Colorectal cancer is one of the most common cancer types seen in the western world. They are adenocarcinomas arising from adenomatous polyps in the colon and rectum, with a majority seen on the left side of the colon. 

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Anatomy of the large intestine

The large intestine is approximately 1.5m in length and stretches from the caecum to the anal canal. Anatomically it can be divided into

• Ascending colon
• Transverse colon
• Descending colon
• Sigmoid colon

Arterial supply

The colon is supplied by the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA)

• Ascending colon – ileocolic and right colic arteries branching from the SMA
• Transverse colon – right colic and middle colic artery branching from the SMA, and the left colic artery branching from the IMA
• Descending colon – left colic artery branching from the IMA
• Sigmoid colon – sigmoid arteries branching from the IMA

Venous drainage

Venous drainage is by the superior and inferior mesenteric vein draining into the portal vein transporting venous blood to the liver.

• Ascending colon – ileocolic and right colic veins -> superior mesenteric vein
• Transverse colon – middle colic vein -> superior mesenteric vein
• Descending colon – left colic vein -> inferior mesenteric vein
• Sigmoid colon – sigmoid veins -> inferior mesenteric vein

Bowel wall

• Mucosa – columnar epithelium with mucus-secreting goblet cells
• Submucosa – containing lymphatics
• Muscularis propria – circular and longitudinal layer
• Serosa – connective tissue

Colorectal cancer

Pathophysiology

• Adenoma-Carcinoma Sequence
  • Inherited or spontaneous mutation of APC (tumour suppressor gene) – deregulation of β-catenin protein
• >90% adenocarcinoma originating in epithelial cells
• Right sided: exophytic – grow outwards from one location
• Left-sided: circumferential– obstruct

Clinical features

Left-sided tumours

• Early obstruction
• Fresh rectal bleeding
• Mucous discharge
• Tenesmus
• Constipation
• Colicky lower abdominal pain
• Abdominal mass

Right-sided tumours

• Anaemia
• Weight loss
• Diarrhoea
• Abdominal mass

Emergency presentations

• Malignant bowel obstruction
• Perforation
• Haemorrhage

Risk factors

Inherited

• Genetic syndromes
  • FAP
  • HNPCC (Lynch syndrome)
  • IBD
  • Acromegaly
• Family history
  • One 1^st degree relative with CRC = 3x risk,
  • Two 1^st degree relatives with CRC = 10x risk
• Ethnicity – Ashkenazi Jews (I1307K APC mutation )

 Modifiable

• Diet high in fat and cholesterol – especially from animal sources
• Obesity – 30% increase if BMI > 30
• Alcohol – 40% increase if > 4 units/day
• HPV (anal cancers)

Assessment

History

• Abdominal pain – SOCRATES
• Bowel habits
  • Establish what is normal for the patient (usually between 3 times per week – 3 times per day)
  • Duration and degree of change in bowel habits
  • Complete vs partial constipation – complete -> no flatus
• Blood – fresh, mixed with stool, melaena
• Constitutional symptoms – weight loss, fatigue, night sweats, signs of anaemia
• PMHx – IBD, diabetes, previous surgery, cardiac/respiratory disease
• FHx – malignancy, autoimmunity (IBD)
• SHx – smoking, alcohol, obesity, WHO performance status

Examination

• Inspection – cachexia, signs of anaemia (conjunctival pallor, koilonychia, angular cheilitis), jaundice, masses
• Abdominal examination – masses, distension, fluid shift, organomegaly, external hernial orifices
• Full lymph node examination
• Digital rectal examination

Investigations

Bedside

• ECG
• Lateral flow/ Rapid Covid PCR
• Urine pregnancy test

Bloods

• Routine: FBC, U&E, LFT, CRP, Mg, bone profile, amylase
• Surgical bloods: G&S, clotting
• Tumour markers – baseline CEA (note: not a diagnostic marker but useful in assessing progression)

Imaging

• CT +/- contrast in suspected bowel obstruction
• Colonoscopy for screening and diagnosis
• CT CAP for staging
• CT colonography/barium enema/flexi-sig if colonoscopy contraindicated
• MRI rectum/anal canal – assess relationship with bowel musculature and other pelvic organs

Management

Classification

Treatment options

• Stage A/B – surgery
• Stage C – surgery with adjuvant chemotherapy 
• Stage D – chemotherapy +/- surgery
  • May be more suitable for stenting, palliative diversions or surgical bypass

Surgery

• Laparoscopy or laparotomy
• Primary anastomosis or de-functioning stoma
• In an emergency, it is safer to perform a proximal stoma than directly attempt anastomosis

Resection of rectal tumours

• High-lying rectal tumours (>3cm from anus): high or low anterior resection
  • Primary anastomosis
  • De-functioning stoma
  • J-pouch
• Low-lying rectal tumours: abdominoperineal resection (APER)
  • Resection of sigmoid colon and rectum
  • Resection of anus through perineum
  • End-colostomy

Screening

• Faecal test offered every 2 years from 50 to 74
• Faecal immunochemical test (FIT) – sensitivity for colon cancer 97%
  • Specific for lower GI bleeding as globin from the upper GI tract is degraded by digestive enzymes
  • No interference from dietary haem, peroxidases or medications

NICE Guidance recommends that patients should be referred for urgent investigation of suspected bowel cancer if:

• ≥40yrs with unexplained weight loss and abdominal pain
• ≥50yrs with unexplained rectal bleeding
• ≥60yrs with iron‑deficiency anaemia or change in bowel habit
• Positive occult blood screening test

Colorectal polyps

• Heterogenous growths in bowel lumen
• Common, but potential for malignant change 

Types

• Neoplastoc – Adenoma or polpypoid adenocarcinoma
• Inflammatory – pseudopolyp (UC)
• Hamartomatous – Peutz-Jegher’s
• Hyperplastic – benign

Familial adenomatous polyposis

• 1% of colorectal cancers
• Autosomal dominant (but 30% are sporadic mutations)
• Inhibition of APC tumour suppressor gene
• Hundreds of adenomatous polyps
• Usually asymptomatic
  • Unexplained rectal bleeding
  • Abdominal pain
  • Diarrhoea
  • cancers start to develop a decade after the appearance of the polyps
• Almost all develop CRC by age 40
• Flexi-sig every 1-2 years starting at age 10-12 to document onset
• Colectomy before the onset of cancer – usually 20s

Hereditary Non-Polyposis Colorectal Cancer (HNPCC)/Lynch Syndrome

• Autosomal dominant inheritance
• Lifetime risk of cancer 85%
  • Endometrial / TCC / gastric / ovarian / pancreatic / biliary / haemotological
  • 3 or more relatives with CRC, two generations
• Mean age of diagnosis of CRC is 45years
• Colonoscopy screening – every 2 years from age 20-25
• Colectomy before the onset of cancer – usually 20s

Peutz-jegher’s syndrome 

• Autosomal dominant
• Multiple hamartomatous polyps usually involving small intestine (ileum predominantly)
• Mucocutaneous hyperpigmented macules of the nose, buccal mucosa, axilla, hands, feet and genitalia
• Risk of
  • Large bowel carcinoma (39% lifetime risk)
  • Small intestine carcinoma (13% lifetime risk)
  • Gastric carcinoma (29% lifetime risk)
  • Extraintestinal malignancies (breast, lung, pancreas)

Written by Dr Freya Bakko (FY2)