CA Rectum
Colorectal adenocarcinoma arising in the rectum (within 15 cm from the anal verge), presenting with bleeding per rectum, tenesmus, and altered bowel habits, often requiring multimodal treatment including neoadjuvant chemoradiation and surgical resection.
| Exam domain | One-glance essentials |
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| Epidemiology / risks |
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| Core mechanism |
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| Clinical picture |
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| Investigations |
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| Management |
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| Complications |
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| Prevention / follow-up |
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| Exam traps |
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References
[1] Lecture slides: Clinical presentation, diagnosis and screening of colorectal cancer_rev1.pdf (p.6, p.9; “MRI pelvis for cancer of the rectum” slide) [2] Lecture slides: Molecular pathways, route of spread and staging.pdf (“Metastatic colorectal cancer” slide) [3] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer section, p.102–108) [4] Senior notes: Ryan Ho GI.pdf (Colorectal cancer and rectal-surgery sections, p.108–109, p.139, p.163, p.166, p.169, p.173, p.175–177) [5] Senior notes: Maksim Medicine Notes.pdf (Clinical oncology section, p.54) [6] Lecture slides: Professor Chiang Chi Leung - Role of Radiotherapy in Rectal Cancer_rev3.pdf (p.3, p.8) [7] Past paper: 2025 Fourth Summative SAQ.pdf (Question 12, p.15)
CA Rectum (Carcinoma of the Rectum)
Carcinoma of the rectum (CA Rectum) is a malignant neoplasm arising from the epithelial lining of the rectum. The rectum is defined differently depending on the context:
- Endoscopic definition: up to 15 cm from the anal verge [1][2]
- Oncological definition: bowel below the peritoneal reflection [1][2]
This distinction matters enormously because it dictates the surgical approach, the role of radiotherapy, and the patterns of local recurrence. The peritoneal reflection is the key landmark — below it, the rectum is surrounded by mesorectal fat rather than peritoneum, which means:
- Radial spread into surrounding pelvic structures is a major concern (unlike colon cancer where peritoneum provides a serosal barrier)
- Total mesorectal excision (TME) becomes the cornerstone of surgical technique
- Neoadjuvant radiotherapy plays a role (unlike colon cancer)
Within the rectum, tumours are further sub-classified by distance from the anal verge:
- Upper rectum: 10–15 cm from anal verge (above peritoneal reflection)
- Mid rectum: 5–10 cm from anal verge
- Low rectum: < 5 cm from anal verge (closest to anal sphincter complex)
This sub-classification is critical because low rectal tumours may threaten the anal sphincter, necessitating abdominoperineal resection (APR) with permanent colostomy, while higher tumours can undergo sphincter-preserving surgery (anterior resection).
Right-sided tumour: tumour before the splenic flexure. Left-sided tumour: tumour after the splenic flexure. [2] Rectal cancer is considered a left-sided/distal tumour.
Why does CA Rectum differ from CA Colon?
Although both are "colorectal cancers," CA Rectum is managed differently from CA Colon because: (1) the rectum lies deep in the bony pelvis making surgical access difficult, (2) it lacks a serosal covering below the peritoneal reflection facilitating local invasion, (3) the proximity to the anal sphincter complex raises continence issues, (4) the close relationship with pelvic structures (bladder, prostate/uterus, sacral nerves) raises concerns about functional morbidity, and (5) neoadjuvant chemoradiotherapy (nCRT) is a key component for locally advanced rectal cancer — a paradigm that does not exist for colon cancer.
2. Epidemiology
Colorectal cancer (CRC) is the 3rd most common cancer worldwide (after lung and breast) and the 2nd leading cause of cancer death globally [3].
- Incidence is highest in developed/high-income countries — Australia/New Zealand, parts of Europe, North America
- Incidence is rising in transitioning economies (e.g., Eastern Asia including China/Hong Kong) due to adoption of Western diets and lifestyles
- Median age at diagnosis is 68 [3]
In Hong Kong, CRC is the most common cancer overall and in males (1st), and the 2nd most common cancer in females [4][3].
- Incidence: 74.1 per 100,000 per year (one of the highest in Asia) [4]
- Mortality: 28.5 per 100,000 per year (2nd cause of cancer death in both sexes) [4]
- Male-to-female ratio ≈ 1.5–1.6 : 1 [3][4]
- Stage at diagnosis: Stage I (10.6%), Stage II (22.5%), Stage III (25.5%), Stage IV (24.0%) — meaning nearly a quarter present with metastatic disease [4]
Rectal cancer specifically accounts for approximately 25–30% of all colorectal cancers. The rectosigmoid is the most common site [4], and approximately 70% of CRC are left-sided tumours [4].
Note: Right-sided tumours are becoming more common [4], a trend observed globally, possibly due to the increasing recognition of serrated polyp pathway lesions and microsatellite instability-high tumours.
- Age > 50 — rare below 40 (unless hereditary syndrome); peak incidence 60–70 years [4]
- Male predominance (M:F ≈ 1.6:1 in HK) [3][4]
- 10–15% have a positive family history [4]
- 25% show non-syndromal familial clustering [4]
High Yield – HK CRC Screening Programme
CRC screening in Hong Kong uses a 2-tier system [5]:
- FIT (faecal immunochemical test) every 2 years starting from age 50
- If FIT positive → colonoscopy (every 10 years) or flexible sigmoidoscopy (every 5 years)
This is part of the government's Colorectal Cancer Screening Programme launched in 2016.
3. Risk Factors
| Risk Factor | Explanation |
|---|---|
| Age > 50 [3][6] | Accumulation of somatic mutations in colonic epithelium over time; adenoma-carcinoma sequence typically takes 10–15 years |
| Male sex [3][6] | Male-to-female ratio ~1.5:1 in HK; possibly related to hormonal protective effects of oestrogen in females (combined HRT is protective) |
| Family history [3][6] | First-degree relative with CRC increases risk ~2–3×; risk higher if relative diagnosed < 50 or if multiple relatives affected |
| Polyposis syndromes [4] | FAP (familial adenomatous polyposis — APC gene mutation, autosomal dominant, near 100% risk of CRC by age 40), MAP (MUTYH-associated polyposis), Peutz-Jeghers syndrome (PJS), Juvenile polyposis syndrome (JPS) |
| Non-polyposis syndromes [4] | HNPCC / Lynch syndrome (mutations in mismatch repair genes — MLH1, MSH2, MSH6, PMS2; autosomal dominant; 60–80% lifetime risk of CRC; also increased risk of endometrial, ovarian, gastric cancers) |
| History of colorectal polyps [3][4] | Especially large ( > 2.5 cm), villous, sessile, or dysplastic adenomatous polyps — these carry the highest malignant potential |
| History of CRC [4] | Metachronous tumours in 1.5–3% in post-op 5 years |
| IBD-related colitis [3][4][6] | 5–15× risk; after 8–10 years in pancolitis, 15–20 years in left-sided colitis. UC > CD. The risk correlates with extent and duration of disease |
| Acromegaly [4] | 2–14× risk — IGF-1 acts as a growth factor for colonic mucosal cells |
| Prior renal transplant [4] | Possibly related to immunosuppression |
| Prior cholecystectomy [4] | 1.16× for right-sided CA — thought to be due to increased bile acid exposure to the right colon |
| Risk Factor | Explanation |
|---|---|
| Diet: red and processed meat, animal fat [4][6] | Heterocyclic amines and polycyclic aromatic hydrocarbons from cooking meat at high temperatures; haem iron generates free radicals and N-nitroso compounds that damage colonic DNA |
| Obesity, DM and insulin resistance [4][6] | 1.15–1.23× risk — hyperinsulinaemia and elevated IGF-1 promote cell proliferation and inhibit apoptosis in colonic epithelium |
| Smoking [4][6] | 1.18× risk, 1.25× mortality — carcinogens in tobacco smoke (e.g., aromatic amines, nitrosamines) reach the colonic mucosa via bloodstream |
| Alcohol [4] | 1.21–1.52× risk depending on intake — acetaldehyde (alcohol metabolite) is a direct carcinogen; also impairs folate absorption (folate is needed for DNA repair) |
| Sedentary lifestyle [4] | Physical inactivity leads to prolonged colonic transit time → prolonged mucosal exposure to carcinogens |
| Androgen deprivation therapy [4] | Used in prostate cancer treatment |
| Protective Factor | Mechanism |
|---|---|
| High fibre diet [4] | Dilutes carcinogens, accelerates transit time, fermented by gut bacteria to produce butyrate (promotes apoptosis of neoplastic cells) |
| Aspirin and NSAIDs [2][4] | COX-2 inhibition → reduces prostaglandin E2 → decreases cell proliferation, increases apoptosis, inhibits angiogenesis. COX-2 is overexpressed in colorectal adenomas and carcinomas |
| Physical activity [4] | 0.73–0.74× risk — reduces insulin resistance, decreases transit time |
| Calcium, vitamin D, dairy products [4] | Calcium binds bile acids and free fatty acids in the colonic lumen, reducing their proliferative effects |
| Dietary folate and B6 [4] | Essential for DNA methylation and synthesis; deficiency leads to uracil misincorporation and DNA strand breaks |
| Combined HRT [4] | Oestrogen may have anti-proliferative effects on colonic epithelium |
| Statins [4] | May inhibit Ras signalling pathway (KRAS is a key oncogene in CRC) |
High Yield – Smoking and IBD/CRC Relationship
4. Anatomy and Function of the Rectum
The rectum is the terminal segment of the large intestine, approximately 12–15 cm in length, extending from the rectosigmoid junction (at the level of S3 vertebra) to the anal canal (at the anorectal junction/puborectalis sling).
Key anatomical relationships:
- Anterior:
- Male: bladder, seminal vesicles, prostate, Denonvilliers' fascia
- Female: uterus, cervix, posterior vaginal wall, rectovaginal septum
- Posterior: sacrum, coccyx, presacral fascia (Waldeyer's fascia), presacral venous plexus, middle sacral artery
- Lateral: lateral ligaments of the rectum (containing middle rectal arteries), ureters, pelvic sidewall, obturator internus
- Inferior: levator ani muscle (puborectalis, pubococcygeus, iliococcygeus), anal sphincter complex
The mesorectum is the fatty envelope surrounding the rectum, enclosed by the mesorectal fascia (a distinct fascial layer). It contains:
- Perirectal lymph nodes (primary nodal drainage)
- Branches of the superior rectal artery and vein
- Perirectal fat
The concept of total mesorectal excision (TME) — removing the rectum along with its intact mesorectal envelope — revolutionised rectal cancer surgery. Before TME, local recurrence rates were 25–40%; with TME, local recurrence dropped to < 5–10%. This is because microscopic tumour deposits (satellite nodules) in the mesorectum are a major source of recurrence.
The circumferential resection margin (CRM) — the closest distance between the tumour and the mesorectal fascia — is one of the most important prognostic factors in rectal cancer [8]. A CRM ≤ 1 mm is considered involved/positive and predicts high local recurrence.
| Artery | Origin | Area Supplied |
|---|---|---|
| Superior rectal artery | Inferior mesenteric artery (IMA) | Upper rectum (main blood supply) |
| Middle rectal artery | Internal iliac artery | Mid/lower rectum |
| Inferior rectal artery | Internal pudendal artery (branch of internal iliac) | Anal canal and lower rectum |
Venous drainage follows a dual pathway:
- Superior rectal vein → inferior mesenteric vein → portal system → liver (explains hepatic metastasis)
- Middle and inferior rectal veins → internal iliac vein → IVC → lungs (explains why distal rectal tumours can metastasise directly to lungs bypassing the liver) [2]
Lymphatic spread follows the arterial supply [8]:
- Upward (primary route): along superior rectal artery → inferior mesenteric lymph nodes → para-aortic nodes
- Lateral: along middle rectal artery → internal iliac lymph nodes (especially relevant for tumours below the peritoneal reflection)
- Downward (rare, only if proximal lymphatics blocked): to inguinal lymph nodes
This is why for low rectal tumours, lateral lymph node dissection may be considered (more practised in East Asian countries, e.g., Japan).
The rectum and pelvic organs are innervated by autonomic nerves that run in close proximity to the mesorectum:
- Sympathetic: superior hypogastric plexus (presacral nerves) and hypogastric nerves → injury causes retrograde ejaculation in males
- Parasympathetic: pelvic splanchnic nerves (S2–S4, nervi erigentes) → injury causes erectile dysfunction and bladder dysfunction
These nerves form the inferior hypogastric (pelvic) plexus on the lateral pelvic sidewall. Damage during TME surgery leads to urogenital dysfunction.
The dentate (pectinate) line divides the upper 2/3 and lower 1/3 of the anal canal [9]:
| Feature | Above Dentate Line | Below Dentate Line |
|---|---|---|
| Embryology | Endoderm | Ectoderm |
| Epithelium | Columnar (→ adenocarcinoma) | Stratified squamous (→ SCC) |
| Nerve supply | Autonomic (inf. hypogastric plexus) | Somatic (inf. rectal n. ← pudendal n.) |
| Venous drainage | Portal system (superior rectal vv.) | IVC (middle + inferior rectal vv.) |
| Lymphatic drainage | Internal iliac and inferior mesenteric LN | Superficial inguinal LN |
This anatomy explains why very low rectal tumours extending to the anal canal may drain to inguinal lymph nodes and have different biological behaviour.
5. Aetiology and Pathophysiology
5.1 Molecular Pathways
Colorectal cancer develops through well-characterised molecular pathways:
This is the classic adenoma-carcinoma sequence (Vogelstein model):
- APC gene (Adenomatous Polyposis Coli, chromosome 5q): tumour suppressor gene; loss of APC leads to constitutive activation of Wnt/β-catenin signalling → uncontrolled cell proliferation. This is the initiating event in most CRCs. In FAP, one allele of APC is inherited in a mutated state (germline mutation), and loss of the second allele (somatic "second hit") leads to adenoma formation — explaining why FAP patients develop hundreds to thousands of polyps.
- KRAS oncogene (chromosome 12p): encodes a GTPase in the Ras-Raf-MEK-ERK signalling pathway. Activating mutations keep KRAS constitutively "on," promoting cell growth and survival.
- SMAD4/DCC (chromosome 18q): tumour suppressor genes in the TGF-β signalling pathway; loss allows cells to escape growth inhibition.
