Colorectal Cancer
Colorectal cancer is a malignant neoplasm arising from the epithelial lining of the colon or rectum, typically developing through an adenoma-to-carcinoma sequence.
Colorectal Cancer (CRC) — Definition, Epidemiology, Risk Factors, Anatomy, Etiology, Pathophysiology, Classification, and Clinical Features
Colorectal cancer (CRC) refers to malignant neoplasms arising from the epithelial lining (mucosa) of the large intestine, encompassing the colon (caecum, ascending, transverse, descending, sigmoid colon) and the rectum. The vast majority (> 95%) are adenocarcinomas — that is, cancers of glandular epithelial origin. The name tells you the story: "adeno-" = gland, "carcinoma" = epithelial malignancy.
Key conceptual points:
- CRC typically arises through a well-defined adenoma → carcinoma sequence over approximately 10–15 years, providing a window for screening and early intervention [1][2].
- A minority arise via the serrated neoplasia pathway or from flat/depressed lesions.
- Malignant polyps are defined as polyps in which neoplastic cells have penetrated the muscularis mucosae into the submucosa — this is the threshold because below the muscularis mucosae there are lymphatics, giving the tumour metastatic potential [3].
2. Epidemiology
- CRC is the 3rd most common cancer worldwide and the 2nd leading cause of cancer-related death globally (after lung cancer) [2].
- Incidence is highest in developed/westernised countries (Australia/NZ, Europe, North America, East Asia including Hong Kong, Japan, South Korea).
- There is a rising trend in younger adults (age < 50) — so-called "early-onset CRC" — now accounting for approximately 10% of new cases globally and prompting many guidelines to lower screening start age to 45 [4].
- Accounts for 16.5% of all new cancer cases (2013 data; by 2022 Hong Kong Cancer Registry data it remains the most common cancer by incidence) [1].
- > 90% of CRC occurs in patients aged ≥ 50 [1].
- M:F ratio ≈ 1.3:1 [1].
- 2nd leading cause of cancer death in both males and females in Hong Kong (after lung cancer) [1].
- Crude incidence rate: approximately 70–75 per 100,000 population.
- The Hong Kong government launched a Colorectal Cancer Screening Programme in 2016 for persons aged 50–75, using a two-tier approach (FIT → colonoscopy) [2].
| Site | Approximate % |
|---|---|
| Rectum | 30% |
| Sigmoid colon | 20% |
| Descending colon | 15% |
| Transverse colon | 10% |
| Ascending colon (including caecum) | 25% |
- Majority of CRC are left-sided [1].
- However, there is a recognized rightward shift in incidence with increasing age and in certain populations.
- Right-sided cancers tend to present later (more occult bleeding, less obstruction) because the bowel lumen is wider and stool is liquid.
Why Does Site Matter?
Left-sided CRC (descending, sigmoid, rectum): presents earlier with obstructive symptoms, change in bowel habit, bright red PR bleeding — because the lumen is narrower and stool is formed.
Right-sided CRC (caecum, ascending, transverse): presents insidiously with iron deficiency anaemia and occult blood loss — because the lumen is wide, stool is liquid, and tumours are often polypoid/fungating rather than annular.
3. Risk Factors
Think of these in a systematic framework: Demographics → Past Medical History → Family History → Social/Lifestyle → Protective Factors.
| Factor | Mechanism / Detail |
|---|---|
| Age > 50 | Dominant risk factor — cumulative somatic mutations with time; incidence rises steeply after 50 [1][3] |
| Male sex | ~30% higher incidence; possibly related to androgens, different lifestyle patterns, and lower uptake of screening |
| Racial background | Ashkenazi Jews have higher incidence (linked to APC I1307K variant); African Americans have higher incidence and worse outcomes [1] |
| Factor | Explanation |
|---|---|
| Previous CRC | Metachronous CRC risk; field cancerisation effect |
| Colonic adenomatous polyps | Adenoma-carcinoma sequence — higher risk if villous, > 1 cm, high-grade dysplasia [1][3] |
| Hereditary CRC syndromes | FAP, Lynch syndrome (HNPCC), MYH-associated polyposis, Peutz-Jeghers, juvenile polyposis, Cowden's syndrome [1][3][4] |
| Inflammatory bowel disease | UC > CD for CRC risk. Risk proportional to duration (> 8–10 years), extent (pancolitis > left-sided), severity of inflammation, and presence of primary sclerosing cholangitis (PSC). Dysplasia-carcinoma sequence rather than adenoma-carcinoma sequence [1][3] |
| Obesity / Central obesity | Insulin resistance → hyperinsulinaemia → elevated IGF-1 → promotes colonocyte proliferation; adipokine-mediated chronic inflammation [1][3] |
| Diabetes mellitus (DM) | Hyperinsulinaemia and IGF-1 promote mucosal proliferation. ~30% increased risk [1] |
| Acromegaly | IGF-1 acts as growth factor for colonic mucosal cells — increased colonocyte turnover [3] |
| Prior abdominal/pelvic radiation | Radiation-induced mucosal injury and chronic inflammation |
| Cholecystectomy (debated) | Theoretical: increased bile acid exposure to right colon, though evidence is weak |
- Family history of CRC present in ~10–15% of patients → confers approximately 4× increased risk [1].
- ~25% of CRC patients have a family history; ~10% have a familial syndrome (FAP, Lynch) [3].
- Family history of colonic adenomatous polyps also increases risk [1].
- First-degree relative with CRC diagnosed < 50 years → particularly high risk.
| Factor | Mechanism |
|---|---|
| Smoking | Carcinogens (polycyclic aromatic hydrocarbons, nitrosamines) → somatic mutations; smoking-related CRC often shows BRAF mutation and MSI [1] |
| Alcoholism | Acetaldehyde (ethanol metabolite) is a direct carcinogen; folate depletion impairs DNA repair [1] |
| Lack of physical exercise | Reduced gut motility → prolonged mucosal contact with carcinogens; insulin resistance pathway [1] |
| Dietary factors | Red and processed meat (heterocyclic amines, N-nitroso compounds from high-temperature cooking); lack of dietary fibre (less stool bulk → longer transit time → prolonged carcinogen exposure); high temperature cooking (generates carcinogenic compounds) [1] |
| High-fat Western diet | Increased bile acid secretion → secondary bile acids (deoxycholic acid) are co-carcinogens |
| Factor | Mechanism |
|---|---|
| Physical activity ≥ 150 min/week | Reduces insulin levels, decreases transit time, anti-inflammatory effect [1] |
| Dietary fibre (whole grains, beans, fruits, vegetables) | Increases stool bulk, dilutes carcinogens, reduces transit time, butyrate production by fermentation is anti-neoplastic [1] |
| Aspirin / NSAIDs | COX-2 inhibition → reduces prostaglandin E2 → decreases cell proliferation and angiogenesis, promotes apoptosis. Evidence strongest for aspirin ≥ 75 mg daily for ≥ 5 years [1][3] |
| Avoid alcohol and smoking | Removes direct carcinogenic exposure [1] |
| Calcium and Vitamin D | Calcium binds bile acids and free fatty acids; Vitamin D has anti-proliferative effects |
| HRT (post-menopausal women) | Modest protective effect, possibly hormonal modulation of bile acid metabolism |
High Yield
The classic exam question: "What are the protective factors against CRC?" → Remember: Exercise, Fibre, Aspirin/NSAIDs, Calcium/Vitamin D, avoid red meat/alcohol/smoking.
4. Anatomy and Function of the Colon and Rectum
Understanding the anatomy is essential because it determines:
- Clinical presentation (right vs. left vs. rectal)
- Surgical approach (which operation for which site)
- Lymphatic and venous drainage (determines metastatic patterns)
- Relationship to surrounding structures (determines local invasion patterns)
The large bowel extends from the ileocaecal valve to the anus (~1.5 m).
| Segment | Length | Key Features |
|---|---|---|
| Caecum | ~6 cm | Blind pouch below ileocaecal valve; intraperitoneal; appendix arises from posteromedial wall |
| Ascending colon | ~15 cm | Retroperitoneal (fixed); right paracolic gutter |
| Hepatic flexure | — | Close to right kidney, duodenum, gallbladder |
| Transverse colon | ~45 cm | Intraperitoneal, suspended by transverse mesocolon; attached to greater omentum |
| Splenic flexure | — | Highest and most fixed point of colon; close to spleen, tail of pancreas, left kidney |
| Descending colon | ~25 cm | Retroperitoneal (fixed) |
| Sigmoid colon | ~40 cm | Intraperitoneal, on a mesentery (sigmoid mesocolon); highly mobile |
| Rectum | ~12–15 cm | Begins at S3; upper 1/3 covered by peritoneum anteriorly and laterally; middle 1/3 anteriorly only; lower 1/3 completely extraperitoneal |
The rectum is divided into three parts based on distance from the anal verge: [1]
| Division | Distance from Anal Verge |
|---|---|
| Upper rectum | 12–15 cm |
| Mid rectum | 7–12 cm |
| Lower rectum | 0–7 cm (some define as < 5 cm) |
- The mesorectum is the fatty envelope surrounding the rectum containing lymph nodes, blood vessels, and nerves, enclosed by the mesorectal fascia (fascia propria of the rectum). This is the target of total mesorectal excision (TME) — the gold standard surgical technique for rectal cancer.
- Circumferential resection margin (CRM): the closest distance between the tumour and the mesorectal fascia. A positive CRM (≤ 1 mm) strongly predicts local recurrence.
- The dentate (pectinate) line at approximately 2 cm from the anal verge marks the transition from columnar to squamous epithelium and is the boundary between the internal and external sphincters' territories.
| Segment | Arterial Supply | Venous Drainage |
|---|---|---|
| Caecum → Splenic flexure | Superior mesenteric artery (SMA): ileocolic, right colic, middle colic | Superior mesenteric vein → Portal vein |
| Splenic flexure → Upper rectum | Inferior mesenteric artery (IMA): left colic, sigmoid arteries, superior rectal | Inferior mesenteric vein → Splenic vein → Portal vein |
| Mid & Lower rectum | Middle rectal arteries (from internal iliac) and inferior rectal arteries (from internal pudendal) | Middle and inferior rectal veins → Internal iliac vein → IVC (systemic) |
Why Does Venous Drainage Matter for Metastasis?
Liver is usually the first site of metastasis since the venous drainage of the intestinal tract is via the portal venous system [1].
Lung can be the first site of metastasis for tumours in the distal rectum because the inferior rectal veins drain into the IVC rather than the portal venous system, bypassing the liver [1].
This is a classic exam question — you must understand that the watershed between portal and systemic venous drainage at the mid-rectum explains why distal rectal cancers can metastasise to lungs first.
- Follows the arterial supply: epicolic → paracolic → intermediate (along named vessels) → principal (at origin of SMA/IMA).
- Regional lymph node involvement is the most common form of spread and usually precedes distant metastasis [1].
- Minimum of 12 lymph nodes should be harvested for adequate staging (AJCC recommendation).
- Sympathetic: via superior and inferior hypogastric plexuses → relevant for erection (sympathetic = ejaculation) and bladder function.
- Parasympathetic: pelvic splanchnic nerves (S2–S4) → relevant for erection and bladder emptying.
- Damage during rectal surgery (especially low anterior resection and abdominoperineal resection) can cause urinary retention, erectile dysfunction, and ejaculatory failure.
- Right colon: primarily absorbs water and electrolytes; stool is liquid. This is why right-sided cancers cause iron deficiency anaemia (chronic occult blood loss mixed into liquid stool) rather than overt obstruction.
- Left colon: stores and propels formed stool. Narrower lumen + formed stool = higher risk of obstructive symptoms and altered bowel habit with left-sided cancers.
- Rectum: reservoir function and controlled evacuation. Rectal cancer disrupts the call to stool, causing tenesmus (a feeling of incomplete evacuation due to tumour mass mimicking stool) and mucoid/bloody stool.
5. Etiology and Pathophysiology
5.1 The Adenoma-Carcinoma Sequence (Vogelstein Model)
MOST colorectal cancers arise from adenomatous polyps by accumulation of mutations in what has come to be known as the adenoma-carcinoma sequence [1].
This is the chromosomal instability (CIN) pathway and accounts for 60–70% of sporadic CRC [1] (some sources say up to 85% [3]).
Key Genes:
-
APC gene (Adenomatous Polyposis Coli, chromosome 5q21) — a tumour suppressor gene
- APC protein is a "gatekeeper" — it degrades β-catenin in the Wnt signalling pathway. When APC is lost, β-catenin accumulates → enters the nucleus → activates transcription of proliferative genes (c-MYC, cyclin D1).
- Mutations in both alleles are necessary to initiate polyp formation (Knudson's two-hit hypothesis) [1].
- Majority of mutations are premature stop codons → truncated APC protein [1].
- APC inactivation alone does not result in carcinoma but sets the stage for accumulation of genetic damage that results in malignancy [1].
-
K-RAS gene (Kirsten Rat Sarcoma, chromosome 12p) — an oncogene
- K-RAS is a signalling molecule in the EGFR pathway which leads to uncontrolled cell division [1].
- RAS is a GTPase. Gain-of-function mutations lock RAS in the "ON" (GTP-bound) state → constitutive activation of RAF-MEK-ERK proliferative cascade.
- Important clinically: KRAS mutant tumours do NOT respond to anti-EGFR therapy (cetuximab, panitumumab) — the mutation is downstream of EGFR, so blocking the receptor is futile.
- Other EGFR signalling molecules such as BRAF have also been implicated in CRC pathogenesis and progression [1].
-
DCC / SMAD4 (chromosome 18q) — tumour suppressor
- DCC = "Deleted in Colorectal Cancer." SMAD4 is a mediator of TGF-β signalling (anti-proliferative pathway). Loss removes the brake on cell growth.
-
TP53 gene (chromosome 17p) — tumour suppressor ("guardian of the genome")
- Initiates apoptosis in cells with irreparable genetic damage [1].
- Loss of p53 is the final "gate" — allows severely damaged cells to survive and accumulate further mutations, tipping the adenoma into frank carcinoma.
-
MYH gene — base excision repair gene [1]
- Biallelic germline mutations cause MYH-associated polyposis (MAP) — autosomal recessive, phenotypically similar to attenuated FAP.
- Colorectal polyps are either adenomatous or hyperplastic [1].
- Adenomatous polyps account for 2/3 of colorectal polyps [1].
- Subtypes by histology and malignant potential:
- Hyperplastic polyps account for 1/3 of colorectal polyps and are NOT pre-malignant except for rare syndrome known as hyperplastic polyposis [1].
- Advanced adenoma is defined as any one of: high-grade dysplasia, size > 1 cm, villous histology [3].
- Progression from adenoma to carcinoma takes at least 10 years on average [1] — this is why screening every 10 years (colonoscopy) is the standard interval.
- Some colonic carcinoma arises from non-polypoid adenomas that are flat or depressed [1].
Morphology of polyps: sessile (flat) / pedunculated (with a stalk) [3]
Paris Classification of Early GI Cancer [3]:
- 0-I (polypoid): 0-Ip (pedunculated) vs. 0-Is (sessile)
- 0-II (non-polypoid): 0-IIa (flat elevated), 0-IIb (completely flat), 0-IIc (superficially depressed)
- 0-III (excavated)
Endoscopic features suggesting malignancy: friability, induration, ulceration, firm consistency [3].
High Yield
A common student mistake: confusing hyperplastic polyps with adenomatous polyps. Hyperplastic polyps are NOT pre-malignant (except in rare hyperplastic polyposis / serrated polyposis syndrome). Only adenomatous polyps and sessile serrated polyps carry meaningful malignant potential. The exam loves testing this distinction.
Many of the remaining CRC are thought to arise from mutations in the MSI pathway — accounting for ~15% of sporadic CRC [1][3].
What are microsatellites?
- Short tandem repeats of DNA (e.g., CACACACA...) scattered throughout the genome. These are prone to replication errors (slippage during DNA polymerase activity).
- Normally, the DNA mismatch repair (MMR) system (MLH1, MSH2, MSH6, PMS2) corrects these errors.
- When MMR is defective → errors accumulate in microsatellite regions → microsatellite instability (MSI) → frameshift mutations in genes with microsatellite sequences in their coding regions (e.g., TGFβRII, BAX, IGFIIR) → loss of growth control and apoptosis resistance.
In sporadic CRC:
- MSI is most often caused by epigenetic silencing of MLH1 via promoter hypermethylation (not a germline mutation).
- Associated with CpG island methylator phenotype (CIMP) and often co-occurs with BRAF V600E mutation.
- Tend to be right-sided, mucinous, poorly differentiated, with prominent tumour-infiltrating lymphocytes (TILs).
- Paradoxically better prognosis stage-for-stage than microsatellite stable (MSS) cancers.
- Poor response to 5-FU but excellent response to immune checkpoint inhibitors (pembrolizumab, nivolumab) because high mutational burden → more neoantigens → more immunogenic.
In hereditary CRC (Lynch syndrome):
- Germline mutation in one of the MMR genes → inherited one defective allele → second hit (somatic) knocks out the remaining allele → MSI.
- Key genes: MLH1 (90%), MSH2, MSH6 (10%) [1].
A "third pathway" increasingly recognized:
- Sessile serrated lesions (SSLs) / traditional serrated adenomas (TSAs) → carcinoma.
- BRAF mutation → CIMP → MLH1 methylation → MSI-high cancers.
- Right-sided predominance; flat morphology makes them easy to miss at colonoscopy (the "interval cancer" problem).
- In ulcerative colitis and Crohn's colitis, chronic mucosal inflammation → dysplasia → carcinoma (bypasses the classic polyp stage).
- Key drivers: chronic inflammation → oxidative stress → NF-κB activation → p53 mutation early (unlike sporadic CRC where p53 loss is late).
- Risk factors: duration > 8–10 years, pancolitis, PSC co-existence, family history of CRC.
