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Carcinoma of the colon

  • Neoplams of colon + rectum – hereditary, sporadic, familial

Etiology

  • Diet – red meat, low fibre
  • Alcohol/smoking
  • Family history
  • Previous cancer
  • Neoplastic polyps
  • Inflammatory bowel disease
  • Familial – FAP
  • Hereditary – HNPCC (AD)

Pathogenesis

  • APC gene is a tumour suppressor gene – on Chromosome 5q
    • mutations can initiate the accumulation of genetic damage
  • Colorectal polyps
    • Any mass that projects into the colon lumen
    • Can be sessile or pedunculated
    • Removed via colonoscopy
  • Peutz Jegher’s syn – AD
    • Harmatomatous polyps + hyperpigmentation of buccal mucosa, lips, digits
    • Polyps may cause bleeding or obstruction
  • HNPCC – no polyps, AD
    • Amsterdam criteria – 3 family members with colon cancer; colorectal cancer in 2 generations; 1 affected family member <50 y/o; FAP excluded

Pathophysiology

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

Chromosomal instability

  • Mutations or deletions of portions of chromosomes arise, with LOH and inactivation of specific TSGs

Microsatellite instability (development of HNPCC)

  • Germline mutations in encoding enzymes involved in repairing errors that occur normally during DNA replication
  • Replication errors accumulate and can be detected in microsatellites of repetitive DNA sequences
  • Result in genetically unstable phenotypes and accumulations of multiple mutations – eventually lead to cancer

Clinical features – see diagram

  • Left colon – fresh rectal bleeding and obstruction
  • Right colon – anemia from occult bleeding, altered bowel habit, obstruction is a late feature
  • Rectum – bleeding, mucus and change in bowel habit, rectal pain
  • Other – pain, mass, weight loss, vomiting

Investigations

  • FBC – anaemia
  • Faecal occult blood
  • Colonoscopy, sigmoidoscopy
  • Barium enema , CT, MRI
  • CEA – levels also increase in pancreas, gastric, lung, breast carcinoma; BPH
  • CA 19-9,alpha-FP
  • TRUS

Spread

  • Local – bladder, ureter (hydronephrosis). Peritonitis or abscess
  • Blood – MC to liver via portal v. Rarely spreads to bone, lungs, skin
  • Lymph – pericolic, epicolic LNs

Staging – Modified Duke’s criteria

Medical treatment (for Duke C)

  • FOLFOX regime

Surgical treatment

  • Right/Left hemicolectomy
  • Sigmoid colectomy
  • Anterior resection – low sigmoid or high rectal tumours
  • Abdomino-perineal resection – Miles, Gabriel, Lloyd Davis Operations
    • For rectal carcinoma
    • Removal of anus, rectum, part of sigmoid colon, assoc LNs
    • Remaining part of the sigmoid brought out permanently – colostomy
  • Proctosigmoidectomy – HARTMANNS OP
    • For emergency bowel obstruction/perforation
    • Resection of recto-sigmoid colon with closure of anorectal stump
  • Endoscopic stenting/ Radiotherapy – palliative therapy

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