- TP53 (chromosome 17p): "guardian of the genome"; loss eliminates cell cycle arrest and apoptosis in response to DNA damage → allows malignant transformation.
Higher risk in large ( > 2.5 cm), villous, sessile adenomatous polyps [2].
The adenoma-carcinoma sequence typically takes 10–15 years, which forms the basis for screening intervals.
- Caused by defective DNA mismatch repair (MMR) genes — MLH1, MSH2, MSH6, PMS2
- Microsatellites are short tandem repeats of DNA. When MMR is defective, errors during DNA replication in these repeats accumulate → "microsatellite instability"
- Hereditary: Lynch syndrome (HNPCC) — germline mutations in MMR genes
- Sporadic: usually due to epigenetic silencing of MLH1 by promoter hypermethylation
- MSI-high tumours tend to be:
- Right-sided, poorly differentiated, mucinous/signet ring histology
- Better prognosis stage-for-stage (more immunogenic — many tumour neoantigens attract immune cells)
- Responsive to immune checkpoint inhibitors (anti-PD-1: pembrolizumab, nivolumab)
- Do NOT benefit from 5-FU-based chemotherapy (important for stage II decision-making)
There is also the serrated pathway (CpG island methylator phenotype, CIMP) [8] — associated with BRAF V600E mutation, sessile serrated adenomas/polyps, right-sided location, and often overlaps with MSI-high phenotype in sporadic cases.
| Syndrome | Gene | Inheritance | Features | CRC Risk |
|---|---|---|---|---|
| FAP | APC (5q21) | AD | > 100 adenomatous polyps; also duodenal polyps, desmoid tumours, osteomas, CHRPE | ~100% by age 40 |
| Attenuated FAP | APC | AD | 10–100 polyps, right-sided | ~70% lifetime |
| MAP | MUTYH | AR | 10–100 polyps | ~80% lifetime |
| Lynch syndrome (HNPCC) | MLH1, MSH2, MSH6, PMS2 | AD | Fulfils Amsterdam/Bethesda criteria; increased risk of endometrial, ovarian, gastric, urothelial cancers | 60–80% lifetime |
| Peutz-Jeghers | STK11/LKB1 | AD | Hamartomatous polyps + mucocutaneous pigmentation | 39% lifetime |
Colorectal cancer spreads via four routes [2][8]:
-
Direct spread (local invasion):
- Radial/circumferential spread — implicated in resectability in rectal cancer [2]
- In rectal cancer, tumour can invade through the rectal wall into perirectal fat, mesorectal fascia, and adjacent pelvic structures (bladder, prostate, uterus, sacrum, pelvic sidewall)
- The CRM (circumferential resection margin) reflects the extent of radial spread
-
Lymphatic spread:
- Along the lymphatic channels following arterial supply
- Virchow's node (Troisier's sign) — left supraclavicular lymphadenopathy indicates advanced disease with spread via the thoracic duct [2]
-
Haematogenous spread:
- Liver (most common site of distant metastasis) — via portal venous drainage [2]
- Lung — upper rectal tumours drain via portal system → liver → lung; but distal rectal tumours can metastasise directly to lungs via middle/inferior rectal veins → IVC → lungs, bypassing the liver [2]
- Bone, brain (less common)
-
Transcoelomic spread (peritoneal seeding):
Key biomarkers that affect management:
| Biomarker | Significance |
|---|---|
| KRAS/NRAS | If mutant → anti-EGFR therapy (cetuximab, panitumumab) is ineffective. If wild-type → anti-EGFR can be added [5] |
| BRAF (V600E) | Poor prognosis; associated with MSI-H in sporadic cases; targeted by encorafenib + cetuximab |
| MSI/MMR status | MSI-H/dMMR → better prognosis, responsive to immunotherapy, do NOT benefit from 5-FU alone in stage II |
| HER2 | Amplification in ~5% of CRC; potential target for trastuzumab/pertuzumab |
| VEGF | Angiogenesis target; anti-VEGF (bevacizumab, aflibercept, regorafenib) can be added regardless of RAS status [5] |
6. Classification and Staging
- Adenocarcinoma (> 90%) — the predominant type; arises from glandular epithelium
- Well, moderately, or poorly differentiated
- Mucinous adenocarcinoma (> 50% mucinous component) — tends to present at advanced stage, worse prognosis
- Signet ring cell carcinoma — very aggressive, poor prognosis
- Squamous cell carcinoma (rare in rectum, more common in anal canal below dentate line)
- Neuroendocrine tumours (carcinoid)
- Gastrointestinal stromal tumour (GIST) — mesenchymal origin
- Lymphoma — rare
| Stage | T | N | M | Description |
|---|---|---|---|---|
| 0 | Tis | N0 | M0 | Carcinoma in situ (intramucosal) |
| I | T1–T2 | N0 | M0 | Tumour invades submucosa (T1) or muscularis propria (T2) |
| IIA | T3 | N0 | M0 | Tumour invades through muscularis propria into pericolorectal tissues |
| IIB | T4a | N0 | M0 | Tumour penetrates visceral peritoneum |
| IIC | T4b | N0 | M0 | Tumour directly invades other organs/structures |
| IIIA | T1–T2 | N1 | M0 | 1–3 regional lymph nodes positive |
| IIIB | T3–T4a | N1 | M0 | 1–3 regional lymph nodes positive |
| IIIC | Any T | N2 | M0 | ≥ 4 regional lymph nodes positive |
| IVA | Any T | Any N | M1a | Metastasis to 1 distant organ (e.g., liver) |
| IVB | Any T | Any N | M1b | Metastasis to > 1 distant organ |
| IVC | Any T | Any N | M1c | Peritoneal metastasis |
T staging details:
- T1: invades submucosa
- T2: invades muscularis propria
- T3: invades through muscularis propria into pericolorectal tissues (mesorectal fat)
- T4a: penetrates visceral peritoneum (above peritoneal reflection)
- T4b: directly invades or adherent to other organs/structures
N staging:
- N1: 1–3 regional lymph nodes
- N1a: 1 node; N1b: 2–3 nodes; N1c: tumour deposits without identifiable LN
- N2: ≥ 4 regional lymph nodes
- N2a: 4–6 nodes; N2b: ≥ 7 nodes
A minimum of 12 lymph nodes should be examined for adequate staging [5].
| Dukes' | Equivalent | Description |
|---|---|---|
| A | Stage I | Confined to bowel wall |
| B | Stage II | Through bowel wall, no LN |
| C | Stage III | Lymph node involvement |
| D | Stage IV | Distant metastasis |
Pelvic MRI is the gold standard for local staging of rectal cancer. Key features assessed:
- T stage: depth of invasion through rectal wall layers
- N stage: mesorectal and lateral pelvic lymph nodes
- CRM (circumferential resection margin): predicted distance from tumour to mesorectal fascia
- CRM > 1 mm = clear
- CRM ≤ 1 mm = threatened/involved → indication for neoadjuvant chemoradiotherapy
- Extramural vascular invasion (EMVI): tumour invasion into veins outside the muscularis propria — poor prognostic factor
- Relationship to anal sphincter complex: determines sphincter-preserving surgery vs APR
7. Clinical Features
CA Rectum may present with [6]:
- Rectal bleeding
- Change in bowel habit
- Anaemia
- Abdominal mass
- Rectal mass
- Tenesmus
- Mucus
- Fistula
- Obstruction
- Perforation
- Asymptomatic (detected on screening)
The most common presentation is rectal bleeding and change in bowel habit.
7.2 Symptoms with Pathophysiological Basis
| Symptom | Pathophysiological Basis |
|---|---|
| Rectal bleeding (haematochezia) [6] | Tumour surface is friable and ulcerated → bleeds on contact with stool. Because the rectum is distal, blood is typically bright red/fresh and may be mixed with or coat the stool surface. Unlike upper GI bleeds which produce melaena (acid-haematin conversion), rectal tumours produce frank red blood because there is no time for bacterial/acid degradation |
| Change in bowel habit [2][6] | The growing tumour narrows the rectal lumen (annular/constricting growth pattern, especially left-sided/distal tumours where lumen is already smaller and stool is more formed). This produces: alternating constipation and diarrhoea (paradoxical diarrhoea — liquid stool passes around the obstruction while formed stool cannot), pencil-thin/ribbon stools (stool squeezed through narrow lumen), increased frequency of defaecation |
| Tenesmus [6] | Latin: "tenesmus" from Greek "teinesmos" = straining. The rectal tumour mass creates a sensation of incomplete evacuation by occupying the rectal ampulla and stimulating stretch receptors, giving a persistent urge to defaecate even after emptying. This is characteristic of rectal (not colon) tumours |
| Mucus per rectum [6] | Mucin-secreting adenocarcinoma or reactive mucus production from inflamed/ulcerated rectal mucosa. Villous adenomas classically produce copious mucus (can even cause hypokalaemia from mucus loss) |
| Rectal/pelvic pain | Dull aching perineal/sacral pain indicates locally advanced disease with invasion into perirectal tissues, sacral nerve plexus (S2–S4), or levator ani muscles. Intractable pain (sacral nerve invasion) is a sign of advanced disease [10] |
| Fistula [6] | Locally advanced rectal tumours can invade into adjacent organs creating abnormal communications: rectovesical fistula (→ pneumaturia, faecaluria, recurrent UTIs), rectovaginal fistula (→ passage of stool/gas per vagina) |
| Symptom | Pathophysiological Basis |
|---|---|
| Intestinal obstruction [6] | Left-sided/distal tumours tend to obstruct [2] because: (1) the lumen is narrower distally, (2) stool is more formed and solid in the left colon/rectum, (3) left-sided tumours tend to grow in an annular/constricting pattern ("napkin ring" appearance). Presents with colicky abdominal pain, distension, absolute constipation, vomiting (late) |
| Perforation [6] | Can occur at the tumour site (direct perforation through necrotic tumour) or proximal to the obstruction (closed-loop obstruction with caecal distension → caecal perforation when diameter > 12 cm — Laplace's law: wall tension = pressure × radius, so the caecum with the largest diameter is at highest risk of perforation) |
| Symptom | Pathophysiological Basis |
|---|---|
| Anaemia (iron deficiency) [6] | Chronic occult blood loss from the tumour surface → depletion of iron stores → microcytic hypochromic anaemia. Right-sided tumours are more likely to present with anaemia [2] because the bleeding is more occult (liquid stool mixes with blood, not noticed by the patient), while left-sided/rectal tumours tend to present with frank haematochezia |
| Weight loss, anorexia, malaise [10] | Cancer cachexia syndrome — tumour-derived cytokines (TNF-α, IL-6, IL-1) increase basal metabolic rate, promote muscle proteolysis, suppress appetite via hypothalamic signalling. Also reduced oral intake if obstructive symptoms |
| Fever | Tumour necrosis, secondary infection of obstructed segment, or abscess formation |
| Symptom | Site of Metastasis | Pathophysiology |
|---|---|---|
| Jaundice, RUQ discomfort [10] | Liver | Hepatic metastases compressing/obstructing bile ducts or replacing hepatic parenchyma |
| Dyspnoea, cough [10] | Lung | Pulmonary metastases; especially from distal rectal tumours that bypass the liver via IVC |
| Bone pain [10] | Bone | Skeletal metastases (less common in CRC than in breast/prostate/lung) |
| Ascites [10] | Peritoneum | Peritoneal carcinomatosis → exudative ascites |
| Abdominal distension | Peritoneum/liver | Massive hepatomegaly or malignant ascites |
| Irritative urinary symptoms [10] | Bladder invasion | Direct local extension of rectal tumour into bladder base |
7.3 Signs with Pathophysiological Basis
| Sign | Pathophysiological Basis |
|---|---|
| Pallor | Chronic iron deficiency anaemia from occult blood loss |
| Cachexia/wasting | Cancer cachexia — TNF-α/IL-6 mediated muscle wasting |
| Koilonychia | Severe iron deficiency anaemia (concave/spoon-shaped nails due to abnormal nail matrix growth from iron depletion) |
| Virchow's node (Troisier's sign) [2] | Left supraclavicular lymphadenopathy — represents end-stage lymphatic spread via the thoracic duct |
| Sister Mary Joseph nodule | Periumbilical nodule from peritoneal/transcoelomic spread |
| Hepatomegaly | Liver metastases — hard, irregular, nodular liver |
| Sign | Pathophysiological Basis |
|---|---|
| Abdominal mass [6] | Palpable mass is uncommon in rectal cancer (rectum is deep in pelvis) but may be felt if the tumour is large or if there is associated bulky mesenteric/omental disease |
| Abdominal distension | Intestinal obstruction (with tympanitic percussion) or ascites (with shifting dullness) |
| Hepatomegaly | Liver metastases — typically hard, irregular, non-tender |
| Ascites | Peritoneal carcinomatosis |
DRE is the single most important examination in CA Rectum — low rectal tumours (within 8 cm of the anal verge, i.e., within finger reach) can be directly palpated.
| Finding | Significance |
|---|---|
| Rectal mass [6] | Hard, irregular, ulcerated mass with rolled edges — characteristic of malignancy. Note position (anterior/posterior/lateral, distance from anal verge), size, circumferential involvement, mobility (fixed vs. mobile — fixity suggests T4 disease with invasion into surrounding structures) |
| Blood/mucus on glove | Confirms presence of bleeding/mucus-secreting lesion |
| Anal sphincter tone | Assess tone (may be reduced if tumour invades sphincter complex) — determines whether sphincter-preserving surgery is feasible |
| Rectovaginal septum / prostate | Assess for anterior invasion |
| Pouch of Douglas nodularity (Blumer's shelf) | Transcoelomic deposits in the Pouch of Douglas, palpable on DRE as a hard shelf anterior to the rectum — indicates peritoneal carcinomatosis |
Never Forget the DRE!
