) [24] | Anti-metabolite → affects all rapidly dividing cells (GI mucosa, bone marrow, hair follicles). Hand-foot syndrome: drug accumulates in palms/soles (high thymidine phosphorylase expression in acral skin) → painful erythema, swelling, desquamation |
| Oxaliplatin | Peripheral neuropathy (dose-limiting) — acute cold-triggered dysaesthesia (tingling/pain in hands/feet/throat triggered by cold, reversible) + chronic cumulative sensory neuropathy (may be irreversible). Myelosuppression | Platinum-DNA adducts damage peripheral nerve axons. Acute cold sensitivity is due to oxaliplatin affecting voltage-gated sodium channels |
| Irinotecan | Early cholinergic diarrhoea (during/immediately after infusion — treat with atropine), late secretory diarrhoea (> 24 hours — treat with loperamide). Myelosuppression | Cholinergic diarrhoea: irinotecan inhibits acetylcholinesterase → excess ACh → increased GI motility. Late diarrhoea: direct mucosal damage by active metabolite SN-38 |
Other general chemotherapy complications:
- Febrile neutropenia: medical emergency. Fever (> 38.3°C once or > 38°C sustained for 1 hour) + ANC < 0.5 × 10⁹/L. Due to bone marrow suppression → impaired immune defence → overwhelming infection. Requires urgent broad-spectrum antibiotics (e.g., piperacillin-tazobactam) and G-CSF consideration
- Tumour lysis syndrome: rare in solid tumours (more common in haematological malignancies)
DPD deficiency: dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for 5-FU catabolism. ~3-5% of the population have partial DPD deficiency → severely impaired 5-FU metabolism → life-threatening toxicity (severe mucositis, diarrhoea, neutropenia). DPD testing before starting fluoropyrimidines is now recommended in many guidelines
| Drug Class | Key Side Effects | Mechanism |
|---|---|---|
| Anti-VEGF (bevacizumab) | Haemorrhage, impaired wound healing, arterial thromboembolic events, hypertension, proteinuria, GI perforation [24] | VEGF inhibition → impaired vascular integrity and angiogenesis (see Management section for details) |
| Anti-EGFR (cetuximab, panitumumab) | Acneiform rash (dose-dependent, correlates with efficacy), pruritus, nail changes (paronychia), diarrhoea, hypomagnesaemia, infusion reactions (cetuximab — chimeric antibody → more immunogenic than fully human panitumumab) [24] | EGFR is highly expressed in skin keratinocytes → EGFR inhibition → disruption of normal keratinocyte differentiation and barrier function → inflammatory rash |
| Immune checkpoint inhibitors (pembrolizumab, nivolumab) | Immune-related adverse events (irAEs): colitis, hepatitis, pneumonitis, dermatitis, thyroiditis, hypophysitis, adrenal insufficiency, type 1 DM | PD-1/CTLA-4 blockade removes immune "brakes" → T cells attack not only tumour but also normal tissues ("autoimmune-like" toxicity). Management: corticosteroids for most irAEs; may require permanent discontinuation |
| Timing | Complication | Mechanism |
|---|---|---|
| Acute (during/shortly after RT) | Radiation proctitis (diarrhoea, tenesmus, rectal bleeding, mucus discharge), radiation dermatitis (perineal skin erythema, desquamation), radiation cystitis (dysuria, frequency), fatigue, nausea | Direct radiation injury to rapidly dividing mucosal cells in the radiation field |
| Late (months to years) | Chronic radiation proctitis (recurrent PR bleeding, telangiectasiae on endoscopy), radiation fibrosis/stricture (bowel obstruction), radiation enteritis (if small bowel in field), fistula formation, secondary malignancy (rare), impaired wound healing (if RT given pre-operatively) | Radiation-induced vascular damage (obliterative endarteritis) → chronic tissue ischaemia → fibrosis and mucosal fragility. This is why pre-operative RT is preferred over post-operative RT for rectal cancer: post-operative RT is associated with increased fibrotic strictures [2] |
| Reproductive | Infertility (ovarian failure in females, impaired spermatogenesis in males), sexual dysfunction | Radiation damage to gonads and pelvic autonomic nerves |
These are essentially the symptoms/consequences of distant spread:
| Site of Metastasis | Complications | Pathophysiology |
|---|---|---|
| Liver | Hepatomegaly, jaundice (if biliary obstruction), ascites, portal hypertension, liver failure, pain (capsular stretching) | Most common site of CRC metastasis (portal venous drainage). Extensive hepatic replacement → loss of hepatic function |
| Lung | Dyspnoea, cough, haemoptysis, malignant pleural effusion | Haematogenous spread (portal → hepatic veins → IVC → lungs; or direct IVC drainage for distal rectal tumours) |
