T1 L10: Bowel Cancer

• For the purpose of public understanding, what areas does the term 'bowel cancer' apply to?

  large intestine, ie colon and rectal cancer
• What are the risk factors for bowel cancer?

  1. Environmental
  2. Longstanding ulcerative colitis
  3. Crohn's disease (to a lesser extent than UC)
  4. Adenoma in large bowel
  5. History of bowel cancer surgery
  6. Family history of bowel cancer
  7. old age
• How does high fibre diet reduce bowel cancer?

  • increase formation of short chain fatty acids: promote healthy gut microorganisms, reduce proliferation of neoplastic cells
  • increase stool bulk: reduce transit time, potential carcinogens in stool have shorter contact with bowel mucosa
  • reduce formation of secondary bile acids (potentially carcinogenic)
• What is a polyp?

  a protruding growth into a hollow viscus

  can be benign, adenoma or malignant
• In bowel cancer screening, a polyp is either 'innocent' or 'precancerous'.
• What is an adenoma?

  a pre-cancerous lesion

  consists of dysplastic epithelium
• What is dysplasia?

  cells that have morphological features of cancer without invasion of surrounding tissue
• Types of dysplasia?

  Low grade dysplasia: early precancerous features

  High grade dysplasia: advanced precancerous features with high risk of invasion if not removed
• Whether a polyp is benign (hyperlastic), dysplastic (adenoma) or cancerous, the diagnosis can only be confirmed on microscopic examination.
• What are the pathological features of polyps?

  • hyperplastic polyp: numerous goblet cells when compared to normal mucosa; lace-like pattern
  • Tubular adenoma: test-tube like appearance
  • Villous adenoma: finger-like appearance
  • Tubulovillous adenoma: mixture

  
• What is the adenoma-carcinoma sequence?

  stepwise progression from normal mucosa to adenoma to cancer

  both phenotypically and genetically
• Evidence for Adenoma-carcinoma sequence

  1. distribution of adenomas follows distribution of cancer
  2. residual adenoma found in most cases of cancer
  3. risk of cancer directly related to number of polyps
  4. removal of adenomas to reduce incidence of bowel cancer
• What is Familial Adenomatous Polyposis (FAP)?

  hereditary autosomal dominant, APC gene

  many polyps in large bowel (500-2500)

  minimum of 100 polyps required to diagnose

  Polyps are dysplastic so called adenomas

  associated with 100% risk of development of cancer by age 30

  patients undergo prophylactic colectomy around age 20.

  
• Genetics of Familial Adenomatous Polyposis in bowel cancer

  hereditary autosomal dominant

  APC gene (Adenomatous Polyposis Coli)

  First hit: germ cell mutation in utero

  Second hit: after birth, in somatic cell; leads to heterozygosity (cells will acquire two identical copies of abnormal gene) causes development of polyps

  Patients have no polyps at birth & require second hit to develop polyps
• The Fearon & Vogelstein model

  adenoma-carcinoma sequence

  
• What is Lynch syndrome?

  (Hereditary Non-polyposis Colorectal Cancer)

  familial cancer affecting caecum and right colon before age of 50

  associated with endometrial, small bowel and cancer of urinary tract

  no precursor polyps

  
• What are the genetics of Lynch Syndrome?

  mismatch of DNA base pairs during replication

  errors accumulate

  microsatellites (tandem repeats; fixed for life) created

  microsatellite instability (shows defective mismatch repair)

  first hit: individual inherits first defective copy in utero

  second hit: aqcuire 2nd copy in life

  develop cancer
• How are Lynch Syndrome patients assessed?

  using the Amsterdam Criteria
• What are the symptoms of Bowel Cancer?

  can be asymptomatic and detected during screening

  change in bowel habit: eg constipation alternating with diarrhoea due to an obstructive cancer

  bleeding from rectum

  anaemia

  abdominal pain due to obstruction

  
• How do we diagnose bowel cancer?

  history + clinical examination

  flexible sigmoidoscopy and colonoscopy with biopsy and histological examination

  CT colonography for patients who can't tolerate colonoscopy

  staging CT scan for distal metastasis

  MRI for rectal cancer to assess local spread
• What is the pathology of bowel cancer?

  Adenocarcinoma

  Grading:

  • well differentiated: resemble normal colonic mucosa
  • moderately differentiated: most common
  • poorly differentiated: minimal or no glandular differentiation

  
• How do we decide the staging of bowel cancer?

  TNM staging
• How is TNM staging used?

  T= Tumour; assesses depth of invasion of bowel wall

  N= lymph node metastasis

  M= Distant metastasis to liver or lung
• T1 stage of bowel cancer?

  Invasion of submucosa; muscularis propria is CLEAR

  
• T2 stage of bowel cancer?

  involves muscularis propria without full thickness invasion - eg invasion of inner layer and not external

  
• T3 stage of bowel cancer?

  Invasion of the full thickness of bowel wall but not the serosa

  
• T4 stage of bowel cancer?

  cancer has gone through bowel wall and is present on serosa

  
• What stage is cancer that has invaded the full thickness of the bowel with lymph node metastasis?

  T3 N1
• What stage is cancer that has liver metastasis from bowel cancer?

  M1

  
• What is bowel cancer screening?

  looking for early signs of disease in healthy people

  can prevent cancer by detecting polyps before they turn cancerous

  will detect early cancers in curable stage
• What are the bowel cancer screenings done in the UK?

  stool test

  faecal immunochemical test (FIT)
• Bowel cancer screening in the UK test for..?

  testing for occult blood (hidden from naked eye)

  FIT: antibody-antigen reaction

  Positive test does not necessarily mean cancer; haemorrhoids & inflammation can also cause a positive test
• What happens after a positive stool test?

  patient referred for colonoscopy

  detect polyps

  however FIT does not detect non-bleeding polyps so test repeated every two years