Up to 70–80% of rectal tumours are palpable on DRE. A common exam mistake is to discuss investigations for rectal cancer without mentioning DRE first. DRE provides information on tumour location, size, fixity, sphincter involvement, and the presence of peritoneal deposits — all of which directly influence management. "If you don't put your finger in it, you'll put your foot in it." — A classic surgical teaching aphorism.
| Sign | Complication |
|---|---|
| Peritonism (guarding, rigidity, rebound) | Perforation → faecal peritonitis |
| Empty rectum on DRE with distended abdomen | Large bowel obstruction |
| Pneumaturia / faecaluria | Rectovesical fistula |
| Passage of stool/flatus PV | Rectovaginal fistula |
Right-sided (proximal) and left-sided (distal) tumours present differently [2]:
| Feature | Right-Sided (Proximal): present later | Left-Sided (Distal): present earlier |
|---|---|---|
| Growth pattern | Polypoid, exophytic | Annular, constricting ("napkin ring") |
| Luminal calibre | Larger | Smaller |
| Stool consistency | More liquid | More formed |
| Predominant presentation | Tend to bleed (occult) → iron deficiency anaemia, dull vague abdominal pain, right-sided abdominal mass | Tend to obstruct → change in bowel habits (tenesmus, reduced stool calibre, mucoid stool), hematochezia, intestinal obstruction |
| Change in bowel habits | Not common (stool is more liquid and colon more spacious) | Common |
Rectal cancer specifically shares left-sided features but with additional features of tenesmus (tumour in the rectal ampulla) and sphincter-related symptoms.
High Yield Summary
CA Rectum — Definition, Epidemiology, Risk Factors, Anatomy, Aetiology, Pathophysiology, Classification, and Clinical Features
-
Definition: Malignant neoplasm of the rectum; endoscopically defined as up to 15 cm from anal verge; oncologically defined as bowel below peritoneal reflection
-
Epidemiology: CRC is the most common cancer in HK (1st in males, 2nd in females); incidence 74.1/100k/yr; M:F = 1.5–1.6:1; peak 60–70y; median age 68; ~24% present as stage IV
-
Key risk factors: Age > 50, male, FHx, FAP, Lynch syndrome, IBD (UC > CD after 8–10 years), obesity, red/processed meat, smoking, alcohol; protective: aspirin/NSAIDs, fibre, physical activity
-
Pathways: CIN pathway (85%) = adenoma-carcinoma sequence (APC→KRAS→SMAD4→TP53); MSI pathway (15%) = defective MMR genes → better prognosis, responsive to immunotherapy
-
Anatomy: Mesorectum is key — TME reduced local recurrence from 25–40% to < 5–10%; CRM is the most important prognostic factor; distal rectal tumours can metastasise to lungs bypassing liver via IVC
-
Spread: Direct (radial — critical in rectal CA), lymphatic (Virchow's node), haematogenous (liver MC, then lungs), transcoelomic (Krukenberg tumour, Pouch of Douglas)
-
Clinical features: Rectal bleeding, change in bowel habit, tenesmus, mucus, anaemia are the cardinal symptoms; DRE is essential — most rectal tumours are palpable; left-sided tumours tend to obstruct while right-sided tend to bleed
-
Staging: TNM (AJCC 8th ed); minimum 12 LN for adequate staging; MRI pelvis is the gold standard for local staging of rectal CA
Active Recall - CA Rectum (Part 1: Definition to Clinical Features)
[1] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer section, p.102) [2] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer section, p.103) [3] Lecture slides: 2024-2025 Clin Epi colorectal cancer.pdf (p.2, p.7) [4] Senior notes: Ryan Ho GI.pdf (Section 3.3.6.1, p.163) [5] Senior notes: Maksim Medicine Notes.pdf (Clinical oncology section, p.54) [6] Lecture slides: Clinical presentation, diagnosis and screening of colorectal cancer_rev1.pdf (p.6, p.9) [7] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p.32) [8] Lecture slides: Molecular pathways, route of spread and staging.pdf [9] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.747 — Anal canal anatomy) [10] Senior notes: Ryan Ho Fundamentals.pdf (p.283) and Ryan Ho GI.pdf (p.108–109)
Differential Diagnosis of CA Rectum
When a patient presents with symptoms suggestive of rectal cancer — rectal bleeding, change in bowel habit, tenesmus, a rectal mass on DRE, or iron deficiency anaemia — the task is to systematically work through the differential. The clinical presentation overlaps significantly with many benign and malignant conditions, and the key is to determine which diagnoses you cannot afford to miss and which clues point towards one diagnosis over another.
A useful framework (from Murtagh's safe diagnostic model, taught in GC CFB lectures) is [11]:
Be systematic in problem solving:
- What is the probability diagnosis?
- What serious disorders cannot be missed (red flags)?
- What conditions are often missed (pitfalls)?
- Could this patient have a "masquerade"?
- Is this patient trying to tell me something else (hidden agenda)?
For a patient presenting with rectal bleeding + change in bowel habit + tenesmus in someone > 50 years old, the probability diagnosis is CA rectum until proven otherwise. But the formal differential is broad.
The differential depends on the presenting complaint. CA Rectum can masquerade as — or be mimicked by — conditions presenting with:
- Rectal bleeding (haematochezia / PR bleeding)
- Change in bowel habit
- Rectal mass
- Iron deficiency anaemia
- Large bowel obstruction
We will organise the DDx by presenting symptom cluster, then synthesise.
Hematochezia refers to passage of bright red blood or blood clots per rectum [12][13]. The colour, pattern, and associated symptoms help localise the source:
- Bright red blood → from left colon or distal [12]
- Dark/maroon blood mixed with stool → right colon [12]
- Blood on surface of stools → anus/rectum [10]
- Blood after defecation → anus (e.g., haemorrhoids) [10]
- Blood mixed with faeces → above sigmoid [10]
| Differential | Key Distinguishing Features | Why it mimics CA Rectum |
|---|---|---|
| Haemorrhoids | Blood coating stools or bleeding following defecation [10]; perianal prolapsing mass, pruritus (mucus), ± pain if thrombosed; at 3, 7, 11 o'clock positions in lithotomy [9]. No weight loss, no change in bowel habit, no mass on DRE (internal haemorrhoids are soft, compressible, not hard/irregular) | Fresh PR bleeding, commonest cause of rectal bleeding; can coexist with CA rectum — so finding haemorrhoids does NOT exclude cancer |
| Anal fissure | History of constipation; severe sharp pain upon defecation [10]; visible tear at anal margin (90% posterior midline); sentinel skin tag; sphincter spasm | Fresh blood on wiping, pain with defecation |
| Diverticular disease | Painless, usually profuse haematochezia (not chronic) [10][12]; right-sided diverticula are common in Asians and have higher haemorrhage risk [12]; bleeding occurs in the absence of diverticulitis | Acute PR bleeding, but typically sudden/profuse and self-limiting, NOT chronic like CA rectum |
| Angiodysplasia | Usually in elderly; may be associated with vascular malformations (e.g., HHT) and aortic stenosis (Heyde syndrome) [10]; painless, less severe than diverticular but tends to be intermittent [10] | Intermittent PR bleeding in elderly; but no mass, no change in bowel habit |
| Inflammatory bowel disease (UC/CD) | Usually bloody diarrhoea [10]; extra-intestinal manifestations: arthritis, episcleritis/uveitis, erythema nodosum [10][14]; younger age group (peak 20–40); UC: continuous rectal involvement with mucosal inflammation; CD: skip lesions, perianal disease | Bloody diarrhoea, tenesmus, rectal mass (inflammatory pseudopolyps); long-standing UC (8–10 years) is itself a risk factor for CA rectum [4][7] |
| Infective colitis | Fever, chills, rigors, nausea/vomiting, diarrhoea, pain [10]; TOCC, immunosuppression (CMV colitis) [10]; previous TB exposure [10]; acute onset, self-limiting | Bloody diarrhoea; TB colitis can mimic Crohn's and even carcinoma (stricturing, mass) — crucial to rule out in HK [7] |
| Ischaemic colitis | CVS risk factors, acute MI, stroke [10]; rapid onset abdominal pain + haematochezia/bloody diarrhoea; "watershed" areas (splenic flexure, rectosigmoid junction) | Bloody diarrhoea in elderly with vascular risk factors |
| Radiation proctitis | History of abdominal/pelvic irradiation [10]; e.g., prior RT for CA cervix, CA prostate; telangiectatic mucosa on sigmoidoscopy | PR bleeding, tenesmus; occurs months to years after pelvic RT |
| Rectal varices | Portal hypertension (cirrhosis); distinct from haemorrhoids — rectal varices are dilated portosystemic collaterals in the rectal submucosa above the dentate line | PR bleeding, but in the context of known liver disease |
| Solitary rectal ulcer syndrome | Young patients; straining, incomplete evacuation; mucosal prolapse; characteristic histology (fibromuscular obliteration of lamina propria) | PR bleeding, tenesmus, mucus |
| Upper GI bleed (massive) | Haematochezia can occur in patients with massive upper GI bleeding [12]; haematemesis, coffee ground vomitus, melaena; should be considered especially in severe haematochezia (10–15% from UGI) [10] | Profuse fresh PR bleeding in a haemodynamically unstable patient — don't forget UGI source |
High Yield – GC Lecture Slide Point
Worrying signs of colorectal CA: alternating diarrhoea and constipation, passage of mucus, tenesmus, pencil-thin stools [10]. These should be sought in ANY patient presenting with rectal bleeding to distinguish malignancy from benign causes. The presence of constitutional symptoms (loss of appetite, loss of weight, malaise) [10] and signs of spread (intractable pain from sacral nerve invasion, irritative urinary symptoms from bladder invasion, ascites, jaundice/RUQ discomfort, bone pain, SOB) [10] dramatically raises the suspicion for CA rectum.
When a patient complains of altered bowel habit — especially alternating constipation and diarrhoea — the DDx includes:
| Differential | Key Distinguishing Features | Why it mimics CA Rectum |
|---|---|---|
| Irritable Bowel Syndrome (IBS) | Diagnosis of exclusion; features that should NOT be found in IBS: weight loss, rectal bleeding, onset in older patients, family history of CA colon or IBD, positive FOBT, anaemia, raised ESR/WBC [15]; Rome IV criteria: recurrent abdominal pain ≥ 1 day/week for ≥ 3 months, related to defaecation; IBS-D is most common subtype [15] | Alternating bowel habit, abdominal pain, bloating. But IBS is a functional disorder — NO alarm features. In an older patient with new-onset symptoms, IBS should be a diagnosis of exclusion |
| IBD (UC/CD) | See above. Chronic relapsing-remitting course; extraintestinal manifestations; younger age group; endoscopic/histological findings | Chronic diarrhoea, PR bleeding, tenesmus |
| Diverticular disease | Altered bowel habit (constipation predominant), LLQ pain, episodes of acute diverticulitis; CRC can only be excluded with colonoscopy after resolution of acute inflammation [16] | LLQ pain, altered bowel habit; CT may show bowel wall thickening mimicking tumour. Features suggesting diverticulitis over CRC: pericolonic/mesenteric inflammation, involvement > 10 cm of colon, absence of enlarged pericolonic lymph nodes [16] |
| Thyroid disease | Hypothyroidism → constipation; hyperthyroidism → diarrhoea | Change in bowel habit but with endocrine features |
| Drugs | CCBs, opioids → constipation; metformin, colchicine, antibiotics → diarrhoea [17] | Altered bowel habit; always take a thorough drug history |
A mass palpable on DRE or found on imaging/endoscopy:
| Differential | Key Features |
|---|---|
| CA Rectum | Hard, irregular, ulcerated, fixed; rolled edges; may be circumferential |
| Rectal polyp (adenomatous) | Soft, pedunculated or sessile; may bleed; pre-malignant (adenoma-carcinoma sequence) |
| Rectal carcinoid (neuroendocrine tumour) | Smooth, firm, submucosal nodule; usually < 1 cm; most are benign; found incidentally |
| Rectal GIST | Submucosal mass; smooth overlying mucosa; diagnosed by biopsy (CD117/c-KIT positive) |
| Rectal lymphoma | Rare; may be part of systemic lymphoma; submucosal mass |
| Endometriosis (females) | Cyclical rectal bleeding coinciding with menstruation; tender nodule in rectovaginal septum |
| Presacral tumours | Extrinsic compression; smooth, palpable posteriorly; includes teratoma, chordoma, schwannoma |
| Inflammatory mass (Crohn's, TB, diverticular abscess) | Tender, ill-defined; associated with systemic inflammation; TB colitis can form a mass mimicking carcinoma [7] |
| Peridiverticular abscess | Mass or tenderness on DRE; presence of distal sigmoid abscess [16] |
| Rectal prolapse | Complete: protrusion of all layers of rectum through anus; partial: mucosa only [18]; circumferential folds visible; elder women |
| Thrombosed haemorrhoids | Acute onset, very tender, perianal mass; below dentate line |
| Pelvic mass (non-GI) | Don't forget pregnancy, ovarian cyst/tumour, uterine fibroid, bladder tumour, prostatic mass [19] |
IDA in an older patient (especially > 50 years) should be considered GI malignancy until proven otherwise. The DDx:
- Upper GI malignancy: gastric cancer, oesophageal cancer
- Lower GI malignancy: CA colon (especially right-sided — occult bleeding), CA rectum
- Peptic ulcer disease: chronic blood loss
- Coeliac disease: malabsorption of iron in the duodenum
- Angiodysplasia: occult intermittent bleeding
- Menstrual blood loss: premenopausal women
- Hookworm: endemic areas
- Dietary deficiency: rare as a sole cause in developed settings
In HKUMed exams, the key teaching point is: In any patient > 50 with unexplained IDA, both upper and lower GI endoscopy are indicated to exclude malignancy.