6. Hereditary Colorectal Cancer Syndromes
Account for ~10% of CRC (remaining 90% are sporadic) [4].
| Feature | Detail |
|---|---|
| Gene | APC gene (chromosome 5q21) |
| Inheritance | Autosomal dominant (AD) with near-complete penetrance |
| Polyps | Hundreds to thousands of adenomatous polyps throughout the colon, beginning in adolescence |
| CRC risk | ~100% if untreated by age 40–50 |
| Mean age CRC | ~39 years |
| Extra-colonic | Duodenal/periampullary adenomas (most common extra-colonic malignancy in FAP); desmoid tumours; osteomas; congenital hypertrophy of retinal pigment epithelium (CHRPE); epidermoid cysts; thyroid cancer; hepatoblastoma (children) |
| Gardner syndrome | FAP + osteomas + desmoid tumours + epidermoid cysts [4] |
| Turcot syndrome | FAP + CNS tumours (medulloblastoma, glioblastoma) [4] |
| Attenuated FAP | < 100 polyps, later onset, right-sided predominance |
| Treatment | Prophylactic surgery: (1) Total proctocolectomy + ileal pouch-anal anastomosis (IPAA) — gold standard; (2) Total abdominal colectomy with ileorectal anastomosis (IRA) — requires lifelong rectal surveillance [1] |
| Surveillance | Annual colonoscopy from age 10–12; OGD from age 25–30 |
MOST common inherited colorectal cancer syndrome [1].
| Feature | Detail |
|---|---|
| Gene | MMR genes: MLH1 (most common), MSH2, MSH6, PMS2, EPCAM [1] |
| Inheritance | Autosomal dominant (AD) |
| Proportion of CRC | ~3% of all CRC (and 2% of endometrial cancer) [1] |
| Lifetime CRC risk | ~70–80% [1] |
| Mean age at CRC | 40–45 years, some in their 20s [1] |
| Colonic features | Predominantly right-sided; arise from adenomas that tend to be larger, flatter, and more likely to have high-grade dysplasia or villous histology; adenoma-carcinoma sequence progresses much more rapidly [1] |
| Extra-colonic cancers | GI: gastric, pancreas, biliary, small intestine; Gyn: endometrial (most common extra-colonic cancer), ovarian; Uro: renal pelvis, ureter; CNS: glioma; Others: sebaceous gland tumours [1] |
| Muir-Torre syndrome | Visceral neoplasms (colorectal, endometrium, ovary) + cutaneous neoplasms (keratoacanthoma, sebaceous tumours) [4] |
Diagnostic Criteria — Amsterdam Criteria (3-2-1 rule): [1]
- 3 or more relatives with Lynch syndrome-associated cancer
- 2 or more successive generations affected
- 1 or more cancer diagnosed before age 50
- FAP should be excluded
- Tumours should be verified by pathological examination
Revised Bethesda Criteria (select patients for MSI analysis): [1]
- CRC diagnosed < 50 years
- CRC + ≥ 1 first-degree relative with HNPCC-related tumour, one diagnosed < 50
- CRC + ≥ 2 first-/second-degree relatives with HNPCC-related tumour regardless of age
- Synchronous/metachronous CRC or other HNPCC-related tumours regardless of age
- CRC with MSI-H-like histology (TILs, Crohn's-like reaction, mucinous, signet ring, medullary) diagnosed < 60
Surveillance: [1]
- Colonoscopy: starting age 20–25, every 1 year (annual)
- OGD with biopsy of gastric antrum: starting age 30–35, every 1–2 years
- USG kidney and bladder: starting age 30–35, every 1–2 years
- Pelvic examination, endometrial biopsy, transabdominal/transvaginal USG, CA-125: starting age 30–35, every 1–2 years
Treatment: [1]
- Total abdominal colectomy with ileorectal anastomosis (IRA) — because of high risk of metachronous CRC, segmental resection is inadequate
- Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) — for risk-reducing gynaecological surgery
| Syndrome | Gene (Inheritance) | Key Features | Associated Cancers |
|---|---|---|---|
| MYH-associated polyposis (MAP) | MUTYH (AR) | DDx of FAP with fewer adenomas (10–100); very high CRC risk [4] | CRC |
| Peutz-Jeghers syndrome (PJS) | STK11 (AD) | Hamartomatous polyps (small bowel > large bowel > stomach); mucosal pigmentation of buccal mucosa & lips [3][4] | Breast, pancreas, stomach, CRC |
| Juvenile polyposis syndrome (JPS) | SMAD4, BMPR1A (AD) | Hamartomatous polyps; associated with HHT if SMAD4 mutation; juvenile polyposis syndrome increases CRC risk, but a single juvenile polyp per se does not [4] | CRC |
| Cowden's syndrome | PTEN (AD) | Multiple hamartomas (periorbital warty trichilemmomas); increased CRC risk [4] | Breast, thyroid, CRC |
| Serrated polyposis syndrome | Polygenic/unknown | ≥ 5 serrated polyps proximal to sigmoid each ≥ 5 mm, or ≥ 20 serrated polyps throughout colon | CRC (via serrated pathway) |
7. Classification
- Adenocarcinoma (> 95%): the vast majority
- Well-differentiated / Moderately-differentiated / Poorly-differentiated
- Mucinous adenocarcinoma (> 50% mucinous component) — more common in MSI-H; worse prognosis if MSS
- Signet ring cell carcinoma — poor prognosis
- Neuroendocrine carcinoma (rare)
- Squamous cell carcinoma (very rare, more typical of anal canal)
- Adenosquamous carcinoma
- Undifferentiated carcinoma
| CMS | Name | Frequency | Features |
|---|---|---|---|
| CMS1 | MSI-Immune | 14% | MSI-H, CIMP-H, BRAF mutation, high immune infiltration, good prognosis |
| CMS2 | Canonical | 37% | CIN, WNT/MYC activation, "classic" adenoma-carcinoma sequence |
| CMS3 | Metabolic | 13% | Mixed MSI, KRAS mutations, metabolic deregulation |
| CMS4 | Mesenchymal | 23% | TGF-β activation, stromal infiltration, worst prognosis |
T — Primary Tumour:
| Stage | Definition |
|---|---|
| Tis | Carcinoma in situ (intramucosal, no invasion through muscularis mucosae) |
| T1 | Invades submucosa |
| T2 | Invades muscularis propria |
| T3 | Invades through muscularis propria into pericolorectal tissues (subserosa/mesorectum) |
| T4a | Penetrates to the surface of the visceral peritoneum |
| T4b | Directly invades or is adherent to other organs/structures |
N — Regional Lymph Nodes:
| Stage | Definition |
|---|---|
| N0 | No regional LN metastasis |
| N1a | 1 regional LN |
| N1b | 2–3 regional LNs |
| N1c | Tumour deposits in subserosa/mesentery without regional LN metastasis |
| N2a | 4–6 regional LNs |
| N2b | ≥ 7 regional LNs |
M — Distant Metastasis:
| Stage | Definition |
|---|---|
| M0 | No distant metastasis |
| M1a | 1 site/organ without peritoneal metastasis |
| M1b | ≥ 2 sites/organs without peritoneal metastasis |
| M1c | Peritoneal metastasis ± other site involvement |
Stage Grouping:
| Dukes | Definition | Approximate TNM Equivalent |
|---|---|---|
| A | Confined to bowel wall (not through muscularis propria) | T1-2 N0 |
| B | Through bowel wall, no LN | T3-4 N0 |
| C | Lymph node involvement | Any T, N1-2 |
| D | Distant metastasis | M1 |
Mode of metastasis: Haematogenous / Lymphatic / Contiguous / Transperitoneal [1].
| Mode | Details |
|---|---|
| Lymphatic | Regional LN is the most common form of spread and usually precedes distant metastasis [1]. Follows arterial supply: epicolic → paracolic → intermediate → principal nodes |
| Haematogenous | Liver is usually the first site of metastasis (portal venous drainage) [1]. Lung can be first for distal rectal tumours (systemic venous drainage via inferior rectal veins → IVC) [1]. Also: bone, brain, adrenals |
| Direct / Contiguous | Local invasion into adjacent structures (e.g., bladder, uterus, small bowel, abdominal wall) |
| Transperitoneal (Transcoelomic) | Serosal breach → peritoneal seeding → peritoneal carcinomatosis; can cause Krukenberg tumours (ovarian metastases) |
9. Clinical Features
The clinical presentation of CRC depends critically on tumour location and stage. Early CRC is often asymptomatic — this is why screening is so important.
Red Flags for CRC in Primary Care
Any patient ≥ 50 (or younger with risk factors) presenting with:
- New iron deficiency anaemia (especially males and post-menopausal females)
- Change in bowel habit > 4 weeks
- Rectal bleeding (especially dark blood mixed with stool)
- Unexplained weight loss
- Abdominal mass → must be investigated with colonoscopy until proven otherwise.
9.2 Symptoms
| Symptom | Pathophysiological Basis |
|---|---|
| Iron deficiency anaemia (most common presentation) | Chronic occult blood loss from friable, ulcerated tumour surface. Stool is liquid in the right colon → blood is mixed into stool and occult (not visible). Right-sided tumours are often large and fungating (polypoid), so they bleed chronically. The patient presents with fatigue, dyspnoea, pallor |
| Vague right iliac fossa / abdominal discomfort | Tumour distension of caecal wall; dull visceral pain (innervated by T10–T12 splanchnic nerves) |
| Palpable right iliac fossa mass | Advanced tumour growing to a large size before causing symptoms (wide caecal lumen accommodates growth) |
| Weight loss / anorexia | Tumour metabolic demands (cancer cachexia); TNF-α and IL-6 release suppress appetite and induce catabolism |
| Occult PR bleeding | Blood mixed into liquid stool; patient usually unaware — detected only on FOBT/FIT or by finding anaemia |
Why does right-sided CRC rarely cause obstruction? Because the caecum has the widest lumen of the colon (~7.5 cm diameter), and stool at this point is liquid. Even a large tumour cannot easily occlude the lumen.
| Symptom | Pathophysiological Basis |
|---|---|
| Change in bowel habit (most common) | Tumour narrows the lumen (left-sided cancers are often annular/constricting "apple core" lesions). Formed stool cannot pass easily → alternating constipation and diarrhoea. The constipation is from obstruction; the diarrhoea is from overflow of liquid stool past the obstruction and increased mucus secretion |
| Colicky abdominal pain | Bowel distension proximal to partial obstruction → stretch of bowel wall → intermittent (colicky) visceral pain |
| PR bleeding (bright or dark red) | Stool is formed and abrades the tumour surface; blood is less diluted so more visible. Sigmoid/rectal tumours bleed more overtly |
| Sensation of incomplete evacuation | Tumour bulk in the sigmoid creates a mass effect mimicking residual stool |
| Large bowel obstruction | Progressive luminal narrowing by annular tumour → complete obstruction. Presents with absolute constipation (no stool or flatus), abdominal distension, colicky pain, vomiting (late feature — "faeculent vomiting") |
| Symptom | Pathophysiological Basis |
|---|---|
| Fresh PR bleeding / blood mixed with stool | Direct contact of formed stool with tumour; rectal tumours are close to the anal verge so blood is bright red and visible on stool or toilet paper |
| Tenesmus ("tenesmus" from Latin "to strain") | Tumour mass in the rectum stimulates stretch receptors → brain interprets this as "there is stool to pass" → repeated urge to defaecate with a feeling of incomplete evacuation |
| Mucous discharge | Mucin-secreting tumour (especially mucinous adenocarcinoma); villous rectal adenomas also secrete copious mucus |
| Change in stool calibre ("pencil-thin stools") | Annular constricting tumour narrows the rectal lumen → stool is moulded into a narrower shape |
| Rectal pain | Late sign; indicates invasion beyond the rectal wall into the perirectal tissues, sacral plexus, or pelvic sidewall — somatic pain (well-localised, constant, aching) |
| Urinary symptoms (frequency, haematuria, pneumaturia) | Direct invasion into the bladder (colovesical fistula) → air and faecal material in urine (pathognomonic pneumaturia = bubbles in urine) |
| Fistulae (rectovaginal) | Direct invasion into the vagina → passage of stool or flatus per vagina |
| Symptom | Pathophysiological Basis |
|---|---|
| Weight loss | Cancer cachexia: TNF-α, IL-1, IL-6 → protein catabolism, lipolysis, anorexia |
| Anorexia | Cytokine-mediated hypothalamic suppression of appetite |
| Fatigue / malaise | Anaemia + cancer cachexia + chronic disease |
| Fever (rare) | Tumour necrosis → pyrogen release; also consider superimposed abscess |
| Symptom | Pathophysiological Basis |
|---|---|
| Right upper quadrant pain / hepatomegaly | Liver metastases stretching Glisson's capsule |
| Jaundice | Hepatic metastases compressing intrahepatic bile ducts; less commonly hilar LN compression |
| Cough / dyspnoea / haemoptysis | Pulmonary metastases |
| Bone pain | Skeletal metastases (rare, late) |
| Ascites | Peritoneal carcinomatosis blocking peritoneal lymphatic drainage; or liver failure from massive hepatic metastases |
| Abdominal distension | Peritoneal carcinomatosis with ascites; or bowel obstruction from carcinomatosis |
CRC may present as surgical emergencies — these are high yield [5]:
| Presentation | Mechanism |
|---|---|
| Large bowel obstruction | Annular tumour completely occluding the lumen. Most commonly left-sided (sigmoid > descending). Presents with absolute constipation, progressive abdominal distension, colicky pain, vomiting. CRC is the commonest cause of large bowel obstruction in adults [5] |
| Perforation | Tumour perforates through the bowel wall → faecal peritonitis (free perforation) or localised abscess (contained perforation). Also: caecal perforation from a competent ileocaecal valve — a closed-loop obstruction where the obstructing tumour is in the sigmoid but the caecum distends until it perforates (Law of Laplace: wall tension is highest where diameter is greatest) |
| Haemorrhage | Massive lower GI bleeding from erosion into a major vessel by the tumour — uncommon but life-threatening |
9.3 Signs
| Sign | Significance |
|---|---|
| Pallor | Iron deficiency anaemia from chronic occult blood loss |
| Cachexia / wasting | Advanced disease; cancer cachexia |
| Koilonychia | Severe iron deficiency (spoon-shaped nails; "koilos" = hollow in Greek) |
| Angular stomatitis / glossitis | Iron deficiency |
| Lymphadenopathy | Left supraclavicular node (Virchow's node / Troisier's sign) — indicates advanced metastatic GI malignancy via the thoracic duct |
| Sister Mary Joseph nodule | Periumbilical metastatic nodule — indicates peritoneal carcinomatosis |
| Acanthosis nigricans | Dark velvety hyperpigmentation in axillae/neck — paraneoplastic (associated with GI adenocarcinomas; mediated by IGF-1-like factors) |
| Mucocutaneous pigmentation | Peutz-Jeghers syndrome (lips, buccal mucosa) — clue to hereditary aetiology |
| Sign | Significance |
|---|---|
| Palpable abdominal mass | Right iliac fossa mass (caecal/ascending colon cancer); may also be palpable in left iliac fossa (sigmoid cancer). A mass suggests at least T3/T4 disease |
| Hepatomegaly (irregular, hard, nodular) | Liver metastases |
| Ascites (shifting dullness, fluid thrill) | Peritoneal carcinomatosis or massive liver metastases |
| Abdominal distension + tympanic percussion | Bowel obstruction; distended loops of large bowel |
| Visible peristalsis | Obstructed bowel proximal to tumour (more common in thin patients) |
| Tenderness / peritonism | Perforation (generalised peritonitis) or localised abscess |
| High-pitched / tinkling bowel sounds | Mechanical bowel obstruction (bowel trying to push content past obstruction) |
| Absent bowel sounds | Late obstruction / peritonitis (paralytic ileus) |
DRE is mandatory in any patient with suspected CRC. Up to 75% of rectal cancers are palpable on DRE.
| Finding | Significance |
|---|---|
| Palpable rectal mass | Hard, irregular, ulcerated, fixed or tethered mass suggests rectal cancer. Note: distance from anal verge (determines surgical approach — APR vs. LAR), size, circumferential involvement, fixity (mobile vs. tethered vs. fixed to pelvic structures) |
| Blood on examining finger | Suggests mucosal lesion (tumour, polyp, or other pathology) |
| Sphincter tone assessment | Important pre-operatively, especially if considering sphincter-sparing surgery |
| Anterior rectal wall invasion | In males: assess prostate involvement. In females: assess rectovaginal septum |
| Manifestation | Mechanism |
|---|---|
| Nephrotic syndrome (membranous nephropathy) | Tumour antigens deposited in glomerular basement membrane |
| Dermatomyositis | Immune-mediated paraneoplastic phenomenon |
| Venous thromboembolism (Trousseau syndrome) | Tumour-derived tissue factor and mucin activate the coagulation cascade → hypercoagulable state |
| Streptococcus bovis bacteraemia | S. bovis (now S. gallolyticus) bacteraemia or endocarditis is strongly associated with occult CRC — always colonoscope these patients! |
Clinical Pearl
Streptococcus gallolyticus (formerly S. bovis) bacteraemia = COLONOSCOPY. The association is so strong that any patient with S. gallolyticus bacteraemia or endocarditis should have a colonoscopy to rule out CRC or colonic polyps, regardless of other symptoms.
| Feature | Right-Sided | Left-Sided / Rectal |
|---|---|---|
| Morphology | Polypoid / fungating / exophytic | Annular / constricting ("apple core") |
| Luminal diameter | Wide | Narrow |
| Stool consistency at site | Liquid | Formed |
| Typical presentation | Iron deficiency anaemia, occult blood, RIF mass, weight loss | Change in bowel habit, PR bleeding, obstruction, tenesmus |
| Obstruction | Uncommon | Common |
| Molecular | More likely MSI-H, BRAF mutant, CMS1 | More likely CIN, CMS2 |
| Response to anti-EGFR | Poorer | Better (if RAS/BRAF wild-type) |
| Prognosis (stage IV) | Worse | Better |
Nodal involvement is the single MOST important prognostic factor in CRC [1].
- 4 or more involved LN predicts a poor survival [1].
- T stage is the single most significant predictor of LN metastasis: T1 = 5%, T2 = 20%, T3–4 = > 50% [1].
- Lymphovascular invasion [1]
- Perineural invasion [1]
- Grade of differentiation (well vs. poorly differentiated) [1]
- Molecular factors: MMR deficiency, RAS and BRAF mutation status [1]
High Yield Summary
Definition: CRC = adenocarcinoma of the colon/rectum (> 95%). Arises from adenoma-carcinoma sequence over ~10 years.
Epidemiology (HK): Commonest cancer; > 90% aged ≥ 50; M > F (1.3:1); 2nd leading cause of cancer death.
Risk Factors: Age > 50, male, family history (10–15%), hereditary syndromes (FAP, Lynch — 10%), IBD (UC > CD), red/processed meat, low fibre, alcohol, smoking, obesity, DM, acromegaly. Protective: exercise, fibre, aspirin/NSAIDs.
Key Hereditary Syndromes:
- FAP: APC gene, AD, hundreds of polyps, 100% CRC if untreated → prophylactic colectomy.
- Lynch: MMR genes (MLH1 most common), AD, 70–80% CRC risk, right-sided, rapid adenoma-carcinoma, Amsterdam 3-2-1 rule → annual colonoscopy from age 20–25.
Pathogenesis: (1) CIN pathway (APC → K-RAS → SMAD4 → p53) — 60–85%; (2) MSI pathway (MMR deficiency) — 15%; (3) Serrated pathway.
Clinical Features by Site:
- Right-sided: IDA, occult bleeding, RIF mass.
