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Colorectal Cancer

Definition

  • Malignant growth breaching the basement membrane in the colon (from caecum to rectum)
  • Most commonly adenocarcinomas from the epithelial cells
  • 71% in the colon, 29% in the rectum

 

Risk factors

  • Family history
    • FAP (APC gene mutation)
    • HNPCC (Lynch syndrome)
  • Polyps, and other polyposis disorders
  • Low fibre diet
  • Smoking
  • Inflammatory bowel disease (especially ulcerative colitis)
  • Age
  • Obesity
  • Sedentary lifestyle

 

Differential diagnoses

  • Inflammatory bowel disease
  • Coeliac disease
  • Haemorrhoids
  • Anal fissure
  • Polyps
  • Diverticulitis
  • IBS

 

Epidemiology

  • Colorectal cancer is the third most common cancer in Western world
  • Incidence is highest in Western world, lowest in Africa and Asia
  • Lifetime risk is about 5%
  • Affects more men than women
  • Is rare in under 40s, average age of diagnosis is 71
  • Survival rate is about 50%

 

Aetiology

  • Genetic factors - syndromes
    • FAP – Familial adenomatous polyposis
      • 100% penetrance normally by age 30
      • Often have prophylactic resection
    • HNPCC – Hereditary non-polyposis colorectal cancer
      • Lower penetrance, but still high change of cancer
    • Family history increases risk several times over (especially if under the age of 45 at diagnosis)

 

Clinical features

  • Right sided (caecal/ascending colon) is most likely to present as iron deficiency anaemia
    • Typical anaemia symptoms
      • Fatigue
      • Weakness
      • SOB
      • Palpitations
      • Tachycardia
      • Pallor
      • Angular stomatitis
      • Glossitis
    • Weight loss
    • Unlikely to have obstruction as stool is still liquid so can push past
    • Slightly looser stool
    • Blood is likely to be mixed in with stool, so not obvious
    • Mass in right iliac fossa
  • More distal
    • Weight loss
    • Obstructive symptoms
      • Abdominal colic
    • Diarrhoea
    • Constipation
    • Noticeable blood in stool
    • Mucus (more common in more distal cancers)
    • Palpable mass
    • Anaemia
  • Rectal
    • Tenesmus
    • Weight loss
    • Fresh blood on defecation
    • Haematochezia (passing blood)
    • Obstruction and colicky pain
    • Change in bowel habits
    • Palpable mass on PR
    • Anaemia

 

Pathophysiology

  • Cancers often start as polyps
    • Pedunculated (stalk) or non-pedunculated
    • 90% are non-neoplastic and won’t go on to be cancerous
    • Neoplastic polps are called adenomas
  • Adenomas arise from dysplastic epithelia (tall, disorderly, cigar shaped nuclei) – 4 histological types
    • Tubular adenoma – tubular glands with smooth surface, most become pedunculated
    • Villous adenoma – villous projections of epithelia
    • Tubulovillous adenoma – mixture of above
    • Serrated adenoma – hyperplastic polyp
  • Carcinomas arise from adenomas
    • Cells typically resemble adenomas (columnar cells), but invade past the basement membrane into the submucosa, muscularis propria and beyond
  • Adenoma-carcinoma sequence is the progression of gene mutations involved in adenomas becoming cancerous
    • It is the accumulation of mutations that is important, rather than their order
    • Initial ‘hits’ may be hereditary, like APC mutation
    • An additional ‘hit’ required in processes of DNA methylation, which inactivate normal alleles
    • Accumulation of tumour suppressor gene (eg p53) mutation and (proto)oncogene mutation (eg k-RAS)

The adenoma-carcinoma sequence

Investigations

  • FBC
    • Anaemia
  • Iron studies
    • Low ferritin
    • High total binding capacity (transferrin)
  • Colonoscopy
  • Biopsy
  • CT colonscopy – can use contrast
  • Barium enema – to show apple-core narrowing
  • CT
    • Lymph nodes, tumour size

 

Management

  • Radiotherapy
    • Pre- or post-operative
  • Chemotherapy
    • Pre- or post-operatively, or palliative
  • Surgery – bowel resection
    • Ileostomy
    • Colostomy
    • Temporary or permanent
    • Stenting is used in palliative care to reduce obstructive symptoms

 

Prognosis

  • 50% 5 year survival
  • Over 90% for stage 1
  • <8% for stage 4
  • Often present late because asymptomatic (especially right sides), or because of embarrassment
Colorectal cancer.docx
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