CA Rectum is the most common cause of large bowel obstruction in adults. The DDx of LBO:
| Cause | Key Features |
|---|---|
| Colorectal carcinoma | Most common cause (~60% of LBO); annular constricting lesion, especially left-sided |
| Sigmoid volvulus | Rotation of sigmoid around its mesentery; massive distension; "coffee bean sign" on AXR; elderly, institutionalised, psychiatric patients, chronic constipation |
| Diverticular stricture | History of recurrent diverticulitis; narrowing at sigmoid |
| Hernias (obstructed/strangulated) | Inguinal, femoral, incisional; palpable irreducible lump |
| Adhesions | Much less common cause of LBO than SBO; history of prior surgery |
| Pseudo-obstruction (Ogilvie syndrome) | Massive colonic dilatation without mechanical obstruction; in critically ill, post-operative, or hospitalised patients |
| Faecal impaction | Elderly, immobile, opioid use; hard stool palpable on DRE |
| Feature | CA Rectum | Haemorrhoids | Diverticular Disease | IBD (UC) | IBS |
|---|---|---|---|---|---|
| Age | > 50 | Any | > 50 | 20–40 (peak) | Any |
| PR bleeding | Mixed with stool; dark or bright | After defaecation, on paper/surface | Profuse, painless, acute | Bloody diarrhoea, mucus | No bleeding |
| Pain | Late; pelvic/sacral if advanced | Only if thrombosed | LLQ, acute episodes | Cramping with defaecation | Abdominal pain related to defaecation |
| Change in bowel habit | Progressive; alternating | No | Constipation predominant | Diarrhoea ± urgency | Alternating but chronic, no progression |
| Weight loss | Yes | No | No | Possible (malabsorption in CD) | Not typical |
| DRE findings | Hard, irregular mass, fixed | Soft, non-tender (internal); tender swelling (external/thrombosed) | Tenderness | Mucosal tenderness, blood | Normal |
| Colonoscopy | Mass, ulcerated, biopsy → adenocarcinoma | Cushions at 3/7/11 | Diverticula | Continuous mucosal inflammation (UC), skip lesions (CD) | Normal |
Critical Pitfall
Haemorrhoids and CA Rectum can coexist. Finding haemorrhoids on examination does NOT exclude colorectal cancer. Any patient over 50 with rectal bleeding, or any patient with alarm features (weight loss, change in bowel habit, anaemia, family history), MUST have a colonoscopy even if haemorrhoids are found. "Treat the haemorrhoids, but scope the colon."
TB Colitis vs CA Rectum — Hong Kong Relevance
In Hong Kong, TB colitis is an important differential for Crohn's disease and can also mimic colorectal carcinoma [7]. TB can form strictures, masses, and fistulae indistinguishable from malignancy on imaging. It is crucial to rule out TB infection before starting biologics (anti-TNF-α) for IBD, as these can cause TB reactivation [7]. Always check for TB history, chest X-ray, IGRA/Mantoux, and send biopsies for AFB stain and culture.
High Yield Summary
Differential Diagnosis of CA Rectum — Key Points
-
Rectal bleeding DDx: Haemorrhoids (most common cause of PR bleeding but can coexist with CA), anal fissure, diverticular disease (acute, profuse, painless), angiodysplasia, IBD, infective/ischaemic/radiation colitis, solitary rectal ulcer syndrome; don't forget massive UGI bleed can present as haematochezia (10–15%)
-
Change in bowel habit DDx: IBS (diagnosis of exclusion — no alarm features), IBD, diverticular disease, thyroid disease, drugs
-
Rectal mass DDx: Adenomatous polyp, carcinoid, GIST, lymphoma, endometriosis, presacral tumour, inflammatory mass (TB, Crohn's, diverticular abscess), rectal prolapse; don't forget non-GI pelvic masses (ovarian, uterine, bladder, prostate)
-
IDA in > 50: Always scope both upper and lower GI to exclude malignancy
-
LBO: CA colon/rectum is the most common cause (~60%); DDx includes sigmoid volvulus, diverticular stricture, hernia, pseudo-obstruction
-
Critical pitfalls: Haemorrhoids + CA coexist → always scope; TB colitis mimics CA in HK → rule out before biologics; IBS is a diagnosis of exclusion requiring absence of alarm features
Active Recall - Differential Diagnosis of CA Rectum
References
[4] Senior notes: Ryan Ho GI.pdf (Section 3.3.6.1, p.163) [7] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p.32, p.41) [9] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.747 — Anal canal anatomy) [10] Senior notes: Ryan Ho GI.pdf (p.108–109) and Ryan Ho Fundamentals.pdf (p.283) [11] Lecture slides: CFB (FM02) Introduction to common problems - Differentiating the normal from the abnormal.pdf (p.6) [12] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.345) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.651) [13] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.651) [14] Lecture slides: Inflammatory bowel disease.pdf (p.9–10) [15] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (p.22) [16] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.644) [17] Senior notes: Maksim Surgery Notes.pdf (p.88) and Maksim Medicine Notes.pdf (p.119) [18] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.763) [19] Lecture slides: Block C - Pelvic mass_ ovarian cancer and cysts; uterine fibroid; pelvic imaging.pdf (p.17)
Diagnostic Criteria, Algorithm and Investigations for CA Rectum
There is no single "diagnostic criterion" for rectal cancer in the way that, say, the Duke's criteria exist for infective endocarditis. Rather, the diagnosis is established through a combination of:
- Clinical suspicion — symptoms, signs, and risk factors
- Endoscopic visualisation — direct visualisation of the tumour
- Histological confirmation via biopsy — this is the definitive diagnostic step [1][4]
The diagnosis of CA rectum is confirmed by colonoscopy with biopsy demonstrating adenocarcinoma (or other malignant histology). Everything else — blood tests, imaging, tumour markers — serves to support the clinical suspicion, stage the disease, or guide management.
The approach follows a logical sequence: Clinical suspicion → Physical examination (including DRE) → Diagnostic endoscopy with biopsy → Staging investigations → Molecular biomarker testing.
3. Investigation Modalities
We organise investigations into: (A) Bedside/Clinical, (B) Blood tests, (C) Tumour markers, (D) Endoscopic investigations, (E) Imaging for staging, and (F) Molecular biomarker testing.
| Investigation | Key Findings and Interpretation |
|---|---|
| Digital Rectal Examination (DRE) | The single most important bedside examination. Tumours within ~8 cm of the anal verge are palpable. Assess: position (anterior/posterior/lateral, clock face), distance from anal verge (determines surgical approach), size and circumferential involvement, mobility vs fixity (fixed = T4, invading surrounding structures), surface (hard, irregular, ulcerated = malignancy; smooth = benign), sphincter tone (invaded sphincter = may preclude sphincter-preserving surgery), blood/mucus on glove, Blumer's shelf (hard shelf of tumour deposits in Pouch of Douglas anteriorly = peritoneal carcinomatosis) |
| Rigid sigmoidoscopy | Allows precise measurement of tumour distance from anal verge (more accurate than flexible scope as the rigid scope does not loop). Also allows biopsy. Important for surgical planning — the exact distance determines whether anterior resection vs APR is appropriate |
High Yield – GC Point
DRE assesses characteristics of stool [20] — this is also important in the context of rectal cancer to detect melaena, fresh blood, or mucus. Always perform DRE before endoscopy.
| Test | Rationale and Key Findings |
|---|---|
| CBC with differential [1] | Anaemia — typically microcytic hypochromic (iron deficiency) from chronic blood loss. May also show normocytic anaemia of chronic disease in advanced cancer. Thrombocytosis can be reactive (inflammatory response to tumour) |
| Iron profile (serum iron, ferritin, transferrin saturation, TIBC) [1] | Confirms iron deficiency anaemia: low serum iron, low ferritin, low transferrin saturation, raised TIBC. Why? Chronic occult blood loss depletes iron stores |
| LFT [1] | Liver metastasis — elevated ALP (from bone or liver), elevated GGT, elevated bilirubin suggest hepatic involvement. Pattern of raised ALP + GGT (cholestatic pattern) suggests metastatic infiltration |
| RFT [1] | Baseline renal function — important for contrast CT planning (contrast nephropathy risk if eGFR < 30), and to assess for hydronephrosis from locally advanced pelvic disease obstructing ureters |
| Coagulation profile | Pre-operative assessment; also relevant if patient on anticoagulants |
Serum carcinoembryonic antigen (CEA) [1]:
- CEA is an oncofetal glycoprotein — normally produced during foetal development, minimal levels in healthy adults
- Cut-off: < 4.7 ng/mL (varies by lab)
- Low diagnostic ability: low sensitivity + low specificity for CRC [1]
So why do we still measure CEA? Because its roles are:
- Prognostication — very high pre-operative CEA ( > 5) correlates with worse prognosis
- Treatment monitoring — declining CEA after surgery indicates successful resection; rising CEA during follow-up suggests recurrence
- Detection of recurrence — even if pre-operative CEA was normal, post-operative CEA can pick up non-portovenous distant metastases (e.g., lung) [1]
- Post-op: takes 4–6 weeks to return to normal [1]
CEA is NOT a Screening or Diagnostic Test
A common exam mistake is to list CEA as a "diagnostic test" for CRC. It is NOT. CEA has too many false positives and false negatives to be used for diagnosis or screening. Its value lies in prognostication, monitoring, and recurrence detection. Do not order CEA to "diagnose" CRC — order a colonoscopy.
D. Endoscopic Investigations
This is the most accurate and versatile investigation for CRC. It is both diagnostic (visualise + biopsy) and therapeutic (polypectomy, stenting).
Endoscopic findings in CA Rectum [4]:
- Majority are endoluminal masses (exophytic or polypoid) but occasionally can be flat [4]
- May have bleeding (oozing/frank bleeding) in friable, necrotic or ulcerative masses [4]
- May be circumferential → may obstruct distal scoping [4]
Biopsy [4]:
- Important to tattoo location in polypectomy for future resection if proven to be invasive carcinoma [4]
- Especially important in distal rectal CA as anorectal SCC is treated by upfront chemo/RT instead of surgery [4] — histological confirmation determines the entire treatment pathway
- Certain histological patterns, e.g., mucinous CA, poorly differentiated CA, are associated with poorer prognosis [4]
Performance [4]:
- Missed CRC only in 2–6% [4]
- Important to scope the entire colon [4] — because:
- Synchronous tumours occur in 3–5% of patients [1][4]
- Synchronous polyps in 30–50% [1][4]
- If malignant obstruction precludes complete colonoscopy, then should consider additional pre-op investigation (CT colonoscopy or flexible sigmoidoscopy) with mandatory post-op repeat colonoscopy or intra-operative colonoscopy [4]
- Colonoscopy is incomplete in 11–12% of cases [4]
High Yield – Why Scope the Entire Colon?
Even when a rectal tumour is found, you must visualise the proximal colon. Synchronous cancers are found in 3–5% and synchronous polyps in 30–50%. Missing a second cancer would be a catastrophic surgical error — you might do an anterior resection for the rectal tumour while a caecal cancer grows undetected.
- Spiral CT with IV contrast, air insufflation, and intraluminal contrast — creates virtual fly-through images
- Requires mechanical bowel preparation (stools can simulate polyps) [4]
- Similar sensitivity to colonoscopy for tumours > 1 cm [1] but cannot detect polyps < 5 mm and sessile (flat) polyps [5]
- Does not offer therapeutic procedures — still need colonoscopy if lesion found [4]
- Provides extraluminal information (lymph nodes, liver, other organs) [1]
- Lower risk of perforation than colonoscopy [1]
- Used when: caecum cannot be reached by colonoscopy [1], patient unfit for colonoscopy, or as pre-operative assessment when complete colonoscopy is impossible due to obstructing tumour
- Considered inadequate for diagnosis given gradual shift towards proximal tumours worldwide [4]
- No sedation required (office procedure) [4]
- Can visualise rectum and sigmoid — useful for rectal tumours specifically
- No bowel prep required [5]
- Misses approximately 25% right-sided cancers [5]
- Still requires colonoscopy if positive finding [5]
- Superseded by CT colonography [1]
- Classical finding: "apple core" lesion — near-circumferential involvement of bowel walls [1] with shouldered edges and mucosal destruction
- Risk of barium peritonitis [1] if there is an unsuspected perforation
- Limited diagnostic value [4]; rarely used in modern practice
E. Imaging for Staging
Once the histological diagnosis is confirmed, staging determines the extent of disease and directly guides treatment (especially the decision for neoadjuvant therapy in rectal cancer).
MRI pelvis is the single most important staging investigation for rectal cancer. It provides exquisite soft tissue contrast in the pelvis, allowing assessment of:
| MRI Feature | What It Tells You | Clinical Significance |
|---|---|---|
| T stage | Depth of tumour invasion through the rectal wall layers (mucosa → submucosa → muscularis propria → mesorectal fat → adjacent organs) | Determines whether neoadjuvant therapy is needed (T3/T4 lesions) |
| N stage | Mesorectal lymph nodes and lateral pelvic lymph nodes; criteria for malignancy include short-axis diameter > 5 mm, irregular border, mixed signal intensity | N+ disease generally warrants neoadjuvant chemoRT for rectal cancer |
| Circumferential resection margin (CRM) | Distance from the tumour to the mesorectal fascia | CRM ≤ 1 mm = threatened/involved → indication for neoadjuvant chemoRT. CRM is the single strongest predictor of local recurrence |
| Extramural vascular invasion (EMVI) | Tumour within veins outside the muscularis propria, seen as tumour signal within the vessel lumen | EMVI-positive tumours have higher risk of distant metastasis; may influence decision for neoadjuvant therapy |
| Relationship to sphincter complex | Distance of tumour's lower edge to the anorectal junction/puborectalis | Determines whether sphincter-preserving surgery (anterior resection) or APR with permanent colostomy is necessary |
| Relationship to peritoneal reflection | Tumour above vs below | Below = truly "rectal"; above = some centres treat more like sigmoid colon |
| Mucinous component | High T2 signal (mucin lakes) | Mucinous tumours respond less well to neoadjuvant CRT; important to flag |
Why MRI and not CT for local staging? CT has poor soft tissue contrast in the pelvis — it cannot reliably differentiate the layers of the rectal wall or assess CRM. MRI's superior soft tissue resolution makes it indispensable for rectal cancer. However, CT is better for detecting distant metastases (lungs, liver) and is faster to perform.