- Left-sided: change in bowel habit, PR bleeding, obstruction.
- Rectal: fresh PR bleeding, tenesmus, mucus discharge.
- Emergencies: LBO (commonest cause in adults), perforation, haemorrhage.
Metastasis: Liver first (portal drainage) except distal rectum → lung first (systemic drainage). Regional LN most common overall.
Key Signs: Pallor, palpable mass, hepatomegaly, Virchow's node, Sister Mary Joseph nodule, DRE mass. DRE is mandatory.
Prognosis: LN involvement is the single most important prognostic factor. 5-year survival: Stage I 90%, II 60–80%, III 60%, IV 10%.
Active Recall - CRC Definition, Epidemiology, Risk Factors, Pathophysiology, and Clinical Features
[1] Senior notes: felixlai.md (Colorectal Cancer sections: pages 675–712) [2] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf [3] Senior notes: maxim.md (Colorectal carcinoma section: pages 85, 198, 203, 205, 212–215) [4] Senior notes: maxim.md (Familial colon cancer syndromes table: page 198, 203) [5] Lecture slides: GC 202. Surgery may cure your cancer Surgical oncology.pdf
Differential Diagnosis of Colorectal Cancer
The differential diagnosis of CRC is really the differential of its presenting symptoms. Since CRC has protean presentations — anaemia, change in bowel habit, PR bleeding, abdominal mass, bowel obstruction — you need to think about what else can cause each of those symptom complexes. The key clinical skill is to never dismiss these symptoms until CRC has been excluded, especially in patients ≥ 50.
Let me organise the differentials by the three major clinical presentations, then provide a unifying approach.
1. Approach to Differential Diagnosis by Presentation
This is the classic presentation of right-sided CRC — the patient presents to a GP or medical clinic with fatigue, pallor, and microcytic anaemia. The differential includes any cause of chronic GI blood loss:
| Differential | Key Distinguishing Features | Why It Can Mimic CRC |
|---|---|---|
| Angiodysplasia | Most common in age > 65; dilated tortuous submucosal vessels lacking smooth muscle; often in caecum/ascending colon; bleeding is venous and tends to be less massive than diverticular bleeding [1] | Right-sided location, occult blood loss, presents as IDA in elderly — identical to right-sided CRC |
| Peptic ulcer disease | Epigastric pain, NSAID/H. pylori history; may cause IDA from chronic erosive gastritis or ulcer ooze | Upper GI cause of IDA that must be excluded — always do OGD as well as colonoscopy in unexplained IDA |
| Coeliac disease | Malabsorption (diarrhoea, steatorrhoea, weight loss), anti-tTG antibodies positive; iron malabsorption rather than blood loss | Can cause IDA through poor duodenal iron absorption; younger patients; must consider in IDA workup |
| Gastric cancer | Weight loss, early satiety, epigastric mass; more common in East Asia | Chronic occult blood loss; like CRC can cause IDA |
| Diverticular bleeding | Painless profuse haematochezia — typically acute and self-limiting rather than chronic; right-sided diverticula common in Asians [1] | Can cause chronic low-grade blood loss, but usually presents acutely rather than insidiously |
Clinical Pearl
In any patient with unexplained iron deficiency anaemia (especially males of any age and post-menopausal females), the standard approach is "top and tail" — OGD + colonoscopy. You need to exclude both upper and lower GI malignancy. Don't stop at finding one lesion — synchronous pathology is common.
This is the presentation that most clinicians associate with CRC. The differential includes conditions that cause similar symptoms:
| Differential | Key Distinguishing Features | Why It Can Mimic CRC |
|---|---|---|
| Diverticular disease / Diverticulitis | Similar clinical features and bowel wall thickening on CT [2]. Features suggestive of diverticulitis over CRC on CT: pericolonic/mesenteric inflammation, involvement of > 10 cm of colon, absence of enlarged pericolonic lymph nodes [2]. CRC can only be excluded with colonoscopy after resolution of acute inflammation [2] | Left-sided, change in bowel habit, LLQ pain, PR bleeding, can cause stricture and obstruction — almost identical to sigmoid CRC |
| Inflammatory bowel disease (UC and Crohn's) | Diarrhoea rather than abdominal pain is the predominant symptom [2]. Younger patients; chronic relapsing course; extra-intestinal manifestations (arthritis, uveitis, erythema nodosum); UC = bloody diarrhoea with mucus; Crohn's = RLQ pain, perianal disease, skip lesions [2][3] | Chronic PR bleeding, change in bowel habit, weight loss, anaemia; and IBD itself is a risk factor for CRC (dysplasia-carcinoma sequence) |
| Haemorrhoids | Fresh outlet-type bleed, blood separate from stool (drips after defaecation or on toilet paper), perianal mass/pain, associated with constipation/straining [4]. Most common cause of PR bleeding in age < 50 [1] | Bright red PR bleeding — but haemorrhoidal bleeding is characteristically "outlet-type" (separate from stool, on paper, dripping into bowl). Critical point: never attribute PR bleeding to haemorrhoids in a patient ≥ 50 without a colonoscopy |
| Irritable bowel syndrome (IBS) | Chronic abdominal pain and altered bowel habits in the absence of an organic cause [3]. Rome IV criteria: recurrent abdominal pain ≥ 1 day/week in last 3 months, related to defaecation, with change in stool frequency/form. No red flag features (no weight loss, no PR bleeding, no anaemia, no nocturnal symptoms) | Alternating constipation/diarrhoea, abdominal discomfort — overlaps with left-sided CRC. IBS is a diagnosis of exclusion — if red flags present, must colonoscope |
| Infectious colitis | Diarrhoea rather than abdominal pain is the predominant symptom [2]. Acute onset; stool cultures positive (E. coli, Salmonella, Shigella, Campylobacter, Yersinia, C. difficile); travel history, antibiotic use [3] | Acute bloody diarrhoea, abdominal cramps — can mimic acute presentation of CRC; C. difficile particularly relevant in hospitalised patients |
| Ischaemic colitis | Rapid onset of abdominal pain, haematochezia or bloody diarrhoea [2]. Risk factors: advanced age, hypertension, DM, atherosclerosis, AF, dehydration, laxative use [2]. Watershed areas (splenic flexure, rectosigmoid) affected. CT shows thumbprinting (submucosal oedema) | Elderly patient with LLQ pain and PR bleeding — similar demographic to CRC. Colonoscopy shows segmental mucosal ischaemia |
| Radiation colitis / proctitis | History of abdominal/pelvic radiotherapy (cervical, prostate, rectal cancer); can occur weeks to years after irradiation [1][3]. Telangiectasias on endoscopy | PR bleeding, tenesmus, diarrhoea — similar to rectal cancer. History of previous pelvic RT is the key distinguishing feature |
| Solitary rectal ulcer syndrome | Presents with abdominal pain, altered bowel habits and bleeding; characteristic histology with thickened mucosal layer and distortion of crypt architecture [3]. Associated with rectal prolapse and excessive straining | PR bleeding and tenesmus — can mimic low rectal cancer. Biopsy is essential to differentiate |
| Anal fissure | Severe pain on defaecation with small amount of bright red blood on paper; visible tear on inspection (usually posterior midline); associated with constipation and hypertonic sphincter | Outlet-type PR bleeding with pain — rarely confused with CRC, but included in the differential of any PR bleeding |
CRC is the commonest cause of large bowel obstruction (LBO) in adults [5][6].
| Differential | Key Distinguishing Features |
|---|---|
| Sigmoid/caecal volvulus | Sigmoid volvulus: elderly, institutionalised, psychiatric patients, chronic constipation; "coffee bean" sign on AXR. Caecal volvulus: younger patients, mobile caecum |
| Diverticular stricture | History of recurrent diverticulitis → fibrotic stricture; CT shows long segment thickening without mass or lymphadenopathy; CRC cannot be excluded until colonoscopy after inflammation resolves [2] |
| Pseudo-obstruction (Ogilvie's syndrome) | Massive colonic dilation without mechanical obstruction; post-operative, electrolyte disturbance, opioids; no transition point on CT |
| Hernia (incarcerated) | Examine hernial orifices — always check! An incarcerated inguinal or femoral hernia can cause LBO |
| Adhesions | More typically cause small bowel obstruction (SBO) than LBO; history of previous abdominal surgery |
| Crohn's stricture | History of known Crohn's disease; can cause stricturing at any point in the GI tract |
Exam Tip
In any patient with large bowel obstruction, the four common causes to remember are: Cancer of colon, Volvulus, Diverticular stricture, Pseudo-obstruction [6]. Always examine hernial orifices and do a digital rectal examination — don't forget the basics.
When a palpable abdominal mass is the presenting feature:
| Location | Differential Considerations |
|---|---|
| Right iliac fossa mass | CRC (caecal/ascending colon), Crohn's disease (ileocaecal mass/phlegmon/abscess), appendicular mass/abscess, ovarian pathology (torsion, tumour), ileocaecal TB, lymphoma |
| Left iliac fossa mass | CRC (sigmoid), diverticular abscess/phlegmon, ovarian pathology, constipated sigmoid colon (faecal loading) |
| Epigastric / central | Transverse colon CRC, gastric cancer, pancreatic cancer, omental metastatic cake, lymphoma |
When the presenting complaint is from the liver rather than the bowel:
Metastatic carcinoma to the liver is commoner than primary liver cancer. The commonest site of primary is the GI tract (portal venous circulation): colorectal, stomach, pancreas [7].
| Differential of Liver Mass/Hepatomegaly | Distinguishing Features |
|---|---|
| CRC liver metastases | Multiple lesions, elevated CEA, primary CRC found on colonoscopy |
| Hepatocellular carcinoma (HCC) | Background of chronic liver disease/cirrhosis, elevated AFP, arterial enhancement on CT |
| Other GI metastases (gastric, pancreatic) | Epigastric symptoms, elevated CA 19-9 |
| Hepatic abscess (amoebic/pyogenic) | Fever, RUQ pain, travel history; single/few lesions with rim enhancement |
| Haemangioma | Asymptomatic, incidental, characteristic peripheral nodular enhancement on CT |
2. Specific Conditions That Closely Mimic CRC
Some conditions deserve special emphasis because they are diagnostic pitfalls:
This is the most important differential in clinical practice and one of the most common exam scenarios [2].
| Feature | Diverticulitis | Sigmoid CRC |
|---|---|---|
| Onset | Acute (hours to days) | Chronic/insidious (weeks to months) |
| Pain | LLQ pain, constant, with tenderness | Colicky pain, change in bowel habit |
| CT findings | Pericolonic fat stranding, involvement > 10 cm, diverticula seen, no enlarged LN [2] | Focal mass, enlarged pericolonic LN, shouldering/irregular wall thickening |
| Colonoscopy | Deferred until acute inflammation resolves (6–8 weeks) | Diagnostic — mass with biopsy |
| Key principle | CRC can only be excluded with colonoscopy after resolution of acute inflammation [2] | — |
Why is this so important? Because on CT, an inflamed segment of sigmoid with diverticulitis can look identical to a perforated sigmoid cancer. You cannot safely colonoscope during acute diverticulitis (risk of perforation), so you must wait, treat conservatively, then scope. If you don't scope, you will miss cancers.
Haemorrhoids are the most common cause of PR bleeding in patients aged < 50 [1], but they also commonly co-exist with CRC. Never assume haemorrhoids are the sole diagnosis in a patient with red flag symptoms.
Red flags mandating colonoscopy even if haemorrhoids are present: age ≥ 50, family history of CRC, change in bowel habit, weight loss, anaemia, tenesmus, mixed blood with stool (not just outlet-type), or positive FIT.
| Feature | Favours CRC | Favours Alternative Diagnosis |
|---|---|---|
| Age ≥ 50 | ✓ (dominant risk factor) | Younger age more typical of IBD, IBS, haemorrhoids |
| Chronicity | Insidious, progressive over weeks-months | Acute onset (diverticulitis, ischaemic colitis, infectious) |
| Weight loss / anorexia | ✓ (cancer cachexia) | Absent in haemorrhoids, IBS |
| PR bleeding pattern | Dark blood mixed with stool | Outlet-type (haemorrhoids), bloody diarrhoea (IBD, infectious) |
| Change in stool calibre | ✓ (annular constricting lesion) | Not typical of other conditions |
| Tenesmus | ✓ (rectal mass) | Can occur with proctitis (IBD, radiation) |
| Family history of CRC / polyps | ✓ | Family history of IBD, coeliac, etc. |
| Iron deficiency anaemia (male/post-menopausal female) | ✓ — CRC until proven otherwise | Coeliac, menorrhagia (pre-menopausal), angiodysplasia |
| CT: focal mass + enlarged LN | ✓ | Long-segment inflammation without LN (diverticulitis) |
| Colonoscopy: endoluminal mass with friability, induration, ulceration [3] | ✓ (diagnostic gold standard with biopsy) | Normal mucosa, diverticula, inflammatory changes, etc. |
| Association | Why It Matters |
|---|---|
| Streptococcus gallolyticus (bovis) bacteraemia → CRC | Always colonoscope — strong association with CRC/adenomas |
| Acromegaly → CRC | IGF-1 as growth factor for colonic mucosal cells [8] |
| IBD (especially UC) → CRC | Dysplasia-carcinoma sequence; risk increases with duration > 8–10 years |
| Hereditary syndromes (FAP, Lynch) → CRC | Family history + early-onset CRC = genetic testing + extended surveillance |
| Dermatomyositis in an older patient → occult malignancy (including CRC) | Paraneoplastic; always screen for underlying cancer |
High Yield Summary
Key Differentials by Presentation:
-
IDA / occult blood loss (right-sided pattern): CRC, angiodysplasia, PUD, coeliac disease, gastric cancer → investigate with "top and tail" (OGD + colonoscopy).
-
Change in bowel habit / PR bleeding (left-sided/rectal): CRC, diverticular disease (most important DDx — cannot exclude CRC without colonoscopy after acute episode resolves), IBD, haemorrhoids, IBS, infectious/ischaemic colitis, radiation proctitis. Never attribute PR bleeding to haemorrhoids in ≥ 50 without colonoscopy.
-
Large bowel obstruction: CRC (commonest cause in adults), volvulus, diverticular stricture, pseudo-obstruction. Always check hernial orifices and do DRE.
-
Abdominal mass: CRC, diverticular abscess, Crohn's phlegmon, appendicular mass, ovarian pathology.
-
Liver mass/hepatomegaly: CRC liver mets (commonest cause of liver secondaries from GI), HCC, other GI mets, abscess.
Critical pitfall: Diverticulitis vs. sigmoid CRC — CT alone cannot distinguish; colonoscopy after inflammation resolves is mandatory.
Active Recall - Differential Diagnosis of Colorectal Cancer
References
[1] Senior notes: felixlai.md (Lower GI bleeding, pages 343, 510–511) [2] Senior notes: felixlai.md (Diverticulitis differential diagnosis, page 641) [3] Senior notes: felixlai.md (Ulcerative colitis / Crohn's disease differential diagnosis, pages 650, 663) [4] Senior notes: maxim.md (LGIB DDx table, page 158) [5] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf [6] Lecture slides: GC 195. Lower and diffuse abdominal pain RLQ problems; pelvic inflammatory disease; peritonitis and abdominal emergencies.pdf (page 28) [7] Lecture slides: WCS 064 - A large liver - by Prof R Poon [20191108].doc.pdf (page 6) [8] Senior notes: maxim.md (Risk factors, page 214)
Diagnostic Criteria, Diagnostic Algorithm, and Investigation Modalities for Colorectal Cancer
1. Diagnostic Criteria — What Establishes the Diagnosis of CRC?
Unlike some conditions (e.g., rheumatoid arthritis with ACR criteria, or SLE with SLICC criteria), CRC does not have a formal "diagnostic criteria checklist." Instead, the diagnosis rests on a fundamental principle:
CRC is diagnosed by histopathological confirmation of adenocarcinoma on biopsy obtained at colonoscopy. There is no substitute — imaging, tumour markers, and clinical features raise suspicion, but only tissue biopsy proves the diagnosis.
That said, there are well-defined criteria and systems used at various stages of the diagnostic journey:
Any of the following "red flags" in a patient should trigger investigation for CRC:
| Red Flag | Rationale |
|---|---|
| Age ≥ 50 with new change in bowel habit > 4 weeks | CRC is the commonest cancer in HK; > 90% occurs in patients ≥ 50 [1] |
| Iron deficiency anaemia in males or post-menopausal females | Right-sided CRC causes chronic occult blood loss; IDA in these demographics is GI malignancy until proven otherwise |
| New rectal bleeding not fully explained by anorectal pathology | PR bleeding mixed with stool, dark blood, or persistent despite haemorrhoid treatment |
| Palpable abdominal or rectal mass | Direct evidence of tumour |
| Unexplained weight loss with GI symptoms | Suggests underlying malignancy |
| Positive faecal immunochemical test (FIT) or gFOBT | Screening test that detects haemoglobin in stool — must be followed by colonoscopy [9] |
Since hereditary syndromes account for ~10% of CRC and demand a completely different management approach (extended surgery, intensive surveillance), recognising them is critical:
Amsterdam II Criteria (3-2-1 rule) [1]:
- ≥ 3 relatives with a Lynch syndrome-associated cancer (CRC, endometrial, small bowel, ureter, renal pelvis)
- ≥ 2 successive generations affected
- ≥ 1 cancer diagnosed before age 50
- FAP must be excluded
- Tumours verified by pathological examination
Revised Bethesda Criteria (lower threshold — selects patients for MSI testing) [1]:
- CRC diagnosed < 50 years
- CRC + ≥ 1 first-degree relative with HNPCC-related tumour, one diagnosed < 50
- CRC + ≥ 2 first-/second-degree relatives with HNPCC-related tumour regardless of age
- Synchronous/metachronous CRC or other HNPCC-related tumours
- CRC with MSI-H-like histology (tumour-infiltrating lymphocytes, Crohn's-like reaction, mucinous/signet ring, medullary, poorly differentiated) diagnosed < 60
Current practice (2024–2026 guidelines): Universal MMR/MSI testing on all newly diagnosed CRC is now recommended regardless of age or family history, because:
- It identifies Lynch syndrome even when family history is incomplete
- It predicts response to immunotherapy (checkpoint inhibitors) in metastatic disease
- It informs adjuvant chemotherapy decisions (MSI-H stage II → no 5-FU benefit; MSI-H stage IV → pembrolizumab first-line)
Once CRC is diagnosed histologically, staging determines prognosis and treatment. This is not "diagnostic criteria" per se, but it is the framework that defines the extent of disease.
| Stage | Definition | Why This Matters |
|---|---|---|
| Tis | Carcinoma in situ — intramucosal carcinoma involving lamina propria with no extension through muscularis mucosae | No metastatic risk (no lymphatics in mucosa above muscularis mucosae) — endoscopic resection curative |
| T1 | Invades submucosa (through muscularis mucosae) | First stage with metastatic potential — submucosa contains lymphatics. LN metastasis risk ~5% [1] |
| T2 | Invades muscularis propria | LN metastasis risk ~20% [1] |
| T3 | Invades through muscularis propria into pericolorectal tissues | Most common T stage at diagnosis. LN risk > 50% [1] |
| T4a | Penetrates to surface of visceral peritoneum (including gross perforation through tumour) | Peritoneal seeding risk |
| T4b | Directly invades or adheres to other organs or structures | En bloc resection required |
Regional Lymph Nodes (N) [1][10]:
| Stage | Definition |
|---|---|
| N0 | No regional LN metastasis |
| N1a | Metastasis in 1 regional LN |
| N1b | Metastasis in 2–3 regional LNs |
| N1c | Tumour deposits in subserosa/mesentery/non-peritonealised pericolic or perirectal tissues without regional LN metastasis |
| N2a | Metastasis in 4–6 regional LNs |
| N2b | Metastasis in ≥ 7 regional LNs |
Distant Metastasis (M) [10]:
| Stage | Definition |
|---|---|
| M0 | No distant metastasis |
| M1a | Metastasis to one site/organ without peritoneal metastasis |
| M1b | Metastasis to ≥ 2 sites/organs without peritoneal metastasis |
| M1c | Peritoneal metastasis ± other sites |
Stage Grouping and Prognosis [1][10]:
| Stage | TNM | 5-Year Survival |
|---|---|---|
| 0 | Tis N0 M0 | ~100% |
| I | T1–2 N0 M0 | 90% |
| II | T3–4 N0 M0 | 60–80% |
| III | Any T, N1–2, M0 | ~60% |
| IV | Any T, Any N, M1 | ~10% |
Modified Dukes Classification (historical, still referenced) [10]:
- Dukes A = tumour within wall of bowel (T1–2 N0)
- Dukes B = tumour invades through wall (T3–4 N0)
- Dukes C = regional LN metastasis (Any T, N+)
- Dukes D = distant metastasis (M1)
Why Do We Need ≥ 12 Lymph Nodes?