| Peritoneum | Malignant ascites, bowel obstruction (carcinomatosis causing multiple points of obstruction), Krukenberg tumour (ovarian metastasis) | Transcoelomic spread — tumour cells exfoliate from serosal surface |
| Bone | Pain (localised, constant, worse at night), pathological fractures, hypercalcaemia, spinal cord compression | Haematogenous spread. Bone metastases can be lytic (osteoclast activation by tumour-derived factors) |
| Brain | Headache, seizures, focal neurological deficits, personality change | Haematogenous spread. Less common in CRC than in lung or breast |
A systemic complication affecting up to 50-80% of patients with advanced CRC:
- Pathophysiology: tumour-derived cytokines (TNF-α, IL-1, IL-6) and proteolysis-inducing factor → muscle wasting (skeletal and cardiac), fat loss, anorexia, chronic inflammation
- Clinical features: > 5% unintentional weight loss over 6 months, sarcopenia, fatigue, functional decline
- Consequences: impaired treatment tolerance (cannot tolerate surgery or chemotherapy), poor wound healing, increased morbidity and mortality
- Management: nutritional support (high-calorie, high-protein diet; oral supplements; enteral/parenteral nutrition if needed), exercise programmes, appetite stimulants (megestrol, corticosteroids — short-term), emerging therapies (anti-IL-6, ghrelin agonists)
Rare but important to recognise:
- Trousseau syndrome: migratory thrombophlebitis / VTE (discussed above)
- Non-bacterial thrombotic endocarditis (marantic endocarditis): sterile fibrin vegetations on cardiac valves → systemic emboli
- Dermatomyositis: may be associated with underlying GI malignancy
- Acanthosis nigricans: velvety dark skin changes in axillae — associated with GI adenocarcinomas
Recurrence occurs in approximately 40% of CRC patients [3]. Most recurrences occur within the first 3 years. This is why structured surveillance is critical:
Follow-up schedule [3]:
| Period | Interval |
|---|---|
| First 2 years | Every 3 months |
| 3rd year | Every 6 months |
| 4th-5th year | Yearly |
| > 5 years | Considered to be in remission |
Investigations at each follow-up [3]:
- CEA, rigid sigmoidoscopy (for rectal cancer), LFT
- CT TAP / PET-CT annually
- Colonoscopy:
- Pre-op incomplete scope: within 6 months of surgery
- Pre-op complete scope: 1 year post-op, then at 3 years, 5 years, then every 5 years [3]
Metachronous tumours (new primary CRC diagnosed > 6 months after the original cancer) must be surveilled for [3]. This is distinct from local recurrence.
High Yield Summary
Disease complications: Obstruction (LBO — #1 cause in adults, left-sided predominance, closed-loop if ileocaecal valve competent → caecal perforation by Laplace's law), perforation (at tumour or diastatic caecal), haemorrhage (chronic occult → IDA; acute massive rare), fistula (colovesical → pneumaturia/faecaluria), abscess, Trousseau syndrome.
Surgical complications by timing:
- Immediate: bleeding, injury to adjacent structures (ureter, spleen, autonomic nerves), conversion to open
- Early (< 30d): SSI, ileus, anastomotic leak (day 5-7, presents with pain/fever/tachycardia/purulent drainage; Ix: CT shows pericolic collection; Mx: NBM + IV Abx + drainage ± re-operation), anastomotic bleeding
- Late (> 30d): stricture (balloon dilatation), fistula (enterocutaneous → conservative; rectovaginal/rectourinary → fecal diversion), adhesive SBO, LAR syndrome (urgency, incontinence, clustering; Mx: antidiarrhoeal, transanal irrigation, pelvic floor rehab, sacral nerve stimulation), perineal hernia (post-APR), impotence (15-50% males), recurrence (~40%)
Stoma complications: Early — necrosis, retraction, bleeding, skin irritation (worst with ileostomy — alkaline enzymatic output). Late — parastomal hernia (#1), prolapse, stenosis.
Chemotherapy complications: 5-FU/capecitabine → mucositis, hand-foot syndrome; oxaliplatin → peripheral neuropathy (cold-triggered, dose-limiting, may be irreversible); irinotecan → early cholinergic diarrhoea (atropine) + late secretory diarrhoea (loperamide). Febrile neutropenia = medical emergency. DPD deficiency → catastrophic 5-FU toxicity.
Targeted therapy complications: Anti-VEGF → bleeding, impaired wound healing, thromboembolism, GI perforation. Anti-EGFR → acneiform rash, hypomagnesaemia. Checkpoint inhibitors → immune-related AEs (colitis, hepatitis, pneumonitis, endocrinopathies).
Recurrence: ~40% of all CRC. Most within first 3 years. Follow-up: Q3m × 2 years → Q6m year 3 → yearly years 4-5. CEA + CT TAP + colonoscopy surveillance.