| Finding | Interpretation |
|---|---|
| Liver metastases | Most common site of distant metastasis. Appear as hypodense lesions on portal venous phase CT. Multiple lesions suggest widespread disease; isolated metastasis may be resectable |
| Lung metastases | Second most common. Round, well-defined soft tissue nodules. Remember: distal rectal tumours can metastasise directly to lungs via IVC [1] |
| Peritoneal carcinomatosis | Ascites, omental caking, peritoneal nodules |
| Retroperitoneal/para-aortic lymphadenopathy | Suggests extensive lymphatic spread |
| Bone metastases | Lytic or sclerotic lesions (less common in CRC) |
| Obstructing tumour | Proximal bowel dilatation, caecal distension (risk of perforation if diameter > 12 cm) |
- Principle: injection of 18FDG tracer → tissues with increased metabolic rate show increased glucose uptake → tracer retained because FDG cannot be incorporated into glycolysis → tissues with increased metabolic rate will "light up" (SUVmax > 2.5) [21]
- High sensitivity for occult metastasis [21]
- Indications in rectal cancer:
- Suspected recurrence (especially rising CEA with negative conventional imaging)
- Evaluation of oligometastatic disease (to determine resectability of metastases)
- Pre-operative assessment when considering metastasectomy
- Limitations:
- False positives: inflammation, infection, physiological uptake (e.g., post-surgical changes)
- Not good for brain metastasis (high background brain metabolic activity) [21]
- Mucinous tumours may be FDG-avid but can also be falsely negative
- Provides high-resolution imaging of the rectal wall layers
- Accurate for early T staging (T1 vs T2) — important when considering local excision (transanal excision or transanal endoscopic microsurgery, TEM)
- Less accurate for advanced T stage (T3/T4) — MRI is superior
- Also assesses perirectal lymph nodes (but MRI is better for this)
- Main role: when considering local excision for early rectal cancer, ERUS helps confirm the tumour is confined to the submucosa (T1) or muscularis propria (T2)
| Investigation | Role |
|---|---|
| Chest X-ray | Baseline; may detect large pulmonary metastases, pleural effusion |
| Abdominal X-ray (AXR) | If presenting with obstruction: dilated loops of large bowel proximal to the obstruction; caecal diameter > 12 cm indicates imminent perforation |
| Liver MRI | If CT findings are indeterminate for liver metastases; MRI with liver-specific contrast (e.g., gadoxetic acid/Primovist) has superior sensitivity for small hepatic lesions |
| RBC scan | For GI bleeding localisation: labelled RBCs detect bleeding rate as low as 0.1–0.4 mL/min; delayed images up to 24h can detect intermittent bleeding [22]. Rarely needed for CA rectum diagnosis but may be used when the source of GI bleeding is unclear |
Once adenocarcinoma is confirmed on biopsy, molecular profiling of the tumour is essential for guiding targeted therapy, especially in the advanced/metastatic setting:
| Biomarker | Test Method | Clinical Significance |
|---|---|---|
| KRAS/NRAS [1][4] | PCR or NGS on tumour tissue | Mutated in ~45% → no response to anti-EGFR therapy (cetuximab/panitumumab) [1]. If wild-type → anti-EGFR monoclonal antibodies can be used [4][5] |
| BRAF (V600E) [1] | PCR or IHC | Poor prognosis; targetable with encorafenib + cetuximab in metastatic setting |
| MMR / MSI status [1][4] | IHC for MMR proteins (MLH1, MSH2, MSH6, PMS2) or PCR-based MSI testing | MMR-deficient/MSI-high → responsive to PD-1 pathway inhibitors (e.g., pembrolizumab) [1][4]; better prognosis; do NOT benefit from 5-FU alone in stage II [5]; also triggers germline testing for Lynch syndrome |
| HER2 | IHC/FISH | Amplified in ~5% of CRC; potential target (trastuzumab/pertuzumab) |
High Yield – RAS/BRAF Testing Determines Treatment
In metastatic CRC:
- If KRAS/NRAS/BRAF mutation present → add anti-VEGF (bevacizumab/aflibercept/regorafenib) [5]
- If no KRAS/NRAS/BRAF mutation (all wild-type) → add anti-EGFR (cetuximab/panitumumab) [5]
This is because anti-EGFR antibodies block the extracellular domain of EGFR, but if KRAS/NRAS is mutated, the downstream signalling is constitutively active regardless of EGFR blockade — so the drug is futile and potentially harmful.
| Purpose | Investigation |
|---|---|
| Diagnosis | Colonoscopy + biopsy (gold standard) [1][4]; DRE; rigid sigmoidoscopy |
| Local staging (rectal cancer) | MRI pelvis (T, N, CRM, EMVI, sphincter relationship); ERUS (for early T staging) |
| Distant staging | CT thorax + abdomen + pelvis; PET-CT (for recurrence/oligometastatic assessment) |
| Bloods | CBC, Fe profile, LFT, RFT, CEA [1] |
| Molecular profiling | KRAS/NRAS, BRAF, MSI/MMR [1][4] |
| If colonoscopy incomplete | CT colonography [1][4]; flexible sigmoidoscopy + post-op repeat colonoscopy |
| Recurrence surveillance | Serial CEA (every 3–6 months for 5 years); CT (periodic); colonoscopy (at 1 year post-op then every 3–5 years) |
| Finding | Investigation | Significance |
|---|---|---|
| "Apple core" lesion [1] | Barium enema / CT | Near-circumferential involvement of bowel walls — annular constricting carcinoma with shouldered edges and mucosal destruction. Classic but rarely seen now as barium enema is superseded |
| Irregular rectal wall thickening with loss of fat planes | MRI pelvis | Suggests T3/T4 tumour invading through muscularis propria into mesorectal fat or adjacent structures |
| CRM ≤ 1 mm | MRI pelvis | Threatened/involved CRM → indication for neoadjuvant chemoRT |
| Hypodense hepatic lesions | CT abdomen (portal venous phase) | Liver metastases |
| "Target sign" | CT/MRI | Concentric rings of bowel wall — intussusception (may be lead point of colorectal tumour) |
| Large bowel dilatation with caecal diameter > 12 cm | AXR / CT | Impending caecal perforation due to closed-loop obstruction from obstructing tumour |
High Yield Summary
Diagnostic Criteria, Algorithm and Investigations for CA Rectum
-
Colonoscopy + biopsy is the gold standard for diagnosis — tissue is needed; CEA is NOT diagnostic
-
DRE is the essential bedside examination — palpates ~70–80% of rectal tumours; assesses distance from anal verge, mobility, sphincter involvement, and Blumer's shelf
-
Staging paradigm for rectal cancer:
- MRI pelvis for local staging (T, N, CRM, EMVI, sphincter) — determines need for neoadjuvant therapy
- CT thorax + abdomen + pelvis for distant staging (liver, lung, peritoneum)
- Molecular profiling (KRAS/NRAS, BRAF, MSI/MMR) for targeted therapy decisions
-
CEA: low sensitivity/specificity for diagnosis; role is in prognostication, monitoring, and recurrence detection; post-op takes 4–6 weeks to normalise
-
Always scope entire colon: synchronous cancers in 3–5%, synchronous polyps in 30–50%
-
CRM ≤ 1 mm on MRI = threatened → neoadjuvant chemoRT indicated
-
Apple core lesion on barium enema is the classical radiological finding of annular constricting carcinoma
Active Recall - Diagnosis and Investigation of CA Rectum
References
[1] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer section, p.103) [4] Senior notes: Ryan Ho GI.pdf (Section 3.3.6, p.166) [5] Senior notes: Maksim Medicine Notes.pdf (Clinical oncology section, p.54) [20] Senior notes: Block A - Coffee ground vomitus tarry stool upper GI bleeding.pdf (p.8) [21] Senior notes: Ryan Ho Respiratory.pdf (p.143–144) [22] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p.62)
Management Algorithm and Treatment Modalities for CA Rectum
Management of CA rectum is fundamentally different from CA colon because of three anatomical realities:
- The rectum sits deep in the bony pelvis — surgical access is constrained, and achieving clear radial margins is technically challenging
- Below the peritoneal reflection, there is no serosal covering — local recurrence is a major problem if the circumferential resection margin (CRM) is not clear
- Proximity to the anal sphincter complex — the surgeon must balance oncological radicality against functional preservation (continence)
These factors mean that neoadjuvant chemoradiotherapy plays a central role in locally advanced rectal cancer — a paradigm that does NOT exist for colon cancer, where surgery is always first [1][4][23].
The management of rectal cancer is decided by a multidisciplinary team (MDT) comprising colorectal surgeons, clinical oncologists (radiotherapy), medical oncologists (chemotherapy), radiologists, pathologists, and specialist nurses. Every case should be discussed at an MDT meeting.
Management principles by stage [5]:
| Stage | Management |
|---|---|
| Stage I | Surgery + analysis of ≥ 12 LN |
| Stage II | Surgery ± adjuvant chemo (consider in high-risk stage II) |
| Stage III | Surgery + adjuvant chemo (FOLFOX) ± adjuvant RT (rectal only) ± neoadjuvant chemoRT (in certain rectal only) |
| Stage IV | Chemo ± surgery for isolated liver metastasis |
For CA rectum specifically, the key decision point is whether the tumour is early, locally advanced, or metastatic, and this is determined primarily by MRI pelvis.
3. Surgical Treatment
Surgical principles for CRC (important!) [1]:
- En-bloc resection of primary tumour and locoregional nodes (75% cure rate) [1]
- Adequate resection margins: at least 5 cm proximally and distally — actual margin depends on blood supply [1]
- For rectal cancer specifically, a distal margin of ≥ 1 cm is generally accepted for tumours treated with neoadjuvant chemoRT (previously 2 cm was required, but studies show 1 cm is oncologically equivalent after downstaging)
- Resect major vascular pedicles and lymphatic drainage basin [1]
- Excise colonic mesentery, ligate arterial supply at its origin, and excise all accompanying lymph nodes [1]
- At least 12 nodes for proper N staging: inadequate LN harvest might require adjuvant chemo [1][5]
- Restore bowel continuity whenever possible [1]
Total mesorectal excision (TME): precise dissection of the mesorectal envelope (containing tumour, surrounding mesorectal fat, lymph nodes and vessels), preserving pelvic autonomic nerves [1]:
- Plane: "holy plane" — avascular areolar plane between presacral and mesorectal fascia [1]
- Benefits: decreased local recurrence rate and decreased post-operative genitourinary dysfunction [1]
- Approaches: transabdominal (open / laparoscopic / robotic), transanal (rarely) [1]
Why TME? Before TME was introduced by RJ Heald in 1982, rectal cancer surgery involved blunt dissection that often left mesorectal tissue behind — containing microscopic tumour deposits. This resulted in local recurrence rates of 25–40%. TME reduced this to < 5–10% by ensuring complete excision of the mesorectal envelope under direct vision, following a defined anatomical plane.
High Yield – TME and the 'Holy Plane'
The "holy plane" is the avascular areolar plane between the mesorectal fascia (surrounding the mesorectum) and the presacral fascia (covering the sacrum). Dissection in this plane ensures the mesorectal envelope is removed intact, autonomic nerves running on the presacral fascia are preserved, and blood loss is minimal. The quality of TME (graded as complete, nearly complete, or incomplete by the pathologist) is one of the strongest predictors of local recurrence.
| Procedure | Indication | Description |
|---|---|---|
| Local Excision (Transanal excision / TEM) | Very early rectal cancer: T1 with favourable features (well/moderately differentiated, no lymphovascular invasion, sm1–2 invasion depth, < 3 cm, < 30% circumference) | Full-thickness excision of the tumour through the anus without abdominal incision. Avoids major surgery but NO lymph node assessment. Risk: if final pathology shows adverse features (sm3, LVI, poor differentiation), salvage radical surgery is needed |
| Anterior Resection (AR) with TME | Mid and upper rectal cancer where adequate distal margin can be achieved while preserving the sphincter complex | Resection of the rectum and mesorectum via abdominal approach. Bowel continuity is restored with a colorectal or colo-anal anastomosis. A temporary diverting loop ileostomy is usually created to protect the low anastomosis (reversed ~8–12 weeks later after confirming anastomotic integrity with contrast study) |
| Abdominoperineal Resection (APR) [1] | Indicated if ANY one of: poor pre-op sphincter function / failure to achieve negative distal margin / locally advanced or recurrent low-lying CA rectum [1] | Combined abdominal and perineal approach. En-bloc removal of sigmoid, rectum, and anus. Construction of permanent end colostomy [1]. This is the operation patients fear most because of the permanent stoma |
| Intersphincteric Resection (ISR) | Very low rectal tumours where the tumour is above the dentate line but close to the anorectal junction — selected cases to avoid APR | Dissection between the internal and external sphincter to achieve adequate distal margin while preserving the external sphincter. Technically demanding; functional outcomes (continence) can be suboptimal |
| Hartmann's Procedure | Emergency setting (obstruction, perforation) where primary anastomosis is unsafe | Resection of rectosigmoid with formation of end colostomy and closure of the rectal stump. Avoids the risk of anastomotic leak in an unprepared, inflamed, or contaminated abdomen |
APR detailed steps [1]:
- Insert catheter to protect membranous urethra in males
- Abdominal part (open/laparoscopic): similar to anterior resection
- Perineal dissection via circumanal incision for en-bloc resection of sigmoid, rectum, and anus
- Construction of permanent end colostomy
Elective surgery: laparoscopic/robotic approach is preferred [1]:
- Benefits of robotic surgery: high-quality 3D vision, restoration of eye-hand-target axis [1]
- Better cosmesis, faster recovery, less adhesion formation
Emergency surgery [1]: Indicated if complicated (obstruction, perforation, haemorrhage):
- Left-sided lesion: Hartmann's operation [1]
- The key difference from elective surgery is that primary anastomosis is usually avoided in the emergency setting due to:
- Unprepared bowel (high bacterial load → risk of anastomotic breakdown)
- Peritoneal contamination (perforation)
- Haemodynamic instability
Endoscopic stenting for malignant obstruction [4]:
- Indications: [4]
- Procedure: self-expanding metallic stent (SEMS), inserted and deployed under endoscopic and/or fluoroscopic guidance [4]
- Contraindications: perforated/strangulated, persistent coagulopathy, distal rectal lesion (≤ 5 cm of anal verge) — excruciating pain if stent migrates beyond the dentate line [4]
- Advantages: avoid stoma for terminal patients; avoid emergency surgery (mortality > 10%); elective operation allows bowel prep → better outcome; more time to stage disease [4]
- Outcome: 92% successful, median patency 106 days, 4.5% perforate, 12% re-obstruction [4]
4. Neoadjuvant Therapy for CA Rectum
This is one of the defining features that separates rectal cancer management from colon cancer management. There is no role for neoadjuvant therapy in colon cancer [1], but it is central to locally advanced rectal cancer.