A minimum of 12 lymph nodes in the resected specimen are necessary for adequate staging [1][10]. This is because with fewer nodes examined, there is a risk of "stage migration" — understaging an N+ cancer as N0 simply because too few nodes were sampled. The number serves as a quality indicator for the adequacy of surgical resection and pathological examination. Paradoxically, higher node counts also correlate with better outcomes because they reflect both better surgery (wider lymphadenectomy) and better pathology (more diligent node retrieval).
The diagnostic pathway for CRC follows a logical sequence: clinical suspicion → bedside assessment → laboratory tests → definitive endoscopic diagnosis → staging → molecular profiling → treatment planning.
3. Investigation Modalities — Detailed Breakdown
I'll organise these as: Bedside → Blood tests → Tumour markers → Endoscopy → Imaging for diagnosis → Imaging for staging → Molecular profiling.
Physical examination findings to look for: [1]
| Examination | What to Look For | Significance |
|---|---|---|
| General examination | Pallor, cachexia, jaundice, lymphadenopathy (supraclavicular — Virchow's node) | Anaemia (IDA), metastatic disease (liver mets causing jaundice; left supraclavicular LN = Troisier's sign) |
| Abdominal examination | Hepatomegaly (hard, irregular, nodular), ascites, palpable mass (RIF or LIF), tenderness, distension, bowel sounds | Hepatomegaly = liver mets; ascites = peritoneal carcinomatosis; mass = locally advanced tumour |
| Digital rectal examination (DRE) | Per rectal bleeding, rectal masses [1] | Up to 75% of rectal cancers palpable on DRE. Assess: distance from anal verge, fixity (mobile/tethered/fixed), circumferential involvement, sphincter tone |
| Proctoscopy | For anorectal pathology — haemorrhoids, low rectal lesions | Quick bedside test; can visualise low rectal tumours and exclude haemorrhoids as sole cause |
Clinical Pearl
DRE is mandatory in every patient with suspected CRC. It costs nothing, takes 30 seconds, and can identify rectal cancers, assess sphincter function (relevant for surgical planning), and detect blood on the glove. Missing a palpable rectal cancer because you didn't do a DRE is indefensible.
| Test | What It Shows | Interpretation / Why |
|---|---|---|
| CBC with differential | Anaemia — specifically microcytic hypochromic (IDA) | Chronic occult blood loss from tumour; right-sided CRC classically causes IDA [1][10] |
| Iron profile (serum iron, ferritin, TIBC, transferrin saturation) | Iron deficiency anaemia pattern: low ferritin, low serum iron, high TIBC | Confirms IDA as the mechanism. Ferritin < 30 μg/L is diagnostic of iron deficiency (< 100 in context of chronic disease/inflammation) |
| LFT | Elevated ALP, GGT ± elevated bilirubin | Suggests liver metastases — ALP rises first (from infiltration/compression of intrahepatic bile ducts). Isolated ALP elevation with normal bilirubin is a common early finding [10] |
| RFT (renal function) | Elevated creatinine, urea | Obstructive uropathy from pelvic tumour; dehydration from obstruction |
| Coagulation profile | Prolonged PT/INR | Liver dysfunction from extensive hepatic metastases |
| Albumin | Low albumin | Marker of nutritional status / chronic disease; prognostic indicator |
3C. Tumour Markers
CEA is a glycoprotein ("carcino-" = cancer, "embryonic" = normally expressed in foetal tissue, "antigen" = protein detectable by antibody) found on the surface of epithelial cells. It is the most widely used tumour marker for CRC, but it is fundamentally a monitoring tool, not a diagnostic test.
| Feature | Detail |
|---|---|
| Cut-off | < 4.7 ng/mL (some use < 5.0) [10] |
| Sensitivity | Low — elevated in only ~50% of CRC; serum level can be normal in 30–40% of patients in early disease [1]. Sensitivity ~30% for early CRC [11] |
| Specificity | Low — false positives: pregnancy, smoking, TB, IBD, other carcinomas (GI tract, pancreas, breast) [10]. CEA may be first-pass metabolised by the liver, so portal-drained tumours may have falsely low CEA [10] |
| Diagnostic role | NOT recommended as a screening or diagnostic test for CRC [1] |
| Clinical significance | (1) Pre-operative baseline to facilitate surgical planning; (2) Post-operative follow-up to detect recurrence or metastasis — a rising CEA post-surgery strongly suggests recurrence; (3) Prognostication — very high pre-op CEA (> 200) suggests advanced/metastatic disease [1][10] |
| Post-op kinetics | Takes 4–6 weeks to return to normal post-operatively [10]. If CEA does not normalise, suspect residual disease |
CEA can pick up non-portovenous distant metastases (e.g., lung) even if pre-op CEA was normal [10] — because when the primary tumour drained via the portal system, the liver metabolised CEA (first-pass effect), keeping serum levels low. If metastases develop outside the portal drainage (e.g., lung), CEA now enters the systemic circulation directly and becomes elevated.
In some cases of primary GI malignancy with liver metastases, elevated CEA or CA 19-9 may be found [7]. CA 19-9 is more relevant for pancreaticobiliary malignancy but can be modestly elevated in CRC.
Exam Pitfall
A common mistake: using CEA to diagnose CRC. CEA has terrible sensitivity for early-stage disease (normal in 30–40% of patients). It is NOT a screening or diagnostic test. Its value is in monitoring — baseline pre-op, post-op follow-up, and detecting recurrence. If the exam asks "what tumour marker do you use to diagnose CRC?", the answer is "none — diagnosis is by colonoscopy and biopsy."
3D. Endoscopy — The Diagnostic Gold Standard
Colonoscopy is the current gold standard in detecting colonic neoplasm [1][10][11].
| Feature | Detail |
|---|---|
| Principle | Direct visualisation of the entire colonic mucosa from rectum to caecum using a flexible fibreoptic endoscope |
| Diagnostic capability | Most accurate — can localise and biopsy lesions through the large bowels [1]. Obtains tissue for histological confirmation of adenocarcinoma |
| Typical findings in CRC | Majority of colon and rectal cancers are endoluminal masses arising from mucosa and protruding into the lumen with exophytic or polypoid appearance. Bleeding may be seen in lesions that are friable, necrotic or ulcerated [1] |
| Synchronous lesions | Exclude synchronous cancers (3–5%) and synchronous polyps (30–50%) [10]. This is why complete colonoscopy to the caecum is mandatory |
| Pre-operative localisation | Tattooing (inject ink to stain tumour) — especially important for small tumours that may not be palpable at surgery; ink marks guide the surgeon intra-operatively [10] |
| Therapeutic capability | Polypectomy for benign polyps; therapeutic modalities include clipping, electrocoagulation, laser, argon plasma coagulation, sclerotherapy [11] |
| Requirements | Diet and bowel preparation ± sedation [11] |
| Complications | Chance of perforation ≤ 0.1% [11]; bleeding (especially post-polypectomy); post-polypectomy syndrome (transmural burn without frank perforation — localised peritonism); sedation risks |
Incomplete colonoscopy occurs when the scope cannot reach the caecum due to:
- Mechanical obstruction by the tumour (obstructing CRC)
- Patient intolerance / inadequate bowel preparation
- Tortuosity / adhesions
In these situations, alternative investigations are used:
Also known as virtual colonoscopy — computer-simulated endoluminal perspective of the air-filled distended colon [1].
| Feature | Detail |
|---|---|
| Indication | Incomplete colonoscopy due to mechanical obstruction or patient intolerance [1]. Accepted alternative to colonoscopy [11]. Useful when colonoscopy is relatively contraindicated [11] |
| Sensitivity | > 90% sensitivity for lesions ≥ 1 cm [11]. Similar diagnostic accuracy for tumours > 1 cm [10] |
| Advantages | Non-invasive (no sedation); provides extraluminal information (can detect incidental findings, lymphadenopathy, liver lesions); lower risk of perforation [10] |
| Disadvantages | High radiation dose; not therapeutic — still need colonoscopy to take biopsy [10]; may miss flat polyps < 6 mm; requires bowel preparation and air insufflation |
| Feature | Detail |
|---|---|
| Principle | Barium + air instilled into colon; provides mucosal detail on plain X-rays |
| Classical finding | "Apple-core" appearance — near-circumferential involvement of bowel walls [1][10] — an annular constricting lesion with shouldered edges and mucosal destruction |
| Current status | Becoming obsolete due to its low sensitivity [11]. Superseded by CT colonography [10]. Risk of barium peritonitis if there is unrecognised perforation [10] |
| When still used | Water-soluble contrast (Gastrografin) enema rather than barium — indicated when colonoscopy is unsuccessful due to obstruction [1]. Gastrografin is preferred over barium in suspected obstruction/perforation because it is absorbed and does not cause peritonitis |
Apple-Core Lesion
The "apple-core" or "napkin-ring" lesion on barium enema or CT is pathognomonic for an annular constricting CRC. It shows a short segment of luminal narrowing with irregular mucosal destruction and overhanging edges ("shoulders"). The name comes from its resemblance to an apple core after the fruit has been eaten around it. This is most commonly seen with left-sided CRC where annular growth patterns predominate.
3E. Imaging for Staging
Once CRC is confirmed histologically, staging determines treatment. The approach differs for colon cancer vs. rectal cancer.
| Feature | Detail |
|---|---|
| Indication | All patients with confirmed CRC [1] |
| What it assesses | Tumour extension, regional lymphatic and distant metastasis, and tumour-related complications (obstruction, perforation, fistula) [1] |
| CT chest | Assess possible metastasis to lungs, particularly from rectal cancer [1] — recall that distal rectal cancers drain via IVC to lungs, so pulmonary mets can occur without liver mets |
| CT abdomen/pelvis | T staging (depth of invasion — though MRI is superior for rectal cancer), N staging (lymph node enlargement), M staging (liver metastases, peritoneal deposits, ascites) |
| Key CT findings | Focal wall thickening with shouldering, pericolonic fat stranding, enlarged regional LN (> 1 cm short axis), liver lesions (hypodense on portal venous phase), ascites |
| Staging accuracy | CT is the most sensitive for T-staging of colon cancer [10]. For rectal cancer, MRI is superior |
MRI is IMPORTANT in ALL rectal cancer for tumour staging to determine whether neoadjuvant chemoradiation is indicated [1].
| Feature | Detail |
|---|---|
| Why MRI over CT for rectal cancer? | MRI is superior to CT in delineating the fat planes for T staging of rectal cancer [1]. The mesorectum is a fatty envelope around the rectum — MRI has excellent soft-tissue contrast to distinguish tumour from fat. CT cannot do this as well |
| Key assessments | (1) T stage — depth of invasion through rectal wall; (2) Mesorectal involvement — tumour extension into mesorectal fat [1]; (3) Circumferential resection margin (CRM) — distance from tumour to mesorectal fascia [10]; (4) N stage — mesorectal and lateral pelvic LN; (5) Extramural venous invasion (EMVI) |
| Clinical decision impact | When the radial margin is threatened or involved, neoadjuvant chemoradiation is recommended [1]. T3/4 or N1 cancers should receive neoadjuvant chemoradiation before surgery due to high risk of recurrence [1] |
| NOT routinely indicated for colon cancer | Because colon cancer surgery does not face the same anatomical constraints as rectal surgery (no narrow bony pelvis, no sphincter preservation decisions) [1] |
Why Is MRI So Important for Rectal Cancer?
Rectal surgery is uniquely challenging because the rectum sits in a narrow bony pelvis surrounded by vital structures (bladder, ureters, seminal vesicles/vagina, sacral nerves). The surgical technique of total mesorectal excision (TME) requires dissecting along the "holy plane" between the mesorectal fascia and the pelvic sidewall. MRI pelvis tells the surgeon:
- Can I get a clear circumferential margin? (CRM threatened = neoadjuvant chemoRT first)
- How deep has the tumour invaded? (T3 with threatened CRM vs. T2 = different approach)
- Are there involved lymph nodes? (N+ = neoadjuvant chemoRT)
Without MRI, you are operating blind. This is why MRI pelvis is mandatory for ALL rectal cancer — no exceptions.
| Feature | Detail |
|---|---|
| Principle | High-frequency ultrasound probe inserted into the rectum; excellent near-field resolution of rectal wall layers |
| Role | Integral part of staging rectal tumours — evaluates depth of invasion, CRM, and LN status [1]. Distinguishes localised cancer involving only mucosa and submucosa from those penetrating muscularis propria or extending transmurally into perirectal fat [1] |
| Best for | T staging — particularly early rectal cancer (T1 vs. T2), where the decision between local excision (transanal endoscopic microsurgery) and radical surgery hinges on depth of invasion |
| Limitations | Operator-dependent; might not admit endoscope for obstructive tumours [10]; limited for N staging compared with MRI; limited field of view (cannot assess CRM as well as MRI) |
| Complementary to MRI | ERUS is excellent for early T staging; MRI is better for advanced T staging, CRM, and overall pelvic assessment. Together they provide comprehensive local staging |
FDG-PET is used in patients with CRC [1].
| Feature | Detail |
|---|---|
| Principle | 18F-fluorodeoxyglucose (FDG) is taken up by metabolically active cells (cancer cells have high glucose uptake due to the Warburg effect). PET detects sites of abnormal FDG uptake; combined with CT for anatomical localisation |
| Indications | Patients with distant metastasis or tumour recurrence [1]: (1) Localising site of recurrence in patients with rising CEA and non-diagnostic conventional imaging [1]; (2) Localising occult disease to permit selection of patients for exploratory laparotomy [1]; (3) Better for detecting distant metastasis than CT alone [10] |
| NOT used for | Primary diagnosis or routine staging (CT TAP + MRI pelvis are sufficient for most patients) |
| Limitations | False positives (infection, inflammation); false negatives (mucinous tumours may be FDG-cold); expensive; radiation exposure |
| Feature | Detail |
|---|---|
| Indication | Useful if there are concerning hepatic lesions on CT scan [1] — when CT is equivocal about whether liver lesions are metastases vs. benign (haemangioma, cyst) |
| Sequences | Gadolinium-enhanced + diffusion-weighted imaging (DWI). Hepatobiliary-specific contrast agents (gadoxetic acid / Primovist) improve detection of small metastases |
| Superiority | Most sensitive imaging modality for detecting liver metastases — picks up small lesions (< 1 cm) that CT may miss |
| Feature | Detail |
|---|---|
| Indication | Baseline investigation; part of pre-operative assessment [1] |
| What to look for | Pulmonary metastases (cannonball lesions), pleural effusion |
| Limitation | Low sensitivity for small metastases — CT chest is far superior |
| Feature | Detail |
|---|---|
| Role | Quick, non-invasive initial assessment for liver lesions; used in follow-up |
| Limitation | Operator-dependent; less sensitive than CT/MRI for small metastases |
3F. Molecular Profiling / Biomarkers
This is increasingly central to CRC management — molecular testing now directly determines treatment eligibility.
| Feature | Detail |
|---|---|
| Methods | Immunohistochemistry (IHC) for MMR proteins (MLH1, MSH2, MSH6, PMS2) — loss of expression indicates deficiency; PCR for MSI — compares microsatellite lengths in tumour vs. normal tissue |
| Why test? | CRCs with MSI/dMMR status have a distinct phenotype: (1) Predilection for proximal (right-sided) colon; (2) Poor differentiation; (3) Better prognosis in terms of stage-adjusted survival; (4) Respond differently to 5-FU-based adjuvant chemotherapy [1] — specifically, MSI-H stage II tumours do NOT benefit from 5-FU; (5) Excellent response to immune checkpoint inhibitors (pembrolizumab, nivolumab) in metastatic setting |
| When to test | Universal testing on ALL newly diagnosed CRC is now standard of care. If IHC shows loss of MLH1/PMS2, reflex testing for BRAF V600E mutation and/or MLH1 promoter methylation distinguishes sporadic (methylation +, BRAF +) from Lynch syndrome (germline MMR mutation) |
| Feature | Detail |
|---|---|
| KRAS & NRAS | Signalling molecules downstream of EGFR; mutated in ~45% of CRC [10]. Mutated RAS → no response to anti-EGFR therapy (cetuximab, panitumumab) [10]. Only RAS wild-type patients benefit from anti-EGFR agents |
| BRAF V600E | Mutated in ~8–10% of CRC; associated with poor prognosis (except in MSI-H context). BRAF V600E mutation + MLH1 loss = almost certainly sporadic (not Lynch). Targeted therapy: encorafenib + cetuximab |
| When to test | For metastatic disease only — determines eligibility for anti-EGFR targeted therapy and immunotherapy [10]. No evidence to support targeted therapy in the adjuvant (non-metastatic) setting [1] |
| Biomarker | Role |
|---|---|
| HER2 amplification | Rare (~3–5%); trastuzumab-based therapy emerging for RAS/BRAF wild-type, HER2+ metastatic CRC |
| NTRK fusion | Very rare (< 1%); larotrectinib/entrectinib — tumour-agnostic therapy |
| Circulating tumour DNA (ctDNA) | Emerging role in minimal residual disease detection post-surgery; may guide adjuvant chemotherapy decisions in future |
While screening is for asymptomatic populations, understanding the modalities is essential:
| Modality | Principle | Key Points |
|---|---|---|
| Guaiac-based FOBT (gFOBT) | Identifies Hb by peroxidase reaction [9] | Requires 3 stool specimens; diet/drug restrictions (red meat, NSAIDs, aspirin, vitamin C > 250 mg); cannot detect polyps; false positives common [9] |
| Faecal immunochemical test (FIT) | Uses antibodies specific to human haemoglobin | Only requires 1 stool sample; no dietary restriction; more specific to LGIB because globin is digested during GI transit (so UGIB doesn't cause false positive unless massive) [9]. Used in HK government screening programme |
| Faecal DNA test | Detects mutated DNA and methylation markers shed by CRC cells into stool | More sensitive and specific (especially for early-stage disease); costly [9] |
| Colonoscopy | Direct visualisation | Gold standard; diagnostic and therapeutic; if normal, repeat Q10y [9]. Requires bowel prep, invasive |
| Flexible sigmoidoscopy | Examines up to splenic flexure | Less stringent bowel prep, no sedation; diagnostic and therapeutic; still require colonoscopy if positive; right-sided cancers missed [9]. Recommended Q5y |
| CT colonography | Virtual colonoscopy | As described above; alternative when colonoscopy contraindicated |
| Capsule endoscopy | Swallowed camera pill | Limited role in CRC screening; more useful for small bowel assessment |
Hong Kong Colorectal Cancer Screening Programme: Two-tier approach for persons aged 50–75:
- FIT (one stool sample) → if positive:
- Colonoscopy (subsidised)
When CRC presents as a liver mass (metastatic CRC discovered before the primary), the diagnostic approach is:
Diagnosis of liver metastases: [7]
- Elevated CEA or CA 19-9 in some cases with primary GI malignancy
- Investigation for primary: CXR, endoscopy, CT scan abdomen
- Biopsy — FNAC or Trucut (ONLY for inoperable cases) [7]
Why biopsy only for inoperable cases? Because in resectable liver metastases, you proceed directly to surgery. Biopsy risks needle-tract seeding and is unnecessary if histology is already confirmed from the primary tumour colonoscopy biopsy. You only biopsy the liver if you need to confirm metastatic adenocarcinoma to plan palliative chemotherapy and the primary is not amenable to biopsy.