Active Recall – Complications of CA Colon
References
[1] Lecture slides: Hallmarks of cancer and relevance to therapy, carcinogenic factors and cancer prevention.pdf [2] Senior notes: Ryan Ho GI.pdf (Section 3.3.6 Colorectal Tumours, pp. 169, 176-177) [3] Senior notes: Maksim Surgery Notes.pdf (Post-operative complications and follow-up, pp. 107-108) [11] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf [12] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (p. 22) [24] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Complications, pp. 896, 902); MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 693, 699, 708) [27] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Intestinal obstruction — Strangulation, p. 617) [28] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (Complications of UC — Perforation, p. 675) [29] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Post-operative complications, pp. 902, 911); MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 699, 708)
High Yield Summary
Definition: CRC = adenocarcinoma arising from colonic/rectal epithelium (~95%); right-sided = proximal to splenic flexure, left-sided = distal to splenic flexure; rectum = below peritoneal reflection or within 15 cm of anal verge.
Epidemiology: #1 cancer in HK by incidence; M:F = 1.6:1; peak 60-70y; ~24% present at Stage IV; rising incidence in Asia.
Risk Factors: Age > 50, male, FHx (25% non-syndromal), FAP/Lynch (10% hereditary), IBD (UC > CD after 8-10y), adenomatous polyps, obesity/DM, red meat, smoking, alcohol. Protective: aspirin/NSAIDs, fibre, calcium/vitamin D, physical activity.
Pathways: CIN (85%) = Vogelstein adenoma-carcinoma sequence (APC → KRAS → SMAD4 → TP53), predominantly left-sided, MSS; MSI (15%) = defective MMR, predominantly right-sided, better prognosis, responds to immunotherapy.
Hereditary Syndromes: FAP (APC, 100% risk, thousands of polyps, prophylactic colectomy); Lynch (MMR genes, 40-80% risk, right-sided, extracolonic cancers — endometrial most common, Amsterdam criteria).
Clinical Features: RIGHT = bleed (IDA, vague pain, mass); LEFT = obstruct (CIBH, haematochezia, pencil stools, tenesmus). Constitutional symptoms, symptoms of metastases (liver > lung > bone > peritoneum). DRE is mandatory.
Spread: Direct (CRM in rectal CA), lymphatic (≥12 LN needed), haematogenous (liver #1 via portal vein; distal rectum → lung via IVC), transcoelomic (Krukenberg, Blumer's shelf).
Screening in HK: FIT every 2 years from age 50 → if positive, colonoscopy. High-risk: start 10 years before youngest affected relative or age 40. FAP: colonoscopy from 10-12y. Lynch: colonoscopy from 20-25y.
High Yield Summary
Approach: Always consider CRC in any patient > 50 with change in bowel habit, PR bleeding, unexplained IDA, abdominal mass, or intestinal obstruction.
Key DDx by scenario:
- CIBH: IBS (diagnosis of exclusion — no alarm features), IBD, diverticular disease, infectious/TB colitis, ischaemic colitis
- PR bleeding: Haemorrhoids (never assume without investigation), anal fissure, diverticular bleeding, angiodysplasia, IBD, UGI bleed (10-15% of haematochezia)
- IDA: CRC (right-sided), gastric/oesophageal CA, PUD, coeliac disease, angiodysplasia, menstrual loss
- Abdominal mass: CRC, appendiceal mass, Crohn's/TB, ovarian mass, lymphoma
- LBO: CRC (#1 cause), sigmoid volvulus, diverticular stricture, pseudo-obstruction
HK-specific pitfalls: TB colitis (mimics Crohn's and CRC), amoebic colitis. Always rule out TB before biologics.
Critical rule: Diverticulitis and CRC look similar on CT — always follow up with colonoscopy after acute episode resolves. IBS is a diagnosis of exclusion — never diagnose IBS without excluding organic pathology in at-risk patients.
High Yield Summary
Diagnosis: Gold standard is colonoscopy + biopsy showing adenocarcinoma. CT colonography is the alternative when colonoscopy is incomplete or contraindicated.
Critical colonoscopy principles: Must scope entire colon (synchronous tumours in 3-5%, polyps in 30-50%). Tattoo polypectomy sites. If obstructing tumour prevents complete scope → CT colonography pre-op + mandatory post-op colonoscopy.
Staging: CT TAP with contrast for all CRC. MRI pelvis for all rectal cancer (CRM assessment). PET-CT only if considering curative metastasectomy or equivocal CT findings.
CEA: NOT for screening/diagnosis. Roles: prognostication, treatment monitoring, detection of recurrence. Elevated in only ~50% of CRC. False positives: smoking, pregnancy, TB, IBD. Takes 4-6 weeks to normalise post-op.