3 main indications (need to know!) [1]:
- Resectable but locally advanced disease: sterilise tumour bed, decrease intra-operative tumour spillage and decrease local recurrence rate [1]
- Borderline resectable disease: downstage the tumour and increase resectability rate [1]
- Low-lying tumour: downsize the tumour and increase sphincter preservation rate [1]
Why neoadjuvant and not adjuvant RT for rectal cancer? The landmark German Rectal Cancer Study Group trial (CAO/ARO/AIO-94) showed that pre-operative chemoRT compared to post-operative chemoRT resulted in: (1) lower local recurrence (6% vs 13%), (2) fewer acute and late toxicities, and (3) higher rate of sphincter preservation. Overall survival was similar, but the toxicity advantage firmly established neoadjuvant as the standard.
| Long-course chemoRT (HK standard) | Short-course high-dose RT | |
|---|---|---|
| Regimen | 5-FU based chemotherapy × 2 cycles + concurrent RT (50.4 Gy = 1.8 Gy daily × 28 fractions) [1] | RT 25 Gy = 5 Gy × 5 days [1] |
| Interval to surgery | Wait 8–10 weeks before surgery [1] | Wait 7–10 days before surgery [1] |
| Post-surgery | 4 cycles of chemo as adjuvant [1] | — |
| Advantages | Standard option; associated with better tumour shrinkage [4]; can downstage/downsize for sphincter preservation | Shorter treatment duration; less time off work |
| Disadvantages | Maximum dose of RT for lifetime [1]; delays surgery [1] | More side effects of high-dose RT [1]; can only sterilise local tumour bed, but not enough time to downstage/downsize tumour [1]; especially unsuitable for cT4 or large bulky tumours [4] |
Totally neoadjuvant therapy (TNT) [4] — an intensified approach:
- Pre-operative oxaliplatin-based chemo followed by long-course chemoRT [4]
- Indications: locally advanced cases at increased risk of margin-positive resection (e.g., T4 or involved mesorectal fascia), node-positive disease, and low-lying tumour [4]
- Advantages: increased chemo compliance (better tolerated pre-op), increased local control, option of watch and wait [4]
- Disadvantages: not suitable for early (e.g., cT3N0) without threatened margin — these patients may not have needed chemotherapy at all [4]
After neoadjuvant therapy, re-staging MRI is performed (usually ~2 months after completion to allow tumour shrinkage) [4].
Clinical complete response (cCR) [4]:
- Definition: no rectal mass felt clinically + no tumour seen endoscopically + no tumour seen radiologically on MRI [4]
- Basis: those with pathological complete response (pCR) after pre-op therapy have excellent prognosis → researchers question whether selected patients with cCR may avoid surgery altogether [4]
- Option of watchful waiting increasingly popular [4]
Watch and Wait — A Paradigm Shift
The "watch and wait" (organ preservation) strategy is one of the most exciting developments in rectal cancer management. In carefully selected patients who achieve a clinical complete response after neoadjuvant chemoRT, avoiding surgery means avoiding permanent stomas, urogenital dysfunction, and major surgical morbidity. However, it requires rigorous patient selection and intensive surveillance, and patients must understand the ~20% risk of local regrowth (which is usually salvageable with surgery).
5. Adjuvant Chemotherapy
Adjuvant chemotherapy: aims to eradicate micro-metastasis and reduce risk of recurrence [1].
- FOLFOX for 6 months: folinic acid (leucovorin) + 5-fluorouracil + oxaliplatin [1]
- XELOX (CAPOX) for 3 months if lower risk (T1–3, N1): capecitabine + oxaliplatin [1]
Drug mechanisms:
- Oxaliplatin: alkylating agent — forms platinum-DNA adducts that crosslink DNA strands, preventing replication and transcription
- 5-Fluorouracil (5-FU): anti-metabolite (pyrimidine analogue) — inhibits thymidylate synthase, blocking DNA synthesis (thymidine production)
- Capecitabine: oral prodrug of 5-FU — converted to 5-FU preferentially in tumour tissue by thymidine phosphorylase (which is overexpressed in tumours); more convenient than IV 5-FU
- Irinotecan: topoisomerase I inhibitor — prevents religation of single-strand DNA breaks during replication, leading to cell death
- Folinic acid (leucovorin): not cytotoxic itself; enhances the binding of 5-FU metabolite (FdUMP) to thymidylate synthase, making 5-FU more effective
Adverse effects of chemotherapy [24]:
- Mucositis, nausea and vomiting, diarrhoea
- Febrile neutropenia (myelosuppression)
- Alopecia
- Hand-foot syndrome (especially capecitabine) — painful erythema, swelling, and desquamation of palms and soles due to drug accumulation in sweat glands
- Oxaliplatin-specific: peripheral neuropathy (dose-limiting; cumulative; cold-triggered paraesthesias)
6. Targeted Therapy and Immunotherapy (Stage IV / Metastatic Disease)
Upfront chemotherapy: dual therapy — oxaliplatin/irinotecan + fluorouracil/capecitabine [5]:
- FOLFOX: folinic acid + 5-FU + oxaliplatin
- FOLFIRI: folinic acid + 5-FU + irinotecan
- XELOX: capecitabine + oxaliplatin
| Biomarker Status | Targeted Agent | Mechanism | Key Points |
|---|---|---|---|
| KRAS/NRAS/BRAF mutant | Anti-VEGF: bevacizumab / aflibercept / regorafenib [5][24] | Bevacizumab: monoclonal antibody targeting VEGF-A [24] — blocks tumour angiogenesis (new blood vessel formation); tumours need blood supply to grow beyond ~2 mm | ONLY indicated in stage IV (metastatic) disease; no evidence to support use in the adjuvant setting [24]. Contraindications: haemorrhage, wound healing impairment, arterial thromboembolic diseases [24] |
| KRAS/NRAS/BRAF wild-type | Anti-EGFR: cetuximab / panitumumab [5][24] | Monoclonal antibody blocking the extracellular domain of EGFR → prevents ligand binding → inhibits Ras-Raf-MEK-ERK proliferation signalling | Wild-type KRAS has a favourable response; mutant KRAS will NOT benefit — KRAS mutation results in constitutive activation of RAS-RAF-ERK pathway leading to resistance to anti-EGFR therapy [24]. KRAS and BRAF mutations are mutually exclusive [24] |
| MSI-H / dMMR | Immune checkpoint inhibitors: pembrolizumab / nivolumab [1][5] | Anti-PD-1 monoclonal antibodies — block PD-1 on T cells, preventing tumour cells from evading immune detection via PD-L1 | MSI-H tumours have high mutational burden → many neoantigens → more immunogenic → excellent response to immunotherapy. Also first-line option in dMMR metastatic CRC (KEYNOTE-177 trial) |
| BRAF V600E mutant | Encorafenib + cetuximab | BRAF inhibitor + anti-EGFR (dual pathway blockade needed because BRAF inhibition alone causes feedback EGFR activation) | Poor prognosis subgroup; BEACON trial showed improved survival vs standard chemo |
| HER2 amplified (~5%) | Trastuzumab + pertuzumab | Anti-HER2 monoclonal antibodies | Emerging evidence; usually in RAS wild-type tumours |
High Yield – Anti-EGFR vs Anti-VEGF Decision
The decision tree is simple:
- Test KRAS/NRAS/BRAF first
- If ALL wild-type → can add anti-EGFR (cetuximab/panitumumab) to chemo backbone
- If ANY mutation → add anti-VEGF (bevacizumab) instead
- If MSI-H/dMMR → consider immunotherapy (pembrolizumab) as first line
This is because anti-EGFR works by blocking the receptor at the cell surface, but if the downstream signalling cascade is constitutively "switched on" by a KRAS or BRAF mutation, blocking the receptor upstream is pointless — like trying to turn off a light by blocking the switch when someone has hardwired the circuit to stay on.
7. Radiotherapy in Rectal Cancer
Radiotherapy (RT) plays a much more important role in rectal cancer than in colon cancer [23].
- The rectum is fixed in the pelvis → the radiation field can be precisely targeted with reproducible anatomy
- Below the peritoneal reflection, there is no serosal barrier → radial spread is the dominant failure pattern → RT can sterilise the mesorectal/pelvic field
- For colon cancer, the mobility of the colon in the abdomen makes it a poor target for RT, and the proximity to small bowel (radiosensitive) causes excessive toxicity
- Neoadjuvant (pre-operative): Locally advanced disease (T3/T4, N+, threatened CRM) — discussed above
- Adjuvant (post-operative): Considered if positive CRM or other adverse pathological features not identified pre-operatively (less common now with improved MRI staging)
- Palliative: Symptomatic locally advanced/recurrent rectal cancer causing bleeding, pain, or obstruction
- Definitive chemoRT: For anorectal SCC (squamous cell carcinoma) — this is treated by upfront chemo/RT instead of surgery [4]
Modern rectal cancer RT uses intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) to:
- Deliver a conformal dose to the tumour and pelvic lymph nodes
- Minimise dose to organs at risk (small bowel, bladder, femoral heads, pelvic bones)
- Patient positioned prone (sometimes with belly board to displace small bowel out of the pelvis)
8. Management of Specific Scenarios
- ~20–25% of patients with CRC liver metastases are candidates for hepatic resection
- 5-year survival after liver metastasectomy: 25–40% (compared to < 5% without surgery)
- Criteria for resectability: technically feasible to resect all disease with clear margins while preserving adequate future liver remnant (≥ 20–30% of total liver volume)
- Peri-operative chemotherapy (e.g., FOLFOX for 3 months pre- and post-hepatectomy) improves disease-free survival
- Pulmonary metastasectomy considered if: isolated lung metastases, primary tumour controlled, all disease can be resected, adequate pulmonary reserve
- Remember: distal rectal tumours can metastasise directly to lungs bypassing the liver via IVC [1]
| Modality | Indication |
|---|---|
| Palliative chemotherapy | Extends survival and improves quality of life in metastatic disease; median OS ~24–30 months with modern regimens |
| Palliative stenting | Malignant obstruction in unresectable disease [4] |
| Palliative RT | Symptomatic bleeding, pain, pelvic recurrence |
| Diverting colostomy | Obstruction not amenable to stenting |
| Best supportive care | When further oncological treatment is inappropriate; includes symptom management, psychosocial support, end-of-life care |
Patients undergoing major rectal surgery may require perioperative nutritional support:
- Enteral feeding is always first choice if the GI tract can be used safely [25]
- Indications for perioperative nutritional support: malnourished patients undergoing major surgery, major operations with prolonged fasting ( > 5–7 days) post-operatively, postoperative complications resulting in increased catabolism and nil food intake [25]
- Enhanced Recovery After Surgery (ERAS) protocols encourage early oral feeding (within 24 hours of surgery), early mobilisation, and minimisation of perioperative fasting
| Modality | Schedule | Rationale |
|---|---|---|
| Clinical review + DRE | Every 3–6 months for 2 years, then every 6 months to year 5 | Detect local recurrence |
| CEA | Every 3–6 months for 5 years | Rising CEA may indicate recurrence before imaging becomes positive |
| CT thorax/abdomen/pelvis | Annually for 3–5 years | Detect distant metastases |
| Colonoscopy | At 1 year post-op, then every 3–5 years | Detect metachronous tumours and polyps |
| Pelvic MRI (for rectal cancer) | Every 6–12 months for 3 years if high risk | Detect pelvic recurrence |
High Yield Summary
Management of CA Rectum — Key Points
-
Surgery with TME is the cornerstone — dissection along the "holy plane" between mesorectal and presacral fascia; decreases local recurrence and preserves autonomic nerves
-
Surgical options: Local excision (very early T1), Anterior Resection with TME (sphincter-preserving), APR with permanent colostomy (low tumours/poor sphincter/positive margins)
-
Neoadjuvant chemoRT is indicated for locally advanced rectal cancer (T3/T4, N+, threatened CRM) — 3 indications: resectable but locally advanced, borderline resectable, low-lying tumour for sphincter preservation
-
Long-course chemoRT (50.4 Gy + 5-FU) is the HK standard; short-course RT (25 Gy in 5 days) is an alternative but unsuitable for T4/bulky tumours
-
Watch and Wait: Clinical complete response after neoadjuvant → option of organ preservation with intensive surveillance; ~20% regrowth rate
-
Adjuvant chemo (FOLFOX/XELOX): Stage III and high-risk Stage II; at least 12 LN for adequate staging
-
Metastatic CRC targeted therapy: All RAS/BRAF wild-type → anti-EGFR; RAS/BRAF mutant → anti-VEGF; MSI-H/dMMR → anti-PD-1 immunotherapy
-
CEA is NOT diagnostic — used for prognostication, monitoring, and recurrence detection
Active Recall - Management of CA Rectum
References
[1] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer section, p.104–107) [4] Senior notes: Ryan Ho GI.pdf (Section 3.3.6, p.139, p.166, p.173) [5] Senior notes: Maksim Medicine Notes.pdf (Clinical oncology section, p.54) [23] Lecture slides: Professor Chiang Chi Leung - Role of Radiotherapy in Rectal Cancer_rev3.pdf (p.3, p.8) [24] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.693) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.896) [25] Senior notes: Ryan Ho Fluids and Nutrition.pdf (p.8–11)
Complications of CA Rectum
Complications of CA rectum can be divided into three broad categories:
- Complications of the disease itself (untreated or advanced tumour)
- Complications of treatment (surgery, radiotherapy, chemotherapy, targeted therapy)
- Complications of recurrence
Understanding the pathophysiological basis of each complication is essential — it helps you anticipate, prevent, and manage them.