Triphasic CT scan findings for liver metastases: hypodense lesion on all phases [10] — unlike HCC which shows arterial phase hyperenhancement and portal venous washout. CRC liver mets are hypovascular (unlike HCC, renal cell, or neuroendocrine mets which are hypervascular).
Understanding the follow-up schedule is crucial — ~40% of CRC patients develop recurrence, and early detection improves outcomes [10].
Follow-up intervals [10]:
- First 2 years: every 3 months
- 3rd year: every 6 months
- 4th–5th year: yearly
- > 5 years: considered in remission
Investigations at each follow-up [10]:
- CEA, rigid sigmoidoscopy, LFT
- CT TAP or PET-CT every 1 year
- Colonoscopy:
- Pre-op incomplete scope: within 6 months of surgery (risk of synchronous tumour = 3–5%)
- Pre-op complete scope: 1 year post-op, then at 3 years, 5 years, then every 5 years
Why Follow Up for 5 Years?
Most CRC recurrences (80%) occur within the first 3 years. After 5 years disease-free, the patient is considered in remission with very low risk of late recurrence. The intensive early schedule (Q3m in years 1–2) reflects this high early recurrence risk. CEA is particularly useful here — a rising CEA with negative conventional imaging → PET-CT to localise occult recurrence.
| Step | Investigation | Purpose |
|---|---|---|
| 1 | History + Examination + DRE | Clinical suspicion; palpable rectal mass |
| 2 | CBC, Iron profile, LFT, RFT, CEA | Baseline bloods; confirm IDA; CEA baseline (not diagnostic) |
| 3 | Colonoscopy with biopsy | GOLD STANDARD diagnosis — histological confirmation; exclude synchronous lesions; tattooing for localisation |
| 4 | If incomplete: CT colonography or Gastrografin enema | Alternative visualisation if scope cannot pass |
| 5 | CT TAP with contrast (all CRC) | Staging: T, N, M assessment for colon cancer |
| 6 | MRI Pelvis (all rectal cancer) | Mandatory for rectal cancer: accurate T staging, CRM, mesorectal involvement → determines neoadjuvant chemoRT |
| 7 | ERUS (selected rectal cancer) | Early T staging (T1 vs. T2) for local excision decisions |
| 8 | PET-CT (selected cases) | Rising CEA with negative conventional imaging; equivocal distant mets |
| 9 | MRI Liver (if equivocal CT liver lesions) | Characterise liver lesions |
| 10 | Universal MMR/MSI testing | All CRC — Lynch screening + treatment implications |
| 11 | KRAS/NRAS/BRAF testing | Metastatic CRC — targeted therapy eligibility |
| 12 | MDT discussion | Treatment planning based on stage and molecular profile |
High Yield Summary
Diagnosis = Colonoscopy with biopsy. Full stop. CEA is NOT diagnostic — it is for monitoring, prognostication, and recurrence detection. Sensitivity for early CRC is only ~30–50%.
Staging:
- Colon cancer: CT TAP with contrast.
- Rectal cancer: CT TAP + MRI pelvis (mandatory — determines neoadjuvant chemoRT). MRI is superior to CT for delineating mesorectal fat planes. Threatened CRM → neoadjuvant chemoRT before surgery.
Molecular profiling (all CRC): Universal MMR/MSI testing (IHC for MLH1/MSH2/MSH6/PMS2 or PCR for MSI). Metastatic CRC: add KRAS/NRAS/BRAF.
Key numbers: ≥ 12 LN for adequate staging; CRM ≤ 1 mm = positive (predicts local recurrence); T1 → 5% LN risk; T2 → 20%; T3/4 → > 50%.
Screening (HK): FIT → colonoscopy if positive. Two-tier programme for ages 50–75.
Follow-up: Q3m for 2 years, Q6m year 3, yearly years 4–5. CEA + colonoscopy + CT TAP.
Active Recall - CRC Diagnostic Criteria, Algorithm, and Investigations
References
[1] Senior notes: felixlai.md (Colorectal Cancer sections: pages 677–690) [7] Lecture slides: WCS 064 - A large liver - by Prof R Poon [20191108].doc.pdf (page 6) [9] Senior notes: maxim.md (Colorectal cancer screening section, page 209) [10] Senior notes: maxim.md (Investigations and staging sections, pages 217–218, 227) [11] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf (pages 20–22)
Management of Colorectal Cancer — Algorithm and Treatment Modalities
Before diving into stage-specific algorithms, understand the three pillars of CRC management and the logic behind each:
| Pillar | Purpose | When |
|---|---|---|
| Surgery | Remove the primary tumour with adequate margins and lymph node clearance — this is the only curative modality for localised disease | Stages I–III (curative intent); selected Stage IV |
| Chemotherapy | Eradicate micro-metastases after surgery (adjuvant); shrink tumour before surgery (neoadjuvant); control disseminated disease (palliative) | Adjuvant: Stage III + high-risk Stage II; Neoadjuvant: locally advanced rectal cancer; Palliative: Stage IV |
| Radiotherapy | Local control — reduce pelvic recurrence in rectal cancer; palliate symptoms | Neoadjuvant chemoRT for rectal cancer (main role); palliative for pain/bleeding |
The fundamental question in CRC management is: Can I cut it out and cure the patient? If yes → surgery ± chemotherapy. If no → systemic therapy ± palliative procedures.
Management overview [10]:
- 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 high-risk rectal only)
- Stage IV: chemo ± surgery for isolated liver metastasis
Before any elective CRC surgery, the patient must be optimised [1]:
| Step | Detail | Why |
|---|---|---|
| Bowel preparation | Mechanical bowel preparation with polyethylene glycol (PEG) solution [1] | Clears faecal content to reduce bacterial load and improve surgical field; however, there is debate about its necessity for right-sided resections |
| IV antibiotic prophylaxis | Significantly decreases wound infections [1]. Typically cefuroxime + metronidazole (covers aerobes and anaerobes) given at induction | The colon is teeming with bacteria (~10¹¹/g stool) — any breach during surgery risks contamination |
| Thromboprophylaxis | Unfractionated or LMW heparin for moderate-to-high risk patients [1] | Cancer patients are hypercoagulable (Virchow's triad: stasis from immobility, endothelial injury from surgery, hypercoagulability from cancer) |
| Nutritional optimisation | Correct anaemia (iron infusion/transfusion), albumin, nutritional support | Malnutrition impairs wound healing and increases complications |
| Stoma counselling and marking | If a stoma is likely (APR, Hartmann's, defunctioning loop ileostomy), mark the optimal stoma site pre-operatively | Improper siting leads to poor appliance fit, leakage, and devastating impact on quality of life |
| Pre-operative tattooing | Tattoo should be placed in the area of tumour at time of endoscopy so it can be reliably identified at colectomy [1] | Small tumours may not be palpable at surgery, especially laparoscopically |
| MDT discussion | Multidisciplinary team: surgeon, oncologist, radiologist, pathologist, stoma nurse, palliative care | Ensures optimal treatment plan tailored to patient, tumour, and surgeon factors |
5. Surgical Treatment — Colon Cancer
Surgical principles (important!) [10]:
- Complete removal of tumour with adequate proximal and distal margin — at least 5 cm proximally and distally [1][10]
- En bloc resection of contiguous structures if there is attachment or infiltration of tumour into potentially resectable organ or structure [1]
- High ligation of arterial pedicle for lymph node clearance — excise colonic mesentery, ligate arterial supply at its origin, and excise all accompanying LN [10]
- A minimum of 12 lymph nodes in the resected specimen for adequate staging [1][10]. Inadequate LN might require adjuvant chemo [10]
- Tension-free anastomosis with good blood supply to the ensuing anastomosis or stoma [1]
- Restore bowel continuity whenever possible [10]
Why 5 cm margins? Because microscopic intramural spread rarely extends beyond 2 cm from the gross tumour edge, and 5 cm provides a comfortable safety margin while accounting for shrinkage of the specimen after fixation.
Why high ligation? The lymph node drainage follows the arterial supply. To clear all potentially involved nodes, you must ligate the feeding artery at its origin from the SMA or IMA and resect the entire mesentery within that vascular territory.
The type of operation depends on the location of the tumour because you must resect the vascular pedicle and its associated lymphatic drainage basin [1][10]:
| Tumour Site | Operation | Vessels Ligated |
|---|---|---|
| Caecum / Ascending colon | Right hemicolectomy | Ileocolic, right colic, right branch of middle colic (all branches of SMA) [10] |
| Hepatic flexure / Transverse colon / Splenic flexure | Extended right hemicolectomy | Ileocolic, right colic, middle colic (SMA); marginal artery of Drummond [10] |
| Splenic flexure / Descending colon | Left hemicolectomy | Left colic artery (from IMA) [10] |
| Sigmoid colon | Sigmoidectomy (high anterior resection) | IMA and left colic artery [10] |
| Synchronous cancers in multiple segments / Lynch syndrome / FAP | Subtotal / Total colectomy | Multiple pedicles |
For splenic flexure tumours: peritumoral subserosal ICG injection can be done to demonstrate the lymphatic drainage of the tumour [10] — because the splenic flexure sits at the watershed between SMA and IMA territories, so lymphatic drainage is variable.
| Approach | Advantages | When |
|---|---|---|
| Laparoscopic (preferred for elective) | Less postoperative pain, faster recovery, shorter hospital stay, better cosmetics, less wound infection, less intra-abdominal adhesions [1] | Standard for elective, uncomplicated CRC |
| Robotic | High-quality 3D vision, restoration of eye-hand-target axis [1][10], less post-op pain, faster recovery | Increasingly used, especially for rectal cancer in narrow pelvis |
| Open | Shorter operative time [1]; no conversion rate | Preferred for complicated CRC (obstruction, perforation) [1]; large/bulky tumours; when laparoscopic conversion needed |
Temporary diverting colostomy is preferred for left-sided anastomosis [10] — because left-sided anastomoses (especially low colorectal/coloanal) have a higher leak rate (lower blood supply, harder stool, greater tension), and a proximal diverting stoma protects the anastomosis during healing.
5D. Emergency Surgery for Colon Cancer
Emergency surgery is indicated if complicated: obstruction, perforation, haemorrhage [10][5]:
| Scenario | Approach |
|---|---|
| Right-sided lesion | Right hemicolectomy with primary anastomosis ± bowel decompression if stable; temporary ostomy if unstable [10] — the right colon can usually be anastomosed primarily even in emergency because the ileum is clean (liquid content, good blood supply) |
| Left-sided lesion | Hartmann's operation [10][12] |
Indications: often an emergency operation [12]:
- Left-sided CRC with complications requiring urgent resection (obstruction, perforation, bleeding)
- Severe complicated diverticulitis (Hinchey III or above)
- Sigmoid volvulus with complications
Procedure [12]:
- Sigmoid resection — remove the diseased segment
- Formation of a temporary end colostomy at LIF — the proximal bowel is brought out as a stoma
- Closure of rectal stump (or mucous fistula if high risk of breakdown)
- Re-anastomosis 2–3 months post-op — second operation to restore bowel continuity (Hartmann's reversal)
Why not primary anastomosis in emergency left-sided surgery? Because in the setting of obstruction or perforation, the bowel is unprepared (loaded with faeces), oedematous, and the peritoneum is contaminated. An anastomosis in this setting has a very high leak rate — a leak is catastrophic (faecal peritonitis, sepsis, death). Hartmann's is the safe option: remove the problem, bring out a stoma, come back later when everything has settled.
Primary resection and anastomosis is possible in selected cases: [5]
- Segmental resection with primary anastomosis (on-table lavage) — the colon is lavaged intra-operatively to clean the proximal bowel, allowing safe anastomosis
- Subtotal colectomy with anastomosis of ileum and distal colon/rectum [5] — removes all the dilated, unprepared colon proximal to the obstruction; the ileum is then anastomosed to the sigmoid or rectum. This avoids a stoma but results in more frequent bowel movements
Stenting for colorectal malignancy has two roles [5]:
1. Definitive palliation [5]:
- Avoids surgery
- Avoids stoma
- For patients unfit for surgery or with unresectable metastatic disease
2. Bridge to surgery [5]:
- Avoids emergency surgery
- Elective operation with bowel preparation
- More time to stage the disease
- Lower operative mortality and morbidity
- Reduces stoma rate
Contraindication: not for distal rectal tumour — can cause tenesmus and pain [10]. Stents in the very low rectum are not tolerated because of the sensory innervation and proximity to the sphincter complex.
Bridge to Surgery vs. Emergency Resection
The concept of "bridge to surgery" is elegant: instead of performing a high-risk emergency Hartmann's on an unprepared, obstructed patient, you place a self-expanding metal stent (SEMS) endoscopically to relieve the obstruction. The patient then has bowel preparation, full staging, nutritional optimisation, and an elective one-stage resection with primary anastomosis — converting an emergency into an elective. However, there is debate about potential tumour dissemination from stent insertion, and some centres prefer primary resection.
6. Stage-Specific Treatment — Colon Cancer
Surgical resection ± adjuvant chemotherapy [1]:
- Adjuvant chemotherapy does not improve survival in Stage I [1]
- Surgery alone is curative in ~90% [1]
Special consideration — Malignant polyps [1]: If a polyp removed at colonoscopy turns out to harbour carcinoma (T1 on histology), the decision is whether the polypectomy was sufficient or radical surgery is needed:
Features requiring radical resection after polypectomy [1]:
- Poorly differentiated histology
- Lymphovascular invasion
- Positive resection margin (< 1 mm)
- Sm3 invasion (deep submucosal invasion)
- Tumour budding
If none of these adverse features are present and the polypectomy margins are clear, the patient can be observed with surveillance colonoscopy.
Surgical resection ± adjuvant chemotherapy [1]:
- Adjuvant chemotherapy does not improve survival in unselected Stage II patients [1]
- Adjuvant chemotherapy can be considered in selected patients with "high-risk" Stage II disease [1][10]
High-risk features for Stage II [1][10]:
- T4 tumour
- Lymphovascular invasion (LVI)
- Perineural invasion (PNI)
- Poorly differentiated histology
- Inadequate LN retrieval (< 12 nodes)
- Positive resection margins
- Bowel obstruction or perforation at presentation
Why doesn't chemo help most Stage II? Because Stage II is N0 — there are no detected LN metastases, meaning micro-metastatic burden is low. The absolute survival benefit of chemotherapy is small (~3–5%), so it is not routinely given. However, the high-risk features listed above identify a subset with higher recurrence risk where the benefit-risk balance favours treatment.
MSI-H and Stage II
Patients with MSI-high Stage II CRC have an excellent prognosis and do NOT benefit from 5-FU-based adjuvant chemotherapy [1]. In fact, 5-FU may be detrimental in this subgroup. This is why universal MMR/MSI testing is so important — it directly changes management. If a Stage II tumour is MSI-H, you can safely withhold chemotherapy even if other high-risk features are present.
Surgical resection + adjuvant chemotherapy [1][10]:
- Adjuvant chemotherapy is routinely given since patients with LN involvement are at significant risk of both local and distant recurrence [1]
- Use of chemotherapy improves survival in this group [1]
Chemotherapy regimen [10]:
- FOLFOX for 6 months: folinic acid (leucovorin) + 5-fluorouracil + oxaliplatin
- Xelox (CapeOx) for 3 months if lower risk (T1–3, N1) [10] — the IDEA trial showed that 3 months of oxaliplatin-based therapy is non-inferior to 6 months for low-risk Stage III (T1–3 N1), with significantly less neurotoxicity
Note: patients with MSI-high Stage III disease do NOT benefit from chemotherapy and therefore molecular profiling can help patients safely avoid systemic chemotherapy [1]. This is a controversial point — current guidelines still generally recommend adjuvant chemo for Stage III regardless of MSI status, but the evidence is evolving (some clinicians omit 5-FU in MSI-H).
Resection in highly selected patients + adjuvant chemotherapy / palliative procedures [1]:
This is the most complex stage — the approach depends entirely on whether metastases are resectable.