Molecular testing (mandatory for all CRC): MMR/MSI (immunotherapy eligibility + Lynch screening), RAS (anti-EGFR eligibility), BRAF V600E (prognosis + Lynch exclusion + targeted therapy).
Key interpretation: MMR-deficient/MSI-H → checkpoint inhibitors work, better prognosis, MSI-H Stage II does NOT benefit from 5-FU chemo. RAS mutant → anti-EGFR will NOT work. BRAF V600E + MSI-H → sporadic (not Lynch).
High Yield Summary
Stage I: Surgery alone. Stage II: Surgery ± adjuvant chemo (if high-risk features: T4, LVI, PNI, poor differentiation, < 12 LN, positive margin, obstruction/perforation). MSI-H Stage II: do NOT give 5-FU chemo. Stage III: Surgery + adjuvant chemo (FOLFOX 3-6 months; 3 months XELOX if low-risk T1-3 N1). Stage IV: Molecular-guided systemic therapy ± curative metastasectomy if resectable oligometastatic.
Surgery: En-bloc resection + ≥ 12 LN. Right hemicolectomy for right-sided; left hemicolectomy/sigmoidectomy for left-sided. Laparoscopic preferred. Emergency: right → primary anastomosis; left → Hartmann's or stent as bridge.
Rectal cancer: MRI pelvis staging. Neoadjuvant chemoRT for cT3-4/N+/threatened CRM. TME standard. No neoadjuvant for colon cancer.
Metastatic CRC systemic therapy: MSI-H → checkpoint inhibitors first-line. MSS + RAS WT + left-sided → chemo + anti-EGFR. RAS mutant or right-sided → chemo + anti-VEGF. BRAF V600E → encorafenib + cetuximab.
Anti-VEGF (bevacizumab): contraindicated in haemorrhage, impaired wound healing, arterial thromboembolism. Stage IV only — no adjuvant role.
Anti-EGFR (cetuximab/panitumumab): ONLY for RAS wild-type. RAS mutant → constitutive pathway activation → anti-EGFR useless. BRAF mutant also unlikely to benefit.
High Yield Summary
Disease complications: Obstruction (LBO — #1 cause in adults, left-sided predominance, closed-loop if ileocaecal valve competent → caecal perforation by Laplace's law), perforation (at tumour or diastatic caecal), haemorrhage (chronic occult → IDA; acute massive rare), fistula (colovesical → pneumaturia/faecaluria), abscess, Trousseau syndrome.
Surgical complications by timing:
- Immediate: bleeding, injury to adjacent structures (ureter, spleen, autonomic nerves), conversion to open
- Early (< 30d): SSI, ileus, anastomotic leak (day 5-7, presents with pain/fever/tachycardia/purulent drainage; Ix: CT shows pericolic collection; Mx: NBM + IV Abx + drainage ± re-operation), anastomotic bleeding
- Late (> 30d): stricture (balloon dilatation), fistula (enterocutaneous → conservative; rectovaginal/rectourinary → fecal diversion), adhesive SBO, LAR syndrome (urgency, incontinence, clustering; Mx: antidiarrhoeal, transanal irrigation, pelvic floor rehab, sacral nerve stimulation), perineal hernia (post-APR), impotence (15-50% males), recurrence (~40%)
Stoma complications: Early — necrosis, retraction, bleeding, skin irritation (worst with ileostomy — alkaline enzymatic output). Late — parastomal hernia (#1), prolapse, stenosis.
Chemotherapy complications: 5-FU/capecitabine → mucositis, hand-foot syndrome; oxaliplatin → peripheral neuropathy (cold-triggered, dose-limiting, may be irreversible); irinotecan → early cholinergic diarrhoea (atropine) + late secretory diarrhoea (loperamide). Febrile neutropenia = medical emergency. DPD deficiency → catastrophic 5-FU toxicity.
Targeted therapy complications: Anti-VEGF → bleeding, impaired wound healing, thromboembolism, GI perforation. Anti-EGFR → acneiform rash, hypomagnesaemia. Checkpoint inhibitors → immune-related AEs (colitis, hepatitis, pneumonitis, endocrinopathies).
Recurrence: ~40% of all CRC. Most within first 3 years. Follow-up: Q3m × 2 years → Q6m year 3 → yearly years 4-5. CEA + CT TAP + colonoscopy surveillance.
CA Rectum
Colorectal adenocarcinoma arising in the rectum (within 15 cm from the anal verge), presenting with bleeding per rectum, tenesmus, and altered bowel habits, often requiring multimodal treatment including neoadjuvant chemoradiation and surgical resection.
CA Lung
Lung cancer is a malignant neoplasm arising from the epithelial cells of the bronchial tree or lung parenchyma, most commonly classified as non-small cell or small cell carcinoma.