1. Complications of the Disease Itself
These arise from the natural history of an untreated or advanced rectal tumour.
| Complication | Pathophysiology | Clinical Features | Management |
|---|---|---|---|
| Intestinal obstruction | Left-sided/distal tumours tend to obstruct [1] — the annular constricting growth pattern narrows the lumen progressively. The rectum has a smaller calibre and stool is more formed, increasing the risk of complete obstruction | Colicky abdominal pain, abdominal distension, absolute constipation, late vomiting. AXR shows dilated large bowel proximal to the obstruction. Caecal diameter > 12 cm → imminent perforation (Laplace's law) | Initial resuscitation ("drip and suck"): NPO, NGT decompression, IV fluids [4]. Consider endoscopic SEMS as bridge to surgery [4] or emergency Hartmann's procedure [1]. Intestinal obstruction is a common surgical emergency; high mortality if complications occur [26] |
| Perforation | Can occur at the tumour site (necrotic tumour wall breaks down) or proximal to the obstruction (closed-loop obstruction → caecal perforation). Perforation leads to faecal peritonitis, which is the most lethal complication | Sudden severe abdominal pain, peritonism (guarding, rigidity, rebound tenderness), septic shock (fever, tachycardia, hypotension). Erect CXR: free gas under the diaphragm (pneumoperitoneum) | Emergency laparotomy — Hartmann's procedure (resection + end colostomy without anastomosis); peritoneal lavage; broad-spectrum IV antibiotics. Mortality is very high (15–30%) |
| Haemorrhage | Erosion of tumour surface into blood vessels. Usually chronic low-grade bleeding causing IDA, but occasionally massive acute PR bleeding | Chronic: progressive IDA, fatigue, pallor. Acute: profuse haematochezia, haemodynamic instability | Chronic: iron supplementation, definitive surgery. Acute: resuscitation, transfusion; if uncontrolled → emergency surgery or angiographic embolisation |
| Fistula formation | Locally advanced tumour (T4b) invades adjacent organs, creating abnormal communications. The tumour outgrows its blood supply → central necrosis → wall breaks down into adjacent hollow viscus | Rectovesical fistula: pneumaturia, faecaluria, recurrent UTIs. Rectovaginal fistula: passage of stool/flatus per vagina. Enterocutaneous fistula: faecal discharge from abdominal wall or perineum (rare) | Proximal faecal diversion (loop colostomy/ileostomy) to divert faecal stream away from the fistula, then definitive resection ± neoadjuvant chemoRT if feasible |
| Sacral nerve/plexus invasion | Locally advanced/recurrent tumour invading the sacral nerve plexus (S2–S4) in the presacral space | Intractable pelvic/perineal pain (neuropathic character — burning, lancinating, worse at night); sciatica-like radiation; bladder and bowel dysfunction | Palliative RT; neuropathic pain management (gabapentin/pregabalin, opioids); nerve block; consideration of pelvic exenteration in highly selected cases |
| Ureteric obstruction | Locally advanced pelvic tumour directly compressing or invading the ureters (more common on the left side due to the anatomy of the sigmoid-rectal junction) | Hydronephrosis → progressive renal impairment (raised creatinine); may be asymptomatic or cause flank pain; bilateral obstruction → post-renal AKI | Ureteric stenting (JJ stent) or percutaneous nephrostomy (PCN); definitive treatment of the tumour |
| Complication | Pathophysiology | Clinical Features |
|---|---|---|
| Hepatic metastases | Most common site of distant metastasis via portal venous drainage (superior rectal vein → IMV → portal vein → liver). Distal rectal tumours may bypass the liver and metastasise directly to the lungs via the IVC [1] | Hepatomegaly (hard, irregular, nodular), RUQ discomfort, jaundice (if mass effect on bile ducts or extensive parenchymal replacement), raised ALP/GGT, deranged LFTs |
| Pulmonary metastases | Haematogenous spread to lungs. Also transcoelomic seeding to pleura | Dyspnoea, cough, haemoptysis, pleural effusion |
| Peritoneal carcinomatosis | Transcoelomic spread — tumour cells shed from the serosal surface into the peritoneal cavity, implanting on peritoneal surfaces | Ascites (exudative), abdominal distension, early satiety, small bowel obstruction from omental caking, Blumer's shelf (pelvic nodularity on DRE), Krukenberg tumour (ovarian metastasis) [1] |
| Bone metastases | Haematogenous spread — less common in CRC than breast/prostate/lung | Bone pain (often sacral/pelvic due to anatomical proximity), pathological fractures, hypercalcaemia |
| Venous thromboembolism | Malignancy induces a hypercoagulable state through tissue factor expression, tumour-derived procoagulant factors, venous stasis (pelvic tumour compression), and immobility | DVT (leg swelling, calf tenderness, Homan's sign), PE (chest pain, dyspnoea, tachycardia, hypoxia). Malignancy is the most common condition associated with VTE in our locality — up to 10% of patients with unprovoked VTE have an underlying malignancy [27] |
High Yield – VTE and Malignancy
Up to 10% of patients with "unprovoked" VTE have an underlying malignancy [27]. For every patient with unprovoked VTE, perform a thorough history (constitutional symptoms), physical examination, and appropriate investigations (CXR, AXR, abdominal ultrasound, tumour markers). Colorectal cancer is one of the common occult malignancies discovered in this scenario.
2. Complications of Treatment
A. Post-Operative Complications (After Rectal Surgery)
These are organised by timing: immediate (intra-operative) → early ( < 30 days) → late ( > 30 days) [1][4][24][28].
| Complication | Pathophysiology | Key Points |
|---|---|---|
| Massive bleeding requiring conversion to laparotomy ( < 10%) [1] | Injury to presacral venous plexus (massive venous bleeding from sacral basal vertebral veins — these are valveless and communicate with the vertebral venous plexus, making haemostasis very difficult), or injury to major vessels (iliac artery/vein) | Presacral venous bleeding can be catastrophic and notoriously difficult to control. Surgical strategies include packing with haemostatic agents, thumbtack pins into the sacrum |
| Injury to neighbouring structures [1][4][28] | The deep pelvis is a tight space with many vital structures in close proximity | Left ureter and gonadal vessels, iliac artery [1]; GB, D2 (right hemicolectomy) [1]; seminal vesicles (LAR) [1]; spleen (splenic flexure mobilisation in TME) [1]; ureteral/bladder/urethral injury [28] |
| Autonomic nerve injury (especially in rectal surgery) [1] | The pelvic autonomic nerves (sympathetic hypogastric nerves and parasympathetic pelvic splanchnic nerves S2–S4) run in close proximity to the mesorectum | Sympathetic injury → urinary incontinence, impaired ejaculation [1]. Parasympathetic injury → urinary retention, erectile dysfunction [1]. TME with nerve-sparing technique minimises this risk. High tie vs low tie: high tie if reducing tension is desired; low tie (distal to left colic artery) avoids damage to the hypogastric nerve and thus lower risk of autonomic dysfunction [1] |
| GI organ injury [28] | Splenic/duodenal/pancreatic/gastric injury during mobilisation | Splenic injury during splenic flexure mobilisation may require splenectomy |
| Complication | Pathophysiology | Clinical Features and Management |
|---|---|---|
| Surgical site infection [28] | Contamination from bowel contents (colorectal surgery is clean-contaminated at minimum); risk factors: malnutrition, DM, immunosuppression, age > 60, ASA > 2, faecal contamination, extensive surgery, prolonged pre-op hospitalisation [4] | Incidence 5–15% [4]. Wound erythema, warmth, swelling, purulent discharge. Management: wound opening, drainage, antibiotics, dressing changes |
| Post-operative ileus [28] | Normal physiological response to bowel handling during surgery; exacerbated by opioid analgesia, electrolyte imbalance (hypokalaemia, hypomagnesaemia), intra-abdominal sepsis | Abdominal distension, absent bowel sounds, nausea/vomiting, inability to tolerate oral intake. Management: supportive (NGT decompression, IV fluids, correct electrolytes), consider prokinetics; prolonged ileus ( > 5 days) should prompt a search for complications (e.g., anastomotic leak, intra-abdominal collection) |
| Anastomotic leak — the most feared early complication [4][28] | Breakdown of the surgical anastomosis — ischaemia at the anastomotic site (inadequate blood supply), tension on the anastomosis, poor tissue quality (irradiated tissue, malnutrition, steroids), or technical error. Classically occurs on day 4–7 [4] | Incidence: 1–5% overall, but up to 10% in low anterior resection [4] (risk increases the lower the anastomosis — ileoileal < ileocolic < colocolic < ileoanal [4]). Risk factors: patient factors (liver/renal impairment, steroid use, suboptimal bowel condition in emergency surgery) and surgeon factors (experience and expertise) [4] |
| Clinical signs: pain, fever, tachycardia, feculent or purulent drainage [28]. Radiological signs: fluid or gas containing collections [28] | ||
| Management: fluid resuscitation + broad-spectrum IV antibiotics, bowel rest, image-guided percutaneous drainage of abscess, temporary faecal diversion, or drainage/resection of the anastomosis [28]. This is why a temporary diverting loop ileostomy is routinely fashioned after low anterior resection — if a leak occurs, faecal diversion is already in place, converting what could be a life-threatening faecal peritonitis into a contained and manageable pelvic collection | ||
| Anastomotic bleeding [28] | Bleeding from the staple/suture line | Management: blood transfusion and correction of underlying coagulopathy [28]. Most settle spontaneously; endoscopic haemostasis or re-operation if severe |
| Pelvic bleeding [4] | Oozing from the raw presacral surface after TME, especially if irradiated tissue | Monitor haemoglobin; transfuse as needed; re-operation if haemodynamically significant |
| Infections [4] | UTI, phlebitis, pneumonia, wound infection | Standard post-operative infection management |
| DVT/PE | Post-operative immobilisation + malignancy-associated hypercoagulability | Prophylaxis with LMWH, early mobilisation, pneumatic compression devices |
Anastomotic Leak — Why is Low Anterior Resection Riskier?
The lower the rectal anastomosis, the higher the risk of leak (up to 10% in LAR). This is because: (1) the blood supply to the distal rectal stump relies on the middle and inferior rectal arteries after ligation of the superior rectal artery at the IMA; (2) the deep pelvis makes technical suturing/stapling difficult; (3) neoadjuvant radiotherapy impairs tissue healing by causing fibrosis and microvascular damage; (4) there is no serosal covering below the peritoneal reflection to seal micro-leaks. This is exactly why a diverting loop ileostomy is created — it does NOT prevent the leak, but it protects the patient from the catastrophic consequences of a free faecal leak into the pelvis.
| Complication | Pathophysiology | Clinical Features and Management |
|---|---|---|
| Low Anterior Resection (LAR) Syndrome [1][4] | Signs/symptoms: change in bowel movement (ranging from constipation to faecal urgency, faecal incontinence) that persists ≥ 1 month after surgery [1]. Pathophysiology: colonic dysmotility, neorectal reservoir dysfunction, and anal sphincter dysfunction [1] | Affects up to 50–90% of patients after LAR to varying degrees. Prevention: post-op pelvic floor muscle exercise, anterograde colonic irrigation via stoma/enema, faecal diversion [1]. Management: antidiarrhoeal agents, transanal irrigation, pelvic floor rehabilitation, sacral nerve stimulation [1]. Patients must be counselled pre-operatively |
| Anastomotic stricture [1][28] | Fibrosis and scarring at the anastomotic site, exacerbated by prior radiotherapy, subclinical leak, or ischaemia | Progressive difficulty passing stool, narrow-calibre stools. Majority do not require intervention [28]. For those requiring treatment: finger dilatation for low anastomosis and endoscopic balloon dilatation for high anastomosis [1][28] |
| Fistula [1][28] | Late breakdown of the anastomosis or radiation-induced tissue necrosis creating abnormal communications | Enterocutaneous fistula: can be managed conservatively since most will close spontaneously [28]. Rectovaginal or rectourinary fistula: should be managed initially with proximal faecal diversion [1][28] |
| Impotence [4] | Damage to pelvic autonomic nerves during TME — parasympathetic nervi erigentes (S2–S4) control erectile function; injury causes neurogenic erectile dysfunction | Occurs in 15–50% of males [4]. Risk is higher with APR, very low tumours, and extensive lateral lymph node dissection. Can be mitigated by nerve-sparing TME technique |
| Urinary dysfunction | Sympathetic nerve injury → bladder neck incompetence → incontinence. Parasympathetic injury → detrusor underactivity → retention | Urinary retention requiring catheterisation, or stress/urge incontinence. May improve over 6–12 months as nerves recover |
| Perineal hernia [1] | Follows APR — the perineal wound creates a defect in the pelvic floor through which abdominal contents can herniate | Perineal bulge, discomfort, rarely obstruction. May require surgical repair |
| Adhesions / Adhesive small bowel obstruction [4] | Post-surgical adhesion formation — fibrous bands between loops of bowel and between bowel and abdominal wall/pelvis | Colicky abdominal pain, distension, vomiting. Management: initially conservative ("drip and suck"); surgery if signs of strangulation or failure to improve |
| Tumour recurrence [4] | Local recurrence in the pelvis (from residual microscopic disease, especially if CRM was positive/threatened) or distant metastasis (liver, lung) | Recurrence occurs in ~40% of CRC patients [1]. Follow-up to detect recurrence: CEA, rigid sigmoidoscopy, LFT, CT, colonoscopy [1]. Salvage resection can confer survival benefit if recurrence is detected early [4] |
Stomas (colostomy or ileostomy) are commonly fashioned in rectal cancer surgery — either as temporary diverting loop ileostomy (to protect low anastomosis in AR) or permanent end colostomy (after APR). Each has its own complications [1][28]:
| Timing | Complication | Pathophysiology |
|---|---|---|
| Early ( < 30 days) | Stomal bleeding [28] | From mucocutaneous junction or mesenteric vessels |
| Stomal necrosis [28] | Ischaemia of the terminal bowel due to mesenteric vessel compromise or excessive tension — appears dark/dusky rather than healthy pink/red. Urgent revision if necrosis extends below fascial level | |
| Stomal retraction [28] | Insufficient bowel length mobilised, excessive tension, or ischaemia → stoma sinks below skin level → poor appliance fit → leakage | |
| Mucocutaneous separation [28] | Breakdown of the suture line between bowel and skin — risk of peritonitis if deep | |
| Skin irritation and dermatitis [28] | Most common in end and loop ileostomy due to high-output and high alkaline enzymatic effluent [28] — the ileal content contains active digestive enzymes that cause chemical burns to the peristomal skin | |
| Late ( > 30 days) | Parastomal hernia [28] | Herniation of bowel through the fascial defect around the stoma — most common late stoma complication. Risk factors: obesity, coughing, wound infection. May require surgical repair with mesh |
| Stomal prolapse [28] | Telescoping of bowel through the stoma — more common with loop colostomies. Usually reducible; surgical revision if recurrent or complicated | |
| Stomal stenosis [28] | Fibrosis and contracture at the skin/fascial level — difficulty with appliance function, obstruction. May require dilatation or revision |
3. Complications of Neoadjuvant/Adjuvant Therapy
| Timing | Complication | Pathophysiology |
|---|---|---|
| Acute (during/shortly after RT) | Radiation proctitis | Direct radiation damage to rapidly dividing mucosal cells → inflammation, oedema, ulceration. Symptoms: diarrhoea, tenesmus, urgency, mucoid/bloody PR discharge |
| Radiation cystitis | Bladder mucosa is within the radiation field → irritative urinary symptoms (frequency, urgency, dysuria, haematuria) | |
| Radiation enteritis | Small bowel loops that fall into the pelvis receive radiation damage → watery diarrhoea, cramping, nausea | |
| Skin reaction | Erythema, desquamation of perineal/gluteal skin — painful but usually self-limiting | |
| Myelosuppression | Radiation to pelvic bone marrow → leucopenia, thrombocytopenia (usually mild with modern conformal techniques) | |
| Late (months to years after RT) | Chronic radiation proctitis | Progressive vascular damage (radiation vasculopathy → endarteritis obliterans) → mucosal telangiectasia → chronic PR bleeding. Can present years after treatment. Management: endoscopic argon plasma coagulation, sucralfate enemas, formalin application |
| Radiation fibrosis | Fibrosis of pelvic tissues → anastomotic stricture, ureteric stricture, bowel stricture | |
| Small bowel stricture/obstruction | Fibrosis and adhesion of irradiated small bowel → chronic SBO | |
| Secondary malignancy | Radiation-induced cancers (rare, latency > 10 years) — sarcoma within the radiation field | |
| Pelvic insufficiency fractures | Radiation damage to pelvic bones (sacrum, pubic rami) → stress fractures. Presents with pelvic pain; diagnosed on MRI | |
| Impaired wound healing | Irradiated tissue has reduced vascularity → poorer healing of the surgical anastomosis and perineal wound (in APR) — this is why pre-operative RT causes less long-term morbidity than post-operative RT, as the tissue has not yet been surgically disrupted [4] |
This is why neoadjuvant RT is preferred over adjuvant RT: pre-op RT is associated with a risk of poor wound healing, but post-op RT is associated with increased fibrotic strictures [4] — and overall, pre-op RT has fewer acute and late toxicities because the tissue being irradiated has intact vascularity.