Resectable Liver Metastases:
- 20% of liver metastases are potentially resectable for cure [1]
- 5-year survival rate improves from 20% to 40% after resection [1]
- ALL patients require adjuvant chemotherapy [1]
Management of colorectal liver metastasis [10][12][7]:
- 5-year survival 40–50% with resection [10]
- Resectability criteria [10]:
- Liver factor: adequate future liver remnant > 25% (normal liver) or > 40% (cirrhotic liver)
- Tumour factor: R0 resection (> 1 cm resection margin); risk scores (disease course, CEA, number and size of metastases)
- Patient factor: fitness for surgery
- Contraindication: unresectable extrahepatic malignancy [10]
- Approach: laparotomy [10]:
- Search for regional LN involvement, peritoneal deposits
- Intra-operative USG to assess number of lesions and determine resectability
- Total vascular exclusion: may allow resection with involvement of major vessels
- Perioperative chemotherapy: FOLFOX [10]
Hepatic resection for CRC liver metastases [7]:
- Can prolong survival in patients with resectable liver metastasis (solitary or ≤ 4 metastases all located within one lobe)
- 5-year survival 25% (older data; more recent series report 40–50%)
- One-third recurrence in the liver remnant
- Biopsy — FNAC or Trucut — ONLY for inoperable cases [7] (to confirm histology for chemotherapy planning; otherwise proceed directly to surgery)
Resectable Lung Metastases:
- 1–2% of lung metastases are potentially resectable for cure [1]
- Long-term survival benefit is approximately 30–40% [1]
- Criteria: isolated pulmonary metastasis, controlled primary, adequate pulmonary reserve
Unresectable Stage IV — Palliative Management:
Palliative management for colorectal cancer [10]:
| Modality | Detail |
|---|---|
| Palliative surgery | Endoluminal stenting for obstruction / bridging to surgery (not for distal rectal tumour) [10]; Palliative colostomy ± tumour resection (palliative intent) [10] |
| Palliative radiotherapy | Control local symptoms: pain, discharge, bleeding, incontinence; bone pain [10] |
| Palliative chemotherapy | Oral capecitabine for disseminated disease [10]; systemic combination therapy (FOLFOX, FOLFIRI) with targeted agents |
| Angiographic embolization | For haemorrhage from primary tumour [1] |
| Bypass surgery | For obstruction when stenting is not feasible [1] |
7. Surgical Treatment — Rectal Cancer
Rectal cancer deserves its own section because it is fundamentally different from colon cancer:
Differences from colon cancer [1][10]:
- +ve: Transanal accessibility — distal 10 cm of rectum accessible transanally [1]
- +ve: Easier to treat with neoadjuvant radiotherapy due to relative paucity of small bowel in the pelvis [1]
- -ve: Confinement to pelvis and presence of sphincter makes wide excision impossible [1][10]
- -ve: Proximity to urogenital structures and nerves (bladder, ureter, prostate, vagina, iliac vessels, sacrum) makes resection more challenging [1][10]
- -ve: More difficult to achieve negative radial margins due to anatomical limitation of pelvis [1]
7A. Principles of Rectal Cancer Surgery
Principles [1]:
- Adequate circumferential margin — narrow distal margin (2 cm) is adequate provided TME is performed [1]
- Total mesorectal excision (TME) — the gold standard technique
- Lymph node clearance with high ligation of the IMA
- Sphincter and autonomic nerve preservation — consideration of continence and urogenital function [1]
Resection margins [1]:
TME: precise dissection of the mesorectal envelope (containing tumour, surrounding mesorectal fat, LN and vessels), preserving pelvic autonomic nerves [10].
| Feature | Detail |
|---|---|
| Plane | "Holy plane" — avascular alveolar plane between presacral and mesorectal fascia [10] |
| Rationale | Rectal cancer cells can spread within mesorectum; TME ensures adequate negative CRM and complete removal of all draining lymphatics [1] |
| Benefits | ↓ Local recurrence rate (from ~30% to < 5%); ↓ postoperative genitourinary dysfunction (pelvic autonomic nerve preservation); less blood loss compared with blunt dissection [1][10] |
| Approaches | Transabdominal (open / laparoscopic / robotic), transanal (rarely) [10] |
Why is the "holy plane" called that? Because finding and staying in this avascular plane is the surgeon's holy grail — it provides a bloodless dissection field that ensures complete excision of the mesorectum without damaging the pelvic autonomic nerves. Straying outside this plane risks catastrophic presacral venous bleeding and nerve injury.
Three factors determine the choice of operation:
- Tumour factor: size, distance from anal verge, distance from anorectal ring, LN status, lateral pelvic wall invasion
- Patient factor: fitness, pre-surgical anorectal sphincter function, pelvic anatomy
- Surgeon factor: experience, hospital equipment [1]
7B. Rectal Cancer Operations
| Feature | Detail |
|---|---|
| Indications | ALL of the following must be met: T1N0, superficial rectal cancer, tumour < 3 cm, mobile and non-fixed, able to achieve clear margins, favourable histological features (well/moderately differentiated, no LVI, no PNI) [1] |
| Techniques | Transanal endoscopic microsurgery (TEM); transanal minimally invasive surgery (TAMIS) |
| Why so strict? | Local excision does not remove mesorectal lymph nodes. T1 cancers have ~5% LN metastasis risk — local excision is only safe if features predict minimal risk |
| Feature | Detail |
|---|---|
| Indications | T2–4 invasive rectal cancer; adequate pre-surgical sphincter function; able to achieve clear margins [1] |
| Technique | MUST be performed with TME [1] |
| Anterior resection: margin and anastomosis above peritoneal reflection | |
| Low anterior resection (LAR): margin and anastomosis below peritoneal reflection — more common [1] | |
| Anastomosis options | Colonic J-pouch reservoir; side-to-end anastomosis; transverse coloplasty — all aim to create a neorectal reservoir to improve functional outcomes |
| Defunctioning stoma | Temporary loop ileostomy usually fashioned to protect a low colorectal anastomosis — reversed in ~3 months after confirming anastomotic integrity with water-soluble contrast enema |
| Feature | Detail |
|---|---|
| Indications | Any ONE of: poor pre-op sphincter function; failure to achieve negative distal margin; locally advanced or recurrent low-lying CA rectum [10] |
| Technique | (1) Insert catheter to protect membranous urethra in males; (2) Abdominal part (open/lap) similar to AR; (3) Perineal dissection via circumanal incision for en bloc resection of sigmoid, rectum and anus; (4) Construction of permanent end colostomy [1][10] |
| Key point | APR results in a permanent colostomy — this has significant quality-of-life implications. One goal of neoadjuvant therapy for low-lying tumours is to downsize the tumour enough to convert an APR into a sphincter-sparing LAR |
| Feature | Detail |
|---|---|
| Indications | T4 locally advanced rectal cancer involving adjacent organs; locally recurrent rectal cancer [1] |
| Technique | Resection of rectum + one or more adjacent organs (total or partial pelvic exenteration); en bloc resection of ureters, bladder, prostate, uterus, vagina; sacrum may be resected up to S2–3 junction [1] |
| Outcome | Permanent colostomy + ileal conduit may be necessary; patients with T4M0 have better 5-year survival than those with M1 disease [1] |
This is a critical concept — no role for neoadjuvant therapy in colon cancer [10], but it is central to rectal cancer management.
Neoadjuvant therapy for CA rectum — 3 main indications (need to know!) [10]:
- Resectable but locally advanced disease: sterilize tumour bed, ↓ intra-operative tumour spillage, ↓ local recurrence rate
- T3/T4 disease → only definite indication proven by RCT (German Rectal Cancer Study Group) [10]
- Nodal disease
- Threatened CRM (< 2 mm)
- Borderline resectable disease: downstage the tumour and ↑ resectability rate
- Low-lying tumour: downsize the tumour and ↑ sphincter preservation rate [10]
Advantages of neoadjuvant chemoradiation [1]:
- Tumour downstaging by treating locally involved lymph nodes
- Tumour shrinkage to increase likelihood of resection and sphincter-sparing procedure
- Associated with similar results but significantly less toxicity than postoperative chemotherapy
Disadvantages [1]:
- Overtreatment of early-stage tumours
- Impaired wound healing
- Increased postoperative complications
- Pelvic fibrosis
Regimens [10]:
| Long-course chemoRT (standard in HK) | Short-course high-dose RT | |
|---|---|---|
| Protocol | 5-FU-based chemotherapy × 2 cycles + concurrent RT (50.4 Gy = 1.8 Gy daily × 28 fractions) → Wait 8–10 weeks before surgery → 4 cycles of chemo as adjuvant | RT 25 Gy = 5 Gy × 5 days → Wait 7–10 days before surgery |
| Advantages | Allows tumour downstaging and downsizing; can achieve complete response | Shorter treatment time; single-week course |
| Disadvantages | Maximum dose of RT for lifetime; delays surgery | More side effects of high-dose RT; can only sterilise local tumour bed but not enough time to downstage/downsize tumour [10] |
Response to neoadjuvant chemoRT [10]:
- Clinical complete remission (CCR) ~20%: consider "watch and wait" for 3 years with MRI Q3m, flexible sigmoidoscopy Q3m, PET-CT/CT Q6m [10]
- Pathological complete remission (PCR) ~15%: surgical specimen found tumour-free; may not require adjuvant chemo (case-by-case) [10]
Total Neoadjuvant Therapy (TNT) — 2024–2026 Update
The latest paradigm shift is Total Neoadjuvant Therapy (TNT): all chemotherapy and chemoRT are given BEFORE surgery (e.g., induction FOLFOX × 4 cycles → long-course chemoRT → restaging → surgery). This increases pathological complete response rates to 25–30%, may allow more patients to undergo "watch and wait," and ensures all systemic therapy is delivered (many patients cannot complete adjuvant chemo after major pelvic surgery due to poor recovery).
8. Medical Treatment — Chemotherapy and Targeted Therapy
Indicated for all Stage III and high-risk Stage II disease [1]:
| Drug | Class | Mechanism | Key Side Effects |
|---|---|---|---|
| 5-Fluorouracil (5-FU) | Anti-metabolite (pyrimidine analogue) | Inhibits thymidylate synthase → blocks DNA synthesis ("5-FU" = fluorine substitution on uracil → the cell incorporates this "fake" pyrimidine into DNA/RNA, causing cell death) [1] | Mucositis, diarrhoea, myelosuppression |
| Capecitabine (Xeloda) | Anti-metabolite (pyrimidine analogue — oral prodrug of 5-FU) | Converted to 5-FU in tumour tissue (thymidine phosphorylase is overexpressed in tumour cells) [1] | Hand-foot syndrome (painful erythema and desquamation of palms/soles — because capecitabine is activated in skin); diarrhoea |
| Oxaliplatin | Alkylating agent (platinum compound) | Forms platinum-DNA adducts → prevents DNA replication and transcription → cell death | Peripheral sensory neuropathy (cold-triggered paraesthesia — "can't open the fridge" — due to oxaliplatin's effect on voltage-gated sodium channels); myelosuppression |
| Irinotecan | Topoisomerase I inhibitor | Topoisomerase I unwinds DNA for replication; irinotecan stabilises the enzyme-DNA complex → DNA strand breaks → cell death | Delayed diarrhoea (cholinergic); myelosuppression; alopecia |
| Folinic acid (Leucovorin) | Reduced folate | Enhances 5-FU cytotoxicity by stabilising the 5-FU–thymidylate synthase complex | Not cytotoxic on its own |
Common regimens:
- FOLFOX = FOLinic acid + Fluorouracil + OXaliplatin → standard adjuvant for Stage III (6 months) [10]
- FOLFIRI = FOLinic acid + Fluorouracil + IRInotecan → commonly used in metastatic setting
- Xelox (CapeOx) = Capecitabine + Oxaliplatin → oral alternative; 3 months if lower-risk Stage III (T1–3, N1) [10]
General adverse effects of chemotherapy: mucositis, nausea/vomiting, diarrhoea, febrile neutropenia, alopecia, hand-foot syndrome (especially capecitabine) [1]
8B. Targeted Therapy (Stage IV Only)
ONLY indicated in Stage IV (metastatic) disease — no evidence to support use of targeted therapy in the adjuvant setting [1]
Bevacizumab (OR) Aflibercept (OR) Regorafenib [1]:
| Feature | Detail |
|---|---|
| Mechanism | Monoclonal antibody targeting VEGF-A [1] ("bevacizumab" → "beva" = derived from humanised antibody, "cizumab" = -cizumab = chimeric/humanised monoclonal antibody). VEGF-A promotes angiogenesis — tumours need new blood vessels to grow beyond ~2 mm. Blocking VEGF starves the tumour of blood supply |
| Indication | Added to cytotoxic chemotherapy backbone particularly for patients with KRAS and BRAF mutations when anti-EGFR are contraindicated [1] — i.e., if the tumour has a RAS or BRAF mutation (making anti-EGFR agents useless), anti-VEGF is the targeted therapy of choice |
| Contraindications | Haemorrhage, wound healing (impaired), arterial thromboembolic diseases [1] — all directly related to VEGF inhibition (VEGF promotes wound healing and vascular integrity; blocking it increases bleeding and thrombosis risk) |
| Side effects | Hypertension, proteinuria, GI perforation, haemorrhage, impaired wound healing, arterial thromboembolism |
Cetuximab (OR) Panitumumab [1]:
| Feature | Detail |
|---|---|
| Mechanism | Monoclonal antibody against EGFR [1]. EGFR is a receptor tyrosine kinase on cell surface; when ligand (EGF) binds, it activates RAS-RAF-MEK-ERK proliferative cascade. Blocking EGFR stops this signal |
| Indication | Added to irinotecan-based cytotoxic backbone for patients with wild-type KRAS and BRAF [1] |
| Key predictive biomarkers | Wild-type KRAS: favourable response [1]. Mutant KRAS: will NOT benefit — KRAS mutation results in constitutive activation of RAS-RAF-ERK pathway leading to resistance to anti-EGFR therapy [1]. KRAS and BRAF mutations are mutually exclusive; mutant BRAF is unlikely to benefit [1] |
| Side effects | Acneiform rash, diarrhoea, electrolyte disturbance (hypomagnesaemia) [1]. The acneiform rash is actually a positive prognostic sign — EGFR is expressed in skin, so rash indicates effective EGFR blockade |
| Tumour sidedness | Right-sided metastatic CRC responds poorly to anti-EGFR even if RAS wild-type (biological differences in right vs. left CRC); anti-EGFR is primarily beneficial for left-sided, RAS/BRAF wild-type metastatic CRC |
| Agent | Mechanism | Indication |
|---|---|---|
| Pembrolizumab (anti-PD-1) | Blocks PD-1 on T-cells → prevents tumour PD-L1 from "turning off" the immune response → restores anti-tumour immunity | First-line for MSI-H/dMMR metastatic CRC (KEYNOTE-177 trial). Also: second-line for MSI-H CRC after progression on chemotherapy |
| Nivolumab ± Ipilimumab | Anti-PD-1 ± anti-CTLA-4 | MSI-H/dMMR metastatic CRC; dual checkpoint blockade increases response rates |
Why do MSI-H tumours respond so well to immunotherapy? Because MSI-H tumours have a very high mutational burden → they produce many abnormal "neoantigen" proteins → these are foreign to the immune system → the tumour is inherently immunogenic. However, the tumour upregulates PD-L1 to evade the immune response. Blocking PD-1 "unleashes" the pre-existing anti-tumour immune response.
| Agent | Target | Indication |
|---|---|---|
| Encorafenib + Cetuximab | BRAF V600E + EGFR | BRAF V600E mutant metastatic CRC (BEACON trial) |
| Trastuzumab + pertuzumab | HER2 | HER2-amplified, RAS wild-type metastatic CRC (rare) |
| Larotrectinib / Entrectinib | NTRK fusion | NTRK fusion-positive CRC (tumour-agnostic approval) |
This is a nuanced surgical decision relevant to left-sided and rectal resections [10]:
| High Tie | Low Tie | |
|---|---|---|
| Definition | Ligate IMA at its origin from the aorta | Ligate IMA distal to left colic artery |
| Advantage | Reduces tension on anastomosis (more length); more LN harvest | Avoids damage to the hypogastric nerve → lower risk of autonomic dysfunction [10]; preserves left colic artery (better blood supply to proximal colon) |
| Disadvantage | Risk of hypogastric nerve injury; may compromise blood supply to proximal stump | Fewer LN harvested; may have more tension on anastomosis |
Immediate: [10]
- Massive bleeding requiring conversion to laparotomy (< 10%)
- Injury to neighbouring structures:
- Left ureter and gonadal vessels
- Iliac artery
- GB, D2 (right hemicolectomy)
- Seminal vesicles (LAR)
- Spleen (splenic flexure mobilisation in TME)
- Autonomic nerve injury (especially rectal surgery): sympathetic damage → incontinence, impaired ejaculation; parasympathetic damage → urinary retention, erectile dysfunction [10]
Early: post-op ileus, infection, anastomotic leak [10]
Late:
- Anastomotic stricture — may require finger/endoscopic balloon dilation [10]
- Fistula: enterocutaneous (conservative), rectovaginal/rectourinary (proximal faecal diversion) [10]
- Perineal hernia (after APR) [10]
- LAR syndrome [10]:
- S/S: change in bowel movement (constipation to faecal urgency/incontinence) persisting ≥ 1 month after surgery
- Pathophysiology: colonic dysmotility, neorectal reservoir dysfunction, anal sphincter dysfunction
- Prevention: post-op pelvic floor muscle exercise, anterograde colonic irrigation, faecal diversion
- Management: antidiarrhoeal, transanal irrigation, pelvic floor rehab, sacral nerve stimulation
Aim: detect recurrence (40%) and metachronous tumours (new primary CA diagnosed ≥ 6 months afterwards) [10].
| Time | Interval | Investigations |
|---|---|---|
| First 2 years | Every 3 months | CEA, rigid sigmoidoscopy, LFT |
| 3rd year | Every 6 months | As above |
| 4th–5th year | Yearly | As above |
| > 5 years | Considered in remission | Discharge or routine screening |
| Imaging | CT TAP or PET-CT every 1 year | Detect distant recurrence |
| Colonoscopy | Pre-op incomplete: within 6 months of surgery; Pre-op complete: 1 year post-op, then 3 years, 5 years, then Q5y | Synchronous / metachronous tumours |
High Yield Summary
Colon Cancer Management:
- Stage I: Surgery alone. No adjuvant chemo benefit.
- Stage II: Surgery ± adjuvant chemo (only if high-risk features: T4, LVI, PNI, < 12 LN, poor differentiation, obstruction/perforation). MSI-H Stage II → NO 5-FU.
- Stage III: Surgery + adjuvant chemo (FOLFOX 6 months or Xelox 3 months for low-risk).
