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MCD > Cancer 13:colorectal cancer as a disease > Flashcards

Cancer 13:colorectal cancer as a disease Flashcards

1
Q

What is the role of the colon

A
  • extraction of water from faeces
  • faecal reservoir
  • bacterial digestion for vitamins
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2
Q

What are the layers of the colon?

A 
epithelium
lamina propria 
muscularis mucosa 
submucosa 
muscularis propria 
fat and blood vessels
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3
Q

What type of cancer is usually found in colon?

A

adenocarcinomas - in the glandular epithelium

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4
Q

What is the role of the crypts of lieberkuhn?

A

cells divide where the stem cells are found and then are shunted to the top of the villus to be shed

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5
Q

What is the turnover of the colon?

A
  • 2-5 million cells die perminute

- proliferation renders cells vulnerable

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6
Q

WHat does the APC gene do and what does a mutation mean?

A

it regulates a number of cellular functions including mitosis, migration and maintenance of genome stability
- mutations prevent cell loss

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7
Q

What protective mechanisms are in place to eliminate genetically defective cells (3)

A
  • natural loss
  • DNA monitors
  • repair enzymes
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8
Q

What is a polyp?

A

any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous

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9
Q

What is an adenoma?

A

a benign neoplasm of the mucosal epithelial cells

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10
Q

What are the main types of colonic polyp types?

A
  • metaplastic/hyperplastic

- adenomas

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11
Q

What are the features of hyperplastic polyps?

A
  • very common
  • less than 0.5 sm
  • 90% of all colonic polyps
  • often multiple
  • no malignant potential
  • 15% have k-ras mutation
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12
Q

What are the colonic adenoma types?

A
  • tubular (>75%)
  • tubulovillous (25-50% villous)
  • villous (> 50% villous)
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13
Q

What are the two different shapes of adenomas?

A
  • pedunculated adenomas are on a stalk

- sessile adenomas are flat and raised

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14
Q

What is the microscopic structure of tubular adenomas?

A
  • columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
  • increased proliferative activity
  • reduced differentiation
  • complexity/disorganisation of architecture
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15
Q

What is the microscopic structure of tubular adenomas?

A
  • mucinous cells with nuclear enlargement, elongation , multilayering and loss of polarity
  • exophytic, frond-like extensions
  • rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia
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16
Q

Define dysplasia

A

-abnormal growth of cells with some features of cancer

indefinite has low grade and high grade

17
Q

Which condition increases the number of polyps?

A

-familial adenomatous polyposis (FAP)

18
Q

What causes adenomatous polyposis coli?

A
  • 5q21 gene mutation
  • site of mutation determines clinical variants
  • many patients have prophylactic colectomy
19
Q

What proportion of adults have carcinomas and how many of them become cancerous?

A
  • 25% of adults at age 50
  • 5% of these become cancers if left
  • large polyps have a higher risk than small ones
  • cancers stay at a curable stage for 2 years
20
Q

How does an adenoma progress to carcinoma?

A
  • most colorectal cancers arise from adenomas
  • residual adenoma in 10-30% of CRCs
  • adenomas precede the cancer by about 15 years
  • removal of polyps decreases the risk of carcinoma formation
21
Q

What are the THREE genetic pathways in colorectal cancer?

A

-adenoma carcinoma sequence

APC is the best known for being damaged but others include K ras, Smads, p53, telomerase activation

-microsatellite instability

these are repeat sequences prone to misalignment and some are involved in inhibiting growth
Mis-match repair genes
HNPCC - germline mutation

-genetic predisposition

FAP, inactivation of APC
HNPCC, microsatellite instability

22
Q

What dietary deficiencies can impact on colorectal cancer and why?

A

-folates are important for nucleotide synthesis and DNA methylation

-MTHFR
deficiency leads to disruption in DNA synthesis and so instability
decreased methionine synthesis leads to genomic hypomethylation and focal hypermethylation so there is gene activation and silencing

23
Q

Which foods are associated with anti-cancer properties?

A
  • vitamin C
  • vitamin E
  • isothiocyanates
  • polyphenols
24
Q

What are the clinical presentations of colorectal cancer?

A
  • change in bowel habit
  • bleeding per rectal
  • unexplained iron deficiency anaemia

other include

  • mucus per rectal
  • bloating
  • cramps
  • constitutional

these tend to be rationalised as getting old/piles/IBS

25
Q

What are the macroscopic features of colorectal cancer?

A

-small carcinomas may be present with larger polypoid adenomas, pedunculated or sessile

26
Q

What is the distribution of colorectal cancer?

A
  • caecum/ascending colon 22%
  • transverse colon 11%
  • descending colon 6%
  • rectosigmoid 55%
27
Q

What are the possible structure of microscopic carcinomas?

A
  • mucinous carcinoma
  • signet ring cell
  • neuroendocrine

almost all of the carcinomas are adenocarcinomas

28
Q

How is the adenocarcinoma graded?

A
  • the proportion of gland differentiation relative to solid areas or nests and cords of cells without lumina

10% are well differentiated
70% are moderately differentiated
20% are poorly differentiated

29
Q

How does Dukes Classification work?

A

Dukes A- growth limited to mucosa/submucosa
Dukes B- growth into or beyond muscularis propria, nodes negative
Dukes C1- nodes positive, apical LN negative
Dukes C2 - apical LN positive

30
Q

What clinical features affect prognosis?

A
  • diagnosis in asymptomatic patients
  • rectal bleeding as presenting symptom
  • tumour location
  • aged less than 30
  • distant metastases
  • preoperative serum CEA
31
Q

What pathological features affect prognosis?

A
  • depth of bowel wall penetration
  • number of regional lymph nodes involved
  • degree of differentiation
  • venous invasion
  • lymphatic invasion
  • perineural invasion
  • local inflammation and immunologic reaction
32
Q

In what circumstances are people screened for cancer?

A
  • previous adenoma
  • 1st degree relative affected by colorectal cancer before the age of 45
  • 2 affected first degree relatives
  • evidence of dormant familial cancer trait
  • Ulcerative Colitis and Crohns disease
  • heritable cancer families
33
Q

What is the definition of screening?

A

the practise of investigating healthy individuals with the object of detecting unrecognised disease or people with an exceptionally high risk of developing disease AND of intervening in ways that will prevent he occurrence of disease or improve the prognosis when it develops

34
Q

What do they look for in screening colon cancer in the UK?

A

-faecal occult blood

if positive 60-75 years are sent for a colonoscopy
55-60 years are sent for a sigmoidoscopy

MCD (13 decks)

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