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Colon Cancer

Etiology

  • Neoplastic polyps
  • Inflammatory bowel disease
    • Ulcerative colitis and Crohn’s Disease
  • Hereditary conditions – FAP, HNPCC/Lynch syndrome
  • Diet – red meat, low fibre
  • Alcohol, smoking

Pathogenesis

  • Results from the accumulation of multiple genetic mutations arising from 2 major pathways

Loss of Heterozygosity pathway (development of FAP)

  • Mutations
    • Mutations in APC gene and KRAS gene
    • Loss of DCC tumour suppressor gene
    • Mutation of p53
  • This pathway carries a poor prognosis

Replication Error Repair pathway (development of HNPCC)

  • Germline mutations in enzymes involved in repairing errors that occur normally during DNA replication
  • These genes are – hMSH2 + SH6; hMLH1 + LH3; hPMS1, + MS2
  • These replication errors accumulate and can be detected in microsatellites of repetitive DNA sequences
    • Leads to microsatellite instability
  • This pathway carries a better prognosis

Classification

Gross classification

  • Annular
  • Tubular
  • Ulcerative
  • Caulifower (proliferative)

WHO histological classification

  • Adenocarcinoma – 90%
  • Mucinous adenocarcinoma
  • Signet ring cell carcinoma
  • Small cell carcinoma – rare, very poor prognosis
  • Squamous cell carcinoma
  • Undifferentiated carcinoma

Staging – Duke’s Criteria

  • A – invasion into but not through the bowel wall
  • B – invasion through bowel wall penetrating the muscular layer, but not involving lymph nodes
  • C – involvement of lymph nodes
  • D – widespread metastases

Clinical features

  • Right sided growth
    • Anemia – due to occult bleeding
    • Palpable mass in right iliac fossa – mobile, non-tender, hard
  • Left sided growth
    • Colicky abdominal pain, back pain
    • Altered bowel habits
    • Abdominal distension due to obstruction
    • Tenesmus – with passage of blood and mucus
  • Other presentations
    • Loss of appetite, weight loss, jaundice, Troisier’s sign (enlarged left supraclavicular lymph node)
  • Pericolic abscess, perforation, peritonitis – can be the first presentation

Spread

  • Local – bladder, ureter (hydronephrosis); can perforate and cause peritonitis or abscess
  • Blood – most commonly to the liver via portal v. Rarely spreads to bone, lungs, skin
  • Lymph – pericolic, epicolic lymph nodes

Investigations

  • FBC – anaemia, abnormal LFTs
  • Colonoscopy, sigmoidoscopy
  • Barium enema
  • CT – for metastases
  • MRI
  • TR-US
  • CEA – not used as a diagnostic marker, but used to monitor disease progression/recurrence

Treatment

Surgery (mainstay of treatment)

  •  Right hemicolectomy – for caecal/ascending colon tumours
  • Extended right hemicolectomy – for transverse colon tumours
  • Left hemicolectomy – for descending colon tumours
  • Sigmoid colectomy
  • Anterior resection – low sigmoid or high rectal tumours

Chemotherapy

  • FOLFOX – folinic acid, fluorouracil, oxaliplatin

Radiotherapy

  • Used as neoadjuvant treatment
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