- Stage IV: Systemic chemo ± surgery for resectable liver/lung mets. Palliative stenting/stoma/bypass for unresectable.
Rectal Cancer Key Differences:
- MRI pelvis mandatory → determines neoadjuvant chemoRT.
- Neoadjuvant chemoRT for T3/4, N+, threatened CRM, borderline resectable, low-lying tumours.
- TME ("holy plane") is the gold standard surgical technique.
- Local excision only for T1N0 with ALL favourable features.
- APR = permanent colostomy when distal margin cannot be cleared.
Targeted Therapy (Stage IV only):
- Anti-EGFR (cetuximab/panitumumab): only for wild-type KRAS/BRAF, left-sided tumours.
- Anti-VEGF (bevacizumab): for RAS/BRAF mutant tumours.
- Immune checkpoint inhibitors (pembrolizumab): first-line for MSI-H/dMMR metastatic CRC.
Emergency CRC:
- Right-sided: right hemicolectomy + primary anastomosis.
- Left-sided: Hartmann's operation (resection + end colostomy + rectal stump closure; reversal in 2–3 months). Or: stenting as bridge to elective surgery.
Active Recall - CRC Management
References
[1] Senior notes: felixlai.md (CRC treatment sections: pages 690–706) [5] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf (pages 49, 53, 59) [7] Lecture slides: WCS 064 - A large liver - by Prof R Poon [20191108].doc.pdf (page 6) [10] Senior notes: maxim.md (CRC management, staging, follow-up sections: pages 218–227, 271) [12] Senior notes: maxim.md (Hartmann's operation: page 198; FAP/Lynch treatment: page 202)
Complications of Colorectal Cancer
Complications of CRC can be organised into three broad categories:
- Complications of the disease itself (i.e., what the tumour does if left untreated or at presentation)
- Complications of surgical treatment (immediate, early, and late post-operative)
- Complications of non-surgical treatment (chemotherapy, radiotherapy, targeted therapy)
Understanding the mechanism behind each complication is far more important than rote memorisation — if you know why it happens, you can predict it, recognise it, and manage it.
1. Complications of the Disease Itself
These are the complications of CRC that may be the presenting feature (emergency presentations) or develop during the disease course.
| Feature | Detail |
|---|---|
| Mechanism | An annular constricting tumour (typically left-sided) progressively narrows the lumen until formed stool cannot pass → complete mechanical obstruction. Left-sided tumours obstruct more readily because the lumen is narrower and stool is solid. Right-sided tumours rarely obstruct because the caecal lumen is wide and stool is liquid [1] |
| Frequency | CRC is the commonest cause of large bowel obstruction (LBO) in adults [5]. ~10–30% of CRC patients present with obstruction |
| Clinical features | Absolute constipation (no stool or flatus), progressive abdominal distension, colicky abdominal pain, late vomiting (may be faeculent — "faeculent" because bacteria ferment the stagnant small bowel content, producing a faecal smell) |
| Closed-loop obstruction | If the ileocaecal valve is competent (in ~1/3 of the population), the obstruction becomes a closed loop — the colon is obstructed distally by tumour and proximally by the competent valve. Pressure builds within the closed loop, and the caecum is at greatest risk of perforation (Law of Laplace: wall tension = pressure × radius; the caecum has the greatest radius) [13] |
| Management | Emergency surgery [10]: Right-sided → right hemicolectomy + primary anastomosis ± decompression. Left-sided → Hartmann's operation (resection + end colostomy) [10][12], or segmental resection with on-table lavage [5], or subtotal colectomy [5]. Endoluminal stenting as bridge to elective surgery for left-sided tumours [5][10] |
Closed-Loop Obstruction
This is a surgical emergency. If a patient has LBO from a sigmoid tumour and a competent ileocaecal valve, the trapped gas in the closed loop progressively distends the caecum. When caecal diameter exceeds 12 cm on AXR, the risk of perforation becomes critical (caecal perforation is life-threatening with high mortality). You must intervene before this happens — either with emergent stenting or emergency surgery.
| Feature | Detail |
|---|---|
| Mechanism | Two patterns: (1) Tumour perforation — the cancer erodes through the full thickness of the bowel wall → faecal peritonitis or localised abscess. (2) Proximal perforation (diastatic perforation) — closed-loop obstruction → caecal distension → ischaemic necrosis of the caecal wall → perforation at the caecum, remote from the tumour itself. In both cases, faecal content spills into the peritoneal cavity |
| Clinical features | Sudden severe abdominal pain, peritonism (guarding, rigidity, rebound tenderness), absent bowel sounds, septic shock (fever, tachycardia, hypotension). Free air under diaphragm on erect CXR or AXR |
| Significance | Perforation upstages the tumour to at least T4a (penetration of visceral peritoneum) → worse prognosis. Also causes faecal peritonitis with high mortality (up to 20–40%) |
| Management | Emergency laparotomy: Hartmann's procedure (left-sided) or right hemicolectomy (right-sided) with peritoneal lavage. Primary anastomosis is generally NOT performed in diffuse peritonitis [1] |
| Feature | Detail |
|---|---|
| Mechanism | Tumour surface is friable, necrotic, or ulcerated → erosion into blood vessels in the bowel wall. Usually venous, causing chronic occult blood loss rather than massive haemorrhage. Rarely, erosion into a larger vessel → acute massive lower GI bleeding |
| Chronic bleeding | Manifests as iron deficiency anaemia (especially right-sided CRC — blood mixes with liquid stool and is invisible). IDA is the most common complication of right-sided CRC, though it is often a presenting feature rather than a late complication |
| Acute bleeding | Acute massive PR bleeding (haematochezia) is uncommon but can be life-threatening |
| Management | Chronic: iron replacement + definitive surgery. Acute: resuscitation → colonoscopy (if haemodynamically stable) → angiographic embolisation or emergency surgery if uncontrolled [1] |
| Feature | Detail |
|---|---|
| Mechanism | Tumour invades through the bowel wall into an adjacent organ, creating an abnormal communication. This is a manifestation of T4b disease |
| Types | Colovesical fistula (colon → bladder): most common fistula from sigmoid CRC; patient presents with pneumaturia (bubbles in urine — pathognomonic), fecaluria (faeces in urine), and recurrent UTIs. Colovaginal fistula: passage of faeces/flatus per vagina. Coloenteric fistula: communication with small bowel |
| Management | Surgery: en bloc resection of tumour + involved organ segment (e.g., partial cystectomy for colovesical fistula). Often requires temporary faecal diversion |
| Site | Mechanism | Clinical Features |
|---|---|---|
| Liver | Commonest site of distant metastasis — portal venous drainage [1]. Hard nodular hepatomegaly, RUQ tenderness, obstructive jaundice (if mets to porta hepatis LN) [10] | Hepatomegaly with or without symptoms from primary; RUQ pain; general features of malignancy: anorexia, weight loss, cachexia [7] |
| Lung | Haematogenous spread. Distal rectal tumours → IVC → lungs (bypass liver) [1] | Cough, dyspnoea, haemoptysis; cannonball lesions on CXR/CT |
| Peritoneum | Transperitoneal/transcoelomic spread; serosal breach seeds peritoneal cavity | Ascites suggest peritoneal seeding from GI or gynaecological primary [7]; abdominal distension; Krukenberg tumour (ovarian metastases) |
| Brain | Late haematogenous; rare | Headache, focal neurological deficits, seizures |
| Bone | Late haematogenous; rare | Bone pain, pathological fractures, hypercalcaemia |
Management of colorectal liver metastases [7][10]:
- Hepatic resection can prolong survival in patients with resectable liver metastasis (solitary or ≤ 4 metastases all located within one lobe); 5-year survival 25% (historical); more recent data 40–50% [7][10]
- One-third recurrence in the liver remnant [7]
- Colorectal metastasis: systemic or transarterial regional chemotherapy may be indicated in patients with unresectable colorectal liver secondaries (response rate 20–30%) [7]
- Perioperative chemotherapy: FOLFOX [10]
| Feature | Detail |
|---|---|
| Mechanism | Serosal penetration (T4a) or tumour cell spillage at surgery seeds the peritoneum; peritoneal deposits cause ascites by blocking peritoneal lymphatic drainage and by secreting fluid |
| Prognosis | Very poor; M1c staging |
| Management | Selected cases: cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC). Palliative: drainage of ascites, systemic chemotherapy |
2. Complications of Surgical Treatment
Organised as: Immediate (intra-operative) → Early (< 30 days) → Late (> 30 days), with complications common to both colon and rectal surgery, followed by those specific to rectal surgery.
Massive bleeding requiring conversion to laparotomy (< 10%) [10]
Injury to neighbouring structures [1][10]:
| Structure Injured | Context / Mechanism | Consequence |
|---|---|---|
| Left ureter and gonadal vessels | At risk during ligation of IMA, sigmoid mobilisation, or pelvic dissection [10]. The left ureter crosses the pelvic brim beneath the sigmoid mesocolon and is easily mistaken for a vessel | Ureteric transection → urine leak, urinoma; if unrecognised → hydronephrosis, renal damage |
| Iliac artery | Lateral pelvic dissection [10] | Haemorrhage |
| GB, D2 (duodenum) | During right hemicolectomy — the hepatic flexure is intimately related to the duodenum and gallbladder [10] | Bile leak, duodenal perforation |
| Seminal vesicles | During LAR — anterior dissection in males [10] | Sexual dysfunction |
| Spleen | During splenic flexure mobilisation in TME — traction on the splenocolic ligament can tear the splenic capsule [10] | Haemorrhage; may require splenectomy |
| Autonomic nerve injury | Especially in rectal surgery [10] | See below |
Autonomic Nerve Injury (Rectal Surgery) — In Detail
This is a critically important complication unique to rectal surgery, and understanding the anatomy explains everything:
Autonomic nerve injury (especially in rectal surgery): sympathetic vs. parasympathetic [10]:
| Nerve System | Anatomy | Function | Injury Consequence |
|---|---|---|---|
| Sympathetic | Hypogastric nerves (presacral plexus) — run along the promontory and anterior to the sacrum, then lateral to the mesorectum | Maintain bladder neck tone (continence); control ejaculation | Incontinence (bladder neck incompetence), impaired ejaculation (retrograde ejaculation or anejaculation) [10] |
| Parasympathetic | Pelvic splanchnic nerves (nervi erigentes, S2–S4) — run anterolaterally from the pelvic sidewall to the pelvic plexus | Detrusor contraction (bladder emptying); penile erection | Urinary retention (detrusor underactivity), erectile dysfunction [10] |
High tie vs. low tie of IMA [10]:
- High tie (at IMA origin): risk of damaging the hypogastric nerve which crosses near the IMA origin
- Low tie (distal to left colic artery): avoids damage to the hypogastric nerve → lower risk of autonomic dysfunction [10]
Why is nerve preservation so important? Because these are young/middle-aged patients who may live for decades after curative surgery. Permanent urinary incontinence, erectile dysfunction, or ejaculatory failure are devastating quality-of-life consequences. TME along the "holy plane" is specifically designed to preserve these nerves while achieving adequate oncological margins.
2B. Early Complications (< 30 days)
| Feature | Detail |
|---|---|
| Mechanism | Contamination of the surgical wound by colonic bacteria (Bacteroides fragilis, E. coli, Enterococcus) during surgery. The colon is the most heavily colonised segment of the GI tract (~10¹¹ organisms/g stool) |
| Prevention | IV antibiotic prophylaxis (significantly decreases wound infections) [1]; mechanical bowel preparation; skin preparation; meticulous surgical technique |
| Presentation | Wound erythema, warmth, discharge (purulent), fever, elevated WCC — typically post-operative day 3–7 |
| Management | Open wound, drain pus (incision and drainage), wound packing, antibiotics if cellulitis |
| Feature | Detail |
|---|---|
| Mechanism | Temporary paralysis of bowel motility following abdominal surgery. Caused by: handling of bowel (inflammatory mediators), anaesthetic agents, opioid analgesics, electrolyte disturbance (especially hypokalaemia). Normal expected duration: stomach 24h, small bowel 24–48h, colon 3–5 days |
| Presentation | Abdominal distension, absent flatus/stool, nausea/vomiting, absent or hypoactive bowel sounds |
| Management | Conservative: NGT if severe, IV fluids, correct electrolytes, minimise opioids, early mobilisation, chewing gum (stimulates vagal activity → promotes peristalsis). Prolonged ileus (> 5–7 days) should raise suspicion of mechanical obstruction, intra-abdominal abscess, or anastomotic leak |
Anastomotic leak is the single most feared complication of colorectal surgery. It carries a mortality rate of 10–20% and is the major cause of morbidity after CRC surgery [1][10].
| Feature | Detail |
|---|---|
| Mechanism | Failure of the surgical join (anastomosis) to heal → breakdown of the suture line → spillage of intestinal content (faecal or enteric) into the peritoneal cavity or pelvis. Caused by: ischaemia of the bowel ends (poor blood supply), tension on the anastomosis, distal obstruction, infection, malnutrition, corticosteroids, smoking, previous radiotherapy |
| Timing | Becomes apparent 5–7 days postoperatively [1] — this is the critical window because it takes this long for the immature anastomosis to break down before fibrinous healing creates a seal |
| Classification | Intraperitoneal or extraperitoneal leakage [1] |
| Clinical signs | Pain, fever, tachycardia, feculent or purulent drainage [1]. Unexplained tachycardia on post-op day 5–7 is anastomotic leak until proven otherwise. Peritonism, sepsis, raised WCC and CRP |
| Radiological signs | Fluid or gas-containing collections on CT [1]; extraluminal contrast leak on water-soluble contrast enema |
| Management | Fluid resuscitation and broad-spectrum IV antibiotics, bowel rest, image-guided percutaneous drainage of abscess, temporary faecal diversion, or drainage or resection of the anastomosis [1] |
| Risk factors for leak | Left-sided anastomosis > right-sided; low rectal anastomosis (LAR) has the highest leak rate; male sex (narrow pelvis); previous radiotherapy; malnutrition; steroids; emergency surgery; no diverting stoma |
Why are left-sided and low rectal anastomoses more prone to leak? Three reasons: (1) The blood supply to the left colon and rectum is less robust (single marginal artery, IMA territory); (2) The pelvis is narrow and deep, making it technically harder to create a tension-free, well-vascularised anastomosis; (3) Stool is formed and under higher pressure in the left colon/rectum compared to the liquid content on the right side.
A defunctioning loop ileostomy does NOT decrease the rate of anastomotic leakage, but decreases the complication rate and risk of reoperation in cases of anastomotic leakage [1] — because when a leak occurs with a stoma in place, the faecal stream is diverted and the leak can heal without contaminating the peritoneum.
| Feature | Detail |
|---|---|
| Mechanism | Bleeding from the suture line of the anastomosis |
| Management | Blood transfusion and correction of underlying coagulopathy [1]. Rarely requires re-operation; most cases are self-limiting |
2C. Late Complications (> 30 days)
| Feature | Detail |
|---|---|
| Mechanism | Excessive fibrosis/scarring at the anastomotic site during healing → narrowing of the lumen. More common after ischaemic leaks (inflammation → fibrosis), low rectal anastomosis, radiotherapy |
| Presentation | Progressive difficulty with bowel movements, obstructive symptoms, thin stools |
| Management | Majority of patients do not require intervention [1]. Those requiring treatment: finger dilatation for low anastomosis; endoscopic balloon dilatation for high anastomosis [1][10] |
Enterocutaneous (colocutaneous), rectovaginal (colovaginal), and rectourinary fistula can occur following colorectal surgery [1]:
| Type | Mechanism | Management |
|---|---|---|
| Enterocutaneous fistula | Leak from anastomosis tracks to skin surface through the wound | Conservative management since most will close spontaneously without operative intervention [1][10] — manage with wound care, nutritional support (NPO / low-residue diet), and control of sepsis |
| Rectovaginal or rectourinary fistula | Anastomotic leak or local tissue ischaemia tracks into vagina or urinary tract; more common after low rectal surgery (proximity to vagina/bladder) | Should be managed initially with proximal faecal diversion [1][10] (defunctioning stoma to allow the fistula to heal). Definitive repair later if it does not close |
| Feature | Detail |
|---|---|
| Mechanism | After abdominoperineal resection, the pelvic floor is deficient where the rectum and anus were removed. Small bowel or omentum herniate through this defect into the perineal wound |
| Presentation | Perineal bulge, discomfort sitting, skin breakdown |
| Management | Mesh repair if symptomatic |
This is one of the most important quality-of-life complications to understand:
| Feature | Detail |
|---|---|
| Definition / Signs and Symptoms | Change in bowel movement (ranging from constipation to faecal urgency, faecal incontinence) that persists ≥ 1 month after surgery [10] |
| Pathophysiology | Colonic dysmotility (denervation from pelvic dissection → loss of coordinated peristalsis), neorectal reservoir dysfunction (the new "neo-rectum" formed by the colon lacks the compliance and capacitance of the native rectum → reduced reservoir function → urgency and frequency), anal sphincter dysfunction (direct damage or nerve injury during surgery) [10] |
| Incidence | 60–90% of patients after LAR experience some degree of LAR syndrome; ~50% have significant symptoms |
| Prevention | Post-operative pelvic floor muscle exercise, anterograde colonic irrigation via stoma / enema, faecal diversion (temporary ileostomy gives the pelvis time to heal) [10] |
| Management | Antidiarrhoeal agents (loperamide), transanal irrigation (retrograde washout), pelvic floor rehabilitation, sacral nerve stimulation (a pacemaker for the pelvic nerves — modulates residual nerve function) [10] |
Why does LAR syndrome occur? Think of it this way — the rectum is a sophisticated reservoir with compliant walls, a rich nerve supply, and coordinated sphincter function. When you remove the rectum and replace it with a straight tube of colon (or a J-pouch), you lose: (1) the reservoir capacity (less volume before urgency), (2) the normal recto-anal inhibitory reflex (the ability to distinguish gas from stool), and (3) some of the nerve supply from surgical dissection. The result is a constellation of urgency, frequency, clustering (multiple bowel movements over a short period), and incontinence.