Adverse effects of cytotoxic chemotherapy [24]:
- Mucositis — direct toxicity to rapidly dividing oral and GI mucosal cells → painful oral ulcers, dysphagia, diarrhoea
- Nausea and vomiting — stimulation of CTZ (chemoreceptor trigger zone) in area postrema and peripheral 5-HT3 receptors on vagal afferents; managed with ondansetron (5-HT3 antagonist), dexamethasone, aprepitant (NK1 antagonist)
- Diarrhoea — direct mucosal injury (especially irinotecan, which causes both early cholinergic diarrhoea and late secretory diarrhoea)
- Febrile neutropenia — myelosuppression → profound neutropenia (ANC < 0.5 × 10⁹/L) + fever → medical emergency requiring urgent IV broad-spectrum antibiotics (e.g., piperacillin-tazobactam), blood cultures, and close monitoring. Neutrophils are the first-line phagocytic defence; their depletion leaves patients vulnerable to overwhelming bacterial sepsis
- Alopecia — damage to rapidly dividing hair follicle cells
- Hand-foot syndrome — especially capecitabine [24] — capecitabine is metabolised to 5-FU by thymidine phosphorylase, which is highly expressed in the palms and soles → localised drug accumulation → painful erythema, swelling, desquamation
- Oxaliplatin-specific: peripheral neuropathy — dose-limiting; cumulative; presents as cold-triggered distal paraesthesias (tingling, numbness in fingers/toes); acute cold-induced laryngospasm. Mechanism: oxaliplatin chelates Na⁺ channels, causing hyperexcitability of peripheral nerves. May be irreversible at high cumulative doses
| Agent | Key Side Effects | Pathophysiology |
|---|---|---|
| Bevacizumab (anti-VEGF) [24] | Haemorrhage, impaired wound healing, arterial thromboembolic events [24]; hypertension, proteinuria, GI perforation (1–2%) | VEGF is essential for normal vascular homeostasis, wound healing (angiogenesis), and endothelial integrity. Blocking VEGF → disrupted vascular repair → bleeding, poor wound healing, fragile tumour vasculature → perforation |
| Cetuximab/Panitumumab (anti-EGFR) [24] | Cutaneous reactions (rash, pruritus, nail changes), headache, diarrhoea, infection [24] | EGFR is highly expressed in skin (keratinocytes); blockade → impaired epidermal proliferation and differentiation → acneiform rash (paradoxically, severity of skin rash correlates with treatment response) |
| Pembrolizumab/Nivolumab (anti-PD-1) | Immune-related adverse events (irAEs): pneumonitis, colitis, hepatitis, thyroiditis, dermatitis, hypophysitis | Checkpoint inhibitors unleash T-cell activity, which can attack normal tissues → autoimmune-like inflammation in virtually any organ. Managed with corticosteroids and, if severe, immunosuppression |
5-year survival by stage [4]:
| Stage | Rectal CA 5-Year Survival |
|---|---|
| Stage I | 74% |
| Stage IIA | 65% |
| Stage IIB | 52% |
| Stage IIC | 32% |
| Stage IIIA | 74% |
| Stage IIIB | 45% |
| Stage IIIC | 33% |
| Stage IV | 6% |
Note that Stage IIIA (T1–2, N1) paradoxically has a similar survival to Stage I — this is because the tumour is small and only 1–3 nodes are positive. In contrast, Stage IIC (T4b, N0) has worse survival despite being "Stage II" — because the tumour directly invades other organs.
Aim: detect recurrence (~40%) and metachronous tumours (new primary CA diagnosed > 6 months afterwards) [1].
Follow-up interval [1]:
- First 2 years: every 3 months
- 3rd year: every 6 months
- 4th–5th year: yearly
- *** > 5 years: considered to be in remission***
Investigations at each follow-up [1]:
- CEA, rigid sigmoidoscopy, LFT
- CT TAP / PET-CT yearly
- Colonoscopy: if pre-op scope was incomplete → within 6 months of surgery (risk of synchronous tumour = 3–5%); if pre-op scope was complete → 1 year post-op, then at 3 years, 5 years, then every 5 years [1]
High Yield Summary
Complications of CA Rectum — Key Points
-
Disease complications: Obstruction (most common presentation leading to emergency surgery), perforation (caecal perforation via closed-loop mechanism — highest mortality), fistula formation (rectovesical, rectovaginal), sacral nerve invasion (intractable pain), VTE
-
Post-surgical complications: Classified as immediate/early/late
- Anastomotic leak is the most feared early complication — classically day 4–7; incidence up to 10% in LAR; diverting ileostomy protects the patient
- LAR syndrome is the most common late functional complication — faecal urgency, frequency, incontinence; multifactorial (colonic dysmotility, neorectal reservoir dysfunction, sphincter dysfunction)
- Autonomic nerve injury: sympathetic → ejaculatory dysfunction/incontinence; parasympathetic → erectile dysfunction/urinary retention
- Stoma complications: early (necrosis, retraction, skin irritation) and late (parastomal hernia, prolapse, stenosis)
-
Therapy complications: Pelvic RT causes radiation proctitis/cystitis/enteritis acutely and fibrosis/stricture/secondary malignancy late; chemo causes myelosuppression, mucositis, neuropathy (oxaliplatin), hand-foot syndrome (capecitabine); anti-VEGF causes bleeding/poor healing/perforation; anti-EGFR causes acneiform rash
-
Recurrence: ~40% overall; detected by serial CEA, CT, and colonoscopy; salvage resection can confer survival benefit if detected early
Active Recall - Complications of CA Rectum
References
[1] Senior notes: Maksim Surgery Notes.pdf (Colorectal cancer section, p.107–108) [4] Senior notes: Ryan Ho GI.pdf (p.139, p.169, p.173, p.175–177) [24] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.699, p.708) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.902, p.911) [26] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf (p.67) [27] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (p.16) [28] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.708) and MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.911)
High Yield Summary
CA Rectum — Definition, Epidemiology, Risk Factors, Anatomy, Aetiology, Pathophysiology, Classification, and Clinical Features
-
Definition: Malignant neoplasm of the rectum; endoscopically defined as up to 15 cm from anal verge; oncologically defined as bowel below peritoneal reflection
-
Epidemiology: CRC is the most common cancer in HK (1st in males, 2nd in females); incidence 74.1/100k/yr; M:F = 1.5–1.6:1; peak 60–70y; median age 68; ~24% present as stage IV
-
Key risk factors: Age > 50, male, FHx, FAP, Lynch syndrome, IBD (UC > CD after 8–10 years), obesity, red/processed meat, smoking, alcohol; protective: aspirin/NSAIDs, fibre, physical activity
-
Pathways: CIN pathway (85%) = adenoma-carcinoma sequence (APC→KRAS→SMAD4→TP53); MSI pathway (15%) = defective MMR genes → better prognosis, responsive to immunotherapy
-
Anatomy: Mesorectum is key — TME reduced local recurrence from 25–40% to < 5–10%; CRM is the most important prognostic factor; distal rectal tumours can metastasise to lungs bypassing liver via IVC
-
Spread: Direct (radial — critical in rectal CA), lymphatic (Virchow's node), haematogenous (liver MC, then lungs), transcoelomic (Krukenberg tumour, Pouch of Douglas)
-
Clinical features: Rectal bleeding, change in bowel habit, tenesmus, mucus, anaemia are the cardinal symptoms; DRE is essential — most rectal tumours are palpable; left-sided tumours tend to obstruct while right-sided tend to bleed
-
Staging: TNM (AJCC 8th ed); minimum 12 LN for adequate staging; MRI pelvis is the gold standard for local staging of rectal CA
High Yield Summary
Differential Diagnosis of CA Rectum — Key Points
-
Rectal bleeding DDx: Haemorrhoids (most common cause of PR bleeding but can coexist with CA), anal fissure, diverticular disease (acute, profuse, painless), angiodysplasia, IBD, infective/ischaemic/radiation colitis, solitary rectal ulcer syndrome; don't forget massive UGI bleed can present as haematochezia (10–15%)
-
Change in bowel habit DDx: IBS (diagnosis of exclusion — no alarm features), IBD, diverticular disease, thyroid disease, drugs
-
Rectal mass DDx: Adenomatous polyp, carcinoid, GIST, lymphoma, endometriosis, presacral tumour, inflammatory mass (TB, Crohn's, diverticular abscess), rectal prolapse; don't forget non-GI pelvic masses (ovarian, uterine, bladder, prostate)
-
IDA in > 50: Always scope both upper and lower GI to exclude malignancy
-
LBO: CA colon/rectum is the most common cause (~60%); DDx includes sigmoid volvulus, diverticular stricture, hernia, pseudo-obstruction
-
Critical pitfalls: Haemorrhoids + CA coexist → always scope; TB colitis mimics CA in HK → rule out before biologics; IBS is a diagnosis of exclusion requiring absence of alarm features
High Yield Summary
Diagnostic Criteria, Algorithm and Investigations for CA Rectum
-
Colonoscopy + biopsy is the gold standard for diagnosis — tissue is needed; CEA is NOT diagnostic
-
DRE is the essential bedside examination — palpates ~70–80% of rectal tumours; assesses distance from anal verge, mobility, sphincter involvement, and Blumer's shelf
-
Staging paradigm for rectal cancer:
- MRI pelvis for local staging (T, N, CRM, EMVI, sphincter) — determines need for neoadjuvant therapy
- CT thorax + abdomen + pelvis for distant staging (liver, lung, peritoneum)
- Molecular profiling (KRAS/NRAS, BRAF, MSI/MMR) for targeted therapy decisions
-
CEA: low sensitivity/specificity for diagnosis; role is in prognostication, monitoring, and recurrence detection; post-op takes 4–6 weeks to normalise
-
Always scope entire colon: synchronous cancers in 3–5%, synchronous polyps in 30–50%
-
CRM ≤ 1 mm on MRI = threatened → neoadjuvant chemoRT indicated
-
Apple core lesion on barium enema is the classical radiological finding of annular constricting carcinoma
High Yield Summary
Management of CA Rectum — Key Points
-
Surgery with TME is the cornerstone — dissection along the "holy plane" between mesorectal and presacral fascia; decreases local recurrence and preserves autonomic nerves
-
Surgical options: Local excision (very early T1), Anterior Resection with TME (sphincter-preserving), APR with permanent colostomy (low tumours/poor sphincter/positive margins)
-
Neoadjuvant chemoRT is indicated for locally advanced rectal cancer (T3/T4, N+, threatened CRM) — 3 indications: resectable but locally advanced, borderline resectable, low-lying tumour for sphincter preservation
-
Long-course chemoRT (50.4 Gy + 5-FU) is the HK standard; short-course RT (25 Gy in 5 days) is an alternative but unsuitable for T4/bulky tumours
-
Watch and Wait: Clinical complete response after neoadjuvant → option of organ preservation with intensive surveillance; ~20% regrowth rate
-
Adjuvant chemo (FOLFOX/XELOX): Stage III and high-risk Stage II; at least 12 LN for adequate staging
-
Metastatic CRC targeted therapy: All RAS/BRAF wild-type → anti-EGFR; RAS/BRAF mutant → anti-VEGF; MSI-H/dMMR → anti-PD-1 immunotherapy
-
CEA is NOT diagnostic — used for prognostication, monitoring, and recurrence detection
High Yield Summary
Complications of CA Rectum — Key Points
-
Disease complications: Obstruction (most common presentation leading to emergency surgery), perforation (caecal perforation via closed-loop mechanism — highest mortality), fistula formation (rectovesical, rectovaginal), sacral nerve invasion (intractable pain), VTE
-
Post-surgical complications: Classified as immediate/early/late
- Anastomotic leak is the most feared early complication — classically day 4–7; incidence up to 10% in LAR; diverting ileostomy protects the patient
- LAR syndrome is the most common late functional complication — faecal urgency, frequency, incontinence; multifactorial (colonic dysmotility, neorectal reservoir dysfunction, sphincter dysfunction)
- Autonomic nerve injury: sympathetic → ejaculatory dysfunction/incontinence; parasympathetic → erectile dysfunction/urinary retention
- Stoma complications: early (necrosis, retraction, skin irritation) and late (parastomal hernia, prolapse, stenosis)
-
Therapy complications: Pelvic RT causes radiation proctitis/cystitis/enteritis acutely and fibrosis/stricture/secondary malignancy late; chemo causes myelosuppression, mucositis, neuropathy (oxaliplatin), hand-foot syndrome (capecitabine); anti-VEGF causes bleeding/poor healing/perforation; anti-EGFR causes acneiform rash
-
Recurrence: ~40% overall; detected by serial CEA, CT, and colonoscopy; salvage resection can confer survival benefit if detected early