2D. Stoma Complications
Stomas (colostomy or ileostomy) are frequently created in CRC surgery — either as temporary defunctioning stomas (loop ileostomy protecting a low anastomosis) or permanent end colostomies (APR). Stoma complications are common and high yield for exams [1]:
| Complication | Mechanism | Management |
|---|---|---|
| Stomal bleeding | Mucocutaneous suture line bleeding; trauma during appliance change | Usually self-limiting; direct pressure; rarely requires suture |
| Stomal necrosis | Ischaemia of the stoma — inadequate blood supply to the bowel segment brought through the abdominal wall (tension on mesentery, thrombosis of marginal vessels) | Inspect with torch — if necrosis extends below fascial level → emergency revision (risk of peritonitis from necrotic bowel); if superficial → observe |
| Stomal retraction | Stoma sinks below skin level — due to tension on mesentery, obesity, or poor surgical technique | Convex appliance to maintain seal; surgical revision if severe |
| Mucocutaneous separation | Breakdown of the junction between stoma mucosa and skin — due to infection, ischaemia, or tension | Wound care; 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 [1]. Ileostomy output contains activated pancreatic enzymes (trypsin, lipase) that digest the peristomal skin | Proper appliance fitting; skin barrier products (stomahesive); reducing output (loperamide, fibre supplementation) |
| Complication | Mechanism | Management |
|---|---|---|
| Parastomal hernia | Most common late stoma complication. Weakness of the abdominal wall around the stoma tract → herniation of bowel/omentum through the defect. More common in colostomies (larger aperture) than ileostomies | Abdominal support belt; surgical repair with mesh if symptomatic or at risk of incarceration |
| Stomal prolapse | Full-thickness intussusception of the bowel through the stoma opening. More common in loop colostomies (the distal limb prolapses because it is not fixed) | Conservative: larger stoma bag, gentle reduction. Surgical revision if symptomatic or impending gangrene |
| Stomal stenosis | Fibrosis and scarring at the fascial or skin level narrows the stoma opening → difficulty in passing stool, obstruction | Finger dilatation; surgical revision if severe |
| Drug | Key Complications | Mechanism |
|---|---|---|
| 5-FU / Capecitabine | Mucositis, diarrhoea, myelosuppression (neutropenia) [1]; hand-foot syndrome (especially capecitabine) [1] — painful erythema and peeling of palms and soles | 5-FU inhibits rapidly dividing cells (GI mucosa, bone marrow); capecitabine is activated in skin by thymidine phosphorylase (overexpressed in tumour AND skin) |
| Oxaliplatin | Peripheral sensory neuropathy (dose-limiting — cumulative; cold-triggered acute dysaesthesia) | Platinum-DNA adducts also damage dorsal root ganglia sensory neurons; voltage-gated sodium channel dysfunction causes cold sensitivity |
| Irinotecan | Delayed diarrhoea (cholinergic mechanism); acute cholinergic syndrome (salivation, lacrimation, diarrhoea during infusion) | Active metabolite SN-38 causes direct colonic mucosal injury; cholinergic effect from acetylcholinesterase inhibition |
| All agents | Febrile neutropenia, nausea/vomiting, alopecia [1] | Myelosuppression; emetic trigger zone stimulation; damage to hair follicle cells |
DPD Deficiency — A Life-Threatening Complication
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for 5-FU catabolism. ~3–8% of the population carry partial DPD deficiency. Complete deficiency is rare but lethal. Patients with DPD deficiency accumulate toxic 5-FU levels → severe mucositis, diarrhoea, myelosuppression, and death. Pre-treatment DPD testing (DPYD genotyping) is now recommended before starting fluoropyrimidine therapy.
| Timing | Complication | Mechanism |
|---|---|---|
| Acute (during or within 6 weeks) | Radiation proctitis (diarrhoea, tenesmus, PR bleeding), radiation cystitis (dysuria, haematuria), skin erythema, fatigue | Direct damage to rapidly dividing mucosal cells in the radiation field; inflammation |
| Chronic / Late (months to years) | Radiation fibrosis → stricture, fistula; chronic radiation proctitis (telangiectasia, bleeding); small bowel injury (if in radiation field — adhesions, stricture, fistula); ovarian failure (if pelvis irradiated); secondary malignancy (very late, rare) | Progressive obliterative endarteritis → ischaemia → fibrosis and tissue atrophy |
| Impaired wound healing; increased postoperative complications; pelvic fibrosis [1] | Fibrosis reduces tissue vascularity; this is a key disadvantage of neoadjuvant chemoRT |
| Agent | Complications | Mechanism |
|---|---|---|
| Bevacizumab (anti-VEGF) | Haemorrhage, impaired wound healing, arterial thromboembolic disease [1]; hypertension; proteinuria; GI perforation (especially in context of intact primary tumour) | VEGF is essential for vascular integrity, wound healing, and angiogenesis. Blocking VEGF → fragile vessels (bleeding), impaired neovascularisation (poor wound healing), loss of endothelial NO production (hypertension), glomerular endotheliosis (proteinuria) |
| Cetuximab / Panitumumab (anti-EGFR) | Acneiform rash, diarrhoea, electrolyte disturbance (hypomagnesaemia) [1] | EGFR is expressed in skin (especially hair follicles — hence acneiform rash in hair-bearing areas); EGFR in colonic mucosa (diarrhoea); EGFR in renal tubules regulates magnesium reabsorption (hypomagnesaemia) |
| Pembrolizumab / Nivolumab (anti-PD-1) | Immune-related adverse events (irAEs): colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, skin rash, adrenal insufficiency | Checkpoint inhibitors "release the brakes" on the immune system — this also unleashes autoimmunity against normal tissues. Any organ can be affected (the "itis" complications) |
While not strictly complications of CRC treatment, these are relevant because colonoscopy is the gold standard diagnostic tool and polypectomy is often performed at the same session:
| Complication | Mechanism | Detail |
|---|---|---|
| Perforation | Mechanical (scope tip) or thermal (polypectomy cautery) | Chance of perforation ≤ 0.1% [11]. Presents with sudden pain, peritonism, free air on imaging. Management: small contained perforations may be managed with endoscopic clipping and IV antibiotics; larger perforations require emergency surgery |
| Post-polypectomy bleeding | Sloughing of eschar covering a vessel at the polypectomy site; typically 5–7 days after the procedure [1]. Can also extend the zone of thermal necrosis to involve deeper blood vessels | Most self-limiting; endoscopic haemostasis (clipping, adrenaline injection); rarely requires surgery |
| Post-polypectomy syndrome | Electrocoagulation injury to bowel wall creating a transmural burn and focal peritonitis without frank perforation [1] | Presents with fever, focal abdominal tenderness and leucocytosis 1–5 days following polypectomy [1]. Management is conservative (IV antibiotics, bowel rest) — surgery is NOT needed because there is no actual perforation. The key is distinguishing this from true perforation (no free air on imaging) |
| Sedation-related | Over-sedation, respiratory depression, aspiration | Rare with modern monitoring; managed with reversal agents (flumazenil for benzodiazepines, naloxone for opioids) |
Post-Polypectomy Syndrome vs. Perforation
Students frequently confuse these two. Post-polypectomy syndrome = transmural burn WITHOUT perforation → focal peritonitis, fever, leucocytosis, but NO free air on imaging → treat conservatively (antibiotics, bowel rest). True perforation = free air on imaging, generalised peritonism → usually requires surgical repair. The distinction is critical because one is managed medically and the other surgically. CT scan is the key differentiator — look for free intraperitoneal air.
7. Long-Term Complications and Recurrence
- ~40% of CRC patients develop recurrence [10]
- Most recurrences (80%) occur within the first 3 years; hence the intensive early follow-up schedule [10]
- Types of recurrence:
- Local recurrence: tumour regrowth at the primary resection site or anastomosis. More common in rectal cancer (especially without TME or with positive CRM)
- Distant recurrence: metastases to liver, lung, peritoneum
- Metachronous tumour: a new primary cancer diagnosed ≥ 6 months after the original CRC [10] — this is not the same tumour coming back; it is a completely new cancer arising in the remaining colon (field effect / genetic predisposition)
- Detection: rising CEA, surveillance colonoscopy, CT TAP, PET-CT
Follow-up protocol (recap) [10]:
- First 2 years: Q3m → 3rd year: Q6m → 4th–5th year: yearly → > 5 years: remission
- CEA, sigmoidoscopy, LFT at each visit; CT TAP/PET-CT annually; colonoscopy per schedule
- Lynch syndrome patients are at particularly high risk of metachronous CRC and extra-colonic cancers (endometrial, ovarian, urothelial, small bowel) — hence the extended surveillance protocols
- History of CRC is itself a risk factor for developing a second CRC — the remaining colon has the same genetic and environmental exposure
High Yield Summary
Disease Complications:
- LBO (commonest cause = CRC); closed-loop obstruction if competent ileocaecal valve → caecal perforation risk.
- Perforation: tumour perforation (T4a) or diastatic (caecal). High mortality. Emergency Hartmann's or right hemicolectomy.
- Haemorrhage: usually chronic (IDA); rarely acute massive.
- Fistula: colovesical (pneumaturia, fecaluria, recurrent UTI), colovaginal (faeces per vagina) — indicates T4b.
- Metastasis: liver (most common, portal drainage), lung (distal rectal via IVC), peritoneum (ascites).
Surgical Complications:
- Immediate: bleeding, injury to left ureter/gonadal vessels, spleen, GB/D2, autonomic nerves (sympathetic → incontinence/ejaculatory failure; parasympathetic → urinary retention/erectile dysfunction).
- Early: SSI, ileus, anastomotic leak (most feared; day 5–7; pain/fever/tachycardia; manage with resuscitation/antibiotics/drainage/diversion).
- Late: stricture (balloon dilatation), fistula (ECF conservative; rectovaginal/urinary → diversion), parastomal hernia, stomal prolapse/stenosis, perineal hernia (APR), LAR syndrome (urgency/incontinence; manage with antidiarrhoeals, pelvic floor rehab, transanal irrigation, sacral nerve stimulation).
Chemo Complications: 5-FU (mucositis, myelosuppression); capecitabine (hand-foot syndrome); oxaliplatin (neuropathy); irinotecan (delayed diarrhoea). DPD deficiency → lethal 5-FU toxicity.
Targeted Therapy Complications: Bevacizumab (bleeding, poor wound healing, thrombosis); cetuximab (acneiform rash, hypomagnesaemia); pembrolizumab (immune-related AEs).
Colonoscopy Complications: perforation (≤ 0.1%); post-polypectomy bleeding (day 5–7); post-polypectomy syndrome (transmural burn, no free air — conservative Mx).
Recurrence: 40% develop recurrence; 80% within 3 years. Follow-up: Q3m × 2 years, then Q6m, then yearly.
Active Recall - Complications of Colorectal Cancer
References
[1] Senior notes: felixlai.md (CRC complications sections: pages 695–706) [5] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf (pages 49, 53, 59) [7] Lecture slides: WCS 064 - A large liver - by Prof R Poon [20191108].doc.pdf (page 6) [10] Senior notes: maxim.md (Post-operative complications, follow-up, metastasis management: pages 218, 226–227, 271) [11] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf (pages 20–22) [12] Senior notes: maxim.md (Hartmann's operation: page 198) [13] Senior notes: maxim.md (Closed-loop obstruction: page 168)
High Yield Summary
Definition: CRC = adenocarcinoma of the colon/rectum (> 95%). Arises from adenoma-carcinoma sequence over ~10 years.
Epidemiology (HK): Commonest cancer; > 90% aged ≥ 50; M > F (1.3:1); 2nd leading cause of cancer death.
Risk Factors: Age > 50, male, family history (10–15%), hereditary syndromes (FAP, Lynch — 10%), IBD (UC > CD), red/processed meat, low fibre, alcohol, smoking, obesity, DM, acromegaly. Protective: exercise, fibre, aspirin/NSAIDs.
Key Hereditary Syndromes:
- FAP: APC gene, AD, hundreds of polyps, 100% CRC if untreated → prophylactic colectomy.
- Lynch: MMR genes (MLH1 most common), AD, 70–80% CRC risk, right-sided, rapid adenoma-carcinoma, Amsterdam 3-2-1 rule → annual colonoscopy from age 20–25.
Pathogenesis: (1) CIN pathway (APC → K-RAS → SMAD4 → p53) — 60–85%; (2) MSI pathway (MMR deficiency) — 15%; (3) Serrated pathway.
Clinical Features by Site:
- Right-sided: IDA, occult bleeding, RIF mass.
- Left-sided: change in bowel habit, PR bleeding, obstruction.
- Rectal: fresh PR bleeding, tenesmus, mucus discharge.
- Emergencies: LBO (commonest cause in adults), perforation, haemorrhage.
Metastasis: Liver first (portal drainage) except distal rectum → lung first (systemic drainage). Regional LN most common overall.
Key Signs: Pallor, palpable mass, hepatomegaly, Virchow's node, Sister Mary Joseph nodule, DRE mass. DRE is mandatory.
Prognosis: LN involvement is the single most important prognostic factor. 5-year survival: Stage I 90%, II 60–80%, III 60%, IV 10%.
High Yield Summary
Key Differentials by Presentation:
-
IDA / occult blood loss (right-sided pattern): CRC, angiodysplasia, PUD, coeliac disease, gastric cancer → investigate with "top and tail" (OGD + colonoscopy).
-
Change in bowel habit / PR bleeding (left-sided/rectal): CRC, diverticular disease (most important DDx — cannot exclude CRC without colonoscopy after acute episode resolves), IBD, haemorrhoids, IBS, infectious/ischaemic colitis, radiation proctitis. Never attribute PR bleeding to haemorrhoids in ≥ 50 without colonoscopy.
-
Large bowel obstruction: CRC (commonest cause in adults), volvulus, diverticular stricture, pseudo-obstruction. Always check hernial orifices and do DRE.
-
Abdominal mass: CRC, diverticular abscess, Crohn's phlegmon, appendicular mass, ovarian pathology.
-
Liver mass/hepatomegaly: CRC liver mets (commonest cause of liver secondaries from GI), HCC, other GI mets, abscess.
Critical pitfall: Diverticulitis vs. sigmoid CRC — CT alone cannot distinguish; colonoscopy after inflammation resolves is mandatory.
High Yield Summary
Diagnosis = Colonoscopy with biopsy. Full stop. CEA is NOT diagnostic — it is for monitoring, prognostication, and recurrence detection. Sensitivity for early CRC is only ~30–50%.
Staging:
- Colon cancer: CT TAP with contrast.
- Rectal cancer: CT TAP + MRI pelvis (mandatory — determines neoadjuvant chemoRT). MRI is superior to CT for delineating mesorectal fat planes. Threatened CRM → neoadjuvant chemoRT before surgery.
Molecular profiling (all CRC): Universal MMR/MSI testing (IHC for MLH1/MSH2/MSH6/PMS2 or PCR for MSI). Metastatic CRC: add KRAS/NRAS/BRAF.
Key numbers: ≥ 12 LN for adequate staging; CRM ≤ 1 mm = positive (predicts local recurrence); T1 → 5% LN risk; T2 → 20%; T3/4 → > 50%.
Screening (HK): FIT → colonoscopy if positive. Two-tier programme for ages 50–75.
Follow-up: Q3m for 2 years, Q6m year 3, yearly years 4–5. CEA + colonoscopy + CT TAP.
High Yield Summary
Colon Cancer Management:
- Stage I: Surgery alone. No adjuvant chemo benefit.
- Stage II: Surgery ± adjuvant chemo (only if high-risk features: T4, LVI, PNI, < 12 LN, poor differentiation, obstruction/perforation). MSI-H Stage II → NO 5-FU.
- Stage III: Surgery + adjuvant chemo (FOLFOX 6 months or Xelox 3 months for low-risk).
- Stage IV: Systemic chemo ± surgery for resectable liver/lung mets. Palliative stenting/stoma/bypass for unresectable.
Rectal Cancer Key Differences:
- MRI pelvis mandatory → determines neoadjuvant chemoRT.
- Neoadjuvant chemoRT for T3/4, N+, threatened CRM, borderline resectable, low-lying tumours.
- TME ("holy plane") is the gold standard surgical technique.
- Local excision only for T1N0 with ALL favourable features.
- APR = permanent colostomy when distal margin cannot be cleared.
Targeted Therapy (Stage IV only):
- Anti-EGFR (cetuximab/panitumumab): only for wild-type KRAS/BRAF, left-sided tumours.
- Anti-VEGF (bevacizumab): for RAS/BRAF mutant tumours.
- Immune checkpoint inhibitors (pembrolizumab): first-line for MSI-H/dMMR metastatic CRC.
Emergency CRC:
- Right-sided: right hemicolectomy + primary anastomosis.
- Left-sided: Hartmann's operation (resection + end colostomy + rectal stump closure; reversal in 2–3 months). Or: stenting as bridge to elective surgery.
High Yield Summary
Disease Complications:
- LBO (commonest cause = CRC); closed-loop obstruction if competent ileocaecal valve → caecal perforation risk.
- Perforation: tumour perforation (T4a) or diastatic (caecal). High mortality. Emergency Hartmann's or right hemicolectomy.
- Haemorrhage: usually chronic (IDA); rarely acute massive.
- Fistula: colovesical (pneumaturia, fecaluria, recurrent UTI), colovaginal (faeces per vagina) — indicates T4b.
- Metastasis: liver (most common, portal drainage), lung (distal rectal via IVC), peritoneum (ascites).
Surgical Complications:
- Immediate: bleeding, injury to left ureter/gonadal vessels, spleen, GB/D2, autonomic nerves (sympathetic → incontinence/ejaculatory failure; parasympathetic → urinary retention/erectile dysfunction).
- Early: SSI, ileus, anastomotic leak (most feared; day 5–7; pain/fever/tachycardia; manage with resuscitation/antibiotics/drainage/diversion).
- Late: stricture (balloon dilatation), fistula (ECF conservative; rectovaginal/urinary → diversion), parastomal hernia, stomal prolapse/stenosis, perineal hernia (APR), LAR syndrome (urgency/incontinence; manage with antidiarrhoeals, pelvic floor rehab, transanal irrigation, sacral nerve stimulation).
Chemo Complications: 5-FU (mucositis, myelosuppression); capecitabine (hand-foot syndrome); oxaliplatin (neuropathy); irinotecan (delayed diarrhoea). DPD deficiency → lethal 5-FU toxicity.
Targeted Therapy Complications: Bevacizumab (bleeding, poor wound healing, thrombosis); cetuximab (acneiform rash, hypomagnesaemia); pembrolizumab (immune-related AEs).
Colonoscopy Complications: perforation (≤ 0.1%); post-polypectomy bleeding (day 5–7); post-polypectomy syndrome (transmural burn, no free air — conservative Mx).
Recurrence: 40% develop recurrence; 80% within 3 years. Follow-up: Q3m × 2 years, then Q6m, then yearly.
Anorectal Fistula
An anorectal fistula is an abnormal epithelialized tract connecting the anal canal or rectum to the perianal skin or another organ, usually resulting from a perianal abscess.
Diverticular Disease
Diverticular disease refers to the formation of abnormal mucosal outpouchings (diverticula) through the colonic wall, predominantly at sites of vascular penetration, encompassing a spectrum from asymptomatic diverticulosis to symptomatic diverticular disease and acute diverticulitis with potential complications such as perforation, abscess, or fistula formation.